Atomic Bomb Survivors In Hiroshima Research Articles

Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950-2003

Objective To investigate the degree to which ionising radiation confers risk of mortality from heart disease and stroke.Design Prospective cohort study with more than 50 years of follow-up.Setting Atomic bomb...

Longitudinal Trends of Total White Blood Cell and Differential White Blood Cell Counts of Atomic Bomb Survivors

In studying the late health effects of atomic-bomb (A-bomb) survivors, earlier findings were that white blood cell (WBC) count increased with radiation dose in cross-sectional studies. However, a persistent effect of radiation on WBC count and other risk factors has yet to be confirmed. The objectives of the present study were 1) to examine the longitudinal relationship between A-bomb radiation dose and WBC and differential WBC counts among A-bomb survivors and 2) to investigate the potential confounding risk factors (such as age at exposure and smoking status) as well as modification of the radiation dose-response. A total of 7,562 A-bomb survivors in Hiroshima and Nagasaki were included in this study from 1964-2004. A linear mixed model was applied using the repeated WBC measurements. During the study period, a secular downward trend of WBC count was observed. Radiation exposure was a significant risk factor for elevated WBC and differential WBC counts over time. A significant increase of WBC counts among survivors with high radiation dose (> 2 Gy) was detected in men exposed below the age of 20 and in women regardless of age at exposure. Effects on WBC of low dose radiation remain unclear, however. Cigarette smoking produced the most pronounced effect on WBC counts and its impact was much larger than that of radiation exposure.

エピゲノム制御異常とMDS: 原爆被爆者AML・MDSの疫学からの考察

エピゲノム制御異常とMDS: 原爆被爆者AML・MDSの疫学からの考察

Analysis of chromosome aberrations in atomic bomb survivors for dose assessment: studies at the Radiation Effects Research Foundation from 1968 to 1993.

Exposure to ionizing radiation causes damage to living cells, especially to DNA in the cell nucleus. The degree of this cellular damage depends on the amount of radiation administered. This review discusses current findings concerning radiation-induced chromosome aberrations that were produced in 1945 and that can still be observed in the somatic cells of atomic bomb survivors in Hiroshima and Nagasaki. The scoring methods of G-banding and fluorescence in situ hybridization are compared. In addition, some findings concerning chromosomal aberrations in citizens of the former Soviet Union affected by the Chernobyl accident are presented.

Answer to the comments by Eric J. Grant et al. in “Radiation unlikely to be responsible for high cancer rates among distal Hiroshima A-bomb survivors”

Eric J. Grant et al. raised three issues concerning our paper “Hiroshima survivors exposed to very low doses of A-bomb primary radiation showed a high risk for cancers” [1]. Their proposed title was “Radiation unlikely responsible for high cancer rates among distal Hiroshima A-bomb survivors”. However, in response, we suggest that a better title would be “Risk analysis in LSS without using an unexposed group is responsible for the apparent low cancer rates among distal Hiroshima A-bomb survivors”. We discuss the reasons for this proposal here.

Radiation unlikely to be responsible for high cancer rates among distal Hiroshima A-bomb survivors

Watanabe et al. [1] (hereafter referred to as WMHY) used A-bomb survivor data from the Radiation Effects Research Foundation (RERF) Life Span Study (LSS) Report 12 (available online at http://www.rerf.or.jp) and mortality rates for Hiroshima and Okayama Prefectures [2] to create standardized mortality ratios (SMR) for LSS cohort members residing in Hiroshima at the time of the bombing. WMHY divided cohort members into three radiation dose categories: very low dose ( 0.1 Gy, HD). At issue are the men in the VLD category, who experienced higher than expected deaths due to cancers compared with prefectural rates (note that, for brevity, we discuss only the solid cancer results). WMHY concluded that the increased cancer deaths among the VLD were due to underestimated neutron doses and/or unaccounted-for residual radiation exposures. We find their conclusions to be implausible and believe that the data show it is far more likely that the observed risks among the VLD are due to nonradiation factors. The reasons are briefly summarized below.

