Atomic Bomb Survivors In Hiroshima Research Articles

Medical X-ray Doses' Contributions to the Ionizing Radiation Exposures of Atomic-Bomb Survivors

Doses from diagnostic radiological examinations were measured in order to evaluate the radiation risks of atomic-bomb survivors in Hiroshima and Nagasaki. Using a phantom human, doses to the active bone marrow, gonads, salivary glands, thyroid gland, lung, breast, stomach and colon were determined by type of examination and by examination site. The results of this dosimetry program will aid in estimating the diagnostic exposure doses received by each participant in the Adult Health Study of the Radiation Effects Research Foundation. The current results of these dosimetry studies also indicate that the effects of A-bomb exposure cannot be reliably assessed unless medical X-ray doses are carefully incorporated into these long-term evaluations.

The Observed Relationship between the Occurrence of Acute Radiation Effects and Leukemia Mortality among A-Bomb Survivors

In an analysis of a follow-up study of a fixed population of 73,330 atomic bomb survivors in Hiroshima and Nagasaki, the slope of an estimated dose response between ionizing radiation and leukemia mortality was found to be steeper (P less than 0.002), by a factor of 2.4, among those who reported epilation within 60 days of the bombings, compared to those who did not experience this sign of acute radiation exposure. The strength of this empirical finding as evidence of biological association in individual radiosensitivity for these two end points is studied here. The major factor complicating the interpretation of this finding as evidence of such an association is the degree of imprecision of the radiation dosimetry system used in assignment of radiation doses to the A-bomb survivors. Using models recently suggested for dealing with dosimetry errors in epidemiological analysis of the A-bomb survivor data, the sensitivity of the apparent association between leukemia mortality and severe epilation to the assumed level of dosimetry error is investigated.

Parathyroid Tumors in Atomic Bomb Survivors in Hiroshima: A Review

Parathyroid tumors in A-bomb survivors in Hiroshima have been studied. Thirteen cases of parathyroid tumor were confirmed from 4,136 autopsy cases between 1961 to 1977, and an elevated incidence of tumor with increase of dose (T65D) was demonstrated (P less than 0.01). A high proportion of 42.9%, 6 out of 14 parathyroid tumors extirpated at Hiroshima University Hospital between 1956 and 1988, were atomic bomb survivors exposed within 4.1 km from the hypocenter. From an epidemiological study using 23 parathyroid tumor cases detected in Hiroshima Prefecture between 1974 and 1987, an elevated incidence of parathyroid tumors with increase of dose (proximally exposed, other exposed and control nonexposed) was demonstrated (P less than 0.001).

Persistent Chromosome Aberrations in the Somatic Cells of A-bomb Survivors, Hiroshima and Nagasaki

Current status of knowledge on the radiation-induced chromosome aberrations persisting since their induction in 1945 to date in the somatic cells of A-bomb survivors in Hiroshima and Nagasaki is reviewed. Dose-response relationship for chromosome aberration frequencies observed with the use of the old A-bomb dosimetry system (T65D) is also demonstrable based on the new dosimetry system (DS86). Despite the fact that the remarkable decrease in the amount of neutron component relative to the total dose in Hiroshima, there still exist inter-city differences in aberration frequency per unit dose both for kerma and bone marrow dose; the dose-square term is smaller in Hiroshima than in Nagasaki. The differential contribution of neutron radiation may be responsible in some part for the observed difference between Hiroshima and Nagasaki, although proof still remains to be obtained. There is a wide variability of the frequency of cells with chromosome aberrations between survivors within a given dose range. Random errors in the dose estimates assigned to individual survivors seem responsible, to a large extent, for the observed overdispersions in aberration frequencies in both cities. New molecular biology-oriented techniques to differentially stain specific chromosomes using fluorescence in situ hybridization with chromosome-specific composite DNA probes seem extremely promising for future rapid, accurate and extensive screening of reciprocal translocations observed predominantly in A-bomb survivors. Such data may be utilized to establish a better biological dosimetry system, especially for those persons who are irradiated in vivo many years before cytogenetic examinations.

