Hem BRA el a me deh Be SE GH OR Radiation Effects Research Foundation BA ial ot He Be A Japan-US Cooperative Research Organization Be OSE A Brief Description ZOE: A kg TLE INABA D BSE FT EI FEZ | RRR GE MI FEIT BME FEI Front: RERF in Hijiyama Park, Hiroshima, Back: RERF Nagasaki Laboratory MeGAA TCS ER Be 2 OSCAR Radiation Effects Research Foundation Z Bw Se A Brief Description BX Contents BX Contents Bees SE! AIMMMOGUICHIONY: 24s eeseci resus At cedt acces a teens aa Panes Acta dacih ca ceeedes tniestteaeta etna a aac deae acess 1 BIL EBY E YAEE Objective and HIStory .o.cc.cccccccsccssessssssesseessessessssssecsscsssssscsucssscsscsusssecsucsussscsucsuecsecauessecscaseases 3 #8 FY Departments PE=ZEB Department of Epidemiology ..........cssscssssssssocsrsessscscessssscssnsessessessaseassdnsessssvencaceusssseisaseosasnsassecsoasaseossoreese 4 HAL uy Department Of Statisties.seccasesveissdeacescussbaevasiesvascerndsvevinsovh acura tdasteseaiaeas des oenticeardienmies Gide 4 RAR SEER Department of Clinical Studies ......c..cccccscscsssssscseessssesecscssscsescsescsvssescscssescssscsussesescseeseseseseesesesesees 4 Gene ub:, Department OF Genetics v.ivsiséss.isieacscavehs cigesssexviahisasa aatsesnssestnsser a vivnentaacssaneacteen eataaasaueenaiensirn 5 NRE DW F/ a FEZ Department of Radiobiology/Molecular Epidemiology.........:.::cccssceseeseseeeeseseesees 5 THERELATES Information Technology Department .........ccscccccsscsessssesesessessscscescsesescsucscscssesessseaauescseseseseseseseseasess 5 BASSE Study Populations .........ccccccsscsscssssssccsessecssccsesssccsscssssscsucsaessccsssascsuccsssasssscsascssessssauecsssussauccsessscascssssaseeses 6 Frimiite (LSS) 42H] Life Span Study (LSS) Sample De Me ech 2 (AHS) 486 hare Se] In Ute MIRA OF TE (F,) OEE] Children of Survivors (F;) Sample ........cccccccscsscsessessescssssesseseesesscsessssesscsesssseeesseees 9 aur = O BUARO FHARZ2 Early Radiation Effects FEVERU UIE Acute Radiation Syndrome ......ccscssssssssessessessessessessessessecsccsccscsscsscsessscsessessecsecscauccucsecseeseesesseeses 10 EMG (ce, AGUS IDG AUI ss2es cers 22s ccs davstorn shits tote ci Gea cacs earsecede stasecs sek oveea tomerate a eteaasn ea taaeaa feels ansdodtledeesh ateatese 11 OTR AABE CGA) Radiation Cataract (Lens Opacity) ..c..cecceccssessessessessessessessestestssteseeseeseeseeseeneenss 11 PETAR BRZE Late Radiation Effects o...ccccccccsecscssssssssssssessssecssnecssnecsssecsssecsssccsssccssecssssesuseessueesssceesneesseecsneesaes 13 BEI ACO Av. ISOlid Cancers «....icecsocasssovsse shasisescossasensxesseadvossedeneseeseg uevendcussedevsssivsnscdtssssnseaseaiensssvesvesseauaeveavesibtasisians 13 PUM pas. MSSM ec fas sas tresses cates tases ene eps cate eet ac atiesde san sseracc ga eanestoncs ceuens eas Ges sttens te eestees se eect scatters 17 TSE. “Benim MUmOrs yeasts saves, 5 vas d seveta rea scale devearsinc ce woes desist shaver te Ataacssisi ntearatete keane coed 19 PBAWNOREIC E SITE Non-cancer Disease Mortality Bete Ee Chromosome Aberrations........cessssssscssssesssssessessesesscesssencevessssncvessescaensnssscsessezetsessessssscnseessnseasestaees AH ZEAE SE ~— Somatic Cell Mutations ......c.cccccccsccsccecsececcesssceccscescsceeceevaceecsesscsessceecaccacsesseecsceacecsaceecaeeaceeeaces 25 Gegee ArMrivenity sess -2eseeeesscsecatiaaes aes seas es aigessav datas eased wei een dae erresaaieah i oee as 25 Wide + 38 Physical Growth and Development ...........::ccssssesessessssessesesseseseeseseeseseeuesecscsesaesessecesessseseesneneetenees 27 ZAG? JA SIND: Aiee acenaranensatihia tines hadtasatin dam emGinnalrniind dandinnaisiinkuatanaie: 27 HAA®ERE In Utero Exposure ithe EOI ~=Mental Retardation and Growth Impairment ............c.ccesceseeseeseceeseeeeeeteeteeees 28 WS AISEEZE * Cancer Incidence iiss. wiainissainasiaaia terest ta uisatietamvenrainrinarntaraish cnet 28 PETAR OIBIRAV RZ = Geretic Effects oo... cccccccessessssessssessessssesessessssesessesseseesesessssessesesseseesesnesesssseeseseeseseesenesseanes 30 THAR REESE = Birth Defects in Fy OffSpring ........cccccccccsssscsessesescseseesesesessescscscsuescsescsuesescsesuesescscsesesssessescsceeeeees 30 ee Ls’ «Sex, Ratio mil Oftsprim % sccszaacdadecs tras cstedacsvasa oP eciveacecaca shaves tesecied acids tasdedensdul sched scalacedisbaastandanaeee testy 32 4e fa {KL Chromosome Aberrations in F, Offspring ....c..c.ceecccscssessesessssessesessesessesesecueseesesesseseesesnssesesseeneaeees 33 MRA AA DZ/KZES Blood Protein Mutations in Fy Offspring......c.cccccccccsesessessecseseseessesesseeseeseeseeseeseeneanes 33 DNA fae > DNA: Studies in: Fy Omtsprintgss.ctsicss.cesccsedgesnszceatcasesepsoenecassatanstcessartessseeancaonsban npeceiinttv aeessasseaeeasconaa 35 Contents BX | FEC LOPS A584E 28 =~ Mortality and Cancer Incidence in Fy Offspring .......c..ccccescessessesseseeseeseeseeseeseeneenes 36 HEARS Radiation Dosimetry PEREZ ASME REHE TE Physical Dose Estimates .........ccccsscscssssssssssessssesssscssssscsssvesssscsessssessssessesccussesessecseateseeecseeseaes 38 WRT SL — Residual Radiation ......ccccccccccccssscssesssscssescscescscesesscssescsscscssesesscsscsesacseacsecsesacssescsecsescasesssecstsacsecacsaes 40 FEA HE TE Biological Dosimetry .......c.cccccscssssesssssssssssesssscesssssssscssssessssesesnessssssecssacsisscsessecssaesescsesseaes 42 fs] .—7— _ Frequently Asked Questions Mi dT a a aca daeen cesarean ae oc aed eedat om neaeaoeemnnnanA 44 Question 1. How many people died as a result of the atomic bombings? BARES 2 FACES ARBRE UC REDS DSA FEE I esc eccceeccseeecseeecsneccsseessscecesecsesecsusecsnsessnseesssecsneecnseesuseesuseesaeeesntensesss 44 uestion 2. How many cancers in A-bomb survivors are attributable to radiation? FR 3 WPA CE 2 ING PALES BEE CVD coccecceesesseeseeeseessneessneessneesseesseesniessaeesnies 45 Question 3. Are radiation-induced cancers still occurring? Eel Aire a SO os cioniesdas cere aateeanctesiaisskescal eel conean Aan em Oae anaEsraniialn 46 Question 4. What radiation effects have been observed in people exposed in utero? (214 2a sat pdt TCE O RMN EHO AICP SCETT. CODA © bea LC. BURR, (2008 4F BITE) “CBEIZ 60 fe EASE LCE TAS, BORRIEIC ATC & > LIB OIE Bese TE CIS G KR 40 AF < OMI DEC H 0. WEIL WE EFIS CHA LSD SAREEtA. LOLI on ECOMABRRD 5S Ch. MOTH SRICROKCEMDD ie te. BURR OLR - tithe COB (cfr nS & EBL, THRO BNR AEE ERM OER RC LT, EEE ODO RICGEASRNTATHH ET. BUSA DFE D FEL, Jed BY LK S 7 BUR HE ORV (2 72S BRA CH Y. CORUM, Fink. IEP DRE COR CHARI LEV bOCT. EK, f€ Head FE & RIT IS Ze Y) eV SES © ELF LCBO ET. BUDS CM 6b ODF & ti ARE IS Ro TC bNKO IE ts eaoeie aan sen a dananenns BARS OO CH % LACS BIIIEK CA ADO CLR jenn area hiens BEM NI BIT SMBEO 6 —-OOGAIL, PER A MN DBR ETE TED eB BE CIT DN TWZLETCT © WR DO PU TETE LAF Ltd 1965 AEC FIO CHERE ELA. FOR 1986 4F (DS86) & 2002 42 (DS02) cb YO oaT SNELL. RETA 5 lk, DSO2 aes HVAZCEEWRLE LEAS, DS86 ECO WERK FRAT (<1 DS86 DEA S71, TRRIC. T6SD Diftse YY AT ASHWV5nNTBY) ETF. DS86 & DSO2 Oikvrld, fi °F CHREO HBULEE CH. BAH PCHEY AT AKO tH 0 EAA. HARI RAHA CI, HAT HET ist (A OL MILER CT AS. FIgHglcbbS & Dso2 CH 8% OMEN ZO. CORA EY ee OTE VATS PRO ELK. HAMIL OLB Ee CBB CREVY WO PMA e UTIL, Db AY VRE PEP RLO Hl a S FY Introduction The Radiation Effects Research Foundation (RERF) is a research institute established in 1975 with joint funding from the US and Japanese governments, as the successor organization to the Atomic Bomb Casualty Commission (ABCC), established in Hiroshima and Nagasaki by the US National Academy of Sciences in 1947 to study health effects among the atomic-bomb (A-bomb) survivors in the two cities. RERF took over the long-term follow-up stud- ies conducted by ABCC without making any significant changes. Ever since that time, the institute has continued its activities based on the mission of maintaining the health and welfare of the A-bomb survivors and researching radiation effects on human health under the unique joint- management arrangement by the two governments. ABCC-RERP'’s research aim is to determine long-term effects of radiation exposure, which had been uncharted territory for scientific research. More than 60 years have already passed (as of 2008) since the initiation of the follow-up studies, but nearly 40 more years will be needed to complete follow-up of those who were young at the time of exposure. Thus, it must be said that RERF’s research is only half done. Despite that, however, quite a few findings have been uncovered by past research, and the organiza- tion’s research results have been utilized as reference in medical care and welfare for A-bomb survivors, consis- tently attracting the attention of international and other organizations as a source of basic information for establish- ing radiation protection standards. RERF research is characterized by the long-term follow- up of a large well-defined population. The scale, structure, and accuracy of the follow-up studies are unparalleled any- where in the world. Health examination participation rates have remained high over many years. That RERF has maintained such a high level of research is thanks to the understanding and cooperation of the A-bomb survivors. At the same time, RERF’s achievements would not have been possible without cooperation from related local organizations, for which we would like to express our sincere appreciation. Another strength of RERF research is that the radiation dose of each A-bomb survivor has been estimated with a high degree of accuracy. The first RERF radiation dosime- try system was announced in 1965, followed by two revi- sions, in 1986 (DS86) and 2002 (DS02). Starting with this version of our brochure, we are now using doses estimated with the DSO2 system. Doses estimated based on the DS86 system will continue to be used for referring to research results obtained during the DS86 period, and doses esti- mated based on the T65D system will be used in the same way. The main differences between DS86 and DSO2 are the accuracy of the data used and the methods of calcula- tion; the basic philosophies and the dosimetry systems real FX Introduction ED FNS RO & Bi LT. PEP 10fF LES DERY VRE CERT SY—AVE (Sv) CHUTE Lko RIK RoTCOMe [HANITENKETLS (Gy) | CHICLICEY GAAKILAC), RRECOF AMOK SoOnePHAL THES. COMMIL, Sv it IL AZ OFEFE TL <¢ WON REO BN CHU ST WSHLCH 0. IC EPR BNE EBS (ICRP) Clt Sv (CA Mit HE RRC AL CR AOC. WECM OUE ER ENLET ETE BCE. DU Sv RN Cito DLV tBrENKPHS CT. ia themselves do not significantly differ. Differences in indi- vidual doses estimated with the two systems are numerous, but on average, DSO2 doses are higher than DS86 by about 8%, and as a result, the risks of effects per unit dose are slightly lower. Please refer to the comparison table below for details. Because of differences between the biological effec- tiveness of gamma rays and neutrons, we have used weighted doses—the sum of the gamma dose plus 10 times the neutron dose. Formerly we designated this with a dose unit called sievert (Sv). However, more recently, for this same calculation, we have expressed the unit as “weighted gray (Gy),” which will be employed in this brochure. One reason for the change is that the Sv unit is mainly used for radiation protection purposes rather than for risk estima- tion. Another reason is that the International Commission on Radiological Protection (ICRP) applies tissue weight- ing factors in deriving Sv estimates; those tissue factors are not applicable to the A-bomb exposures, so it causes confu- sion to apply Sv units to RERF doses. DS86 & DS02 OME t Differences between DS86 and DS02 DS86 JA & Hiroshima eet 17 Bomb yield E38 aE Height LE SASINE 15+U hy 15 kton 580 m Ba 14. Location WY viist Gamma-ray dose Hp Fist Neutron dose fell} Nagasaki eet HJ] Bomb yield HRS Height E3801 Location 2140} Y 21 kton 503 m HE tse Neutron dose DS02 16+ bY 16 kton 600 m 15 m Pi-\f%8) Moved to the west by 15 m Ai FHI (1LO%LAA) Slight increase (<10%) 45 Fit Slight decrease Zt 72 L No change 2% 72 L No change 3 m PU\*28) Moved to the west by 3 m 1-2km C#Fi8h (#4) 10%) Slight increase at 1-2 km (about 10%) 2-3 km CijitZ> Decrease at 2-3 km 1-2 km 6 25% L)_ EO iik“> Decrease by more than 25% at 1-2 km Objective and History KILO BN CIA ff ILO AN CAS Objective and History ax 2) BAY Objective AAO Fic, BUND IUKIC RIES REN EB E The objective of RERF is to conduct research, for UCHIZE SPIE AIELLO ERE MERE LU peaceful purposes, on the medical effects of radiation on bic torevic, BAO ILE ICRA man, with a view to contributing to the health and welfare fi FURS 4 I. AGO PME AAO TALE: (= 65 F- of the A-bomb survivors and to the enhancement of the ALECHA HUCMANITA. 34%, 1975 4F). health of mankind (Act of Endowment, Article 3, 1975). ® = History BUwls, ARBIRIRICHEOAR, AROS - BARA RERF was established on 1 April 1975 as a nonprofit AWE L. #7: AKERS CEB ZB ASE foundation under Japanese civil law, within the jurisdic- i A Ac3 joo Met _,, | tion of the Japanese Ministries of Foreign Affairs and MELT INS F4 HV AIREL A BIE 1947 SICK Health and Welfare, and in accordance with an agreement pa ESD BAAO Bal Lo CABREL BEA LE | between the governments of Japan and the United States. ABCC CH). 224A ICID B EDLY EER ASAI =| «~RERF was preceded by ABCC, which was established in LC, SECA 2: HEIRS © REFURB Lee. 1955 1947 by the US National Academy of Sciences with fund- KILI G vy ABBA L ZAHEER GDN. % ing from a US Atomic Energy Comnussion. mpee initi- ated extensive health studies on A-bomb survivors in coop- van Aa =. a)- A Zr Beaad ay é am : : Om, WRATH A URS SUI SUT A 8 IT BLT eration with the Japanese National Institute of Health of AAO TEPER SE DIE 0 the Ministry of Health and Welfare, which joined the 1975 42.0 Hi SZtA@ Pea RIC. «HOKE IC £ aR research program in 1948. A comprehensive review of Hee DEM ZLERON. CHEE. fit ABCC work in 1955 (the Francis Committee) led to exten- we ee os poet a sive revisions in research design and laid the foundation SATO AEE BRS ROBES Lo CHS SHEA | for the population-based studies that continue today. (TV, wa ROT SE a BS EO BE CHR S 114 BP When ABCC was reorganized to form RERF in 1975, ame AR OE UTS Fe CED ON TWD. HEE k REHOME L. WEILA ARISE SHS SIR. ORE nership between Japan and the United States. Accordingly, REREF is managed by a binational board of directors, and its scientific research activities are guided by the annual sy jij | it was deemed essential that research continue in full part- 7m J ra [LDA EB HE CRT ENTS. recommendations of a binational scientific council. Funds for RERF’s operation are provided by both governments, by Japan through the Ministry of Health, Labour and Wel- fare, and by the United States through the Department of Energy. 0) S8F5 Departments ab PA Ba FEFRO ERIE, Ch ORUYMURERIC LAY AD * SMAI ko CHS AIT SCL CHS. (EE 50 “Elo 720 Apara ze (LSS) SRE, JAAR A, BROT (F,) ORME TC 20 FADED RRS & £0 FH BMA LCA. ACNRUNOU AZ AF BL BO, Hist HRB LODA OAK O BY AO fT ICE BESTA. MERMOKEA & LHR RAI, £ TOE DPO SEE S CIBDIOR SI BVT. LSS ILE BIC BU SHUN O PACT SHR CH BEER ELEC HD FEAL Ee REI HR LORD 5 MIMS AE SRO EA BE (BALE) ANTWSo CNS ORIRHE IC LUM SENET — 4 ld, RRR OAR 6 TARE ILBIS BA OBERT SRB AHL Ro TW. ra tat ab Beat IL, BA CHES TBR RAE CEST ZS TPO fe Br. SEB CTD NCW SMBIM GS Stats & TF SWORE CET OTS. EK, Mat ee eL. BOGUT CRABS NKAA=-— 7 BHAT — 9 ILS Sd Lv sitet Aly Mere @ BSE IO LCV So EET DO fa HEC AB ETE aT b CATER CIT DTW 0 fa PROT Stab MORO ZEHS Clk, LSS BE & IRA PERSE D> 5 HETIL TEKEMRIC, 1958 FEM 6M ERE ZE (AHS) % Seti L TWH, CHld24ElC 1 REO WHR ERR Cho. WAY Ze ERE MT CML - PROPRIO EDI. HARERO KVECBU SRE. ARO RHICBITS RIV EY BIE, Feo CE wae IC BUT S GEPRAEO MEE, EF 7 AA. AR fi, HIG COR RIL S SABRES iti ST Do RBICE VB SNK MOALZNIS £ OBS FEMA? 5. UE O ERK & RU cz) FHMC A Bo RRL TS CAH TL, PEGE, HP BR CARO RD ICMICORMeMT LCS. Bhi SHEP — ¥ LL-H CRAIC 1, AAR BELL AN O EEE TIED Ke OILTAAF ENTS. D Be) fe BER AEE CAA O FCSE L Ze RAR EDA id AE US ft 0c UE Departments Department of Epidemiology The primary task of the Department of Epidemiology is to clarify through population-based studies the risks associated with human radiation exposure. For almost 50 years, follow-up studies of more than 200,000 survivors and their children have been conducted through the Life Span Study (LSS) cohort of A-bomb survivors, the cohort who were in utero at the time of the bomb, and the F, cohort of persons conceived after the bombings. Analyses focus on mortality and cancer incidence in relation to radia- tion dose, allowing for risk factors other than radiation. The LSS is the most important epidemiological study of radiation effects in humans in the world both because of the size and well-characterized nature of the study popula- tion and because of the duration and completeness of follow-up studies. The department is also entrusted by Hiroshima city, Hiroshima prefecture, and Nagasaki prefecture to operate local tumor registries. The collected data serve as a unique source of information on cancer incidence for both A- bomb survivors and the general population. Department of Statistics The Department of Statistics analyzes the information collected by other departments on radiation effects, pro- vides statistical support and advice to research scientists in other RERF departments, and assists with data manage- ment. Members of the department aid in designing studies, and they develop and apply statistical procedures for ana- lyzing RERF’s unique research data. Management of the dose information and calculation of individual doses are further responsibilities of the department. Department of Clinical Studies The Department of Clinical Studies conducts biennial medical examinations of participants in the Adult Health Study (AHS), a selected subset of the LSS and in utero cohorts. The AHS program was begun in 1958. In addition to standardized clinical examinations and routine labora- tory tests of blood and urine, special tests are conducted, for example, to detect bone density changes in postmeno- pausal women, perimenopausal