P09: Elevated levels of plasma-reactive oxygen species and inflammatory markers among atomic-bomb survivors

Even after more than 60 years have passed, exposure to atomic-bomb (A-bomb) radiation continues to have long-term health effects in survivors, whose risks of inflammation-related diseases increase with increasing radiation dose. It is known that persistent inflammation underlies several cancers through increased production of reactive oxygen species (ROS) and endogenous tumor promoters (e.g., TNF-α). In our previous study, plasma levels of inflammatory cytokines and biomarkers, IL-6, TNF-α, CRP, IFN-γ, Igs, and erythrocyte sedimentation rate (ESR), increased significantly with radiation dose. We have recently developed an automated plasma ROS assay system based on use of a clinical chemistry analyzer. In this study we investigated association between radiation dose, plasma ROS levels, and sub-clinical inflammatory status in A-bomb survivors in Hiroshima. Excluding patients with history of cancer, rheumatoid arthritis, chronic bronchitis, or myocardial infarction, we randomly selected 442 study subjects from the Adult Health Study population, consisting of A-bomb survivors and unexposed people. We observed statistically significant radiation-associated increase in plasma ROS levels. ROS levels were positively associated with the inflammatory biomarkers IL-6, TNF-α, CRP, and ESR ( P It is evident that total ROS production increased with enhanced inflammatory status, suggesting a plausible mechanistic pathway between radiation-induced persistent inflammation and cancer.

Prevalence and Cause of Death in Patients with Monoclonal Gammopathy in Atomic Bomb Survivors in Hiroshima

Purpose: To examine the effect of Atomic bomb (A-bomb) radiation exposure condition on the development M-proteinemia in A-bomb survivors in Hiroshima.Back ground: The influence of radiation exposure on the development of M-proteinemia remained unclear. The screening test for monoclonal gammopathy in A- bomb survivors in Hiroshima was started from Sep. 1988 at the Hiroshima Atomic Bomb Casualty Council Health management center to challenge this problem with the free access policy.Materials: The peak year of the examined population was 1989, which was examined 42915 survivors. This population was designed as study population. This population consisted of five groups of irradiated conditions as follows, 60% was exposed directly in all over the Hiroshima city at A- bombing, 27% entered to center of Hiroshima city within 14 days after A-bombing, 9% helped the victims of A- bombing at the suburbs and 1% was exposed in prenatal state.Examination study: Each participant was examined one test yearly. Routine laboratory tests, such as complete blood cell counts, serum biochemical examination and serum protein electrophoresis on cellulose acetate were performed for the first step screening. M-protein or low level of gammaglobulin was subsequently assessed in a detailed analysis by immunoelectrophoresis of serum and urine, and measurement of serum concentration of immunoglobulin andβ2-Microglobulin.Results: One thousand and hundred eighty two cases of M-proteinemia were detected for 18 years. The over all prevalence rate was 2.75%, and 4.1% in males and 2.1% in females. Nine hundred twenty nigh cases of MGUS(78.6%), 147 cases of MM(12.4%), 80 cases of IgM Macroglobulinemia(6.8%) and 26 cases of two clone M-proteinemia(2.2%) were detected. Of these M-proteinemia, 669cases(2.6%) were developed in directly exposed population, 368cases(3.1%) were in entered population and 133 cases(3.4%) were in helper population. The prevalence rate of these M-proteinemia was increased depend on aging. Forty three cases (4.6%) of MGUS moved to overt MM for 18 years. The mean duration time from MGUS to overt MM was 8.9 years (2~18 years). Four hundred sixteen cases (35.2%) were died with MM or lymphoproliferative diseases (99cases,23.8%), cancer (93cases,22.3%), infection (50cases,12%), cardio or cerebral vascular diseases (89 cases,21.4%) and others (85cases,21%). The 101 cases (13.2%) of 766 living cases combined some cancer throughout the follow up. No significant differences in the prevalence rate of M-proteinemia and death from MM or combination with cancer were observed among any A-bomb irradiated conditions.Conclusions: There were no clear correlations between the development or disease state of M-proteinemia and the irradiated conditions. We are now starting to analyze the individual radiation dose effects longitudinally on the development of M-proteinemia.

Bone Sarcomas in Atomic Bomb Survivors of Hiroshima and Nagasaki

Ionizing radiation-induced bone sarcomas have traditionally been associated with exposure to high levels of ionizing radiation. The role of exposure to lower levels of ionizing radiation in the development of such lesions remains speculative. Also, the appropriate dose-response model of radiation dose exposure to excess relative risk (ERR) in association with bone sarcomas is questionable.