Radiation Cataract

This report reviews the relationship of ionizing radiation to the occurrence of cataracts (posterior lenticular opacities) among the A-bomb survivors in Hiroshima and Nagasaki. The new DS86 doses are available for 1,983 (93.4%) of the 2,124 A-bomb survivors analyzed in 1982. The DS86 kerma neutron component for Hiroshima is much smaller than its comparable T65DR component, but still 4.2 fold higher (0.38 Gy at 6 Gy) than that in Nagasaki (0.09 Gy at 6 Gy). Thus, if the eye is especially sensitive to neutrons, there may yet be some useful information on their effects, particularly in Hiroshima. Under the best fitting dose-response model, an L(gamma)-L(neutron) with two thresholds, both the gamma and neutron regression coefficients of the occurrence of cataracts on dose are positive and highly significant for the DS86 eye organ doses. The DS86 gamma coefficient is almost the same as that associated with the T65DR gamma dose, the ratio of the two coefficients being 1.1 (95% confidence limits: 0.5-2.3) for DS86 kerma in the individual dose data, and if the risks based on the DS86 eye organ dose and DS86 kerma are compared, the ratio is 1.3 (0.6-2.8). However, the risk estimates associated with neutron exposure are 6.4 (2.2-19.2) fold higher for the DS86 kerma than the T65DR kerma and 1.6 (0.5-2.3) fold higher for the DS86 eye organ dose than for the DS86 kerma.

Hyperparathyroidism

An epidemiological survey on hyperparathyroidism (HPT) among A-bomb survivors in Hiroshima has been conducted since August 1986. The results are summarized based on proceedings of meetings. The survey demonstrated that the prevalence rate of HPT increased with A-bomb radiation dose. Further analysis is now under way on the relationship between HPT prevalence and radiation dose, sex and age, the results of which will be published in the near future.

Medical X-ray Doses'' Contributions to the Ionizing Radiation Exposures of Atomic-Bomb Survivors

Doses from diagnostic radiological examinations were measured in order to evaluate the radiation risks of atomic-bomb survivors in Hiroshima and Nagasaki. Using a phantom human, doses to the active bone marrow, gonads, salivary glands, thyroid gland, lung, breast, stomach and colon were determined by type of examination and by examination site. The results of this dosimetry program will aid in estimating the diagnostic exposure doses received by each participant in the Adult Health Study of the Radiation Effects Research Foundation. The current results of these dosimetry studies also indicate that the effects of A-bomb exposure cannot be reliably assessed unless medical X-ray doses are carefully incorporated into these long-term evaluations.

Phagocytic and Bactericidal Activities of Leukocytes in Whole Blood from Atomic Bomb Survivors

This study evaluated the phagocytic and bactericidal activities of peripheral blood leukocytes from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression for age, sex, radiation exposure, city of exposure, and neutrophil counts. No significant radiation effect was observed for either blood phagocytic or bactericidal activities. The only significant variable for these functions was the neutrophil count.

Calculating Excess Lifetime Risk in Relative Risk Models

When assessing the impact of radiation exposure it is common practice to present the final conclusions in terms of excess lifetime cancer risk in a population exposed to a given dose. The present investigation is mainly a methodological study focusing on some of the major issues and uncertainties involved in calculating such excess lifetime risks and related risk projection methods. The age-constant relative risk model used in the recent analyses of the cancer mortality that was observed in the follow-up of the cohort of A-bomb survivors in Hiroshima and Nagasaki is used to describe the effect of the exposure on the cancer mortality. In this type of model the excess relative risk is constant in age-at-risk, but depends on the age-at-exposure. Calculation of excess lifetime risks usually requires rather complicated life-table computations. In this paper we propose a simple approximation to the excess lifetime risk; the validity of the approximation for low levels of exposure is justified empirically as well as theoretically. This approximation provides important guidance in understanding the influence of the various factors involved in risk projections. Among the further topics considered are the influence of a latent period, the additional problems involved in calculations of site-specific excess lifetime cancer risks, the consequences of a leveling off or a plateau in the excess relative risk, and the uncertainties involved in transferring results from one population to another. The main part of this study relates to the situation with a single, instantaneous exposure, but a brief discussion is also given of the problem with a continuous exposure at a low-dose rate.

Calculating excess lifetime risk in relative risk models.