hormonal changes, cogni- tive impairment in the elderly, and various other disease conditions, such as cataracts, thyroid nodules, and uterine tumors. Biochemical and physiological data from these examinations enable long-term evaluation of the health of A-bomb survivors. Participants are fully informed of examination results and, if necessary, are referred to local physicians for further evaluation and treatment. Accumu- lated data are used in epidemiological and clinical studies, and biological specimens are stored for use in laboratory THELRVW, PRBS CH AD, BIEL 70-80% DE CHA. ein +a HBT Clk, MM ad AE & OF dE & TT TVD. MAHER AUER Cli, BURT OA DIEU ie DHERILAT SEO, PEAO) VY NERC BIS Bea RR WRES RAF Cb MAL CS. RICE AY FMB AVC. PHO LF XV ICIS S NPIL < PURE OIE SITIO CS. PLUME EME CL, BE EE & EOF Hd 5 HEHE S 1 7e MLN AV CBOE WER BEDS TAL D ZEAE PABA ABT SI 5 2% DNA V NV CEL TVS 0 MARE OF /DFRAR RON RAD / YP BELTBIL, AA POSES & APE PAIL D> 5 BLY . MANIC 33 IF % PALS EE DS ALAR IC BUS FEDS AEF PDS AMM EF OAK FR, WONRO RBEHEIK ISTH RR CEMFEL THOS. IB B- RIFOEL UCWBRICEDEMPElcbkho CRS WUT SAGA IOV CT, ROALD Sh BAEC L DDD ITDILTWA 0 Te ends HiT ab TPRBONEB ISL Y AF LD BMTERC EAR RDS & S © VAS APRIL, BPH SKO ay CaF OFF - MAOIED, BERRY bI-Z OME DICE RS HiT — FI N\— AOMBERENE PAT SREOOT TY 7— Yay: FUSFAOWBEE ETOCS!) Bled, AM IZ BIT DER Ze FI CHIT & FT 2 TWH 0 MARS. BUNS - ee EPL > ZAR DIRE? . WORT ODT FE it SC ASEAN EI PBA S 1S ETO RUSE ETI oC. EK, WME LOFRIERO alse ¢ HL, ABCC- RUG ORE eA EOIE & He REREEITO, CHOOFRAA-AN-VECHETC AZEGICLTW4S. Hie, MANP SDN OF Aira Mi BRAOMM Adee ENA IMI L TW So Departments #8F4 {i research on radiation health effects. The AHS is one of the most comprehensive clinical follow-up studies ever under- taken. Although examinations are voluntary, participation rates are regularly between 70 and 80%. Department of Genetics The Department of Genetics performs cytogenetic and molecular genetic studies. In the cytogenetics laboratory, long-term research on the frequency of chromosome aber- rations in lymphocytes from A-bomb survivors is carried out to aid in assessing individual radiation doses. The labo- ratory also uses the electron spin resonance method to evaluate radiation doses recorded in tooth enamel. In the molecular genetics laboratory, studies at the DNA level use blood specimens provided by survivors and their chil- dren to determine if mutation frequencies in offspring are related to parental radiation dose. Department of Radiobiology/Molecular Epidemiology The Department of Radiobiology/Molecular Epidemi- ology comprises the cell biology and immunology labora- tories, which investigate somatic mutation frequencies in blood cells, mutations of oncogenes and tumor suppressor genes in cancer tissues, and possible radiation effects on immune function. Tumor specimens stored over several decades, mainly by local pathologists in Hiroshima and Nagasaki, are analyzed with newly developed molecular biological techniques. Information Technology Department The Information Technology Department comprises the Systems Technology Section and the Library and Archives Section. The Systems Technology Section provides, maintains and integrates RERF computers, maintains the RERF net- work under secure conditions, and develops various data- bases and application programs necessary for RERF researchers. Further, the section is also involved in techno- logical cooperation with organizations both inside and out- side of Japan. The Library and Archives Section supervises RERF’s professional library, with its focus on radiation medicine and biology, and carries out work related to the publication of RERF research papers in scientific journals. The section collects, stores, catalogs and manages research papers, aca- demic meeting presentations and other important ABCC- RERF materials, making available such information on RERF’s Internet homepage. It also responds to inquiries from both inside and outside RERF and to requests for papers and documents. §) AE Study Populations il Se 1955 4EI2 ABCC IL, VI YYARRRSOMEELZLUIT, 1950 46D EAA ASE CFT 0 11 7o RRS ED 5 435 1 RANEY CT. AERMOM RG Ie NES A OB Wie Ais fem Le. CORAM AIC LY 2854-108 AS) BEE DERE S TL. COP OR 20 7B ADS 1950 4 4 HE BES: RRO SAA IMEL Cuz (SEATS). 1950 4E BAL LIME, ABCC — BURT CSI S eR AE IS TATOO [HAH] POBIINLAMKEM ICO CHD MeKR (H1)o MURMACL, FRAGA - EBEO ASEH eC. FIA Ca ABR Y ILE L 7 HK IC Ado 0 te < TORIC Ste ALLIS. BAD BABS BEL Clk, WIMO MEG + ACRE b OTR OA mol, J IFUL (CPR SIS) (CLO MAE TOTS. AMS BIE Yam Study Populations In response to the recommendations of the 1955 Francis Committee, ABCC used data from the A-bomb survivors survey, conducted at the time of the 1950 Japanese national census, to develop a comprehensive roster of persons eli- gible for inclusion in fixed study cohorts. The survey iden- tified 284,000 Japanese survivors, of whom nearly 200,000 were resident in either city at the time of the census. Subsamples of this original Master Sample have formed the basis for all studies conducted by ABCC-RERF since the late 1950s (Table 1). In all mortality studies, informa- tion on cause of death, regardless of location in Japan, is obtained through official permission from the Ministry of Health, Labour and Welfare and the Ministry of Justice. Information on cancer incidence is obtained through the local tumor and tissue registries and is limited to current residents of Hiroshima and Nagasaki prefectures. Addi- (OV Clk, KB OSE & EREIRBE ICES 4 IBHINFER DS & | tional information on disease incidence and health status is Ze available for AHS participants. #1. ERMA TUF IA EHRAR Table 1. Major RERF research programs and population sizes a) AE AT AE Studies Subjects Firat: Life Span Study 120,000 py eked te Adult Health Study 23,000 IRAE Hz = In Utero Study 3,600 i {ta*f Ze ~=Genetic Studies TK EASA EZ ~=Mortality and Cancer Incidence 77,000 Mitta 4 ~=Cytogenetic Studies 16,000 ifa(ta# Biochemical Genetic Studies 24,000 43 F-iateedd4e Molecular Genetic Studies 1,500 fii As EE we #E «= Clinical Health Survey 12,000 Fimadz (LSS) Hi Life Span Study (LSS) Sample “40 LSS EAL. [ZEAE CE EN SREAOHTC, AR CAR OMTTEML) DRED CH. 1950 ECT DERSMICFELEL. BRN HEB AE & WY REIS TS EHD \lRUT 6 AUT RHE eM ET AOD 5S THIOL DP (CUANZA DPOSHMANTWS,. FRbdDb, BLO sLth2> 5 2,000 m LIA CHER L 7 [SEAT | PER aE a5 BAHU TV-G EEREREET) . 58 2 TR: BRD 2 5 2,000 — 2,500 m C#REE L 72 [ARATE] SRS TR: 1 PEL EWG TERS -BRTSD EDEN BEDI 5S 2,500- 10,000 m CHER LZA GH IRRERURE). BLOG 4 TF: As initially defined, the LSS cohort consisted of a sam- ple of survivors from the Master Sample who were resid- ing in the cities in 1950, whose honseki (place of perma- nent family registration) was in Hiroshima or Nagasaki, and who met certain eligibility criteria that would facilitate effective follow-up. The LSS originally included a) a core group of all eligible Master Sample survivors who were within 2,000 meters of either hypocenter at the time of bombing (ATB) (proximally exposed); b) all eligible persons in the Master Sample within 2,000 and 2,500 meters; c) a sample of eligible survivors between 2,500 and 10,000 meters (distally exposed), matched to the a) Pek as 1 EG EDS Be HLF CHIEN 7, 1950 SET *AICIK ES + RIC TERE LC 2 PSUR IST AIC POKACH So 54 HIDE AATES CMPD, J RR S0OHUADAT SH CtnUMOATHb BENTH Bo 2447) 99,393 Ade 5 fink S Cvs LSS BAIS. 1960 4246 BRAFICHEK SN, ABM IC BER ¢ 2,500 m DLA CHEER L te [SEAHE| @R BOK. UVC 1985 iC MICU KS tr C [AH] OS RIFRREAS EO 5h, FA CIRO ASULG FF 120,321 Kt BoTWS ($H2). COBB, ke Litizs 6 10,000 m LAA CHER L 7 93,741 A & JEUERIRFTHA AER 26,580 ABE EN THA CNS 93,741 ADF 5, 86,671 AlZOvs Cla PRR ae HE FE OT 5 TL TWD DS, 7,070 A (2 D4 b 95% tk 2,500 m LIA CHEEL TWH) UZ OV TILE? HUFB IC LB WERT D BEHE S PARTS Ze UE KP FOR OM MAHL CA TRV. BIE. LSS EE Study Populations H&E fj group by sex and age; and d) a sample of persons, age- and sex-matched to the a) group, who were living in Hiroshima or Nagasaki in the early 1950s but who were not in either city ATB. The so-called “not-in-city” group included peo- ple who entered Hiroshima or Nagasaki within 30 days of the bombings and others who returned to the cities at later dates. The original LSS cohort included 99,393 persons. In the late 1960s it was expanded to include all Master Sam- ple survivors exposed within 2,500 meters regardless of place of family registration. In 1985 the cohort was further expanded to include all Nagasaki survivors in the Master Sample. At present, the LSS cohort has 120,321 members (Table 2), including 93,741 survivors who were within 10,000 meters of the hypocenters and 26,580 persons not in the cities ATB. Among the 93,741 LSS survivors, indi- vidual dose estimates are available for 86,671. Because of complex shielding by buildings or terrain or inadequate shielding data, doses cannot be evaluated for the remaining 7,070 survivors, 95% of whom were exposed within 2,500 22. AiMmMELMOARE HERAT (DS02) Table 2. LSS subjects by estimated radiation dose (DS02) LSS 42HIO AB LSS subjects BANU Leekiiiie (Gy) Wy is Fe IG & at Weighted colon dose (Gy) Hiroshima Nagasaki Total <0.005 PAINS} 16,823 38,536 0.005—0.05 17,207 6,227 23,434 0.05-0.1 5,507 1,005 6,542 0.1-0.25 6,273 1,270 1,048 0.25-0.5 3,842 956 4,798 0.5-1.0 2,376 1,052 3,428 1.0-2.0 1,151 614 1,765 >2.0 436 189 625 Be # a Ni) CER ENA 3,449 3,621 7,070 Dose unknown Bae AS Bua Ar 61,984 31,757 93,741 Total survivors AA ES (LAT) Not in city (early entrants) pyiee oat eet HAA eA) Not in city (late entrants) 16,238 8,823 aU 26t Se De ies ant 20,230 6,350 26,580 Total not in city : Ae LSS RE Set 82,214 38,107 120,321 LSS total §) AE Study Populations (cla, TAEAREE] (ICA TW 2,500 m WA OPED UE SABENSDS, Rica 4 ia LBA NTs So. FRbb, 1950 4 AEE CIHR L RR E (1950 EAR AO HAO 30%). HARIZEIC MAO BR FURIE HTC O A ARERR, BL OSE Fe (CHELA, HEARS) deen TRY, WEOTE PSH. Bebsthe 5 2,500 m WA OPE O MBER AEO WHICRoTRALBAZSNS. AR (AHS) SH CORAL, 2 4FiC 1 EO ERE WT CRI FEES CMR OWREMETACEXR AWE LCRESNK. Be PER RAC Ko. ERDOTA TORE & ERAN WeSUEL. BAP TOMORROW & REE LON ee Wt L. LSS RA OPEB ODA D5 BIC OWT, AUFRICFED ¢ TERIAL CL GG 5 WZ VR LE & D VS BEE LOGREAFCE 4S. 1958 FORA, AHS 524 ID LSS EADS HILINZ 19,961 APSO. PAV F tk, 1950 4224 RRAE FEL CVE, eb die 5 2,000 m LILAC PERL. AERC UIE © AR LL 72 4,993 ASA RSMS. © Oleic, ABI + AR PER COMA V— PERS LEONA WM—F (WFNS POA V—TSEILAR) BE £N4. TRbDH, 1) BMWA S 2,000 m WAN CHREEL. VETER SE PORA, 2) KE CIEE DHA 5 3,000 - 3,500 m, fellfi-Clt 3,000 — 4,000 m OPFARE CHIR LEA, B EU 3) URC STHOMC SAPO ATCHS. 1977 F<, eR BUR OWL & REL TC. MAKI SO O77 V—-Fx lz AHS BAM LUKL, Fat 23,418 LE LZ. tb, 1) LSS#HOI 5, 1965 EEE RN LDS 1 Gy LE CHS 2,436 \OWIRAEA, 2) CNS6OK EF Hinds LOE ECS AZ ARO IR, BLOB) HR AER 1,021 CH 4S. AHS MRE RIEIE 50 AF ETE 2005 *ESIZE. 1 AGE < DATEL TAD, FOI 5H 6 FA ASAT MIRAE LY BIS SD 70% (BLE 4,300 A) 4d BOER ATO 7S AICBIML TW 40 IRA Riese Sl JRA BERS IC BAS Be & Ze AEDS 1940 EK LO 1950 SEARCH S 172. 1960 EICIL. URED 5 1946 46 5 AK ECICAB: RMON E Lit CHELLB LA AD AUSRICZEOR. JAAR O [MPR AAL) BO [FECES EAE | OR OIL LODO BET J AERM PRE S 1, AIA AS PARA S AL 0 meters. While the LSS now includes virtually all survivors from the Master Sample who were within 2,500 meters of the hypocenters ATB, there are other proximal survivors who are not included. In addition to survivors who had moved away from the cities by the late 1950s (about 30% of the 1950 census survey respondents), the LSS does not include survivors who did not respond to the survey, Japa- nese military personnel stationed in the cities ATB, and non-Japanese citizens (e.g., Chinese and Koreans). It is believed that the cohort includes about half of all survivors who were within 2,500 meters of the hypocenters ATB. Adult Health Study (AHS) Sample The AHS was created to collect disease incidence and health information through biennial medical examinations of LSS survivors. The examinations make it possible to diagnose the full spectrum of human illnesses and physiol- ogic disorders, to study incidence patterns for both cancers and non-cancer diseases in relation to radiation dose, and to obtain clinical and epidemiological information not accessible through the records-based mortality and cancer incidence follow-up of the full LSS cohort. When estab- lished in 1958, it consisted of 19,961 persons drawn from the original LSS. At its core were all 4,993 survivors known to be alive in 1950 who were within 2,000 meters of the hypocenters ATB and who reported signs and symp- toms of acute radiation syndrome. The remainder of the AHS included three city-, age-, and sex-matched samples drawn from the LSS, each similar in size to the core group. The three groups were: a) survivors without acute radiation syndrome who were within 2,000 meters of the hypocen- ters ATB; b) survivors 3,000 to 3,500 meters from the hypocenter in Hiroshima and 3,000 to 4,000 meters in Nagasaki; and c) persons not in the cities ATB. In 1977, because of concerns about attrition among high-dose survivors, the original AHS sample was enlarged to 23,418 persons by adding a) all 2,436 surviv- ing LSS members with assigned tentative 1965 dose esti- mates in excess of one gray, b) an equal number of age- and sex-matched distal controls, and c) 1,021 in utero- exposed survivors. As of 2005, nearly 50 years since the creation of the AHS cohort, nearly 10,000 cohort members are still alive, of whom about 6,000 live in the contacting areas and 70% of them (nearly 4,300 members) continue to participate in the AHS clinical examination programs. In Utero Sample Various studies of persons exposed in utero were cat- ried out during the 1940s and 1950s. Beginning in 1960, two overlapping fixed cohorts, one for clinical studies and one for mortality follow-up, were assembled from records of about 10,000 births occurring in or near Hiroshima and Nagasaki between the time of the bombings and the end of May 1946. [RACE ARSE | Uk. ee LKEA@EBE, TE + ABT % WHE Bt. 1,608 AAO O HbA 5 1,500 m LIN CHAN BEER —ESRMFARKOIOOE SMlice@eEn, £057 5O 1,021 Ald AHS f€227 0 7 F 2 [a BENTWA, Ramee Se Scie es BTL AMER ad EE | SHEE ORM IL RAGA HEM SIT So BUETF DTW S A 58 AE BE Bl % Atte 3,654 Adss) AIZBIL Tl 0.005 Gy DI LOBENTWS] . BebHEA S 2,000 m LIA CHAAR L (1118 A) POMARDAV-Pk, bie c HAAN BOE (\CEBS SAA Cla, RRP ARSEAT & FETS RSE 2,817 \WGENTHY), EOI > 1964 AIL RETE ILOVWCOREKSB LOM tR L 20 TBY. F044 1,060 Lk CPi 0.28 Gy) £v.4 Hise BUN Ra Os SUT, Rae OE (F;) O£H ABCC ICBIFS MMO CL, BIRO LENO ifs WED SS SLICE S24 CHK. 1950 EAABIZE Clic, 77 PA OPTS 2 Ot RC AE PR ES EOE (LOU CHIARA TT DILTEDS, RAHA O SLES BS F-V PSL, BREGBE NET SAIL Lone LIACHoK. UML 1955 ILI FY Y ARB RILRG DF EO Atte ahd FEO BEE % GBD TZESER O wee 2 TE Lko COPEICBOS. F, FECA AE AAS 1950 4EACIC OUNCE SN, TOPRZ RI DK YUKSNK. “OO F, SAIL, 1946425 A 1 AAS 1958 4F RE Cle AEE ALTE 54,243 AP5 BY. CO 5D 53,518 Al2OwT EET — FAME SNCS. HAW Tld, PRC ES POA BLA 5 2,000 m LIA CHEER L Fe F HE —HSteIootlt HS. GMEMLIFHBRO, ERT UV — TORE S76 LE SPO-ADSEE DHA 5 RAY oO D lhe 7 IV — Tid, VE + ERR % BOLT V—-Tit, YD 2,500 — BLE Sc 10,000 m OPBBEC BE L SAN JEL EBERE | nS UW, AC 7 WS 10,000 m WAI RABoORADEILN. SOROUL KOA, F, MIS 88,485 Al AR. TRbob, HHO bie < & &-HAGEK LSS BMI FEN, 1946465 8 1 7 PS 19844F 12H 31 AOMICEENKT NCO LHI brik. KRRLIELMREMILW 7A TTACH A. OO F, MOBO AUCH L CHAN A, EE El ete CREA Ze ABCC — RUSH AA AEIE TTF DAFT DIL CAs Study Populations B#H fj The clinical cohort included all Japanese survivors in utero within 1,500 meters of the hypocenters ATB, together with sex- and city-matched samples of similar size from two comparison groups. This cohort includes 1,608 persons, of whom a subset of 1,021 were enlisted as voluntary participants in the AHS. The mortality cohort includes 2,817 subjects, 771 of whom are also in the clinical cohort. The mortality cohort was established in 1964 and consists of all persons exposed in utero within 2,000 meters of the hypocenters (1,118 survivors) with matched comparison groups. Current analyses of mortality and cancer incidence among persons exposed in utero make use of combined data from these two cohorts. This combined group now includes 3,654 persons of whom 1,060 have estimated doses of 0.005 Gy or more (mean dose 0.28 Gy). Children of Survivors (F,) Sample The search for evidence of detectable genetic effects in the children of survivors was a primary focus of early ABCC research. By the early 1950s, based on data on birth defects and early deaths in about 77,000 births, it appeared that data on early signs of genetic effects provided no evi- dence suggesting any dramatic effects. Nevertheless, the Francis Committee in 1955 recognized the need for contin- ued follow-up of survivors’ children and suggested that a fixed cohort be defined. On the basis of that recommenda- tion, the original F, mortality cohort was defined in the 1950s. It was later enlarged on three occasions. The original cohort included 54,243 persons born between | May 1946 and the end of 1958; follow-up data are available for 53,518. The cohort included a) all eligible children with at least one parent within 2,000 meters of either hypocenter ATB and b) two sex- and age-matched comparison groups of the same size as the core. The first comparison group included children with at least one par- ent exposed between 2,500 and 10,000 meters. The second group included children with neither parent within 10,000 meters. Later extensions increased the F; cohort size to 88,485 by adding all children born between 1 May 1946 and 31 December 1984 with at least one parent in the extended LSS cohort, but the epidemiological study cohort consists of about 77,000 children. Overlapping subsets of the F, cohorts have been used in various ABCC-RERF study programs, including cytogenetic and biochemical genetic studies. Wh HO FBS Early Radiation Effects WHR BSS SER hee PERCE] CMP ASN SRABIL, HO BUR (J 1-2 Gy 5 10 Gy) (CER L RD 5 BH AOC