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PubMed1991

A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Biochemical genetics study.

After 40 years of studies on the children of atomic bomb survivors and a suitable control population in which no statistically significant genetic effects of A-bomb radiation were observed, two new projects have been initiated in order to detect mutations in the DNA and RNA molecules. Permanent cell lines from peripheral B-lymphocytes from approximately 500 families composed of exposed parents and their children and approximately 500 control families are being established by Epstein-Barr virus transformation. Cells will be sources for DNA and RNA samples in the screening for mutations. After comparison of efficiencies of the scanning techniques, we selected the denaturing gradient gel electrophoresis (DGGE) of DNA fragments amplified by polymerase chain reaction (PCR) for our purpose. A small scale pilot study has started to solve problems and obtain a better efficiency in this approach. Current thinking about the most efficient procedures is presented.

Humans↗
PubMed1991

A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Residual radioactivity in neutron-exposed objects and residual alpha radioactivity in black rain areas.

The residual Eu-142 radioactivity due to the atomic bomb explosion in 1945 was first found in 1976 by in-situ high resolution gamma-ray spectrometry at Hiroshima. Since then, various studies on this nuclide have continued not only in Hiroshima but also in Nagasaki and they have contributed to the reevaluation of the neutron dose due to the A-bombing. By radiochemical separation methods and alpha-ray spectrometry, rather high levels of plutonium were found in the surface soil and in the bottom sediment of water reservoir which were collected at "Black rain area" in Nagasaki. The U-234/U-238 activity ratios for the uranium leached with 0.1 HNO3 from the surface of soil samples were found to be relatively higher for the samples which were collected at "Black rain area" in Hiroshima.

Alpha Particles↗
PubMed1992

Specific activities of 60Co and 152Eu in samples collected from the Atomic-Bomb Dome in Hiroshima.

Neutron-induced activities 60Co and 152Eu have been measured for samples collected from the Atomic-Bomb Dome locating at 161 m from the hypocenter of the Hiroshima Bomb. Specific activities 60Co/Co and 152Eu/Eu at the time of the detonation have been determined as 10.0 +/- 1.0 Bq mg-1 (steel sample S4) and 80 +/- 9 Bq mg-1 (granite sample G1), respectively. Detailed measurements of 60Co and 152Eu activities for samples collected from various locations of the Dome show almost no directional dependence whether the sample faced to the epicenter or not, nor vertical height dependence between 17 m height and the ground level. In addition, 152Eu was not detected in the sample collected from the basement. It has been shown that the present 60Co activity value, the nearest steel one to the hypocenter, as well as other short distance data are systematically lower than the calculated values based on the neutron fluence of the DS86.

Cobalt Radioisotopes↗
PubMed1992

Factors that determine the in vivo dose-response relationship for stable chromosome aberrations in A-bomb survivors.

An overview is given of the dose-response relationship for stable chromosome aberrations (i.e., translocations and inversions) in the peripheral blood lymphocytes of A-bomb survivors in Hiroshima. Special emphasis is placed on (i) the overdispersion of survivor cases with either unexpectedly high or low aberration frequencies relative to the estimated DS86 kerma values assigned to individual survivors, termed "cytogenetic outliers", and (ii) the correlation of chromosome aberration frequencies with other biological endpoints, such as acute radiation symptoms (severe epilation). A new molecular biological technique, known as fluorescence in situ hybridization (FISH) with composite, whole-chromosome probes to paint differentially the target chromosomes, has facilitated rapid, efficient, and extensive scoring of translocation-type chromosome aberrations in which the target chromosomes are involved. Using this methodology, the observed findings on translocation frequencies in A-bomb survivors have shown that the frequency of stable chromosome aberrations, which have persisted for years without change in frequency in irradiated persons, is indeed useful as an indicator for biological dosimetry.

Chromosome Aberrations↗
PubMed1995

Anti-Human T-lymphotropic virus type-I antibodies in atomic-bomb survivors.