When assessing the impact of radiation exposure it is common practice to present the final conclusions in terms of excess lifetime cancer risk in a population exposed to a given dose. The present investigation is mainly a methodological study focusing on some of the major issues and uncertainties involved in calculating such excess lifetime risks and related risk projection methods. The age-constant relative risk model used in the recent analyses of the cancer mortality that was observed in the follow-up of the cohort of A-bomb survivors in Hiroshima and Nagasaki is used to describe the effect of the exposure on the cancer mortality. In this type of model the excess relative risk is constant in age-at-risk, but depends on the age-at-exposure. Calculation of excess lifetime risks usually requires rather complicated life-table computations. In this paper we propose a simple approximation to the excess lifetime risk; the validity of the approximation for low levels of exposure is justified empirically as well as theoretically. This approximation provides important guidance in understanding the influence of the various factors involved in risk projections. Among the further topics considered are the influence of a latent period, the additional problems involved in calculations of site-specific excess lifetime cancer risks, the consequences of a leveling off or a plateau in the excess relative risk, and the uncertainties involved in transferring results from one population to another. The main part of this study relates to the situation with a single, instantaneous exposure, but a brief discussion is also given of the problem with a continuous exposure at a low-dose rate.

Effects of Prenatal Exposure to Ionizing Radiation

Prenatal exposure to ionizing radiation induces some effects that are seen at birth and others that cannot be detected until later in life. Data from A-bomb survivors in Hiroshima and Nagasaki show a diminished number of births after exposure under 4 wk of gestational age. Although a wide array of congenital malformations has been found in animal experimentation after such exposure to x rays, in humans only small head size (exposure at 4-17 wk) and mental retardation (exposure primarily at 8-15 wk) have been observed. In Hiroshima, small head size occurred after doses of 0.10-0.19 Gy or more, and an excess of mental retardation at 0.2-0.4 Gy or more. Intelligence test scores were reduced among A-bomb survivors exposed at 8-15 wk of gestational age by 21-29 IQ points per Gy. Other effects of in-utero exposure to atomic radiation include long-lasting complex chromosome abnormalities.

放射線誘発がんの生涯リスク評価におけるリスク予測モデルに関する考察

Lifetime cancer risk estimates depend on risk projection models. While the increasing lengths of follow-up observation periods of atomic bomb survivors in Hiroshima and Nagasaki bring about changes in cancer risk estimates, the validity of the two risk projection models, the additive risk projection model (AR) and multiplicative risk projection model (MR), comes into question. This paper compares the lifetime risk or loss of life-expectancy between the two projection models on the basis of BEIR-III report or recently published RERF report. With Japanese cancer statistics the estimates of MR were greater than those of AR, but a reversal of these results was seen when the cancer hazard function for India was used. When we investigated the validity of the two projection models using epidemiological human data and animal data, the results suggested that MR was superior to AR with respect to temporal change, but there was little evidence to support its validity.

A chromosome study of 6-thioguanine-resistant mutants in T lymphocytes of Hiroshima atomic bomb survivors

Cytogenetic characterizations were made of lymphocyte colonies established from somatic mutation assays for 6-thioguanine (TG) resistance in Hiroshima atomic bomb survivors. G-banded chromosomes were analyzed in both TG-resistant (TG r) and wild-type colonies. Included were 45 TG r and 19 wild-type colonies derived from proximally exposed A-bomb survivors, as well as colonies from distally exposed control in dividuals who did not receive a significant amount of A-bomb radiation (18 TG r and wild type colonies). Various structural and numerical chromosome abnormalities were observed in both TG r and 9-wild type colonies. Aberrations of the X chromosome, on which the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus in present, were found in 6 colonies: 2 resistant colonies from controls (45,X/46,XX; 46,X,ins(X)), 3 resistant colonies (45,X/46,XX/46,X, + mar; 46,X,t(Xq+;14q−); 46,Y,6,Y,t(Xq−;5q +)), and 1 wild-type colony (45,X/47,XXX) from proximally exposed persons, In cases with exchange aberrations, each of the break points on the X chromosome was situated proximally to band q26 where the HPRT locus is known to be assigned. DNA-replicating patterns were also studied, and it was found that abnormal X chromosomes showed early replicating patterns, while normal X chromosomes showed late replicating patterns.