HLS. ERE, PERRIS BD 5 1S MIL, UR CHA D5 BOW IC DIT CHU SD PH, MABE CO ink Sr. HHI. BEE. PEO RPE IE OCHS PRIS FANN PE OSE FH Few (FEAL MLE swe ik PROM MPMPADNSLOILECA. tilt, Me Ger in caine a anni HAD BEeE LIS ROILZOEPKDNSD, EPICA EE LKITSO CIE earn oO Ree NS. BOA WETEIL. FP EO MS GSE SLUT ERE SO ZIVDS ONEIDA JO [LMM BEV. VF 4S ON, BE CER EURD HS. ILEAEPRLTWBAWED Zed, AP HHRE) Clee SL, ROA te MMals BUNS LAGHESIPETU DS CHS. BUNMORE DY t AL, BOB EILISE A EAC Zee. aici aS BiSHlL, PUT MILPEURK 10-20 HAI REOBOBE C, HAW HVT 1-2A ALAC EICPHOGEC. F WESMIEIC BE DW HEVEDSH Zo HEME 3B4O 2 LOMO) THFLEAOF Ak. BON SURER SE ORR Lica ty. BUN RLO Bees 1 Gy CDT PRE L DBO SNRVADS, SNEED elle HD & elt ite & ECAC Tse (5 Gy Lh ECHBADP Bo TK ZEIICALZZOlS PAIK IC ESN TVARMOLEZSNTWS,) Bs Bs oo Early Radiation Effects Acute Radiation Syndrome’? Illnesses collectively called “acute radiation syn- drome” occur within a few hours to months after exposure to high-dose radiation (from approximately 1-2 Gy to 10 Gy). The principal signs and symptoms include vomiting within a few hours, followed within days to weeks by diarrhea, reduced blood cell counts, bleeding, hair loss (epilation), and temporary male sterility. Diarrhea results from damage to cells lining the intestines, reduction in blood cells from death of hematopoietic stem cells in bone marrow, and bleeding from declining blood platelets gener- ated from such stem cells. Hair is lost due to damage to hair-root cells. Hairs do not fall out but rather become thin- ner and eventually break off. Sterility occurs in men from damage to sperm-generating stem cells. Except for vomiting, these signs and symptoms are closely related to frequency of cell division, rapid cell divi- sion being more sensitive to radiation than slow division (e.g., muscle and nerve cells). If the radiation dose is low, the syndrome will seldom if ever occur. Conversely, if the dose is high, death can occur within 10 to 20 days after exposure due to severe intestinal damage, or subsequently within one or two months, mostly from bone marrow failure. Figure | shows the relation of severe epilation (loss of more than 2/3 of scalp hair) to radiation dose. Although there is only a small effect up to | Gy, epilation increases sharply with dose thereafter. (Above 5 Gy, the declining frequency probably reflects overestimation of dose.) Ba 1. BEDE & BR RR BE RIE ? Figure 1. Severe epilation and radiation dose” 100 80 fo>) (=) BEREDZE (%) & Percent with severe epilation 20 0 1.0 2.0 HY VRE PEFIROS 3.0 4.0 5.0 6.0 atte (Gy) Total dose of gamma rays and neutrons (Gy) SEU WUC ES APEEC OMERRIL, SOUT RUN O at lc RIS. & CMO SNA’ LTS. RAO 50% AEE TS HCHMO Bilst & FET LDsy (SOM BOBS) 25d 4. PRERIAM 2 7 ADA OSE & AVESEE & LTH 6 LD5o IE JIVE © BR LYRA OER ARAL, BHOGEICLS TERE AICS Z HIM k ORRYYE CHS. COLI BREIL, &LOPAWSILIL, WH 27 AWAITS. PHO MA Cla, RRO KAO MRE HET. 50%O MBS RoKEBRA SNS DD 5 OFME CAE Clk 1,000— 1,200 m, ll}-Clk 1,000- 1,300 m) 25 LDsp AK DoeNK. LM LIER S SRA CRPOK DC, BUR REED OIRGUL CA D2 eo ACTH WO JK GE Ze ROERASHAT SL, EMIS BES Z HE TEAST HE Ic Ze 0. PER 60 HA DFECERA 50% (oe SA ies It 2.7 —3.1 Gy (OreeetHese Wak DSO2 CHET ZS E 2.9-3.3 Gy) edie Si 7, CML, ABIL BI SED 5 1,600 m DAD AARERA CORRE L 7 2,500 TOK 7,600 AMF — IRboESNKbDCHS. HEREN ORES 78 AL RO, COLA REWOPEAL MCR SRO, MHA ORC BURR ie ROC TOPS CHS. Heb Hic (SERUM O mlLS D3 7S, TARR ICM k ARO EB FRG ABV TEC KRDO AO ROE BRD GEST. ARE BCH) DLAC O HBC LUAU RHEL, MH BG PIPEIL LSA SORES SOIL CH OK. Mb GeeijciwcLSReCe RNAs EOI, Ke CiTpon 7 baido fr Cld, BRUNIA S SEB ASNAENT -ACARMUILHALEY KR, COLARMUl, HERON LAARICE-7IELTW A] EG CN AR FB AOR Cll, ERE BUR THOREE, BIL ORCA ORICHEOW TC, F BED LDsooo KHEFEL TIA, CMICEL AL, KRMIZLA LWECH ROB, COME 2.5 Gy. +4 ER ASW HERBS IES Gy PEE SNA] ARABS (7k SatRIEIR) o-§ BUNPAPIBEIL, 7A O—BBITIZ OU BAEC ALOT 2). AKAMA fe Ze TH & 729 GE UT MMC EAT Do WMATA, Raiiae Cd ld <¢ 1-248, SHE 1) (Eititee C db MULE b RE TP STEALS © BNE AAAS £40 ¢ 5 OMIBE CHE O HUIS & EL ALE LIC HERS ZODILH SA CLRWD, HULA DN HAE CIL, Pit eS RAAB EPIL 1 Gy 470 # 20-30% © iF CH7 ro BURG IIC HBL 2 BCR ABE IS Ove CIs, Early Radiation Effects HAGOFHES fj Acute Death‘ The probability of dying directly from radiation expo- sure depends on the dose received. A commonly used index is the dose at which 50% of a population dies (LDso = 50% lethal dose). Acute death is defined as death within about two months of exposure. At the LDs, level, bleeding and infection due to immunodeficiency resulting from bone marrow depletion are the main causes of death. Recovery from such depletion sufficient to prevent death usually occurs within two months. Early estimates from survivor interviews measured the LD, in terms of the distance from the hypocenter at which 50% of people survived: 1,000 to 1,200 meters in Hiroshima and 1,000 to 1,300 meters in Nagasaki. Dose estimation was not possible at that time because of insufficient shield- ing information. Later analyses of extensive records at RERF were able to make estimates of shielding and to cal- culate that a bone marrow dose of 2.7 to 3.1 Gy caused 50% mortality within 60 days (with the new DSO2 dosime- try system, the corresponding doses would be 2.9 to 3.3 Gy). The data came from about 7,600 survivors in 2,500 households exposed inside Japanese houses located within 1,600 meters of the hypocenter in Hiroshima. Survivors inside Japanese houses received special scrutiny because the homogeneity of such housing structures allowed better estimation of individual radiation doses. The closer one was to the hypocenter, however, the higher the radiation dose received and the more severe the effects of blast and heat in terms of destruction of houses and subsequent fires. It was thus impossible to classify deaths that occurred within a few weeks after the bombings as due to radiation, injuries, or burns. To avoid deaths from injuries and burns, the above RERF analyses therefore focused mainly on delayed deaths; such deaths peaked at about one month after exposure. Based on this information from A-bomb survivors, together with other information from cases involving expo- sure to accidental radiation or radiation therapy, the United Nations’ Scientific Committee on the Effects of Atomic Radiation has estimated the bone marrow LDsojo at around 2.5 Gy when little or no medical assistance is avail- able and at 5 Gy or more with extensive medical care. Radiation Cataract (Lens Opacity)*® Radiation cataract causes partial opacity or cloudiness in the crystalline lens and results from damaged cells covering the posterior surface of the lens. Symptoms can appear as early as one or two years following high-dose exposure and many years after exposure to lower doses. It is unclear how frequently radiation cataracts advance to severe visual impairment, although we have documented in a recent study about a 20-30% excess at | Gy of cata- racts that prompted cataract surgery. A low-dose threshold may exist below which radiation cataract does not arise, &HRO PMB Early Radiation Effects OEE Ce Mkt CO [LAV] BHSDbLNE DWEBLSNTOOD, MILO MAC. LAVMHILAY PD HokeELTSH 0-08 Gy HE CLRV DE RIBS TWH. MBS NARA AEP IL, ARCHOS HT SYA TO’OCHS (RE FTAAMALORAAAN Mt) BO2 12. AKER ARR BORIC BES 4 Bie BUS ART although our recent analyses suggest that there may not be a threshold, or if one exists, it is somewhere in the range of 0 to 0.8 Gy. The excess cataracts seen are of the types gen- erally associated with radiation: posterior subcapsular and cortical cataracts. Figure 2 shows the relation between radiation dose and cortical opacity of lens. Bel 2. AH PRB TDG BRL BURL © Figure 2. Cortical opacity of lens and radiation dose® Ay ZX be Odds ratio OR/Sv = 1.29 (95%CI: 1.12, 1.49) 2 4 BAHIITLEARRS (Gy) Weighted eye dose (Gy) WHRO RSS AEBS SUE IL. AMMEN LY. REA Ze ALE & | SHO LHSZILEORV Mae U Gy LE) cho TECK. WHAAIZ, DSA CRS < HORS) OL HERB, AE RR TANIA (
0.005 Gy. The excess number of solid cancers is esti- mated as 848 (10.7%) (Table 3). The dose-response rela- tionship appears to be linear, without any apparent thresh- old below which effects may not occur (Figure 3). Wh RHO BRS Late Radiation Effects #3. LSS LMR SRIBAAREDY AZ (EH). 1958 - 1998 4 1° Table 3. Excess risk of developing solid cancers in LSS, 1958-1998" 28A Cancers BAC L oti aie ee en ee Weighted colon dose WRAL PARE HET BL a 28 (Gy) LSS subjects Observed Estimated excess Attributable risk 0.005-0.1 27,789 4,406 81 1.8% 0.1-0.2 5,527 968 75 7.6% 0.2—0.5 5,935 1,144 gs) 15.7% 0.5-1.0 3,173 688 206 29.5% 1.0—2.0 1,647 460 196 44.2% >2.0 564 185 111 61.0% at Total 44,635 7,851 848 10.7% 3. LSS RMI BItS ABA A BE OBA XZ (BUR). 1958 — 1998 461° RU ERRIL, BERENE ERD 30 ig—D AB 70 BITE LUA YG TL OR, BR FHI Y XZ (ERR) ORVERUEIUS SRF. KUDU, PKA XZ EAE LIED YING RA BU YZ HEN CH ORO BEBE © OFFA CHEE EO EF 1 RRERECRT. Figure 3. LSS solid cancer incidence, excess relative risk by radiation dose, 1958-1998." The thick solid line is the fitted linear sex-averaged excess relative risk (ERR) dose response at age 70 after exposure at age 30. The thick dashed line is a non-parametric smoothed estimate of the dose category-specific risks and the thin dashed lines are one standard error above and below this smoothed estimate. RIS AZ Excess relative risk BAIT Litt e (Gy) Weighted colon dose (Gy) JERE BIC EO PERE NCASA SAU ATER GEDRI-AEVE The probability that an A-bomb survivor will have a VAX) lt, SIPC SRMERSS LOVE HRA LC) Cancer caused by A-bomb radiation (excess lifetime risk) 7 ae cok depends on the dose received, age at exposure, and sex. WA. M4 lc, 1 Gy (CRE LEO IY AZ & eB Fi ian igure 4 represents excess relative risk and excess absolute MEM VAD (HRP) ENF. CHSOMAY AZ 0, risk (sex-averaged) exposed to 1 Gy. Both expressions of PUREMEIDYRUIZEV AZ CEeARLTWHS. © | excess risk indicate that higher risks are associated with DlEMIL YH, KPEILIVLEL 0 WER IC EASA AZ ~~ younger age at exposure. Other analyses (not shown) indi- PEERS LMA POTS. cate that females have somewhat higher risks of cancer from radiation exposure than males do. Late Radiation Effects KHGORZS [fl BU 4. 1 Gy BeMEIC £ SED A DIRE VX 7 1 REF BRIE tt Ze S OVC BYE FO BE"? Fe BME IB AUAXT VX Z (ERR), A BUSH RMX XZ (EAR) ICL BRA. Figure 4. Effects of age at exposure and attained age on the excess risk of solid cancer (incidence) following expo- sure to 1 Gy.'° Left panel represents excess relative risk (ERR) and the right panel excess absolute risk (EAR). 4 Acta Res FE Bh Age at exposure wo 1 GyS4EY ORI AD Excess relative risk at 1 Gy nN 0 i T r T 20 40 60 80 BIE im (ak) Attained age (years) ry fii, BPR. ARG. REE. FLBB. SNE FRIKIR, BZ BREODEBRHBRADBGEICIL. AR RIB) 27 ASB OSLNCWA. Mary PILARCHASA Dit ClLRWPD, {LOZ < OPBMIZBIFSARAIL SY AY OVIMADBHY 5 Do tho CT. MRO F— Fit, PNM ELT ATO MMILBITS WA OEY AZ LUM SAD Lvs 7 WUE PRULTWHSA. MAG AZ lL, EDC BRREME BIC EY Bree ee eee Ts eee TEE ig 30 i (AI) OD ADS 70 MIG LEMFOY AZ ELTH-Y ERT CE CHMOD AZ & IRL TS CHEOREE Cd, BIIBASA & Ft eA A 7 (ERR) ld. 1 Gy ORC MREE C 47% ChS.— HAL CU PICERBHALIICMAZA SPD, \FHOA OWT HEAT AY 1c ILMB. CMILBALIS Eo TILA TEMES 7 WlkS-HERDTWS, M6 SU AZ (HERIO A SRO RAES Lvs AEE) LOW CHEHOMILUT— 9 ERT. BADIA FEMA (Ay ANILARS) BaROKO VES (147 BI). fii (117 Bl). Ete (78 Bil) (63 fl), BLOW (54 PI) CHoK. MOILGUDS A OFT — FY OME IL. DA OPC A LU SBMBRWVCEBBW, BRS, BERRA, L D BV irae det LD. HURIR ASA PRS AO £4 % BEE OIL DAO 58 EM e HEI T D5 CHS. TTOMBBA EG DUA &, HRIATY AZ (ZO T 4. JS4EFE (1 Gy 47) 47%) EDEL (42%) IZ (4, 8 (150 fil), . FARR Hore, i Hot AZ iooOu Clk, BARRIER DO LOTR CHO (LAA Gy 4%) Oil TE PI Rt 2% 52 Bil, FETCEE 27 Bill) RO => 60 yo =2 ee > o 407 Wa M$ os 3 204 @ Rg SS ley 0 20 40 60 80 BER (mm) Attained age (years) Significant excess risks are seen for many of the major types of solid cancer, including cancers of the stomach, lung, liver, colon, bladder, breast, ovary, thyroid, and skin. Although not always statistically significant, excess risks are also seen for most other types of cancer. Thus, the sur- vivor data are consistent with the notion that radiation is associated with excess risks for virtually all cancers. Since site-specific risks can differ by sex and age at exposure, Figure 5 adjusts for such differences and compares risks among sites by presenting sex-averaged data showing the risk at age 70 after exposure at 30 years of age. Under these conditions, the excess relative risk value (ERR) for all solid cancers combined is 47% following exposure to 1 Gy. While differences in site-specific risks are apparent, the range of variation is not statistically significant, partly because the numbers of cancer cases at given sites are limited. Figure 6 presents similar site-specific data in terms of attributable risk (i.e., what percent of total cases are associ- ated with radiation). The largest excess number of cases (given in parentheses) were for cancers of the stomach (150), female breast (147), lung (117), rectum (78), thy- roid (63), and liver (54). Analyses of site-specific cancer incidence data are often superior to those of cancer mortality studies. This is because incidence studies provide better diagnostic infor- mation and are better able to assess the occurrence of less fatal cancers, such as thyroid and skin. For all solid cancers combined, the excess relative risks were comparable for incidence (47% excess per Gy) and mortality (42%), but the excess absolute risk was 1.9 times greater (52 versus 27 excess cases per 10,000 person-years per Gy, respectively). Wh) HHROBWS Late Radiation Effects 5. LSS RHIC BF 3 BERENEE tit 30 i (BKFID) OAD 70 EIT L72NFO I Gy 4729 O BBCI AA RAE OAS XZ BEBE 90% HE Ae RT. Figure 5. Excess relative risk per Gy for the incidence of site-specific cancers in the LSS cohort. The risk is standardized as exposure at 30 years of age (sex-averaged) and diagnosed at age 70. The horizontal bars indicate 90% confidence intervals.’ 4/H1720\A All solid cancer ASB Bladder XtEFLE Female breast fifi Lung fi Brain FAAKER Thyroid #8 Colon #38 Esophagus SNS Ovary & Stomach ET fi Liver fiefs Pancreas iB Rectum ig (2 iB2RR<) Non-melanoma skin + Uterus AU IZER Prostate 0.0 0.5 1.0 1.5 2.0 1 GySEY ORAZ Excess relative risk at 1 Gy 6. BEBEHE (20.005 Gy) ICE CE MMHODATEAE, 1958-1998 2. A DEBAA BGR BB IC ED RICA CEH DNS SO. Figure 6. Number of site-specific cancer cases occurring in the exposed group (20.005 Gy), 1958-1998. The white portion indicates excess cases associated with radiation.’” f& Stomach fifi Lung AT iit Liver + Uterus RB Rectum fiz fist Pancreas #38 Esophagus AB Gallbladder XtEFLE Female breast 5S Ovary FSA Bladder BIIZER Prostate FAK AR Thyroid Ai /R4R4HHE Brain CNS R058 Oral cavity/pharynx Biz Renal Bile (iB &BR<) Non-melanoma skin ~€Mtth Others 0 500 1,000 1,500 2,000 FE PBX Number of cases Ai '419 FASS LL hs Se? BLO HAM K ERAS, Ae Fee BADIICEAS BRAD Oi CDS BONIS AS 4 AL EO |s SIAL. A WEY EW 7 FEB Ze D Zee PUBS eV). URI, (ARIF AE CHE) LCE 2 46 C38 LIAM. PUR eo HETIL, arate (LSS) Bt NOC, JE Ic 4E LAME @O TTA Gy DLE Oitae & Fr sil A iL r§ OD SEAL IL. VERE (< sie & HEC BUN BUA LARGE CHS. 1940 ERB MOTMITWR. CNB MITER IL & PEERS EO He Se Seti) BEDE PARR. EF. WNC L Pt DSRS Ce CLL CC. ARE BUR O IAC S x Bote fA 6-8 FEO TE | EL FEAL (| 1950 46.0 [| Aad HE % JE | IMG NCS. HATA LEWES BD 5A <. KEO elie sened 2CT. A SEL. Alli) AZO 1950 4E{CHIAE ICES 70 DYVAZIL, ROONMCELA % Fifi D SEAL L Amy (ke DR RIDE HB % 3 CT A yg (LR A. RL CBE CHA. THF A GLP LE-Z7IZ#EL X LEARY, TATE S Y AZ OMAP IL 1950 B® A 0.005 4 Am 5, 2000 FE Cle 204 HO IO 4 5 JTRS Bl (46%) CHS (#4). Distt KOS ES elk — EL Zine Ss CPU SIS DEABEDO 5ILTWRA ( FESTA 49,204 AO 4 MIC PIA HERE STB YY HATS CHEE SN Sia LOL 0.2-0.5 Gy OAK ila he HI MALL 94 fHOASA ELM RRASIC. AG HC a Obie CL HBL Ze DOUATIMES BoTWS. FCB Cb AMG) AZ E17). Late Radiation Effects KHGORZS fl Leukemia™* Excess leukemia was the earliest delayed effect of radiation exposure seen in A-bomb survivors. Japanese physician Takuso Yamawaki in Hiroshima first noted an increase of leukemia cases in his clinical practice in the late 1940s. This led to the establishment of a registry of leu- kemia and related disorders and to the initial reports on ele- vated leukemia risks published in the early 1950s. Risks for radiation-induced leukemia differ in two major respects from those for most solid cancers. First, radiation causes a larger percent increase in leukemia rates (but a smaller number of cases since leukemia is relatively rare, even in heavily exposed survivors), and second, the increase appears sooner after exposure, especially in chil- dren. The excess leukemias began appearing about two years after radiation exposure, and the excess peaked at about 6-8 years after exposure. Today, little if any excess of leukemia is occurring. Because the LSS cohort was based on the 1950 national census, quantitative descriptions of leukemia risks in A-bomb survivors have been based on cases diagnosed from that year on. As of the year 2000, there were 204 leu- kemia deaths among 49,204 LSS survivors with a bone marrow dose of at least 0.005 Gy, an excess of 94 cases (46%) attributable to A-bomb radiation (Table 4). In con- trast to dose-response patterns for other cancers, that for leukemia appears to be nonlinear; low doses may be less effective than would be predicted by a simple linear dose response. Even for doses in the 0.2 to 0.5 Gy range, how- ever, risk is elevated (Figure 7). 24. LSS HM CBF S FUMIE E SHC OMB E HEEL, 1950 - 2000 4 1 Table 4. Observed and estimated excess number of leukemia deaths in LSS population, 1950-2000" Heaths Le eB anise Weighted marrow dose WRAL LEE EL HEE eA BL a 28 (Gy) Subjects Observed Estimated excess Attributable risk 0.005-0.1 30,387 69 4 6% 0.1-0.2 5,841 14 5 36% 0.2-0.5 6,304 Pall 10 37% 0.5-1.0 3,963 30 tS) 63% 1.0-2.0 Le 39 28 72% >2.0 737 25 28 100% fat Total 49,204 204 94 46% Wh RHO BRS Late Radiation Effects 7. DS02 —€ DSS ITLAAMIBD) LNG RX bU » Z Hse, 1950 — 2000 *F. BERBIEE tit 20 — 39 EDAD 1970 FIZBIFSEBRPFHY KF" Figure 7. DS02 and DS86 non-parametric dose response of leukemia, 1950-2000. Shown is the sex-averaged risk in 1970 for exposure age 20-39." 