Adult T-cell leukemia (ATL), induced by human T- lymphotropic virus type-I (HTLV-I), is endemic in Nagasaki, Japan. To investigate the effects of atomic-bomb radiation on development of this specific type of leukemia, 6182 individuals in the Radiation Effects Research Foundation (RERF) Adult Health Study sample in Hiroshima and Nagasaki were examined for positive rate of HTLV-I antibody. Several lymphocyte parameters were also studied for 70 antibody- positive subjects in Nagasaki. The HTLV-I antibody-positive rate was higher in Nagasaki (6.36%) than in Hiroshima (0.79%) and significantly increased with increasing age, but no association was observed with radiation dose. Whether relationship existed between antibody titer levels and radiation dose among antibody-positive subjects was not The frequency of abnormal lymphocytes tended to be higher in antibody-positive subjects than in antibody-negative subjects, and higher in females than in males regardless of radiation dose. The lymphocyte count was lower in antibody-positive subjects than in antibody-negative subjects and lower in female than in male subjects. No evidence was found to suggest that atomic-bomb radiation plays an important role in HTLV-I infection.

Adult↗
PubMed1998

Specific radioactivity of europium-152 in roof tiles exposed to atomic bomb radiation in Nagasaki.

Specific radioactivities of residual europium (Eu)-152 were measured in six roof tile samples exposed to the Nagasaki atomic bomb at two locations. The ground distances of the two locations from the hypocenter are 1020 m and 1060 m. In order to obtain reliable data, Eu-enriched samples (from 207 to 855 mg) were prepared by separating Eu from each roof tile sample (from 1 to 2 kg). For the major aliquot of the Eu-enriched sample, residual radioactivity of 152Eu was measured using a low-energy photon spectrometer. For the minor aliquot of the Eu-enriched sample, Eu content was determined by neutron activation analysis. Results of the specific radioactivity (152Eu/Eu, Bq mg-1) corrected to the time of bombing were in a range from 0.080 to 0.446. Although the measured values showed some scattering, they are moderately consistent with the calculated values by the DS86 methodology, i.e. the average ratio of the calculated to measured values is 1.3 +/- 0.8.

Architecture↗
PubMed1999

Biological dosimetry of atomic bomb survivors exposed within 500 meters from the hypocenter and the health consequences.

Seventy-eight atomic bomb survivors were examined for biological dosimetry using chromosome abnormality. They had been exposed within 500 meters from the hypocenter in heavily shielded conditions and were found from NHK-RIRBM joint study carried out from 1966 to 1971. Estimation of the exposure doses for these survivors was made under the following steps; 1) calculation by DS86 system (physically estimated doses) in survivors who had been exposed within 1,500 meters and had precise records of exposure conditions. RBE for the neutron was defined as 10. 2) setting of exposure dose-chromosome aberration curve, and 3) observation of chromosome aberrations in the proximally exposed survivors, for whom biological doses were estimated. Estimation of the exposure doses were possible from the aberration rate of chromosome in the peripheral lymphocytes, even 25-40 years after the exposure. Of the 78 survivors, 96% were estimated to have exposed more than one Sv. Detection of transforming gene(s) of N and K RAS genes in DNAs from non-leukemic survivors was carried out as one of the biological investigations for these heavily exposed survivors. All four survivors examined showed N or K RAS gene mutation. Three of the four healthy survivors had cancer or leukemia 7-10 years after the examination. Further continuous follow-up study of these heavily exposed people will give us more information on the late effects of A-bomb radiation, which may arise in the future.

Animals↗
PubMed2001

Liver cancer in atomic-bomb survivors: histological characteristics and relationships to radiation and hepatitis B and C viruses.