Hydrogen analysis for granite using proton–proton elastic recoil coincidence spectrometry

In an effort to develop DS02, a new radiation dosimetry system for the atomic bomb survivors of Hiroshima and Nagasaki, measurements of neutron-induced activities have provided valuable information to reconstruct the radiation situation at the time of the bombings. In Hiroshima, the depth profile of (152)Eu activity measured in a granite pillar of the Motoyasu Bridge (128 m from the hypocenter) was compared with that calculated using the DS02 methodology. For calculation of the (152)Eu production due to the thermal-neutron activation reaction, (151)Eu(n,gamma)(152)Eu, information on the hydrogen content in granite is important because the transport and slowing-down process of neutrons penetrating into the pillar is strongly affected by collisions with the protons of hydrogen. In this study, proton-proton elastic recoil coincidence spectrometry has been used to deduce the proton density in the Motoyasu pillar granite. Slices of granite samples were irradiated by a 20 MeV proton beam, and the energies of scattered and recoil protons were measured with a coincidence method. The water concentration in the pillar granite was evaluated to be 0.30 +/- 0.07%wt. This result is consistent with earlier data on adsorptive water (II) and bound water obtained by the Karl Fisher method.

Skin dose from neutron-activated soil for early entrants following the A-bomb detonation in Hiroshima: contribution from β and γ rays

Epilation was reported among atomic bomb survivors in Hiroshima and Nagasaki, including "early entrance survivors" who entered the cities after the bombings. The absorbed dose to the skin by neutron-activated soil via beta and gamma rays has been estimated in a preliminary fashion, for these survivors in Hiroshima. Estimation was done for external exposures from activated soil on the ground as well as skin and hair contamination from activated soil particles, using the Monte Carlo radiation transport code MCNP-4C. Assuming 26 mum thickness of activated soil on the skin as an example, the skin dose was estimated to be about 0.8 Gy, for an exposure scenario that includes the first 7 days after the bombing at 1 m above the ground at the hypocenter. In this case, 99% of the total skin dose came from activated radionuclides in the soil, i.e., 0.19 and 0.63 Gy due to beta and gamma rays, respectively. In contrast, contribution to skin dose due to skin contamination with soil particles was found to be about 1%. To make it comparable to the exposure by neutron-activated soil on the ground, a soil thickness on the skin of about 1 mm would be required, which seems to be difficult to keep for a long time. Fifty-five percent of the 7-day skin dose was delivered during the first hour after the bombing. Our estimates of the skin dose are lower than the conventionally reported threshold of 2 Gy for epilation. It should be noted, however, that the possibility of more extreme exposure scenarios for example for entrants who received much heavier soil contamination on their skin cannot be excluded.

Intercomparison study on 152Eu gamma ray and 36Cl AMS measurements for development of the new Hiroshima–Nagasaki Atomic Bomb Dosimetry System 2002 (DS02)

In the process of developing a new dosimetry system for atomic bomb survivors in Hiroshima and Nagasaki (DS02), an intercomparison study between (152)Eu and (36)Cl measurements was proposed, to reconcile the discrepancy previously observed in the Hiroshima data between measurements and calculations of thermal neutron activation products. Nine granite samples, exposed to the atomic-bomb radiation in Hiroshima within 1,200 m of the hypocenter, as well as mixed standard solutions containing known amounts of europium and chlorine that were neutron-activated by a (252)Cf source, were used for the intercomparison. Gamma-ray spectrometry for (152)Eu was carried out with ultra low-background Ge detectors at the Ogoya Underground Laboratory, Kanazawa University, while three laboratories participated in the (36)Cl measurement using accelerator mass spectrometry (AMS): The Technical University of Munich, Germany, the Lawrence Livermore National Laboratory, USA and the University of Tsukuba, Japan. Measured values for the mixed standard solutions showed good agreement among the participant laboratories. They also agreed well with activation calculations, using the neutron fluences monitored during the (252)Cf irradiation, and the corresponding activation cross-sections taken from the JENDL-3.3 library. The measured-to-calculated ratios obtained were 1.02 for (152)Eu and 0.91-1.02 for (36)Cl, respectively. Similarly, the results of the granite intercomparison indicated good agreement with the DS02 calculation for these samples. An average measured-to-calculated ratio of 0.98 was obtained for all granite intercomparison measurements. The so-called neutron discrepancy that was previously observed and that which included increasing measured-to-calculated ratios for thermal neutron activation products for increasing distances beyond 1,000 m from the hypocenter was not seen in the results of the intercomparison study. The previously claimed discrepancy could be explained by insufficient understanding of the measured data.