10 8 ‘ © — Ds02 xR > za 4 — - vse eS 6 a] S So SN, dee we 4 a u 8 < 3 Rg x 0 BATITLEBHERE (Gy) Weighted marrow dose (Gy) *PY = J4F, CO CE ITE4EY LAA SE Y OE A UE PIELER *PY = person-years, in this case the number of excess leukemias per 10,000 persons per year 8. BBIFERG Ze 5 OIC BIER £ SBA MAIC RM XZ) ORF (1 Gy BROW A)” Figure 8. Effects of age at exposure and attained age on the excess deaths from all types of leukemia (1-Gy exposure)" 8 1BAFGySEY OWFIC HR Excess deaths per 10,000 PY-Gy & ee Efi Age at exposure Lss Mic bv Clk, BEB LOBHO FE HE A MG & MEY VERMEER O AIL AZ OVID FD STV Bo MAT ANAL ALG CREME CLARE CHE ET ADS IKRES CISIEL A ERBE LTR) 2. TMEV DV SERPER Wes (PG a ER & (LAR CHPHR AIS AAS CLS HB Ic E 1) ILILY AY OAR IMLID SNTORWY. IBRBAO FVEY AZ ERIC. AIO ZAY AZ > EERIE clk BEF (mm) Attained age (years) Leukemia risk among LSS survivors has been increased only for acute and chronic myelocytic leukemias and for acute lymphocytic leukemia. No evidence of increased risk is seen for adult T-cell leukemia (endemic in Nagasaki but virtually non-existent in Hiroshima) or for chronic lymphocytic leukemia, which, in marked contrast to western countries, is extremely rare in Japan. As in solid cancer risks, the leukemia risk also largely depends on the age at exposure (Figure 8). The different age effect WICKS CHOBE SITS (8). FROM IC Lo CAM WOIATIASHODSH) . AME VONSIEERE A MS RILS < LON SAS, Wes LOVER BEE Ug IS Hie Ice< blond. FA MME 11 HEB EOC. URE O FET A 7 Ik KEK ChEMRE UTHA RBG ITIL S (BS. wpb, Allis LSS RHOFNTOMAIC LSREO 13%. BLOSHEO 1% ATMICT Se. AMI kS RICE BEL, BUED LE CA LSS CAO BCP BEER IC EA HET SMALL SPEC ALON 16% HOTS. K FEL TWRWVAARAICBW Clk, Ala OAIEY AZ (Ih) TASLFACH So. CMICK LT, LSS IS BITS 0.005 Gy DEORE e SIRE CHauettae 0.2 Gy) AVE ALM AZ (S89 10 BIL/ FA ERT A 7 (EK 1.5) Ch. Ri teheee-2" FEPEC Ze EG (BR VENEUR) (ORS S VERTU RO gt lk, (EEA LOA) ER AE (AHS) D5 1R56 NT WS. FURR, BIALKIR, HERS LOPE O BE, BOEUICA ORY —PILOW CHEAT ON TRIS. WH Oty GS \< > HUN RE CO RMADSIED 67. CHE LK FRAIC. PEO ON IEE O PAW PAE Old, VER BIB O PDGF IRD OND, SNM ldhhonepoks FHO RENE IC BV CHI 6 De ite BUDE LO ILANT . PUREED 1 Gy Din FOAM A FIZ 15 (95% fai 1.27-1.70) CHS. Late Radiation Effects KHGORZS fl involves different types of leukemias; acute lymphoblastic leukemia is more common among young people whereas chronic myelogenous leukemia and acute myelogenous leukemia are more common among elderly people. Because leukemia is a rare disease, the absolute num- ber of leukemia cases among A-bomb survivors is rela- tively small even though the relative risk is high. Leukemia accounts for only about 3% of all cancer deaths and fewer than 1% of all deaths, although it presently constitutes about 16% of all excess LSS cancer deaths from radiation exposure. In an unexposed Japanese population, the life- time risk of leukemia is about seven cases per 1,000 peo- ple. For typical survivors in the LSS, who received 0.005 Gy or greater (a mean dose of about 0.2 Gy), the lifetime leukemia risk increases to about 10 cases per 1,000 (or the relative risk is nearly 1.5). Benign Tumors'*! Information about the influence of A-bomb radiation on non-malignant, or benign, tumors comes mostly from research in the clinical Adult Health Study (AHS). Studies have been conducted with respect to benign thyroid, para- thyroid, salivary gland and uterine tumors, and gastric pol- yps. In each case, a relationship to radiation dose was seen. In contrast, no clear excess of pathologically-confirmed benign ovarian tumors was seen except for sex-cord stro- mal tumors. Figure 9 shows a distinct radiation dose- response relationship for benign uterine tumors. The rela- tive risk value at 1 Gy is 1.5 (95% confidence interval: 1.27-1.70). 9. FEBMOHMU AD BEE), AHS, 1958 - 1998 4201 KRIE 95% 13 FARE RF 0 Figure 9. Relative risk by radiation dose for uterine myomata, AHS, 1958-1998.'” The dotted lines indicate 95% confidence bounds. HU AD Relative risk 2 3 4 BAtItTLEFBReE (Gy) Weighted uterine dose (Gy) Wh) HHROBLS Late Radiation Effects 10 (lathe MEERA IC BUT BIRR BE TOE (GE (cA PERU RII ICL) DATES Y & i RRUR BLOM CORRES. siti: 1 Gy 400 SHEP A bth AiR BlL, WHR LIER L TC 4 fF (95% (BRAK 1.7-14.0) Ro CWS. ARO MMS, HC FP WORE IC BV CHEE CH Ko Figure 10 shows AHS prevalence data for hyperpara- thyroidism (caused mainly by benign parathyroid tumors) in relation to radiation exposure and age ATB. The preva- lence at a 1-Gy tissue dose for all cases combined was four times greater than for controls (95% confidence interval: 1.7-14.0). The prevalence increase was particularly marked for persons who were children ATB. 10. AHS €HIZBIFS 1 Gy OBR PRIZE LEGG OF FARRAR RE TT IEE AWE (BERET mney) 1° Figure 10. Prevalence of hyperparathyroidism, AHS, at 1 Gy radiation dose, by age ATB”” BiBO te Prevalence ratio (log scale) 10 PLIERS © Few (ise) Age at the bombing 30 PALDADRBIC KSECo"” LSS HUF — ¥ (1950-1997 42) OFFICE YL DA DORIC LSE Ae bie & FEC CRT HY I AR MLTRACERPHW SME RoR. TRAE ILE EO PEE ISBROENTILYBWVYEF CHS. DS86 Hi iML2S 0.005 Gy DLE® 49,114 KOH, 18,049 ABABA DIOKUE CE ¢ RoTwA (MIB IC EAU CIECORICGENTWIR VW) > PERRIER DS © IL6 OFC OE 60% & HO, AGRE FB GRR Gt) ILekOR) 15%, MPO AIL 10% % HOTA. MRE & BRK DA LAORBIC LARC OP CHUN PERICLES Se Abi 4 RICE ARIE. 150 PID 5 300 BIE HET RW TV3S. 0.2 Gy PRL DS 0.005 Gy LLEO HIRE 49,114 OFS tiie) ORNL SIEAILBITS FOUL BIL, HOMER EK YW 3% MOTHS, CN (LEIA AOL INZS (30 we CHE Lc. HELEC 7%, EVE 12%) EHS TRY EDNCHS. COMB ISOTBIRIZOV> TLE CH S (M11). Tn, ¢ 100 1,000 Non-cancer Disease Mortality?” Analyses of LSS mortality data (1950-1997) show a statistically significant dose-response pattern for death from diseases other than cancer. The excess does not seem limited to any particular disease. Among the 49,114 LSS survivors with colon doses of at least 0.005 Gy (DS86), 18,049 non-cancer deaths occurred (excluding deaths attributed to diseases of the blood). Circulatory diseases account for nearly 60% of these deaths, with digestive diseases, including liver diseases, and respiratory diseases accounting for about 15% and 10%, respectively. Aside from diseases of the blood, the number of excess non-cancer deaths associated with A-bomb exposure is estimated at 150 to 300 cases. The death rate following exposure to 0.2 Gy (the mean radiation dose for the 49,114 survivors with doses >0.005 Gy) is increased by about 3% over normal rates. This is less than the death rate increase for solid cancers, where corresponding increases are 7% in men and 12% in women (age 30 ATB). The dose-response pattern is still quite uncertain (Figure 11). Late Radiation Effects KHGORZS fl 11. 1968 -— 1997 FOMMEIZIV CORBA LHORE OD Bt IE BIER (DS86) 0° FERE CAR L 72 RRIL, BERBIEE Bit Ved Br (LAVEE MBC LS AEA O Ze OBE ERR CF VERLTHIS. KLAR DW ERR HEE TC BY, FRCL 72 HBL 5 F972 FICHE MAF 7 DERUISSAAACHEE MEK OU TO 1 BRE RZED ERBBEOPRERT 2 ARMLREIIE MEO BULEBD & EO PRIICIN LZ BE DOCHS. Figure 11. Non-cancer dose-response function for the period 1968-1997 (DS86).° The solid straight line indicates the fitted linear ERR model without any effect modification by age at exposure, sex or attained age. The points are dose category-specific ERR estimates, the solid curve is a smoothed estimate derived from the points, and the dashed lines indicate upper and lower one-standard-error bounds on the smoothed estimate. The right panel shows the low-dose portion of the dose-response function in more detail. 0.6 o ns RIX VAD Excess relative risk [-) NO 0.0 05 1.0 1.5 20 25 3.0 0.2 0.1 0.75 1.00 BATHIT LEHR (Gy) Weighted colon dose (Gy) BALAN MBP BIS Ek SPEEIL OMT } AC RE & NBER SNTHIS. COLIBRBICHL Tit FEA OD MLO REPENS ELA DS A HETK & ER LT SD SLNBWO CRMC AZ L 7. PARA AFCA If WEABCITDTT DITA 128 HORADNAO PeIHIZ LAE CelcOu TLS LH 45% (LABS Ds (CEE LO OLE FICHE NCHY). OM ISAM E CIEMADBAL PUTS IVT 9 FEY (LHEGIAEE Ch > LEME 4 © AAI 2 ALALBASNTRRWRVOTC, COCH#S TUT ER OSH EAR IO hh PASSAIC LARC ORAM CL DLODEDPERBATS O&EPBBECHS. LPLIN E Cm LEB Y Clk RICHER RHE IC OV TILE 0 MOISE LEAS), CNODRAICL ) CORRE SAIL MHT4ZOEICARPOK. AHS W481 BIT ABSA WI OVER D FEA BAAS ClL, T- BORCHERS. FREE (Bl 2 ISEB TS). BEEF BB. AAR SEO MEICOV CT. RBC OSZBEDS MENTS (M12). EL. LSS HCP — FH, WPM APRA 384 al SB AMZ B LOBE BIC OVC bites & BEL Ze AI EADAR EN TWA (P13). YN A significant radiation dose-response pattern was also seen for non-cancer blood diseases. Such diseases were studied separately since they may represent various hema- tologic malignant or premalignant conditions. Among the 128 deaths for which medical records were available and in which hematologic reviews were performed, about 45% were clearly classified as non-neoplastic blood diseases, 6% were diagnosed as leukemia or other hematopoietic cancers, and the remainder were potentially preneoplastic. In the absence of known biological mechanisms, it is important to consider whether these results might be due to biases or to diagnostic misclassification of cancer deaths. Investigations have suggested that neither of these factors can fully explain the findings, especially for circulatory diseases that have been investigated more fully. AHS incidence studies of non-cancer diseases show relationships with A-bomb dose for benign uterine tumors, thyroid disease (e.g., thyroid nodules'®), chronic liver disease, cataract, and hypertension (Figure 12). The LSS mortality data also show dose-related excesses for respira- tory diseases, stroke, and heart diseases (Figure 13). Wh) HHROBLS Late Radiation Effects 12. BEEBE 1 Gy D AHS HRA ICBITS BA LIAOREBA OM Y XZ (1958 — 1998 4) 17 Figure 12. Relative risk for AHS incidence of non-cancer diseases at 1-Gy exposure (1958-1998)"” + = Hie Uterine myoma FAK ARES Thyroid disease Bik: PREG Calculus of kidney and ureter Z850u£ Dementia (StEHRBSEKUBE Chronic liver disease and cirrhosis 11542 Myocardial infarction FAKE Cataract AMZ Stroke KABA Aortic aneurysm MIME Hypertension MIMEtt DB Hypertensive heart disease 8% Gastric ulcer \—+L VV 3R Parkinson’s disease 4A] Glaucoma 0.75 1.00 1.25 1.50 1.75 2.00 1 GySRUOHEMMUAD Estimated relative risk at 1 Gy B13. LSSRAICBIFSBALDMORIC LEH COMM AZ. AF TI —-B HSWVILLMPE, PAEH WEBER, TAGE ClABATIICAEIC YU XZ DIMI TOS. BEBE 90% TAHA ERT 0? Figure 13. Excess risk of mortality in the LSS due to non-cancer diseases. The increase is statistically significant for all non-cancer diseases, or specifically heart diseases, stroke, respiratory diseases, and digestive diseases. The horizontal bars indicate 90% confidence intervals.? RAUNDTATORB All non-cancer diseases IRB Heart diseases AZA cp Stroke Ma eS Respiratory diseases Albee RB Digestive diseases RRB Infectious diseases EOWHORE Other diseases -0.2 0.0 0.2 0.4 0.6 0.8 1.0 1 GySKY ORIN UAD Excess relative risk at 1 Gy LSS AIO LBC KAP P— 9 Db, WOE FIC IMEVES £ O49 3 IPED BEE & EDS SCE DAB IBS TWA, AHS T-F7 DS, -LIPPHBEBLOT TS O—A-ESIIRM GE KORG AIL) & > EDS mH So EMMIBENTW4A. fEoT. AHS HRT ¥ BLEU LSS FORA LO BR RICE BUS) Ic BIT Sy Although the LSS data on heart disease mortality sug- gest that radiation is associated mainly with hypertensive and congestive heart disease, AHS data also suggest an association with myocardial infarction, as well as with a measure of atherosclerosis (aortic arch calcification). There is particular evidence, therefore, from both AHS clinical data and LSS mortality studies, that the rates of car- Vib MS BO FEARS ASAI LCS E (LIEIZPAME CH So LD EF CARO IE L Le BA AEMEO dy HE WENO RIE IC BAL CHSEDMTDILTW Bo hu fe {A eee 27 Bete Pe A < CHV DNA FP OAM SIT So AME DCN? DSA WAILERS 5 SNS E, DNAIYNSZLE BHT. SOU WDE & AA BRC ot & (di 9 CIBER C AD ERBHS. CFU CHEKOB ICED fEQMANK OO [REM] CIRO. Ciiciilaay ROPE | SD. Ye te (he iy BABE SANDS SUF 72 BUN RO ee (LEB LCS vio peared Ze tb AE ye oieac al & LT WHELEMCES. DEY. HSPUEMOMMBY vANTKE VERE A O HUN RR IT SEER D> 5 iB IR IR RD T BS, COMRICHOW TC, MADDY YASERIC BITS BG SHED 5 BUR Mat EHETET ZO CHS. eA ERB OD 6B, SBR SAILOR AD Io Be CAZOC, TOMELE DS cL CH SNT WS. LAL, 1THOBBRIC HS 2 (HO GAAS MEST SRD, SAREE FEO A © SAE SBE DERE CHL FT 4. flo TT. SHVAAKORE Liat OR ILDAAM CHS. VAR BRE EME % Bil (WR (PRUE L TW SOC, SBR HAPE IL (LP AE EN he Mm iclt#FeCa& Rv. enictbot, eA (BELO B) ashe, SRBORE, Re mE ILD OBA LD VD CHATS OSES 5 TeV, pe Nr ane comment DY IE CL EO BG OM SHE Ls £3 5 ASH > 7% Ji fej + BIRR OD HARARE CREB L Ke AIO THER DFE fie CHIE S 7H GEICHRE) EAT DAMNAOHA CE Sof) & DS86 tits & ORR 14 (oR LZ. AEBS RIGA IDO SNAHF HY CULHSSPAE-HLREIL, MTT OWE BICBU ZRHREAOBICLALOMSLUNAVL, DS86 tac al EC BU A TO AeA zele LZALOMS LNA, Bite. moO WE s Bie (Ht in situ?\4 TY FA t—ya Ve, FISH) HW CKBOMEMIC BY Cit DPIEG OREO DT OAT DITO So. Bette 1 . 4 HLH Ble, SO eet HCE BS Ue AA ERIC ES ERO LA Olli HES il | ult WE TNC IEMEICIRIH CAA EAC Rok (M15). FISH TRICE VERO EY AAI. EIEMiTbNAL ote Uae Ts AAR IS DTA VITA) ze SNTRI4Ao SE OMRIC ES HCN BURERO Late Radiation Effects KHGORZE fl diovascular disease are increased in A-bomb survivors, especially, it appears, for persons exposed at young ages. Studies regarding possible underlying biological mecha- nisms are being conducted. Chromosome Aberrations”? *” Chromosomes are composed of long thin molecules of DNA. When cells are exposed to radiation or carcinogens, DNA sometimes breaks, and the broken ends may rejoin in different patterns from their original arrangement. The abnormalities that result are termed “chromosome aberra- tions” and may be visualized at mitosis when cells divide. The frequency of chromosome aberrations increases with radiation dose to the cells and serves as an indicator of radiation dose received, i.e., a biological dosimeter. In vitro irradiation experiments using blood lymphocytes can provide a dose-response relationship that can be used to estimate radiation dose to individuals on the basis of the aberration frequency detected in their lymphocytes. Among different types of aberrations, dicentric chro- mosomes are relatively easy to detect, and their frequency is therefore useful as a biological dosimeter. However, dicentric frequency declines within a few years because the presence of two centromeres in one chromosome inter- feres with cell division. Thus, the frequency of dicentric chromosomes can be applied to recent exposure cases only. Since A-bomb survivors were exposed to radiation many years ago, dicentric frequency is no longer useful for biodosimetry, and the frequency of translocations (and inversions) is used instead. Such aberrations have a single centromere per chromosome and hence can divide so that the altered chromosome persists for many years. However, they were more difficult to detect by conventional staining methods. Figure 14 shows the relation between DS86 dose and the mean fraction of cells with aberrations (mainly translo- cations) measured by conventional staining in survivors exposed in typical Japanese houses in Hiroshima and Nagasaki. The small but consistent differences between the two cities may be due either to different scoring effi- ciency of aberrations in the two laboratories or to differen- tial errors in DS86 dose assignments. Currently, chromosome studies for survivors in both cities are examined solely in the Hiroshima laboratory, using a modern chromosome painting method (fluorescence in situ hybridization [FISH]). Chromosomes 1, 2, and 4 are stained yellow and other chromosomes red so that translo- cations between yellow and red chromosomes can be detected unambiguously (Figure 15). The FISH technique has made translocation detection easier and more accurate and has been used successfully in studies of radiation expo- sure accidents, such as Chernobyl. Although fetuses had been regarded as radiosensitive, chromosome aberration data for survivors irradiated in Wh) HHROBLS Late Radiation Effects 14. AHS HARB ABET OREM CAF SMOG & Bid & OBR Figure 14. Relationship between fraction of cells with chromosome aberrations and radiation dose to AHS survivors exposed in typical Japanese houses 30 20 Ds Hiroshima y = d “Bell : Nagasaki 10 Percent of cells with aberrations LERRE EH OMMOZIS (%) 0.0 0.5 1.0 ies) 2.0 2.5 BAILA BRE (Gy) Weighted marrow dose (Gy) 15. #06 in situ7\4 FU YA C-Y a VE CHRMSENRAR AAA. A7CBRULIE RS FIBRE (KE) BAF. Figure 15. Metaphases labeled with fluorescence in situ hybridization (FISH). The left metaphase shows a normal cell and the right, a translocation indicated by arrows. Fa VAIS RIC L CRED LEZ SU TAHRAS JAN BRIERE OF ARREICE TS 7-4 (40 eH fe CO IL BY YONERB) > 5 (SCN O BEL BIR S RPO Ko VIA Ho TRC b, BOIS IS EER BA Lb Ne DS, JAVEHAIC IRR SNL A 20 IC MNEIG GLE HO Lb6NRpPoK. Ek, AANCECE 7 OY A (Foe RE eRPOMALIE) OBA RR & AMICI S CLICEY, 7 — Y MAINO RE LALO TK RotTwS (H% DHT LAKERS) DEI PeERBALE. FOR Fy URN ANS SR O DAMS AN IBE S HZ BDO AMAIA ERS! BU OIG Cw LIU. TIAAE D REZ BILD HF FEDS NEA OE BRIE SITUS EWI CEL, BUND FOFEDSEE EK DNA [Cf E14 HW ICE Le CEeBRLTWS. flo. BUNRIC ED AH (SEE PHPRIC BU SAAMI OM) (CAR RE DRS NTR4ONCULRVPEBHDNE. FOC. MMH & VZTEEO DO BIKE FIR TE DRA 6 IPEDS, ARMMERIC BIVSAVATAUY A (GPA) GIRS ORAB RMS ROME DSIRE SNORT EAH SG Ale LAL GPA ifn FFA EAMES, CIC BE LC tes Reena ae Nein 1A AO Bee ie MSIL TRC EDS DOK PARA oy BP) Ove. Wh k& Oe HERE O GTR TILK E RACLAVY (fl ea ie ee DEMS, GPATA BLA @ face lc (L5H LCV ze WAS, WEF BRM LEO AO tet & PRM OY ZILA DS HED S LIZ. tea keo th fe32—-37 SO FEAL RCN BIC < CHEILP TC EDM SWNT Bo CHa, RH TY VNB LOB Y YN GHD SE KOPSEARMRAME) (CBESNETRE-VA (MILO PUTS WFC) 1,000 mGy group (DS86 uterus dose). The right panel shows the effects of 1 Gy exposure at different ages®*. The X-axis represents the age at exposure and the Y-axis the radiation effects in cm per Gy. Circles represent females and squares males. Vertical bars indicate 95% confidence intervals (CI) at various age ATB, and dashed lines 95% CI of the linear regression