Histological features of primary liver cancer among atomic-bomb survivors and their relationship to hepatitis B (HBV) and C viral (HCV) infections are of special interest because of the increased risk of liver cancer in persons exposed to ionizing radiation and the high and increasing liver cancer rates in Japan and elsewhere. We conducted a pathology review of liver cancers occurring from 1958 to 1987 among subjects in the 120,321 member cohort of 1945 Hiroshima and Nagasaki residents. A panel of pathologists classified tumor histological types and defined accompanying cirrhotic changes of the liver. Archival tissue samples were assessed for HBV using pathology stains and PCR. Reverse transcriptase (RT) PCR was used to determine HCV status. We used unconditional logistic regression to compare 302 hepatocellular carcinoma (HCC) cases to 53 cholangiocarcinoma (CC) cases, adjusting for age, year of diagnosis, sex and viral status. Cirrhotic changes occurred significantly more often among HCC than CC cases (76% in HCC and 6% in CC). Compared to CC cases, HCC cases were 10.9 times more likely to be HBV-positive (95% confidence interval: 2.1-83.2) and 4.3 times more likely to be HCV-positive (95% confidence interval: 1.1-20.5). No significant differences were found between HCC and CC cases in radiation exposures. The predominance of HCC in the atomic-bomb survivors follows the background liver cancer pattern in Japan. Our findings suggest that HBV and HCV are involved in the pathogenesis of HCC with or without cirrhosis and are significantly less important in that of CC.

Aged↗
PubMed2002

Measurement of residual 60Co activity induced by atomic-bomb neutrons in Nagasaki and background contribution by environmental neutrons.

Residual 60Co activity in five steel samples induced by neutrons from the Nagasaki atomic bomb has been measured within about 1000 m from the hypocenter. The chemical separation of cobalt and nickel from steel samples was performed, and cobalt-enriched samples were prepared for all samples. Gamma-ray measurements were carried out with a low-background well-type germanium detector. The gamma-ray spectra for five samples were compared with the spectrum of a control sample to ensure that the observed 60Co was actually induced by A-bomb neutrons. The activation of cobalt by environmental neutrons was also investigated. It has been shown that the present 60Co data are consistent with earlier Hashizume's data.

Background Radiation↗
PubMed2002

Reassessment of the cancer mortality risk among Hiroshima atomic-bomb survivors using a new dosimetry system, ABS2000D, compared with ABS93D.

The aim of the present study was to examine the excess relative risk for leukemia mortality and all cancers, except leukemia, among Hiroshima atomic-bomb survivors by applying ABS93D and ABS2000D. Particular attention was given to any difference in the neutron-dose estimates between the two dosimetry systems. The study subjects were 51,532 atomic-bomb survivors registered in a database of the Research Institute for Radiation Biology and Medicine of Hiroshima University (RIRBM). The results obtained by both dosimetry systems are similar: the excess relative risk per Sv for leukemia mortality and all cancers except leukemia is significantly higher compared to the control group. In addition, the difference in the excess relative risks between the two systems is not significant. Therefore, it is indicated that a modification of the neutron-dose estimates would not markedly change the conclusions about the cancer mortality risk.

Cohort Studies↗
PubMed2006

Genetic effects of radiation in atomic-bomb survivors and their children: past, present and future.

Genetic studies in the offspring of atomic bomb survivors have been conducted since 1948 at the Atomic Bomb Casualty Commission and its successor, the Radiation Effects Research Foundation, in Hiroshima and Nagasaki. Past studies include analysis of birth defects (untoward pregnancy outcome; namely, malformation, stillbirth, and perinatal death), chromosome aberrations, alterations of plasma and erythrocyte proteins as well as epidemiologic study on mortality (any cause) and cancer incidence (the latter study is still ongoing). There is, thus far, no indication of genetic effects in the offspring of survivors. Recently, the development of molecular biological techniques and human genome sequence databases made it possible to analyze DNA from parents and their offspring (trio-analysis). In addition, a clinical program is underway to establish the frequency of adult-onset multi-factorial diseases (diabetes mellitus, high blood pressure, and cardiovascular disease etc) in the offspring. The complementary kinds of data that will emerge from this three-pronged approach (clinical, epidemiologic, and molecular aspects) promise to shed light on health effects in the offspring of radiation-exposed people.

Abnormalities, Radiation-Induced↗
PubMed2005

Did fertility go up after the Oklahoma City bombing? An analysis of births in metropolitan counties in Oklahoma, 1990-1999.