Gamma-ray exposure from neutron-induced radionuclides in soil in Hiroshima and Nagasaki based on DS02 calculations

As a result of joint efforts by Japanese, US and German scientists, the Dosimetry System 2002 (DS02) was developed as a new dosimetry system, to evaluate individual radiation dose to atomic bomb survivors in Hiroshima and Nagasaki. Although the atomic bomb radiation consisted of initial radiation and residual radiation, only initial radiation was reevaluated in DS02 because, for most survivors in the life span study group, the residual dose was negligible compared to the initial dose. It was reported, however, that there were individuals who entered the city at the early stage after the explosion and experienced hemorrhage, diarrhea, etc., which were symptoms of acute radiation syndrome. In this study, external exposure due to radionuclides induced in soil by atomic bomb neutrons was reevaluated based on DS02 calculations, as a function of both the distance from the hypocenters and the elapsed time after the explosions. As a result, exposure rates of 6 and 4 Gy h(-1) were estimated at the hypocenter at 1 min after the explosion in Hiroshima and Nagasaki, respectively. These exposure rates decreased rapidly by a factor of 1,000 1 day later, and by a factor of 1 million 1 week later. Maximum cumulative exposure from the time of explosion was 1.2 and 0.6 Gy at the hypocenters in Hiroshima and Nagasaki, respectively. Induced radiation decreased also with distance from the hypocenters, by a factor of about 10 at 500 m and a factor of three to four hundreds at 1,000 m. Consequently, a significant exposure due to induced radiation is considered feasible to those who entered the area closer to a distance of 1,000 m from the hypocenters, within one week after the bombing.

Thyroid Diseases in Atomic Bomb Survivors Exposedin Utero

The objective of the study was to evaluate the association of thyroid disease with radiation dose in atomic bomb survivors exposed in utero. This was a cross-sectional study. The study was conducted in atomic bomb survivors in Hiroshima and Nagasaki, Japan. Participants included 328 atomic bomb survivors exposed in utero (mean age 55.2 yr, 162 males) who participated in the thyroid study at the Radiation Effects Research Foundation. Examinations were conducted between March 2000 and February 2003. The relationships of various thyroid conditions to atomic bomb radiation dose were measured. Among the 319 participants excluding nine participants whose exposure radiation dose was not estimated, the mean maternal uterine radiation dose was 0.256 Gy. We observed no significant dose-response relationship for the prevalence of solid thyroid nodules (odds ratio at 1 Gy, 2.78; 95% confidence interval 0.50-11.80, P = 0.22), but the risk estimate was similar to the estimate for childhood exposures. The prevalence of cysts and autoimmune thyroid diseases was not associated with radiation dose (P > 0.30). We could not evaluate the dose response for malignant tumors or benign nodules due to the small number of cases. We did not observe a statistically significant linear dose response to radiation for thyroid nodules or autoimmune thyroid diseases 55-58 yr after participants' in utero exposure. However, the risk estimate for solid thyroid nodules was similar for those exposed in utero and those exposed in childhood. Because the study had limited statistical power to detect moderately sized effects, further studies are needed for a definitive conclusion.

High Frequency of AML1/RUNX1 Point Mutations in Radiation-Associated Myelodysplastic Syndrome Around Semipalatinsk Nuclear Test Site

It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients with MDS/AML among the residents near the Semipalatinsk Nuclear Test Site (SNTS), where the risk of solid cancers and leukemias was increased due to the radiation effects. AML1 mutations were identified in 7 (39%) of 18 radiation-exposed MDS/AML patients. In contrast, no AML1 mutation was found in 13 unexposed MDS/AML cases. The frequency of AML1 mutations in radiation-exposed patients with MDS/AML was significantly higher compared with unexposed patients (p < 0.05).We also found a significant correlation between individual estimated doses and AML1 mutations (p < 0.05). Considering these results, AML1 point mutations might be a useful biomarker that differentiates radio-induced MDS/AML from spontaneous MDS/AML.