line. 170 3 Bt Male ~S 160 RS a ® att = AE so Female f= § 150 . Female Q€é Lz Fo D ew wk 140 K g 1 a § ee | Seah ~ @ 130 Me || | 9 9 Ssecco a #3, 120 110 =A 107 1 i213) 14, 15 16; 17> As 0 by 10 15 20 IE RRERR (RE) RAS ERG (iE) Age ATE (years) Age ATB (years) HAE 41-45 Aging*** HEV LERD O, HUME S12 Bea Animal experiments have shown that radiation expo- sure shortens the lifespan. The results were once inter- CBELERDP OWS. COMBMAIL, PO TILK é fog ae t preted as being due to radiation-induced non-specific SARIS LS IPA IE DUR O NEI LS LDEDBR — acceleration of aging, but later studies showed that tumor DHOOM, TOROMEDS, Fearsswiolse A ithe | induction accounted for essentially all of the life ) HHROBLS Late Radiation Effects PRIZED Lene eee nae JSR DUES I< 38 1T S IPP RAY Ze DIME HE & AN EPL IE Be OH EWE IGE FWRI BYTE, (ZEAL MOSM IR (MAIL. WAS, filitia, (RO wl fi REN OBOE, HEI, HEI, HSV LAL RED te SILA). LL. ANRBLOT ST O— APEBIIRMULO ANGE? SUR IC REL emi OZ IVERA AU CNVOB{EI OV Clk. BUR LIC AE L 78 IMAL SALTS 0 HEE ASIE AG IE MOTI % 5 | & eC TREAD PEM MITA RO. Sted ABEL 7 PIE DUE TC dD 6 Ra te amEebSkLOKRBES * PER UC BSE L Ze) BEE BOL OH ti D FE AE HG 1950 4E(C EE ICPEICH SIS SN TW. BLEEDS 0.005 Gy Aili HERE S RARE IC BY TIE, 1,008 AFF OA (0.8%) IC HREAPAGET DS LYE SNE OI LL. BREEDS 0.005 Gy LE & HEE SNE BES Ic BV Tid, 476 A 21K (4.4%) 2H RAHE CIS Ne. COBH bi nomena ld, PRUE Rat BL OPEEREED AGG CRC FEIE OR LUBE) CGRV BO PRAS D0 HAGE OI aoe SNA 8 — 15 CPE Le ACHP IC TEE CH YY SHAE 16-25 A CRRLEACTLEN EV ODE PORK WS, SAH O-7 I, Eeld 26-40 ACHR LEA CLE (boner (B 17). Ev, HEC ev Beeb, SHARK 8-25 A CRRLEAIC. MeOH MMe PSE MH IQ TEELONR PDIBD SN (18). FEVEE BOD 3639 Hl b BA Alc 6 A DE EYEE (COU CLAM ORERAENS ER TDS fTbrCTBY, CARIN AAPSAAA AMET SL, Hii D Hee (CAH Ae RRB ASG ARC ENA LAPBSHN TH. EWU (E16) LR. EMEA DNA HURT O BRUTE CS. ERE IC BV TRAE (18 ine) ne {SEO AE TEHY Te DP DE SILT Ho IO Ni im 1; cH Ny Tea Keo Sa PL, TEP BERREG O AGED alls (LBS PADS Ze > 18 A Ses HE Wt, IA Bee cya ine E COMMAICA CR BA WBE ZOU. 12 REAPS 55 AEF — 7 DO LRAT DIN 0 JAPA BRR Clk. 1 Gy 47%) OWA AZ (ERR) 2 1.0 CHE ERLE IDPS 5 17D, BERRIEMENG 5 ide EC BWR (ERR IE 1.7) ELEN CHARICE ADC DH) IL PK. LPL, eRe CIs FiO Ha hm c FES shortening. In studies of A-bomb survivors, there is little or no evi- dence for non-specific accelerated aging in most physiol- ogic parameters or morphologic effects (e.g., radiation dose is unrelated to breathing capacity, ability to focus vision, skin elasticity, grip strength, and hearing ability, or to tissue differences at autopsy). However, radiation- related increases are seen in the prevalence of cataract and atherosclerosis, as well as in altered immune-inflammatory serum protein levels. Continued data collection is neces- sary to determine whether radiation exposure leads to non- specific aging. In Utero Exposure Mental Retardation and Growth Impairment** By the late 1950s, exposure-related increases in small head size and mental retardation were noted in persons exposed to radiation in utero. Severe mental retardation has been diagnosed in 21 of 476 in utero survivors (4.4%) whose doses were 0.005 Gy or greater compared with nine of 1,068 (0.8%) whose doses were below 0.005 Gy. The prevalence was strongly associated with radiation dose and gestational age (1.e., particular developmental stages) ATB. Excess mental retardation was especially pronounced in persons exposed at 8 to 15 weeks after conception, and to a lesser extent among those exposed at 16-25 weeks, but no excess was seen after exposure at 0-7 weeks or 26-40 weeks after conception (Figure 17). Dose- related decreases in school performance and IQ scores also were observed among the 8—25 week groups of in utero survivors, after excluding severely mentally retarded chil- dren (Figure 18), and increased seizure disorders were also evident in those groups. Magnetic resonance imaging scans of the brains of six severely retarded in utero survivors suggest that radiation exposure during the third and fourth months of pregnancy may result in distinctive physical abnormalities in brain structure. As in persons exposed as children (Figure 16), annual body measurements of survivors exposed in utero have demonstrated an overall reduction in adult height and weight by age 18 in the high-dose group. These effects do not differ by sex or gestational age ATB. Cancer Incidence*?”° A recent analysis of cancer incidence at ages 12 to 55 compared data for survivors exposed in utero with those exposed in early childhood. For the in utero survivors there was a significant dose response with an excess relative risk (ERR) of 1.0 per Gy, a risk not significantly less than that for survivors exposed during the first five years of life (ERR = 1.7). However, the temporal patterns of the excess absolute rates which increased rapidly with age for early- sie 7234 TEV ta AD HOT EDS UE ST AZ OWA LC. RAPER CIEE FL FAOMMA Lonewv kj Chok. RELMHO Id, BURR CldHATHIICA EE CILE V3. PRC EB, PRICE AMR MMOBAY AZ ASSAM IS EY CMAN CE Le CE DHE LCR ZACH4AI. Late Radiation Effects KHROBRS I childhood exposures did not increase following in utero exposure, but the difference between the two was not statis- tically significant at this time. It can at least be concluded that adult cancer risk from in utero exposure is not greater than that from early childhood exposure. 17. HEAR IA BUT S Beit © Ne PLL a HY D BEG ALE He *7 Figure 17. Severe mental retardation by radiation dose and gestational age among A-bomb survivors exposed in utero BSE A (%) Risk of severe mental retardation (%) 0 0.10 0.20 0.30 0.50 47 8-15 JAR 8-15 weeks 16-25 iB 16-25 weeks 1.00 1.50 BAT lt LEAT E ERE (Gy) Weighted uterine dose (Gy) 18. RABE ICBITS FEM (DS86) BL OAM AFIY 1Q FREE 95% fa Figure 18. Mean IQ scores and 95% confidence limits by uterine radiation dose (DS86) and gestational age among A-bomb survivors exposed in utero’ 130 120 ° . ; #5 110 1 3 "Or st 9 I re. S2 t99 | 8 = 190 80 t-OH xt FB# Control (<0.01 Gy) +@4 0.01-0.09 = La 0.10-0.49 Lv 0.50-0.99 HOH >1 Gy Fae 0-7 8-15 16-25 264 age SAAB OD ELIS Age in weeks after conception Wh) HHROW NZS Genetic Effects RHRO ahs = EE AERCN LD HEME DAE SAMO DNA (cf (Ze GAR OTL, GEMRKOUK (F)) ea, (owt LC PRAMS AEC RARE RIL ROU Ic fab S TENE, Eb OARS AM LEIA FEAR EEL, RC Ekipibe C I BEC bd. isles i mn CRRA Ze EE CHHAERPRE SS ee MRT eC) DH CSAS, CHETOL = JERE @ Ff CHRIS E Ze VA VERE NY Ze OBE & AE Ze EVI PELL SITY. TBIO FSB DIB {RVC PRURMEEE O ORAIL CPEB % 1c 0.14 Gy) RBIS TUL, COMRILE SAAC E CLE, BECO AV ARAWLERDSOFUN ERLE) TEENY PACILEIS SBRYO, E RISB RICe LOW ALLE VIRGEERT DIT CRW IE ERIBL TWA. #65 (clk 1940 EHR A 5 ABCC — HiT CE LT & 7 ERB OF HEISE T SROMPOU MELAS . Hh PRE Be) TEx F, RA OPEC IMA AE MET SEE BIC, Fy HARE Kenran. PekRe ce CO FED 5 tet S 17 MHLO DNA VS CHE BAP EU SIV ORE TOTS, Genetic Effects When ionizing radiation causes DNA damage (mutations) in male or female reproductive (“germ’’) cells, that damage can be transmitted to the next generation (F)). This is in contrast to mutations in somatic cells, which are not transmitted. Detection of human germ cell mutations is difficult, especially at low doses. While high doses in experimental animals can cause various disorders in offspring (birth defects, chromosome aberrations, etc.), no evidence of clinical or subclinical effects has yet been seen in children of A-bomb survivors. Given the relatively low average dose to survivors (median doses of about 0.14 Gy for both the fathers and mothers), this result is not surprising. It is consistent, in fact, with the predictions of mouse experi- ments and suggests that humans are not more radiosensi- tive with respect to heritable changes. Table 5 lists the several kinds of genetics studies con- ducted at ABCC-REREF since the late 1940s in children of A-bomb survivors. Active studies involve ongoing mortal- ity follow-up of the F, cohort, an F, clinical examination program, and various molecular studies of DNA from cells of survivors and their children. #5. ABCC — WGPWZ BUT BIERERIET OD FEO te ANY APE Table 5. ABCC-RERF genetic studies of children of A-bomb survivors al I Al Studies HAERPSe a GCRE. IGHESE HH ze XC) Birth defects (stillbirth, malformation, etc.) {KE Weight }EIE Sex ratio Ye ff ($524 Chromosome aberrations 48 A/S Sk 8) Protein electrophoresis FOE, DSA FBAZS Gitte) Mortality, Cancer incidence (ongoing) a le sat Clinical examination program DNA wl #e (AikiCHF) DNA studies (ongoing) HAE RE RES (1948—1954 4) 51—54 ERWURE OF HEC BU SB HERBS ¥ ELE OF DUE Wr RR ES Dea CA CBM L 7 EVs 9 SSE LEB MONT. Keg RMPOIET A CORAM S MAAS 1948 AEC AAA ST 6 ELV COR HTA 76,626 AAS, ABCC ORM LABGRe LIK. HAD EAD AFK Population size 77,000 72,000 141,000 16,000 24,000 77,000 12,000 1,000 Zhe families (1,500 ,O-+fE offspring) Birth Defects in F, Offspring (mainly 1948- 1954)°'-*4 No statistically significant increase in major birth defects or other untoward pregnancy outcomes was seen among children of survivors. Monitoring of nearly all preg- nancies in Hiroshima and Nagasaki began in 1948 and con- tinued for six years. During that period, 76,626 newborn Wa S17 ARO AA CIS, RED BEIT OVC ACG HB DS FROM TW PAS, 20 ALLE O KEM COV CSE BI ALPS Hook, COPPA B HI CREST STHRICBOV CC, THIS BU A RAED 90% DLE ASMERE S 1 TERRE EEO BALD SA HEC Ro HAR 2AM UA PAO BSBIck YO. HAR MAT, ROVE, VE. PAVWIOME, BLOLER MARE LOU CHRO 5 N17. TURRET. ALO BE % PLO Pest BIC 6. 7, SICAT. AAAI MRED Ze VT BLA 5 AEE IL. JIT OH 3 7% 65,431 ADHD BAK HV HAE PEE EAE BS (594 PI, 0.91% (2424) Id, HO AR + EERE CHP NK ARADO WEIS SARL Ha EO RM RE -RL CWA. COMBE CHES 17 HE (AR REE CIS ADS Ze APS, 0.92% ILFHBAILS TVs Bo CORIO HURST b BLO BUN iia E 7 (SME ORRe AR SB POK. OS (HBO OAC HARE IL, ARIE, OR, RA (ARBRE CE ODER CLE OSS). ARE, Sisie (POPS 5 ARES SK) BLOGHHE (248 DhLORAIKIE) Chok. CNS5ORHIL, H8 OI YA 594 OF 5D 445 Kh (75%) IHD SNK. HH AE Fee ESE OD HEL, RIC SER EC ESE Ze EO EF Uc PAE VAMC ILFEL LBV BE OBHAODC. HRS AAMDS 107 A AIRED bin. HARE Sit 7 FH 18,876 AM7 By 378 KA (2.00%) IL -OYED HV BEE DSW 5 nko CILLBHOMEIL, AR 2 AADADRE CIS 0.97% Chek. COCO MO RERH tie ¢ OR REEL WHRENRPokK. KAK Ro CTHNARERHADSL % FEO 72 Fy HARE ARDY T A172. 2008 “E 8 ABEL tix 4) D CASE HE (Radiation Research 2008; 170) CHA. Fe 6. JR BETTIS BUT 3 MEER BPE, Genetic Effects KHROWGHRS infants were examined by ABCC physicians. When surveillance began, certain dietary staples were rationed in Japan, but ration regulations made special provision for women who were at least 20 weeks pregnant. This supple- mentary ration registration process enabled the identifica- tion of more than 90% of all pregnancies and the subse- quent examination of birth outcomes. Physical examination of newborns during the first two weeks after birth provided information on birth weight, prematurity, sex ratio, neonatal deaths, and major birth defects. Newborn frequencies of untoward pregnancy out- comes, stillbirths, and malformations are shown in Tables 6, 7, and 8 according to parental dose or exposure. The incidence of major birth defects (594 cases or 0.91%) among the 65,431 registered pregnancy terminations for which parents were not biologically related accords well with a large series of contemporary Japanese births at the Tokyo Red Cross Maternity Hospital, where radiation exposure was not involved and overall malformation fre- quency was 0.92%. No untoward outcome showed any relation to parental radiation dose or exposure. The most common defects seen at birth were anen- cephaly, cleft palate, cleft lip with or without cleft palate, club foot, polydactyly (additional finger or toe), and syn- dactyly (fusion of two or more fingers or toes). These abnormalities accounted for 445 of the 594 (75%) mal- formed infants in Table 8. Since many birth defects, especially congenital heart disease, are not detected in the neonatal period, repeat examinations were conducted at age eight to ten months. Among the 18,876 children re-examined at that age, 378 had one or more major birth defect (2.00%), compared with 0.97% within two weeks of birth. Again, there was no evidence of relationships to radiation dose. To avoid over- looking the adult-onset diseases, an F, clinical health sur- vey was conducted during 2002 to 2006 which focused on lifestyle diseases. The first report is in press (Radiation Research 2008; 170) as of August 2008. WE. HAR 2 AHMUADEL) OELD (BOWIN, SEB HIES 172-LHKOR, 1948 - 1953 4f)? Table 6. Untoward pregnancy outcomes (stillbirths, malformations, and neonatal deaths within two weeks of birth) among A-bomb survivors, by parental radiation doses and cases/children examined, 1948-1953°° EESLO Hathlt LEBER RHOBAH I L cist Father’s weighted dose (Gy) Mother’s weighted dose (Gy) <0.01 0.01-0.49 20.50 <0.01 2,257/45,234 81/1,614 29/506 (5.0%) (5.0%) (5.7%) 0.01-0.49 260/5,445 54/1,171 6/133 (4.8%) (4.6%) (4.5%) 20.50 63/1,039 3/73 7/88 (6.1%) (4.1%) (8.0%) ) RHHROW NZS Genetic Effects #7. VERE BERET NZ BUT B WERE HEPA WIFE ES 7172 FOR, 1948 - 1953 fF) °4 Table 7. Stillbirths to A-bomb survivors by cases/children examined, 1948-1953 *! BEBO REEL Mother’s exposure THA Ee conditions Not in cities HAASE 408/31,559 Not in cities (1.8%) {EHP tat 279/17,452 Low to middle doses (1.6%) Tue 26/1,656 High doses (1.6%) RHO WREKIN Father’s exposure conditions {EFF ae faye Low to middle doses High doses 72/4,455 9/528 (1.6%) (1.7%) 139/7,881 13/608 (1.8%) (2.1%) 6/457 2/144 (1.3%) (1.4%) B88. AEB 2 IAD BIS 17 IE SEN APES 7EL LE OR, 1948 - 1953 4f)*" Table 8. Malformations diagnosed within two weeks of birth by cases/children examined, 1948-1953 *! EEBLO MERKUL Mother’s exposure THA HE conditions Not in cities THA ASE 294/31,904 Not in cities (0.92%) JERE ites 144/17,616 Low to middle doses (0.82%) Bee 19/1,676 High doses (1.1%) PIE (1948—1962 4) 55 FB YAOME—O X Beta RISA BLIC HRT SOC. BED DIC BER LWA ICE XK EERO FEB ECL YKVORMERSS ¢ 0. ORICA LEW clk ED X FBLA IEA SNZAOCHEOHMARS CREEBRA SITTER 3 72. 1948 FERS 1953 4F (AUT THLE SIUC UR BU DF LIZ ET SO F— Vik, COMMLOFMW EC -BL EAS, wERTHIIC AE CR MOK. SO CHHPVEL 1962 4E E CHEER W728 Sit 140,542 A, £045 73,994 Alam ELILZO—-F DSEUERIC BEER). TORRILELLAO BUN RED GORE & BET IT ACER HSEMOKS COR, VERE ROR. Nad LODO MIN BITS X ERO ARM NY — ve COM ASS RRS 1, X ERR EBB EO EF ICL BBE SR SOMFUT So ELMER ESR SENSEZIC DED EDS, BE CISHLICAS 4 RISA OIE (AEB ORE LC LCA SO LISS AZ SNTW RY Reo ho QPOR ENKI Father’s exposure conditions {EEE le ie Low to middle doses High doses 40/4,509 6/534 (0.89%) (1.1%) 79/7,970 5/614 (0.99%) (0.81%) 6/463 1/145 (1.3%) (0.7%) Sex Ratio in F, Offspring (1948-1962)°° In the past, lethal recessive mutations of the X chromo- some were thought to alter the birth sex ratio in favor of females if mothers were exposed to radiation, since the single X chromosome in males is derived from mothers, and in favor of males if fathers were exposed, since the male X chromosome is transmitted only to daughters. Early observations concerning births to A-bomb survivors (1948-1953) favored this hypothesis but were not statisti- cally significant. Further data collected through 1962 (140,542 births, 73,994 with one or both parents exposed) did not support any radiation effect on sex ratios. Subsequent considerations regarding errors in sex chromosome number and patterns of X chromosome inacti- vation in embryonic and extraembryonic tissues have made it difficult to determine how X chromosome muta- tions may affect sex ratios. Under these circumstances, it seems doubtful that sex ratio measurements can be useful as indicators of genetic radiation damage. REAR (1967-1985 tf) 5657 TBC PRI 1 EV) BL Az SPA A Re ee 9 (0.11%) 7 (0.08%) Parental origin untested & at Total 25 (0.31%) 18 (0.22%) * SJE at 0.60 Gy Mean dose 0.60 Gy MREABORRER (1975—1985 sf) 8-6 1976 4F 4lkelk DNA D2VA BER & EADY -Y T BEUINDEPOLOTC. MEH CILKOD 2 FED ZEKE SE RARE LUCHAA TONE. old, Hise me FIZEIRIE SEC ho CHOA BAUM LO [En] PRIM CRITE RAMEE AV CHS NZ ED CH OK. ft FERRARA SER BA AE! ChHokK. Blood Protein Mutations in F, Offspring (1975—1985)°s©° In 1976, since no techniques were available for direct screening of DNA mutations, RERF used two kinds of pro- tein alterations as potential indicators of mutation. One was a rare electrophoretic variant arising from base substi- tution mutations and was detected by one-dimensional electrophoresis. The other was an enzyme-deficient pro- tein variant caused by deletion mutations. Wh) HHROW NZS Genetic Effects 10 4A IC 70, LSS 4EBII HOFLOE - IR Ae ES WEES LY RAEL (Zé 10), IZOVWrT 11) ° POL i) ail AE ie a ae DS 0.01 Gy L LIBS SRR BL OSPR AW 25 4FAI OC, MEO 30 OR EO} ERM IAAK CILEVER DEBE (ZO CORRE bar (#¥ EOF EE BUR He) & 0.01 Gy ANOS EE OOPHRHE) @ 2 FEI DRG, | E dk 7s FE UK LE DER WR HD FEE er hengan eee san BORA CH 0. POA HAMAD ICA D728 $4 OWE KHL FDS 6 Bi, BID I PIOACH OK. BRIAGKIC ES! ZS BL PLUR AES 2 Bil, OPHRBRIC 4 BURR S GE WMD ANT ARE SE 1 PLETE UC DARI DE 1,233 Bl. TEE eat 47 SVR SNe. CNS BRM ERO HH BEST EDD BE LI. t CORRK-E IS FENRIS HBC a = FIAECIL, ZEIK hk Ek. B pRIE SZ Over ten years, nearly 24,000 children of LSS survi- vors or controls were screened for electrophoretic variants of 30 blood proteins (Table 10); 10,000 of these children were also tested for enzyme-deficient variants (Table 11). The children were classified into two groups according to the combined parental gonadal dose of each child, either 0.01 Gy or greater (exposed group) or below 0.01 Gy (control group). A total of 1,233 electrophoretic variants and 47 enzyme-deficient variants were detected. Studies of parents showed that most variants were pre-existing and that only six electrophoretic variants and one enzyme-defi- cient variant originated from new mutations in parental germ cells. In the study of electrophoretic variants, two new mutations were detected in the exposed group and four in controls. The only enzyme-deficient mutant found was in the exposed group. 