46 DETECTION OF HPRT MUTATION IN A HUMAN STEM CELL BEFORE DIFFERENTIATION INTO T OR B CELLS

We have been measuring the frequency of in vivo HPRT mutant T cells in the peripheral blood of atomic bomb survivors in Hiroshima. The mean frequency of mutant T cells in 30 survivors (5.2 × 10−6) was significantly higher than that in 17 controls (3.4 × 10−6) and was found to correlate with the radiation dose estimates. In the course of this study, extremely high mutant frequency (2 × 10−4) was identified in one male survivor (59 y.o. radiation dose=199 rad). All the mutant colonies examined had the same chromosome aberration (20 q-) and the same alteration of DNA at the HPRT locus, indicating that all these mutants were derived from a single cell. However, the pattern of T cell receptor gene rearrangement was different between colonies. Furthermore, mutant B cells possessing the same aberration and HPRT gene alteration have also been cloned from this individual by using EB virus transformation. All these results indicate that all the mutant cells were derived from a single stem cell which can differentiate into at least T and B cells. Thus, a single mutational event in an undifferentiated stem cell produced a large number of mutant lymphocytes in periphery in the person studied here.

A case-control study of congenital malformations and occupational exposure to low-level ionizing radiation.

In a case-control study, the authors investigated the association of parental occupational exposure to low-level external whole-body penetrating ionizing radiation and risk of congenital malformations in their offspring. Cases and controls were ascertained from births in two counties in southeastern Washington State, where the Hanford Site has been a major employer. A unique feature of this study was the linking of quantitative individual measurement of external whole-body penetrating ionizing radiation exposure of employees at the Hanford Site, using personal dosimeters, and the disease outcome, congenital malformations. The study population included 672 malformation cases and 977 matched controls from births occurring from 1957 through 1980. Twelve specific malformation types were analyzed for evidence of association with employment of the parents at Hanford and with occupational exposure to ionizing radiation. Two defects, congenital dislocation of the hip and tracheoesophageal fistula, showed statistically significant associations with employment of the parents at Hanford, but not with parental radiation exposure. Neural tube defects showed a significant association with parental preconception exposure, on the basis of a small number of cases. Eleven other defects, including Down syndrome, for which an association with radiation was considered most likely, showed no evidence of such an association. When all malformations were analyzed as a group, there was no evidence of an association with employment of the parents at Hanford, but the relation of parental exposure to radiation before conception was in the positive direction (one-tailed p value between 0.05 and 0.10). Given the number of statistical tests conducted, some or all of the observed positive correlations are likely to represent false positive findings. In view of strong contradictory evidence, based on no demonstrated effects in genetic studies of atomic bomb survivors in Hiroshima and Nagasaki, it is unlikely that these correlations result from a cause and effect association with parental radiation exposure.

Age-related alteration in the composition of immunocompetent blood cells in atomic bomb survivors.

A total of 1328 atomic bomb survivors in Hiroshima were studied to determine alterations in the number of blood lymphocytes belonging to T-cell subpopulations, the number of CD19 antigen-positive B cells and the number of Leu 7 and CD16 antigen-positive lymphocytes. Overall, with increasing age, significant decreasing trends in the numbers of some lymphocytes in T-cell subpopulations and of B cells were observed. Furthermore, the number of blood lymphocytes positive for CD5 antigen was significantly lower in the people exposed to radiation (greater than 1 Gy) in the older age group (more than 30 years old at the time of the bombing). A similar tendency for decreases in the numbers of CD4, CD8, and CD19 antigen-positive cells was observed in these older survivors, although the differences were not statistically significant. These results suggest that aging of the T-cell related immune system is accelerated in the irradiated people of advanced age. This may be explained by the age-related decrease in thymic function in those subjects who were older at the time of the bombing resulting in a decreased functional ability of the immune system after radiation injury. On the contrary, the number of Leu 7 or CD16 antigen-positive cells was found to be increased significantly in the older age group compared to the younger group, although there was little dependence on dose.