Radiation Dose-Response Relationships for Thyroid Nodules and Autoimmune Thyroid Diseases in Hiroshima and Nagasaki Atomic Bomb Survivors 55–58 Years After Radiation Exposure

Radiation Dose-Response Relationships for Thyroid Nodules and Autoimmune Thyroid Diseases in Hiroshima and Nagasaki Atomic Bomb Survivors 55–58 Years After Radiation Exposure

The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose

In papillary thyroid carcinogenesis, the constitutively activated mitogen-activated protein (MAP) kinase signaling pathway caused by a genetic alteration such as RET/PTC rearrangement or mutation of RAS and BRAF genes, is thought to be a major early event. Among these, the recently identified BRAF(V600E) mutation has been found at high frequency in adult patients with papillary thyroid carcinoma (PTC). However, the association between this mutation and radiation exposure in adult PTC is still unknown. In this study, we examined the BRAF(V600E) mutation in 64 PTCs among adult atomic bomb survivors in Hiroshima, Japan, comprising 17 nonexposed (0 mGy) and 47 exposed patients who developed the carcinoma after the bombing, and assessed the association of BRAF(V600E) mutation with clinico-pathological and epidemiological variables. The median radiation dose in PTCs with the BRAF(V600E) mutation was significantly lower than that without the mutation (18.5 vs.156.9 mGy, Wilcoxon rank-sum test, P=0.022). A significant difference was found in the median latency period (years elapsed from atomic bombing to diagnosis) between exposed patients with and without BRAF(V600E) mutation (29 vs. 21 yr, Wilcoxon rank-sum test, P=0.014). These findings were further confirmed by logistic regression analysis with BRAF(V600E) mutation status as a dependent variable and taking into account possible interactions between the variables. We found that the log-transformed radiation dose and latency period were independently associated with the BRAF(V600E) mutation (P=0.039 and P=0.010, respectively). These results suggest that involvement of BRAF mutation in thyroid carcinogenesis in exposed people may differ from that in the nonexposed people.

Radiation Exposure and Thyroid Disease in Hiroshima and Nagasaki Atomic Bomb Survivors

Radiation Exposure and Thyroid Disease in Hiroshima and Nagasaki Atomic Bomb Survivors

Radiation Exposure and Thyroid Disease in Hiroshima and Nagasaki Atomic Bomb Survivors—Reply

Radiation Exposure and Thyroid Disease in Hiroshima and Nagasaki Atomic Bomb Survivors—Reply

Effective dose of A-bomb radiation in Hiroshima and Nagasaki as assessed by chromosomal effectiveness of spectrum energy photons and neutrons

The effective dose of combined spectrum energy neutrons and high energy spectrum gamma-rays in A-bomb survivors in Hiroshima and Nagasaki has long been a matter of discussion. The reason is largely due to the paucity of biological data for high energy photons, particularly for those with an energy of tens of MeV. To circumvent this problem, a mathematical formalism was developed for the photon energy dependency of chromosomal effectiveness by reviewing a large number of data sets published in the literature on dicentric chromosome formation in human lymphocytes. The chromosomal effectiveness was expressed by a simple multiparametric function of photon energy, which made it possible to estimate the effective dose of spectrum energy photons and differential evaluation in the field of mixed neutron and gamma-ray exposure with an internal reference radiation. The effective dose of reactor-produced spectrum energy neutrons was insensitive to the fine structure of the energy distribution and was accessible by a generalized formula applicable to the A-bomb neutrons. Energy spectra of all sources of A-bomb gamma-rays at different tissue depths were simulated by a Monte Carlo calculation applied on an ICRU sphere. Using kerma-weighted chromosomal effectiveness of A-bomb spectrum energy photons, the effective dose of A-bomb neutrons was determined, where the relative biological effectiveness (RBE) of neutrons was expressed by a dose-dependent variable RBE, RBE(gamma, D (n)), against A-bomb gamma-rays as an internal reference radiation. When the newly estimated variable RBE(gamma, D (n)) was applied to the chromosome data of A-bomb survivors in Hiroshima and Nagasaki, the city difference was completely eliminated. The revised effective dose was about 35% larger in Hiroshima, 19% larger in Nagasaki and 26% larger for the combined cohort compared with that based on a constant RBE of 10. Since the differences are significantly large, the proposed effective dose might have an impact on the magnitude of the risk estimates deduced from the A-bomb survivor cohort.