2210. xt LBC S 3 Gt Table 10. Results of screening for electrophoretic protein variants mate Le HED Be Children examined Ewen Le wate FAL Leg Loci tested New mutations (xt HaH Controls) PIRES / TBF / TAC <0.01 Gy 20.01 Gy* (@kUETE Exposed) 12,297 11,364 589,506 544,779 4 2 0.7x 10° 0.4x 10° Mutation rate/locus/generation * BAIT Lee ieitite 0.49 Gy * Weighted mean dose 0.49 Gy #211. AERIGPEOI P LERMBBRC FS OR Table 11. Results of screening for enzyme-deficient protein variants <0.01 Gy (xT ARE Controls) 20.01 Gy wate Le HEO Re Children examined aa L ett EL Loci tested SERIE RIL New mutations PRB ER / TBE / TR Mutation rate/locus/generation (@kUETE Exposed) 5,026 4,989 61,741 60,529 0 1 0 2x10° DA ED REAR LD RG FEE HEA ed EIA ERO EPL NT SOCTLAW. LDL. MRE L O AIL. BUNKLO BORE Toy Ze al HORRIL TD & & 3 CHR TS I ILBUE AY SFRACLIMA. Rice C, BAN MOE RMI eG AHO TOMMY TEN CHMAD LOB REO BMEILE CIS CCE DMS MICROKOTC. Lido MARIA Clik. CC CHEIL, DNA ZAREROE FEN ADZY-AYVTATONCWA’ DNA #8 (1985 4 —3R7E) ©1-6 AIM BY V7SERICHS 4 EB UA VAICE OB Bite HRS M7 RP EMMITR A CERRO DNA alte SEH LTS, ECMEOMAIL, WBLE ILS O—FA 0.01 Gy DLE CBE L TS 500 RIK L OMBLO VW FI & AZ ple SLIT TV Ze) 500 ZED 5 BLA 1,000 RHEOBL CALRUISE DNA studies of survivor families make use of Epstein- Barr-virus transformed cell lines established from peripheral blood B lymphocytes. Cells come from parents and all available children of 1,000 families, 500 with one or both parents exposed to doses of 0.01 Gy or greater and 500 with neither parent exposed to significant doses. Uncultured lymphocytes and polymorphonuclear leuko- cytes are also preserved. New techniques for DNA analy- sis such as DNA chip technology are currently being developed. A pilot study has been initiated to examine DNA in 100 families, 50 exposed and 50 controls. Minisatellite genes comprise high tandem repeats of core sequences (more than a few base pairs), which are located at many places in the genome, and are known as highly polymor- phic in its repeat number (or total length). As such genes are highly unstable in nature and the spontaneous mutation rate is high, genetic effect of radiation can be detected with tests of a relatively small number of offspring. The results by eight probes and DNA fingerprints analysed by a multi- locus probe, 33.15, are shown in Tables 12 and 13. No effects attributable to radiation have yet been observed. Among new mutations at minisatellite loci, more than 80% are derived from male parents (the production of sperm involves many times more cell divisions than that of eggs). RERF results on the minisatellite mutations are in contrast to the results obtained by an English group on radiation- exposed families (but the exposed doses are much smaller than those in A-bomb survivors) after Chernoby] nuclear power plant accident etc., but the reasons are not yet understood. Recently, a pilot study was conducted that used microarrays as one of the DNA studies related to genetic effects of radiation. The microarray used consisted of about 2,500 DNA clones (termed PAC or BAC) that were selected among the huge number of clones prepared for human genome project. The array could detect copy-num- ber changes (CNV; deletion or duplication) of sufficient length (>30 kb) in the genome. Among the 80 offspring examined, 251 CNVs were detected but all of them were inherited from either parent. No suspected case was found that could have occurred newly following parental expo- ) HHROWENZS Genetic Effects aanty LELENSILTNTHIKEB SRO ICFFEL TREND CHOK. MORES EL CHE as EVER BED ALA) PIL Pork. GRILLS ¢ DT) LEME LC ade % 17 9 ETC S © 2212. REBR OLED I AGF IA bitte fHelc BUTS PRB GE 81 Table 12. Mutations at minisatellite loci in children of A-bomb survivors™ BM LV ARAB RB AE L ACB ju-7 New fattationnenmetes examined Probes <0.01 Gy 20.01 Gy* XTM-18 0/183 0/65 ChdTC-15 0/183 0/65 Pags 0/183 1/65 AMS-1 11/183 1/65 CEB-1 11/183 4/65 Pc-1 0/183 0/65 B6.7 6/160 3/56 CEB-15 7/182 0/63 fat Total 35/1,440 9/509 (48 Frequency) (2.4%) (1.8%) * BAP Uc -Fiitie 1.9 Gy * Weighted mean dose 1.9 Gy RCBEBKLUPA HERS 6 REA CL, LSS BANBS ABER OTHE, 5 Aae5 198446 12 ECILAHENEACOWT, SUZ LODA AE & PRA LCS. CORMO Fiepls 2007 EOKERLC 23 HEADS 61 EO SEPA HY . PEt ATI CHS. CME COMRMRICL SL, 20m GTS Vd 20 RELAIS BIT A DAFA E LILWABEOT OF FRICKE ARCO PMSA SNC, LAL COPMICLBIVAREOILLEA FISGRBETS EM DIN BOC, FREEZES BLO ETON ERO 52 (= BY 1946 4F oe = ra LC bait EE ¢ 72. SRE RW Oe AA KECH So. F, RMI BW SMEARS — 7 RIA (LECH Ko sure to A-bomb radiation. Further studies are under consideration. #138. DNA 71 YA-TVY hICBIFSE RRB © Table 13. Mutations in DNA fingerprints® <0.01 Gy 20.01 Gy FED Bi cinibless c a HI LINY FORSBEL Total bands examined a deal BT LV ZEPR IE FRE 13 1 New mutations* (1.2%) (1.1%) *Z EF MET O— 7 33.15 ic £0 RH *Detected by a multilocus probe, 33.15 Mortality and Cancer Incidence in F, Offspring®*©® RERF is monitoring mortality and cancer incidence in persons born between May 1946 and December 1984 to LSS survivors. As of 2007, cohort members ranged in age from 23 to 61, with a mean age of 47 years. To date, there has been no evidence of increased cancer incidence or increased mortality from cancer or other diseases either up to age 20 or after age 20. Much longer follow-up is needed to reach any conclusions regarding the effects of parental A-bomb exposure on disease occurrence, since most of the disease occurrence in this cohort is still in the future. Table 14 shows recent summaries of mortality data for this F, cohort. Genetic Effects KHROBGHRS i 2614. BHT OS MIC BUT SB AFM LUZ BABEORBALIOREICAF SE VF— FILE (20 weit E 20 LAKE) . QTNOGHS. RANCHER EF— KROME SN TPZ. Table 14. Adjusted hazard ratio for cancer and non-cancer mortality before and after 20 years of age in F, offspring.™ No statistically significant increase in hazard ratio has been observed for cancer or non-cancer mortality. ~SASCLE Cancer death DSALWSH-OXEE Non-cancer death 1-19 ink 20 ine DAK 1-19 ise 20 ink LAE Age 1-19 years Age 20+ years Age 1-19 years Age 20+ years BLAST L eta Weighted dose LR FH FER Aoi We AOR FER Vor (mGy) No. cases Hazard ratio No. cases Hazard ratio No.cases Hazard ratio No. cases Hazard ratio RBLO ER Paternal exposure <5 (ASFaHE Control) 8 1.00 73 1.00 219 1.00 110 1.00 5-149 22 0.84 74 1.05 50 1.39 | 6 | 0.84 150-500+ 20 0.90 64 0.92 31 0.99 EE BLO BUR i Maternal exposure <5 (A}FaHE Control) 16 1.00 128 1.00 331 1.00 176 1.00 5-149 68 1.43 126 1.04 119 1.01 | 12 | 0.79 150-500+ 38 0.94 102 1.00 53 1.09 ) #42 Radiation Dosimetry HRS Radiation Dosimetry ies hie tee 8 Physical Dose Estimates®*5 FAZER ICD A HEE aK Ik 2002 FE ICH A Ke The Dosimetry System 2002 (DSO2) provides individ- 4 (D802) C, #EERH A TEMPUS BIS 2 WRIC IES ual dose estimates based on information regarding each a gine eps ’; tsye,- SUrvivor’s location and shielding situation ATB. This sys- VCR 4 A ORI @ HERE TS So DSO2 IIA Re «FMI tem was introduced in 2002 and is based on the physical (EFA SURED DBRS HC. BC S aU BUNRO HH nature of the bombs dropped on Hiroshima and Nagasaki 7p OIC PUR MDS Zee EO EF CHB. ESE A(K | and theoretical models developed by nuclear physicists for DOMES HET SIC POLS EBBESVIEMICOWT the amount of radiation released, how this radiation was transported through air, and how it was affected by passage through physical structures and human tissue. These mod- DCHS. DET WIL, KEOBU BA CHET Y 4 IV? ote were validated using measurements of existing exposed LEE) OPER RIA EA MAED Ze SITS. Hl 191k, | materials, such as wall and roof tiles. Figure 19 shows air Zerh wee (> 7p db, WERROZVMIRAE) £ELIMibg > OHH | doses (i.e., no shielding) according to distance from the AEB ICT Li bOTCHS. BEOTD, MORE DS OR hypocenters and makes reference to corresponding biologi- ieee _ cal effects and to comparable doses from other sources. BETNICLSZEWMSN VE SAT o DIZ EBA ED BERNE PV ICFEOVS CHAT SNES 19. BEDI 5 OFERE L ZB Rit & ORR. BREN CREA CBIR LEGA BHRBIZ 50% LEMD TS 0 AMIE RB CAEDFIIER, BEOCOMORH RUC EB RIB EAT Figure 19. Relationship between distance from hypocenters and radiation dose in air. If inside a typical house, the dose is reduced by 50% or more. Shown at the right are general biological symptoms and radiation doses from other sources. 100 50rS. — [KS Hiroshima SS ea Rllé Nagasaki REO RRL ko CéM APS BCARIAIC1 00% TS 10 a 100% death within several days to weeks with modern medical Soe interventions 5s cS HVE 1 oe Gamma rays t got, mt&4 Vomiting, nausea 05 Bee tL SERB Decrease of lymphocyte counts Ss BE FOBAD5S RR RIE COR DO B ARO & Se Cumulative dose of residual radiation beyond the first day hee NSN 1+ BOR (HRB) Say Gastric fluoroscopy (skin dose) zechipe (Gy) Air dose (Gy) ic *S\\Neutrons s. + FV WI7DOK (BR) RS 0.001 , e| Annual background dose 1 + BLY 7 ARR 500 1,000 1,500 2,000 2,500 Chest X-ray photography IRL HDS © FEBE (m) Distance from hypocenters (m) FEA Ze PRIL, 1940 4E(R BEE 1950 4ECCHIAEIC LSS Basic shielding information is available from data AIO ISIE (ot L CH DN MERRO PF [EO obtained through interviews conducted in the late 1940s ~ and early 1950s for nearly all LSS members. In the late y . SpA EAE SP ACHIAE IZ fe CIS a ES PDO ie tee TG Pe ESS ei 1950s and early 1960s more detailed shielding histories OLEH OK ke CILEE LSA #9 1,600 m LIAL, FIRS Were obtained for nearly 85% of LSS survivors who were (£2,000 m LIN MHI) OH 85% (COU C HICH EAE = proximally exposed (within 1,600 meters of the hypocen- AMEN. CNOEOF—V¥ ICH, HA 10,000 m | ter in Hiroshima and 2,000 meters in Nagasaki). On the DAPS-CHEBE L 72 LSS SEF 93,741 A. 5 86,671 A, (92%) Ic basis of these data, DSO2 dose estimates (Table 2 on page Ceo: cae 7) have been computed for 86,671 of the 93,741 LSS VST DS02 HEE BRE ASATSE SIU TW S (TR —- YD, HK2) | survivors (92%) who were within 10,000 meters of the (2,000 m LAA CIE 84% ) 0 UHRA BEES VMSA ZIRE CH= hypocenters ATB (and 84% within 2,000 meters). DS02 WELT (ay 7 — EMA ORR &) 7,070 A Oiutiheeee | dose estimates could not be computed for the 7,070 proxi- PRY (ZO VT lk DS02 HEGEBURO SMELL CR TEE mally exposed survivors with complex or unknown shield- ing (e.g., exposed in a concrete building). Radiation Dosimetry HARE fj {a 2 Opt ee Mlk, A < OBIT NAR BRBSSL Individual dose estimates are imprecise for various rea- DILMIEM REO DHS. AVC S SEMEL L__-- 8ONS, including inaccuracies in reported survivor locations SIEM CEPR ORL, WRBICe CEO EF BUND 5 IGS UTWL PINT © FL CIT SC CILAATHET | technical issues regarding their radiation characteristics and the impossibility of accounting in detail for all aspects of shielding. In addition, the yields of the bombs and some hokrtBhpns. BHicld, MRPoMMHSNeL*AW can only be estimated. Generally speaking, it is believed 3 DOHC OPE EIS BI S BOOM Ze RH BA la, He that standard errors in individual dose estimates may be on WIS ALPE AV. HRATICIL, 1A AOE AES PEARSE LW 35% C DEF ZENTWSA!, TILK the order of 35%. Special statistical methods reduce the Ait < Tul systematic effect on risk estimation arising from such errors. PRAEDS AT HEFE NK MES ARH HOE IM SES ED Most radiation exposure was from gamma rays with a \ARBE e RESEDA ENTS small neutron component. In Nagasaki, the neutron compo- EBUMOIEL Alby WELCH ORD, HELO RE nent appears to be virtually negligible. In Hiroshima, it is LAN RS ‘) 77) WK re ay en DOoPLFELK. COMMF ORG, RICE OK DTD somewhat larger, up to a few percent of gamma dose for shallow tissues at the most proximal distance where survi- Choke Ikke Cltklliy £ Y Rar < . Heb WEEE CHELZ —-vors were located, but this ratio of neutron to gamma-ray DV —S Die ERE CLT V VEE OBL% TERE CH 7 Fed8, | dose is lower for deeper tissues and falls off rapidly with HY VOLES ZCOMUEF- OMSL, MBOPEMBIC ES UE distance (Figure 20). Neutrons are believed to have a CMR EN EERE 5 OPTREIC AE IMR Le (1K greater biological effect per unit dose than gamma rays. Thus, many analyses use a weighted total dose in gray 20) 0 HEF IL Ay Vik EO} BUNGEE 29 OAR DENYS (Gy) units, which consists of neutron dose multiplied by RIBREW. COC. HEF Hoe LOFT SHAT LT | ten plus gamma dose. AY hee IM 7s [hy EDS ¢ OAT CHV 5SIVTWSo 20. ACERS GOR LS BBL SVC BITS DY CRI TB PEF MUO WG © WI SHEFREORMA (%) Ratio of neutron to gamma-ray dose (%) Figure 20. Neutron dose as percentage of y-ray dose for successive levels of shielding and self-shielding®? I & Fe ly Hiroshima 10 Nagasaki WT SPEFREOSIA (%) Ratio of neutron to gamma-ray dose (%) 0.3 0.3 iy ug = 5 9 0.1 bss 0.1 \ ‘ 0.03 0.03 1,000 1,500 2,000 2,500 1,000 1,500 2,000 2,500 ei sthD 5 OD EBBE (m) ie tth D5 OD EBBE (m) Ground distance (m) Ground distance (m) Air dose* WIRE Shielded dose Marrow dose —-—-—#éla#= Colon dose “ROR LUIA OZ Re Air dose without shielding ) #42 Radiation Dosimetry DS02 (2 ko 15 MAO EO WY VBL L AEF O hie HEE CAA. CNS OMA IL, AED TERCIKULD 1S Dic, BURFOMKO IA S PRA BML TABI L 4 likeat DRUK D AICA NCS BAH ODS A & MATS S & RIL Slee DAV SITS 6 Vv FB at RO” ee NIL. PERO HEIC SOO EBONVEM Flic LS¢DICKWMSENS. POH CIS. ERIN TRA BL% BEN TOPE, WHERIBTAC EI koTHE US ROHED DEC. BRIMBIGIEVIE CHEBS Us, CINE Clit SNE Cd, ERED 5 SH ICES E COR WON Mes LED CRA 0.8 Gy URIS) B EU 0.3-0.4 Gy (Rle}) EBRGSNTTWHIHS. ERED 5 O IRAEDS 500 m PACED Hb lc BIT SHOR 1/10, 1,000 m Clk #9 Wl00 EBLRSENTWH. COBB HELE FARE WAC FEI Le (M21). T#ebb, Hee 1 AA Lit HOW 80%. 2-5 HAE CIM 10%. 6 HALA (FE) LOWDMHSNLEBLZSNTIS. Hebd Els, KEBORSBAECILEAEMBAY) CARMOKRCE EAA L, PHONIC LA ithe lt, hace DIO {HM 20% UK ES ClE 0.16 Gy, ElFCIL 0.06-0.08 Gy) % WAZ EIMELALRPOKOCLAVPLEDNS.] DLEIE DS86 Ic FEO < HEE CH 4S. DS02 (CHO < HEA Ze FT FULTON CRRA, AEF ORC &b LAV AR BVICSRULAHVNERO LO, MRE A ER CICK SLEBRGNSA.Q WUNTERE Flt, BE LCE OD FAVA SAW IE FV RAD LORD RO RGR C7 HUNTED A ICHRS A © FRGHO KER & FEC HN ED Alt LA LGH SN, ZO—* Fumi c eo CMO WEhETELE (BURO ER hor Se oe DMWTWREO, TRILL ¢. AE ClSIEG ab (EEF WIGENS HY VRBEDE b Borde - AX SPE TIAN). RI CULES (PH LUHW IX) 1c CEU COMERS EST Y VRAORKIMMBEE MBL, bOLRHEZCICEEEDKRERELT. KBOD 22 + EAM Clk 0.01- 0.03 Gy, EMFO VENA Cle 0.2 —0.4Gy CHEE SNA. BeLHICBIT SMP ICES PURPLE IL LILO MOM INO bCBASN WS. EK, PWM O COARAICE AB L 7. ARSC TEES 2 Rp aT OBE PRO CERI ETCH lc k SURO Hse os, PLL Hh D-MOEREMRI CT bnk. SABMAEATH Re CIC E ee eget ieee pl pal Ix DS02 provides estimates of gamma-ray and neutron doses to 15 organs. These organ doses account for shield- ing of the organs by the body and consider the survivor’s orientation and position ATB as well as external shielding. Analyses of cancer risks at specific tissue sites are based on these organ doses. Residual Radiation”*”” There are two types of residual radiation: induced radioactivity and radioactive fallout. Induced radioactivity results from the interaction of neutrons (a small component of A-bomb radiation) with materials. Doses due to induced radioactivity were highest at the hypocenters. Past investi- gations have suggested that the maximum cumulative doses of residual hypocenter radiation since the bombing are 0.8 Gy in Hiroshima and 0.3 to 0.4 Gy in Nagasaki. At 500 and 1,000 meters from the hypocenters, the respective estimates are about 1/10 and 1/100 of the hypocenter value. The induced radioactivity decayed very quickly with time (Figure 21). In fact, nearly 80% of the above doses were released within a day, about 10% between days 2 and 5, and the remaining 10% from day 6 onward. Con- sidering the extensive fires near the hypocenters that prevented people from entering the cities until day 2, it seems unlikely that any person received more than 20% of the maximum induced doses (0.16 Gy in Hiroshima and 0.06 to 0.08 Gy in Nagasaki). All the calculations were based on DS86. Detailed calculations have not been per- formed for DS02, but would be very similar due to the similar numbers and energy spectrum of neutrons. Radioactive fallout primarily came from radioactive atoms produced by nuclear fission of the uranium or pluto- nium in the bombs. Radioactive material in the bomb fire- ball ascended and cooled, a fraction falling as “black rain” which contaminated the ground (although the black rain was primarily soot particles from the extensive fires). Because of wind directions, the rain fell mainly in northern and western Hiroshima, with the highest measured gamma dose rates from fallout being in the Koi-Takasu area to the southwest, and in eastern Nagasaki, in the Nishiyama area. The maximum estimates of fallout dose from external exposure to gamma rays, assuming that a person remained in one place throughout life, are 0.01 to 0.03 Gy in Koi- Takasu, Hiroshima, and 0.2 to 0.4 Gy in Nishiyama, Nagasaki. The corresponding fallout doses at the hypocen- ters are believed to be only about 1/10 of these values. The doses due to internal deposition of long-lived fallout radioi- sotopes present in the environment, i.e., due to dietary intake, were estimated for a sample of Nishiyama residents based on measurements including whole body counting to determine each person’s body content of a key radioiso- tope, '37Cs_ and were found to be minimal. Now, more than 60 years after the bombings, ultrasen- Radiation Dosimetry HARE [fj B21. REDAORL 1 m (CBT S PNP L BRIER O REET Figure 21. Radiation dose at one meter above ground level at hypocenters, by time after detonation 15 1 minute TREY KW ORY VERE (Gy) Gamma-ray dose (Gy) per hr 1 BSTal 1 hour 1 fel | S= 1 week 1 year 148 |) Zaz 1 day |1 month BRB RROD LAL Background radiation level 10 10° 10° 10* 10° I FE12 O Beef] (h) Time after detonation (hours) eatW LMA, HERES OK DTD CHOK. 60 ELLA REL BUE CIS. PSN TIE WIGET S 72 (o LARGE Ze ER REO BPE CHS (Lb YRS FEO CWDEMILIEAD DF PLARY). Ee. BUNVEM PW DUE dBA CLE (1950 4E(KDS 1960 FARIS BUT CHR CAT DN EK ART RIC ESIC KW SO DHE LOBE Ch So JAR + RUMOR BUNS ES tm (SBE. PHN FD Re EO ARB RIC LS LAVEIS MIP Ho THOS (221). BONER Wb E OFF BUN BE FE + BAIL Ove Clk, DS86 REO 6 Hla AN ee ADS 4% © sitive equipment is needed to measure induced radioactivi- ty, and only a few exposed buildings remain in which it can be measured. Measurement of radioactive fallout is dif- ficult, and