肺癌とその環境因子

Besides clinically recognized lung cancers, a careful histological examination of the respiratory tract of autopsied men who were previously exposed to mustard-gas revealed significantly higher frequency of abnormal lesions including dysplasia and microscopical early cancer within the bronchial epithelium. These findings were encountered in not only individuals exposed to the gas and suffered later from clinical lung cancer, but also those exposed to the gas and suffered later from various diseases other than lung cancer, and also those not exposed to the gas but suffered from clinical lung cancer. Smoking effects appeared to be also significant in lung cancer development. According to the investigation of the Radiation Effects Research Foundation, the relative risk of lung cancer increased significantly with radiation dose in A-bomb survivors in Hiroshima and Nagasaki. Small-cell type lung cancer showed somewhat greater sensitivity than other types of lung cancer. An annual relative frequency of malignant mesothelioma in the major diagnoses of all autopsy cases has been increasing dramatically during the past 2 decades in Hiroshima district. The majority of examined cases with malignant mesotheliomas showed a significant accumulation of asbestos bodies within pulmonary alveoli. Ninety-nine per cent of our recent autopsy cases showed an intraalveolar deposition of asbestos bodies and proportional distribution of cases with dense exposure to asbestos appeared to be greater than previous investigations reported by others from other districts. Aforementioned unfortunate phenomena in regard with either chemical or radiation carcinogenesis, admonish us to be wise enough to make an urgent effort for the exclusion of such an exogenous carcinogenic agent as asbestos from our living circumstances.

Electrophoretic variants of blood proteins in Japanese. V. Ceruloplasmin.

The plasma ceruloplasmin of 22,367 children of A-bomb survivors in Hiroshima and Nagasaki was examined for variants by electrophoresis. The sample was composed of 14,964 unrelated children and 7,403 siblings of the unrelated persons. A total of seven types of electrophoretic variants were detected; four migrating anodally and three cathodally to the normal B band. We have reported two of these variants, CP ANG1 and CP CNG1, previously but the other five, CP ANG2, CP AHR1, CP AHR2, CP CHR1, and CP CHR2, are newly identified. The allelic frequency ofCP*CNG1 was 0.00916, so that the variant is considered to be a polymorphic allele. Homozygosity for theCP*CNG1 allele was detected in five individuals. This is the first report of a homozygous phenotype for a ceruloplasmin variant in a Japanese population. Family study of the new five variants all demonstrated patterns of codominant inheritance.

Histologic review of breast cancer cases in survivors of atomic bombs in Hiroshima and Nagasaki, Japan.

A panel of Japanese and American pathologists reviewed existing histologic material used to study breast cancer risk among the A-bomb survivors in Hiroshima and Nagasaki, a population in which incidence studies have found a strong relationship between breast cancer risk and radiation dose. The primary charge to the panel was to define a body of confirmed cases in the Life Span Study sample of the Radiation Effects Research Foundation that would require little or no review for inclusion in future studies of breast cancer incidence. Broad agreement on histologic type was reached for 298 of 300 confirmed cases. The distribution of histologic types was, overall, similar to that seen in other studies of breast cancer in Japanese women, and did not appear to depend on dose; thus radiation-induced breast cancer appeared to be no different histologically from other breast cancer. Also, no evidence was found of variation in histologic type by city, age at exposure, age at diagnosis, or calendar time.

Ophthalmologic Changes Related to Radiation Exposure and Age in Adult Health Study Sample, Hiroshima and Nagasaki

A 2-year ophthalmologic study of age and radiation-related ophthalmologic lesions among the atomic bomb survivors in Hiroshima and Nagasaki was conducted in 1978-80. The study sample in both cities was composed of all persons exposed to 100+ rad, their controls, and all other persons with a previous record of axial opacities or posterior subcapsular changes. Most of the losses were due to persons who refused to participate or for whom it was not possible to arrange for an ophthalmologic examination at the time of the regularly scheduled medical examination. It should be emphasized, however, that the loss of persons in both the control and the 100+ rad groups did not change systematically with increasing age by city. Increased lenticular opacities, other lens changes, and loss of visual acuity and accommodation occurred with increasing age in both exposed and control subjects as manifestations of the normal aging process. A highly significant excess risk for all age categories in the 300+ rad group in comparison to those in the control group was observed for both axial opacities and posterior subcapsular changes in Hiroshima, but not in Nagasaki. A stronger radiosensitive aging effect for persons who were under 15 years old at the time of the bombing (ATB) was observed for both axial opacities and posterior subcapsular changes in Hiroshima.