distinguishing the fallout caused by the bomb- ings from that produced around the world by atmospheric nuclear tests in the 1950s and 1960s is usually not possible. Current annual doses from residual radiation in Hiroshima and Nagasaki are far below levels of natural background radiation from cosmic radiation, radon, etc. (Figure 21). Chapter 6 of the DS86 Final Report provides an extensive documentation of measurements and calculations related to both fallout and induced activation. §) #848 Radiation Dosimetry yA GB ee o8 Mmigeh £k OPRAH A VAICIL, RERUN BLO BAERS BEV AW Catgr STH. BUN ile OA AO ze Lc AIT SCE ASMHECHS (Z 15). MMe ASAE CL, % AR TEOW(ZFO DNA D ede (Few 7s we) 7 Uefa fRIC4E Ue DNA OSE eK) LUT AS. UP LU RM lobe) ACERI SLWVI RCA, CNECOLI ARBAB ICE S4ZbOlk%V. AHS KA HORO TWA REED ye fh (KE BVEIL, ARREBA CH LCN OFEe Re & PEEL RARBED) b 30-40% KY CEA Pork. COIL, Tai ABU D BLED HE TE RR se & GRAM SU BEDS H SLLEMRBLTWIS. oth Biological Dosimetry’® Some effects of A-bomb radiation are “recorded” at molecular levels in blood cells and tooth enamel. As a result, years after exposure, blood cells and teeth can be useful for quantitative biological measurements of radia- tion dose (Table 15). Methods using blood cells measure DNA damage to specific genes (mutated cells) or to chromosome structure (chromosome aberrations). To date, chromosome aberra- tions are the best long-term indicator of radiation dose. Chromosome aberration frequencies for AHS factory workers in Nagasaki have been found to be 30-40% lower than those for survivors with the same estimated dose who were exposed in houses. This difference suggests that the current factory-worker dose estimates need to be re- evaluated. E15. NBER SHEET 4 720 DEWPT Table 15. Biological methods for estimating radiation dose Ti 2 mi Bh Methods Materials Y VINER BUS ERG Chromosome aberrations in lymphocytes IfL#Z Blood 2 cc TF fk Characteristics (sae Spapiling Useful any time after exposure Bi 2 IVE< BIT 4 ESR BA UE EIS ESR in tooth enamel Extracted tooth Useful any time after exposure Y YNERIZ BI S TCR RARER TCR mutation in lymphocytes PUR EAM b Ro CRO POMEF ICAL CHT ONE PRBE SR) YIN ERAS CUS UU O BOE & PRI TSE BCKRPOK. Bic, RARERISH MIC Lo COA CZbOCLEVOTC, DNA BARE RUEEO AA MELB bNTWS. RABRIL, MATRIC PRo TARICE LS SNH), CNOORBMMIOMGIL, Fite ICH Ly SOMEICILKA BIW AEDED5NS. COLIAR TUL CL, Dae O BRUNO HAE HIS — © USARICHEL Vo Ex, MAIL DNA GEIST HEADS OCS CIK it CLG CHS. filo CT. GHOREL Ait ite EIT Che ¢. RURORAE CSIC OA SND AER DEO EERE DS, HIRE ASPEN E LIER) TAU HO UN REE C > Th. RO EF (CBR IC PRER LZ Grek, FrVIT 4 V BRROGRMIMIEDAD ED CRM pkKoCPL FORM: LU SHEE CIS, Be RIC SLU LEY BOD DHAKA Vo PRD RX VAIS NK COD FV AVEWET ATE IflL¥Z Blood 1 ec RS < PUR eB ALA HT He Possibly useful within a few months after exposure Various assays of lymphocyte gene mutations did not detect A-bomb radiation effects when tested many years after exposure. The usefulness of DNA mutation assays is further limited because mutations are not caused by radia- tion alone, but by a variety of other environmental toxi- cants as well. Mutations also arise naturally when cells divide, and their frequency increases with age and can vary greatly from person to person. Under such circumstances, the effects of low-dose radiation are particularly difficult to detect. Cells are also able to repair certain kinds of DNA damage, especially at low dose levels. The extent of dam- age depends, therefore, not only on total radiation dose but also on modality of exposure or dose rates (acute vs. chronic exposure, single vs. fractionated or repeated dos- es). The effects of acute single-dose exposures, as in the case of the atomic bombings, are greater than the effects of the same total dose received over a long period of time in repeated or continuous low-dose exposures, as in the case of people living in the area contaminated by the Chernobyl] accident. Measuring CO, chemical radicals in tooth enamel is b, HADSIRAY VREORMMICAACHSZ. COW Slick, TAR EOP CRP 5 Lt AW A HE LC, BEA YIEIB (ESR) EW OAECI VA Vie Eilll FEF Ao ESR OFS FOURS (LST HNO ILE BIS A DOC, PORN P Pb St. WRAY te A abil & i PET AC LACKA. COPE FovsT747F Hitz CIS BU S REE O hee lc A SITS 0 Ye ARH OWI, BURR. RVMEA eR ICIS PER PLA ERG ILHE LV. SORPRIL, MY 78 SRL PM 5S <6 ORME ER CEEN TSC 440% OC, PRATT E LV 3 ERI DREAL CT LED 4, AS LTWSAY YIANERD ED < SW ORADHRERLZEY VY 7NER ROD (HOWL BBE Lea MIC RT Sb ORD BD) DADS BWOBS CHA. I CURR ICOW THO ESR F—¥Y EY YINSERO RRS TY EMA G DEN IX. £0 TEWE eA Ae © EE CA SPSLNA Vo ait Radiation Dosimetry HAGE an effective assay for gamma radiation dose. Enamel is separated from teeth that have been extracted for medical reasons, and the presence of radicals is quantified by a method called electron spin resonance (ESR). Because the ESR signal intensity is linearly correlated with radiation exposure, it can be used as a direct measure of physical total dose, regardless of exposure modality. Presumably, this method can be useful in assessing radiation doses in situations like the Chernobyl accident. Chromosome aberration data by themselves are not enough to calculate radiation dose directly when years have passed since exposure. This is because blood lympho- cytes are produced through various steps from bone mar- row stem cells, and it is unclear what fraction of the cells examined are derived from irradiated lymphocytes (or derived from irradiated bone marrow stem cells) when dec- ades have passed since radiation exposure. Examination of both tooth enamel ESR and chromosome aberration fre- quency in blood lymphocytes from the same donors may help us get better biological estimates of radiation dose. 43| a ij a—7-— Frequently Asked Questions Bija-7— Bl 1 RRC kSRCRR 8 WRRBIC EARL, PEK IHC OK SEO CBIMOH GIB & MIC EAH) OlEDICKICRoTHECK SO HOR RERIC KSC) SBMLAEINILR SRW. LAL. HRA RIC BES S ACGRILERL. RREABE CRORE ILI ERE CA SZABWVEY, BSN TADREDAH Z EO BAC. IEME Ze A BUSH 6 > Cle Vo PUR 5 FERRO 1950 4FICT ONL HAMA O REA ELO MR(ChLSe. BBAEKILRIC RELL] EBA 7c AlEH 28 BAI EDT So RELY WdwS ATER 4 SME PRIA AKA) lk COMIC EN TVR, JK Eel) ClLAB AT 34 GF -35 BAO 7 6, REE FR 2 - 4H AVAIL 9-165 6OFADHEL, Riles 1257-27 BAIL 6-8 AAAI LE CHEE SI TWH. HP S Bibl2 BAR RERICHA ST ODA EE # 16 ld, LSS RMICBUAPASSER (AMIE ILO vs Tld 1950 — 2000 4E, IIB ASA FEE BLIC Os Tlk 1958 — 1998 4E) © PRES IUEDC CRLE DOD CHS. HONE RARACHAILRZUES< RoR EBL SNSZAORMEIL (IFSP KGL ES BROWSE & ARR). Be HIVE Kav (KIBLVK4I4 SM). RET. AMLBLCOW “PRE FEEDS A FETERLOM 10% DR PER ICI 4 & ZASNAS!. LSS CMM TOL OM EME RET WL, 2000 4EE COM MRE ICHAT SCBA SNS} ASIEBBULY 1,900 PI CHEH E14. #217 (SED 5b OTHE C RUN PE OBIE KE Alc LMREDCHSA.W Frequently Asked Questions Question 1. How many people died as a result of the atomic bombings?** Deaths caused by the atomic bombings include those that occurred on the days of the bombings due to the over- whelming force and heat of the blasts as well as later deaths attributable to radiation exposure. The total number of deaths is not known precisely because military person- nel records in each city were destroyed; entire families per- ished, leaving no one to report deaths; and unknown num- bers of forced laborers were present in both cities. The 1950 Japanese national census, carried out five years after the bombings, provided a rough estimate of the number of persons who were exposed and survived the bombings. Approximately 280,000 persons indicated that they had been “exposed” in Hiroshima or Nagasaki. The so-called “early entrants,” who entered the cities after the bombings, are not included. In Hiroshima, an estimated 90,000 to 166,000 deaths occurred within two to four months of the bombing in a total population of 340,000 to 350,000. In Nagasaki, some 60,000 to 80,000 died in a population of 250,000 to 270,000. Question 2. How many cancers in A-bomb survivors are attributable to radiation? Table 16 summarizes the number of cancers (from 1950 to 2000 for leukemia deaths and from 1958 to 1998 for solid cancer occurrence) in LSS A-bomb survivors in relation to radiation dose. The proportion of cancer deaths attributable to radiation exposure is considerably higher in those exposed closer to the hypocenters (as is the case with acute deaths from injuries and burns) (see also Tables 3 and 4). Overall, nearly half of leukemia deaths and about 10% of solid cancers are attributable to radiation exposure. If one assumes that LSS survivors represent about half of all survivors in the two cities, the total number of cancers attributable to radiation exposure through 2000 may be about 1,900 cases. Table 17 presents the rough idea regarding the dis- tance from the hypocenters and radiation dose. Frequently Asked Questions #4] —7— B #16. MAN OMA MAH CULE 5 OU HIE DS A FENE ATL Table 16. Excess numbers of leukemia deaths and solid cancer occurrences in relation to dose nlite sp 1eam [VAS A 58 9E Leukemia deaths" Solid cancer occurrences’” HANI LE WRK Alm Ween wSeele WRAR DATE Hen FSG ie No. No. 92 Attributable No. No. 3% Attributable Weighted subjects leukemia Estimated fraction subjects cancers Estimated fraction dose* (Gy) excess (%) excess (%) <0.005 7 HEE Control 37,407 92 0 0% 60,792 9,597 3 0% 0.005-0.1 30,387 69 4 6% 27,789 4,406 81 2% 0.1-1 16,108 all 34 48% 14,635 2,800 460 16% 21 25109 64 56 88% 2,210 645 307 48% I REAS BURRS aT 49,204 204 94 46% 44,635 7,851 848 11% Exposed total *AMROWALBANU Le Ahi CHEF Re LOR LR SDEAYVREOA). A EIS A OMG lLBA LT Wott. BAT AR DHA 5 OFPBElCOVe TlL# IT EB. *Weighted bone marrow dose (10 X neutron dose plus gamma-ray dose) for leukemia and weighted colon dose for solid cancers. For indication of the corresponding distance, please see Table 17. TH AAN tee (NIC) #ISIBASAICILE EN THAD, Al OIA GISELE EM TW RV **These include not-in-city (NIC) group, which is not included in the leukemia data. #17. LSS HRAODBRALS U7 HUB FIR EE DID 6 OFLHEO PIR. U MANIC E 2 CHERUB BAEDC. oOphit Ee AHED PIGS WELZ CB FET 24 TILE SHU TlEBUO.W Table 17. Mean weighted colon dose of LSS subjects and the corre- sponding distance from the hypocenter." Since shielding conditions differ among the survivors, this radiation dose-distance relation does not apply to everyone. BARU Loti Bebb 6 OB Ee OPE Approximate distance from hypocenters Weighted colon dose JA%§ Hiroshima fell} Nagasaki 0.005 Gy 2,500 m 2,700 m 0.05 Gy 1,900 m 2,050 m 0.1 Gy 1,700 m 1,850 m 0.5 Gy 1,250 m 1,450 m 1 Gy 1,100 m 1,250 m BS MHP RA CEAZSHNSPAISS EUTUWSD BURR A LEZ ONABAILS > REF ICA LT So AMA OTRAS, BCP AO RC HER LEA BIBER ICL SN, BIBS 10 EMI DIRS BDO, SO PAIS IEFTE] ORE LTE LL BE CISIE & A EE PE Hone Rok. CHNICHL TC. AMR LDAOBA (IZA A) Oi A 7 ILBUE D iV TB. PEO AE HEX IC CHMOSNALH DNS. mE ot Question 3. Are radiation-induced cancers still occurring? Cancers attributable to radiation are still occurring among A-bomb survivors. The excess risk of leukemia, seen especially among those exposed as children, was high- est during the first ten years after exposure, but has decreased over time and has now virtually disappeared. In contrast, excess risk for cancers other than leukemia (solid cancers) has stayed constant and seems likely to persist throughout the lifetime of the survivors. a ij a—7-— Frequently Asked Questions Bil4 BARRE ORS BRR IL. CRE CE SC BASEO b IRD 5 NCTWS. TRG, PRM OPM PED AIETTELO 1k Py pt QUET IC BUT HIE OBA REDA , Woke + 5 BORE ECHS. CNEOHPBOS < ik, HMR CA Hi) 8 — 15 AOD PAVICBEER LL Ze CARCI ONAEI ChE. CNEDKORERP RA DWE lLOVWT b IED BAT DITA, Lhnild, FAROE CBRL EAC bb 5IN4AD EMRE IC. PERE OREM PER CAS AAS SAMI Abo, RAILOT— ¥ LIGA O AY A 2 AMR MEI] AR L TWH (28-—-Y). BS jap BUNA REE OF He CO LIRBBE GROTH IZ, BURR ( PONE SNEEEO-OCHok. wtRhe BERIT SLOOWKE BAAS 1940 AERA 5 BMS 1, BED HITS MTWAD, CME CHAS NERY CLR ERIS LV RENT RY. L®LY One CO MAD ULSD HTN AE PRI SO (a L TCREWVEDSHOKOC, COLEIUDF LEWES WOLERRLTRIA DICER. DEEWMBZICBITS ROLOWARICE Y. Wifey (DNA) VA COWEHHEEO PASH HEL Ro TKR. EC CHG Clit EH VAO WIAD 72D (CMA OUR eT CS BRIBE O FH MRCBLOSA BAIS S AE b Kise L CIT DIL CWA. ER. MAI Ro CET ZAGREB ICOV TC BLO TREO PAD ONSPE PEWS DILTS Ze@lZ, 2002 4E AS 2006 4EIL AIT CHRO FAED HARE HED WHR WD Ci bik, CHETCOL SA, RAH LB SRE IHRE 4 A PBS SL Ce WAS, COMA ALE CIRM AOC. tame HT IC ILEICRT+EAO MEDS YE CHS LB DNS] Bi6 Meet CHEL CUSRRAOLA FUP BA DBE EM lobko CIRM ZOO AMEN iE SCL e ANE LT. 19504F 10 A OES APSR ICIA kbih € 7c (SRI ICHEA CUI 7e 28 FAO BER FOHDS, MOH 4AM Nk. COISHS 4 FADE LHD 5 2,500 m LIA CAH EE Ze CN ie LC BEER LY BEV DAAAIL 2,500 mk) SHIT CORED 72D, BR HISAR CHV. COMIC. ARAL BIPRETTO LS Sali wd), 1950 4EO RAMA IC EG OH POTTICHEA THR ASRS AIC Poke 2ATIFAD. BERL T Weevil & L CHAT Ric eo TWH. WEOFV— Buh au Fy] Question 4. What radiation effects have been observed in people exposed in utero? Many health effects are associated with radiation expo- sure before birth. Effects noted among A-bomb survivors exposed in utero include a reduction in IQ with increased radiation dose, a higher incidence of mental retardation in those heavily exposed, and impairment in physical growth and development. Many of these effects seem particularly pronounced in persons exposed between weeks 8 and 15 of gestation. Death rates and cancer incidence are being monitored for this group. Previous data suggested a dose- related increase in cancer risk similar to that seen in A- bomb survivors exposed as children, but more recent data indicate that the risk is lower in the survivors exposed in utero (page 28). Question 5. What have been the genetic effects of radiation exposure? One of the earliest concerns in the aftermath of the atomic bombings was how radiation might affect the chil- dren of survivors. Efforts to detect genetic effects began in the late 1940s and continue. Thus far, no evidence of increased genetic effects has been found. This does not necessarily mean that no effects exist because some past studies were limited in their ability to detect genetic dam- age. Recent advances in molecular biology make it possi- ble to evaluate genetic effects at the gene (DNA) level. RERF scientists are preserving blood samples that can be used for such studies. Monitoring of deaths and cancer inci- dence in the children of survivors continues, and a clinical health survey was undertaken for the first time during 2002 to 2006 to evaluate potential effects of parental radia- tion exposure on late-onset lifestyle diseases. To date, there is no radiation-related excess of disease in adulthood, but it will require several more decades to fully determine this, as this population is still relatively young. Question 6. Who make up the RERF study population? To establish a population framework in which to con- duct long-term follow-up of mortality and cancer inci- dence, about 94,000 people were selected from 280,000 A-bomb survivors who were resident in Hiroshima or Nagasaki at the time of the October 1950 Japanese national census. Of these, about 54,000 were exposed to significant radiation doses within about 2,500 meters from the hypocenters. Another 40,000 members of the study population were exposed beyond 2,500 meters and received very low doses. An additional 27,000 who were not in Hiroshima or Nagasaki at the time of the bombs, but whose family registries were in Hiroshima or Nagasaki and who lived in either city at the time of the 1950 census also were included as an unexposed comparison group. These groups constitute the 120,000-member LSS cohort. TR IZA ADSMAARTAAA (LSS) RMA HML TS. oO [Hara EA | OlEDIC, Tae AE (AHS) SEAL], RASA, EST OF HE CF) OE] 28 4. AHS SBA 1958 ELIS 2 4F OE (HOTS SEH LT WOE ITO BIC. AF aT RAO Hp 6 ILI W253 FADS MAS! 0 FRAP SEA SECURES TP FRR BE BLO JAP CARE L 72 3,000 A225 KA 0 HURT OFED F Mlk 1946 4E5 AL AMS 1958 FARE CASH E Kit ISTH CAE REM TAT AC. BRL ECB BLUR LCR RBA 5A EME PEO MASE ENT 4A. ra ras ra bri HH B77 HAWRALSRRAOMAD 1950 EO RAMA C [Pik L EI] EBA MEH 28 BA IZLEo TWH. CNSEOKO HC, THM Cb 2 #9 2.5 km DIA CHEE) (COV TAB ES 50%, BERBE POUR (DHA 5 2.5 km Dike CHI) (OV Tl BLE 5% PRAT Ric Ro CWSEBZSNTWS. LML, AALS ALA TS EAR CO RPOK OC, TEER CEI CLV. Bes PATRBOPCCHETCKCL Tho TAK. LoL, SRR bokOC. MIDBbHCLe <<. KB eines rey bX). fel CIS (PALL HK) Bok. LAL. CNS OUTER wis, BUEC a ESP WE KwIAHE LY < SU bt CHA o BRAEWADS 7 —-OD CARL, PRET MASH OE Pio4tzoTHUSbEOCHS. (PUPIL HLO 1lO%LLF Chok. PETRUS + BUS L CRE y im IBEX SASH So EE BUNIROK-E © HOS Ay Vise INLCOE A RPEMLEV>.) HF LTCELMANEWEAO TPIS EH CH oO, BECILI VaARVY5 LEA ERT Question 10. How long were Hiroshima and Nagasaki radioactive after the bombings? Doses from residual radioactivity in both cities are now far below the annual background dose (0.001—0.003 Sv); hence, there are no detectable effects on human health. Radioactivity was over 90% gone by one week after the bombings and was less than the background level by one year (Figure 21). There are two ways radioactivity is produced from an atomic blast. The first is from the fallout of fission prod- ucts or nuclear material itself (uranium or plutonium) that then contaminates the ground, like the contamination that occurred as a consequence of the Chernobyl accident. The Hiroshima and Nagasaki bombs exploded 500 to 600 meters above the ground, and the explosions created huge fireballs that rose with ascending air currents. The material then cooled and started to fall with rain. Because of the wind, the rain did not fall directly on the hypocenters but rather in northwestern Hiroshima, in the Koi-Takasu area, and in eastern Nagasaki, in the Nishiyama area. Now, the radioactivity is so miniscule that it is difficult to distin- guish it from background radiation or the trace amounts of radioactivity caused by atmospheric nuclear weapon testing. The second way radioactivity is produced is by neu- tron irradiation of soil or buildings. (Neutrons comprised 10% or less of A-bomb radiation. Nonradioactive materi- als become radioactive after absorbing neutrons. In con- trast, gamma rays, which comprise the majority of A-bomb radiation, do not induce radioactivity.) Most of this induced radioactivity decays very quickly, so that now it is infinitesimal. ERARAOFIL AABINSLVUAKMOLRGH Rot lt, THRO RR - WIRES, AKA, JARED ERAT - ME CORMMAET OV 27 be eHL. SRR OME BROUKL. BUR TAA BREE IL IIL T TS. CO LIRKMPAUV eZ bPELTIA, KEWL YE SN CWA MIRA ABER, ADIDAS ATE OH WEES LSHRRS MM). BLOUEINOKS & HC {TON TWSRA CHER S. EK. KREODY YEVREBEOAAKKAS © ie & OFC. JERI MCE ICS SHORES L OMAP € TI OO W—bhFHY IVP + PUA FABUETH CHA. Hic, WH UL RAR CDR o CABEZA AMET (NCI) chee & JEP RFE & FEI] CAT FW ADL THY, SORR, HK WROTE CBS SB < OIC DER STW 6 HRA c Berets BET OMAR, UAH ORMAO MCA < MS, FET SILT Do WRENKEF— FIL, BRO MEAD BOE O SEDA & EIB HY Ze WC RG EAE ME O RTE IL KS RAE RRELTW 4S. HMO It, HRB MD BEA A (ICRP), ESE GURNEE (UNSCEAR), AEC RHE - WIFZER RA (NCRP), AEA BIT SE AEBUN LOA WF SCI RAS Sas (BEIR) REE LCR OD HAT ICR HRCI HAC WA. ER, MORE CNSOREBRORALLT Mth b1T2 TW So 1986 4FOF 2 VAT 4 VY SHORES. JERR CNL PUEDE L < FR 28 SHOES BUT SBR O BB BO RMEICD DD SRAMIBA TKK. CN ODIHOZ Cd. TM RMERE (WHO). FIBRE (AEA), 8 LOU E14 Y DEAE TSE& VY ¥ — (GSF) &EORAL SE] LUCE LTS EOC. RIC DLRSD BOARD HOEE © AL CSO ARO IEE & LCRA, 1995 4B AS 2004 EEC KE NCL EORBMICLY, AY TM FV TIC Bt BTWVEAVLEETBOHORS LOSS O JA CRU (PUR Le ARR OBE AARC TI Le. E7e. 2001 M5 2005 El IT TlLAKH LAU F—-4EORHICL Y, UY TOWRMRCHALT. FV AVAZEMICAT Sf HEROES LO iar ti se mat & EME LET S LO OMEE FEF — FIN ADB Tork. Bic, APT AD vy Al EID LS NFFY AD CHT PINAR EY is (cK batt Collaborative Programs HMMAARFOFTL I Collaborative Programs Japan Domestic and Japan-US Collaborations RERF conducts collaborative research projects with physicians and scientists from other medical and research institutes, universities, and hospitals to expand our research fields and strengthen findings on A-bomb survi- vors. RERF is currently involved with the local tumor reg- istries managed by Hiroshima city and Nagasaki prefec- ture; site-specific cancer studies that include pathological case review by external pathologists; and a variety of specific collaborative projects with local universities. We have an ongoing consortium with the University of Washington and Kurume University that is conducting a series of epidemiological and statistical studies of A-bomb radiation effects. For many years we have had a collabora- tive contract with the US National Cancer Institute (NCD to conduct a number of epidemiological studies that have resulted in many publications about radiation effects. International Collaborations and Information Dissemination The results of studies conducted at RERF are analyzed and disseminated throughout the world. Collected data elu- cidate the effects of radiation exposure on humans and are applied in establishing international radiation protection standards. RERF researchers interpret study findings in cooperation with the International Commission on Radio- logical Protection (ICRP), the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), the US National Council on Radiation Protection and Measurements (NCRP), and the NAS Advisory Commit- tee on the Biological Effects of Ionizing Radiation (BEIR). Members of RERF serve on several of these committees to evaluate and provide timely information on radiation risks. Following the Chernobyl accident in 1986, RERF has become more directly involved in studies of radiation effects in other populations whose exposures markedly dif- fer from the exposures of atomic-bomb survivors. These efforts have included collaborations with the World Health Organization (WHO), the International Atomic Energy Agency (IAEA), and Gesellschaft fiir Strahlung Forschung (GSF) to evaluate the effects of prolonged radiation exposure. In a similar effort, RERF provided direct support, under contract with NCI from 1995 through 2004, for efforts to strengthen epidemiologic studies of workers and members of the general public exposed to radiation as a consequence of plutonium production in the southern Urals of the Russian Federation. RERF also collaborated with Russian research institutes, under contract with the US Department of Energy from 2001 through 2005, for development of a unified database to facilitate and i HAT OTF L Collaborative Programs Be L 7c FRE RO PERE HE ED 7 DOT — YN ARR IZOVT H, 2004 4ED5 ARO MBE OM SBE TA WT BUN FEET EAT ¢ IIL TW So BROILER. KBE RIO MIC BUNS J ERS Hh 0 HE Et EA—HICARE, BLOM - Crv7 Y v ERE A—NASHIM) ¢iG3S RHA TOT Bo LI 6 OPEL ABU Ze NRF LAE & 72 Ee (oY BOROORR - HHBMRe IT See SIC, CNS OE Xe OPTED AAR CHAS MB Slt Se OO RE SHEL CS. HM CIAEL UCI VY EDS O RM WHE & EER NZI AN TS. TAEA 471 EEE ARR A: 5 OWE Ze LL Hah k VMMEBBLOGMA DRM eA COS. BIB (Ik, 1979 4E2>5 WHO OUR AAT ev ¥ — Ic, 1988 4E 25 1k WHO BUN REA GSH FHM « Be Ay hY—-7 (REMPAN) ©2% VIN IHRE RN TWA. strengthen health effect and dosimetry studies on the Ozy- orsk populations. Furthermore, collaboration with the Kazakh Medical and Environmental Research Institute in Semipalatinsk began in 2004, with support from the Japanese Ministry of Education, Culture, Sports, Science and Technology, for construction of a database for health effects study of those exposed to low-dose radiation from nuclear tests in Semipalatinsk, Republic of Kazakhstan. In addition, RERF cooperates with two local organiza- tions in Hiroshima and Nagasaki, the Hiroshima Interna- tional Council for Health Care of the Radiation-exposed (HICARE) and the Nagasaki Association for Hibakushas’ Medical Care (NASHIM). The two groups provide advi- sory medical and technical personnel to countries where major radiation accidents have occurred and funding for staff from these countries to receive specialized training in Japan, with RERF accepting several long-term trainees each year, mainly from the former Soviet Union. RERF welcomes trainees and visitors from around the world, including researchers from the [AEA and United Nations-related agencies. The World Health Organization has designated RERF as a WHO Collaborating Center for Radiation Effects on Humans since 1979 and a member of the WHO Radiation Emergency Medical Preparedness and Assistance Network (REMPAN) since 1988. RERF Publications, Use of RERF Data RAHM. HBP 5 OSTA I esti Gh tc TOAFDE Dinah BICFU4T LC re [Se YY — A J (E1993 SEICBEILS UC [WOOT] Iehbor, CMs Sait MEG CFB RM S AU 7e ICO Alli Y ( B bay RMX AT (EAR) BUS MURR CBU SHOU AZ DS. HOR LIC BOR LE PoRRMIL BI ZHiM AZD (AR AZ) BAI ROD, BUA BE LIEBE RIZHEOD 7 5, WON PRECAST S LER GN SRE LIRCOMEC. MALL IIT Bo 0.005 Gy WE (ARR RRL) IC PRUR Le era se IrBWC, AMMO Gate S YU A 7 iL) 50%, HVBASAD le] AZ (L#T 10% 0 s Bias & HEAR HHP L lL, COMAPI BUT S 176 IK GR (. HATREMIC BV CHAMOIS AOA. FEZ eld, SOM GH 1 4A) (Ble VI LAOHC PRICEOWMAIROKAOHME TC. FOMMPICEEL RPE PIL ko CHBE LUE. yes as ZEA O) Reese I PORE VC EB ae aE ARS, BeLHD S 2 km WA CHR LEA ETT AS, He VEO O IC Cla, HERE ARLE AS 0.005 Gy Lh LOA CHT WEILAV5bN4S. REOWE, JAE CLE DMD 59 2.5 km DA, Bele ClLa 2.7 km LIAN CHR L 7 ASS TILED. 10* person-years or 10‘ person-year-Gy (i.e., per 10* person-years per Gy). Whereas RR expresses degree of excess risk, or strength of causation, AR describes the num- bers of people affected and hence the public health impact in a population. For instance, the RR for leukemia is the highest among various late effects of radiation (RR approximately 5-6), but the total number of radiation- caused cases of leukemia in LSS survivors is estimated to be only about 90-100 (Table 16). In contrast, the RR for solid cancers is much smaller (RR approximately 1.5), yet the total number of survivors who have developed such cancers due to bomb radiation is estimated to be about 850 (Table 16). Excess Relative Risk (ERR) Excess relative risk is expressed as RR minus one, or that portion of the RR accounted for by the particular risk factor under study (A-bomb radiation, in this instance). Excess Absolute Risk (EAR) Excess absolute risk is expressed as the difference in AR between exposed and control populations. Attributable Risk Attributable risk refers to the fraction of diseases or deaths that is estimated to result from exposure to radia- tion. It increases with dose. Total attributable risk for leukemia deaths is nearly 50% and for solid cancers about 10% among LSS survivors who received 0.005 Gy or more (significant dose). Prevalence versus Incidence Prevalence refers to the rate of patients who have been diagnosed with a disease or medical condition at a given point in time, regardless of when the diagnosis was first made. Incidence refers to the rate of patients newly diag- nosed in a given time period (usually one year), whether or not they may have died during that time. Hypocenter The location on the ground vertically below the bomb air-burst point. Proximally Exposed This term originally referred to persons exposed to the atomic bombings within 2,000 meters of the hypocenters. However, more recent RERF publications use the term to refer to survivors who have estimated doses of 0.005 Gy or above, which approximately corresponds to persons exposed within 2,500 meters of the hypocenter in Hiroshima and 2,700 meters in Nagasaki. a Be RS KES CIE Dab 5S 2.5-10 km OFERC. ECS HbA 5 2.7-10 km Osi CHEE Le, 4 0.005 Gy Ait} ON FET TEBE BUN PRL DS Glossary BH OME I Distally Exposed This term refers to persons exposed to the bombings at distances of 2,500 to 10,000 meters of the hypocenter in Hiroshima and 2,700 to 10,000 meters in Nagasaki. Their estimated radiation doses are less than 0.005 Gy. a RIC Abbreviations RIC Abbreviations ABCC Atomic Bomb Casualty Commission JRE 5H HZ BS A-bomb atomic bomb Jsi--ssl# AHS Adult Health Study bk ) (#5 a2 AR absolute risk #fix}) A 7 ATB at the time of the bombing(s) #£28IRF (Age ATB : #K ERIE ZEN) BEIR Advisory Committee on the Biological Effects of Ionizing Radiation #2 BERUN MELO EWA Wye 28 ICED S % ae REA RAR CO, carbon dioxide =PR(biEX DNA deoxyribonucleic acid 74 + KYM DS02 Dosimetry System 2002 2002 4F-ii sete 7 Fst DS86 Dosimetry System 1986 1986 4Fittarde ze 77 xt EAR excess absolute risk 19) fax} 1) AZ ERR excess relative risk #4#I4H%t AZ ESR electron spin resonance Ef AE Y HIB F, first filial generation #-fkOs3—tHt{t (ie., the children of A-bomb survivors : #R OF ft) FISH fluorescence in situ hybridization (a technology to visualize chromosomes) #36 in situ?\7 TU Y4B@-Yav (Bete th & wikia F 4 Bae) GPA glycophorin A gene 7) A740 Y Aleta Gy gray 7% HICARE Hiroshima International Council for Health Care of the Radiation-exposed JCP EE ET IR EIS ih FFE ME hie IAEA International Atomic Energy Agency EMS 7483 ICRP International Commission on Radiological Protection uae maeARS Kerma kinetic energy released in materials 7—Y WB IHH S 7c a EHV FE LDsp 50% lethal dose 50% BOE HLRE LSS Life Span Study Farid # NAS US National Academy of Sciences *EI4#E/5é NASHIM Nagasaki Association for Hibakushas’ Medical Care Ell} - EAT YD ~ RRA NCI US National Cancer Institute 7 5 BEA E CO/F AI 9 RD 6 Fhe SRE CL MACS BIR COMECHAET. MACHOL, KEISER, FEI ILE E CH SODPUM OMB KEV. CRA, CO Mee LET. Ey BIC 4S OAM ASH ll, FM. Fry 7A, RAN -VPbSOBMVA DET + -—ARE CHEM E CHhHEC KS. HL < ISR AN wwwrrerf.jp) %# CHES RSV. YD (http:// BB: T 732-0815 JA eT rs X Sta Akal 5-2 BUNA TSCA WG : 082-261-3131 (4¢¥) 77 VDA : 082-263-7279 Fel} T 850-0013 Rll HII—T A 8-6 BUN LAE TSCA #iah : 095-823-1121 (*t#e) 7777 RA 2 095-825-7202 RERF Tours and Further Information FLE#HO BAIS OUYT | REREF Tours and Further Information Our Hiroshima and Nagasaki facilities are open for tours by individuals or groups Monday through Friday from 9:00 to 17:00, excluding national holidays. For a res- ervation of guided tour, please contact the Public Relations and Publications Office, Hiroshima, or the General Affairs Section, Nagasaki. In addition, you may write, fax, or use the inquiry forms on RERF’s homepage with questions concerning the atomic bombings. For details, please visit our homepage: http://www. rerf.jp. Hiroshima: Radiation Effects Research Foundation 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815 Phone from outside Japan: 81(country code)-82-261- 3131 (Switchboard) (from inside Japan, use area code 082) Fax from outside Japan: 81(country code)-82-263- 7279 (from inside Japan, use area code 082) Nagasaki: Radiation Effects Research Foundation 8-6 Nakagawa 1-chome, Nagasaki 850-0013 Phone from outside Japan: 81(country code)-95-823- 1121 (Switchboard) (from inside Japan, use area code 095) Fax from outside Japan: 81(country code)-95-825- 7202 (from inside Japan, use area code 095) i) S25: References BZ Mk References SMBH RE Acute Radiation Syndrome 1. http://orise.orau.gov/reacts/index.htm 2. Stram DO, Mizuno S: Analysis of the DS86 atomic-bomb radiation dosimetry using data on severe epilation. Radia- tion Research 1989; 117:93-113. 3. HORA. Set, FE ae : BORER EE. AMEE 5 1995. SE5EC Acute Death 4. Fujita S, Kato H, Schull WJ: The LD;, associated with exposure to the atomic bombing of Hiroshima and Nagasaki. Journal of Radiation Research (Tokyo) 1991; 32(Suppl):154-61. (A review of 45 years’ study of Hiroshima and Nagasaki atomic-bomb survivors) BARBANK (7kgk14i2)H) Radiation Cataract (Lens Opacity) 5. Otake M, Schull WJ: Radiation-related posterior lenticular opacities in Hiroshima and Nagasaki atomic-bomb survi- vors based on the T65DR and DS86 dosimetry system. Radiation Research 1990; 121:3-13. 6. Minamoto A, Taniguchi H, et al.: Cataract in atomic bomb survivors. International Journal of Radiation Biology 2004; 80:339-45. 7. Nakashima E, Neriishi K, Minamoto A: A reanalysis of atomic-bomb cataract data, 2000-2002: A threshold analysis. Health Physics 2006; 90:154—60. 8. Neriishi K, Nakashima E, Minamoto A, Fujiwara S, Akahoshi M, Mishima HK, Kitaoka T, Shore R: Postoperative cataract cases among atomic bomb survivors: Radiation dose response and threshold. Radiation Research 2007; 168:404-8. EliZ+5A. Solid Cancers 9. Preston DL, Shimizu Y, et al.: Studies of mortality of atomic bomb survivors. Report 13. Solid cancer and noncancer disease mortality: 1950-1997. Radiation. Research 2003; 160:381—407. 10. Preston DL, Ron E, et al.: Solid cancer incidence in atomic bomb survivors: 1958-1998. Radiation Research 2007; 168:1-64. 11. Preston DL, Pierce DA, et al.: Effect of recent changes in atomic bomb survivor dosimetry on cancer mortality risk estimates. Radiation Research 2004; 162:377-89. 12. DVRTEIR, WKAR SS EERE BU RR IR GG TIE EL ho UTR O WME 1992. MICH + 1992, pp 23-104. 13. Ron E, Preston DL, et al.: Cancer incidence in atomic-bomb survivors. Part IV: Comparison of cancer incidence and mortality. Radiation Research 1994; 137:98-112. Ail Leukemia (SCHR 11 % BHR. See also reference 11.) 14. Preston DL, Kusumi S, et al.: Cancer incidence in atomic-bomb survivors. Part III: Leukemia, lymphoma, and multi- ple myeloma, 1950-1987. Radiation Research 1994; 137:S68-97. 15. Bavillsr2. ACERMN. GREET 5S: ITI CRORE PR IR EL ah I HEHE Lah ho ER BUN TRO Ab 1992, MERE ; 1992, pp 35-47. RMI Benign Tumors 16. Imaizumi M, Usa T, et al.: Radiation dose-response relationship for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55-58 years after radiation exposure. JAMA 2006; 295:1011-—22. 17. Yamada M, Wong FL, et al.: Noncancer disease incidence in atomic bombs survivors, 1958-1998. Radiation Research 2004; 161:622-32. 18. Inai K, Shimizu Y, et al.: A pathology study of malignant and benign ovarian tumors among atomic-bomb survivors— 19. 20. 21. References SSX ff case series report. Journal of Radiation Research (Tokyo) 2006; 47:49-S9. Fujiwara S, Sposto R, et al.: Hyperparathyroidism among atomic-bomb survivors in Hiroshima. Radiation Research 1992; 130:372-8. Ron E, Wong FL, Mabuchi K: Incidence of benign gastrointestinal tumors among atomic-bomb survivors. American Journal of Epidemiology 1995; 142:68—75. Kawamura S, Kasagi F, et al.: Prevalence of uterine myoma detected by ultrasound examination in the atomic bomb survivors. Radiation Research 1997; 147:753-8. BASS} ORRICK SFIEL Non-cancer Disease Mortality CHK O & 17 % BHR. See references 9 and 17. 4ef4{42 Chromosome Aberrations 22. 23. 24. 25. 26. 27. Nakano M, Kodama Y, et al.: Detection of stable chromosome aberrations by FISH in A-bomb survivors: Comparison with previous solid Giemsa staining data on the same 230 individuals. International Journal of Radiation Biology 2001; 77:971-7. Kodama Y, Pawel D, et al.: Stable chromosome aberrations in atomic bomb survivors: Results from 25 years of inves- tigation. Radiation Research 2001; 156:337—-46. BaP BESS: AAI SERDAR ERTS 0 BATT GRIER i I HE Ee 0 UIT IR O A 1992, MIE > 1992, pp 220-30. 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PRILECAY + BOER IS 48 T Z PRAISE PAE FR I Id BT TU a IR EL aah TO SE HE TES ho SUERTE DMMERZEE 1992, SOE 5 1992, pp 244-52. Akiyama M: Somatic cell mutations. Shigematsu I, Ito C, et al., eds. Effects of A-bomb Radiation on the Human Body. Chur, Switzerland: Harwood Academic Publishers; 1995, pp 276-85. Ishioka N, Umeki S, et al.: Stimulated rapid expression in vitro for early detection of in vivo T-cell receptor mutations induced by radiation exposure. Mutation Research 1997; 390:269-82. Sl 1 ReelC ESSEC HR Question 1. How many people died as a result of the atomic bombings? 84. JA kati Felliy THR Ea oR Ze Si EG + BUNT ORR. HORE: BE + 1979. 85. Committee for the Compilation of Materials on Damage Caused by the Atomic Bombs in Hiroshima and Nagasaki, ed. Ishikawa E, Swain DL, translators: Hiroshima and Nagasaki. The Physical, Medical, and Social Effects of the Atomic Bombings. Hiroshima and Nagasaki Cities; 1981. 86. Ohkita T: Annex 4. 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Tmax thaw AB 5-2 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815 Japan Tel 082-261-3131 ({t32) 7850-0013 Ril FIII—T B 8-6 8-6 Nakagawa 1-chome, Nagasaki 850-0013 Japan Tel 095-823-1121 ({t#) http://www. rerf.jp/ 377 ER 209A Publication date : September 2008 Elia] LA-TLARRSAt Printer : Letterpress Co.,Ltd.