Political and sociocultural events (e.g., Brown v. Board of Education in 1954 and the German reunification in 1989) and natural disasters (e.g., Hurricane Hugo in 1989) can affect fertility. In our research, we addressed the question of whether the Oklahoma City bombing in April 1995, a man-made disaster, influenced fertility patterns in Oklahoma. We defined three theoretical orientations--replacement theory, community influence theory, and terror management theory--that motivate a general expectation of birth increases, with different predictions emerging from time and geographic considerations. We used two different empirical methodologies. First, we fitted dummy-variable regression models to monthly birth data from 1990 to 1999 in metropolitan counties. We used birth counts to frame the problem and general fertility rates to address the problem formally. These analyses were organized within two design structures: a control-group interrupted time-series design and a difference-in-differences design. In these analyses, Oklahoma County showed an interpretable, consistent, and significant increase in births. Second, we used graphical smoothing models to display these effects visually. In combination, these methods provide compelling support for a fertility response to the Oklahoma City bombing. Certain parts of each theory helped us organize and understand the pattern of results.

Adolescent↗
PubMed1988

Cancer incidence in the population of Nagasaki City 30 years after atomic bombing.

In order to attest the evolutionary hypothesis of non-epithelial-epithelial tumor shift (Okuyama and Mishina 1986), the published cancer incidence data for the population of Nagasaki City during the period of 1973-1977 was studied along with appropriate control populations of Fukuoka City, and Miyagi and Osaka prefectures. Significant increments of non-epithelial tumors including leukemias, and epithelial tumors such as cervical cancers and choriocarcinomas were observed. An inference was made to the post-atomic bomb radiation carcinogenesis that different organ systems responded to that irradiation with different oncogenic patterns: Neoplasms of the pre-vertebral organs (non-epithelial organ systems) were the first to react and tapered long (curve type I); Tumors of the vertebral but pre-mammalian (those of the digestive tract, respiratory and thyroid) could have formed two separate peaks, one for the early and high dosage and the other for the late and low dosage (II); With breast cancer or the mammalian symbol tumor, there was a single peak reflecting the cohort of reproductives (III). The evolutionary and phylogenetic progression could have taken place from I through III. Thus, cancer incidence analysis may be helpful in deciphering the atomic bomb radiation carcinogenesis.

Adolescent↗
PubMed2000

Radiation dose dependences in the atomic bomb survivor cancer mortality data: a model-free visualization.

Chomentowski, M., Kellerer, A. M. and Pierce, D. A. Radiation Dose Dependences in the Atomic Bomb Survivor Cancer Mortality Data: A Model-Free Visualization. The standard approach to obtaining nominal risk coefficients for radiation-related cancer involves fitting linear or linear-quadratic dose-response functions. This is usually complemented by a more direct visualization where the data are subdivided into distinct dose categories and the effect level is quantified for each of these categories. Such model-free computations, however, can be quite dependent on the arbitrary choice of the cutpoints in dose. The method proposed here largely avoids this arbitrariness by choosing a dose category width-constant on a log scale-to obtain the desired degree of smoothing, and then superimposing results for all placements of the resulting log-dose grids. The method is applied to leukemia and solid cancer mortality of the A-bomb survivors.

Cohort Studies↗
PubMed2000

Prevalence of anti-hepatitis C virus antibody and chronic liver disease among atomic bomb survivors.

To investigate whether exposure to atomic bomb radiation altered the prevalence of hepatitis C virus (HCV) infection or accelerated the progress toward chronic hepatitis after HCV infection, the seropositivity of antibody to hepatitis C virus (anti-HCV) was determined for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. The seropositivity of anti-HCV antibody was 2.5 times higher among those with a history of blood transfusion and 1.2 times higher among those with a family history of liver disease, whereas acupuncture showed no association with anti-HCV. Although the prevalence of anti-HCV was lower for survivors with positive dose estimates than for those with 0 dose (relative prevalence 0.84, P = 0.022), there was no evidence of a smooth dose-response relationship. However, these data suggested that the radiation dose response for chronic liver disease among HCV antibody-positive survivors may be greater than that among HCV antibody-negative survivors (slope ratio 20). In conclusion, no dose-response relationship was found between anti-HCV positivity and radiation dose; a possible increase in the radiation dose response of chronic liver disease among anti-HCV-positive individuals was found. Thus radiation exposure may accelerate the progress of chronic liver disease associated with hepatitis C virus infection.

Aged↗
PubMed2001

Organ doses from radiation therapy in atomic bomb survivors.

Previous surveys of radiation therapy among the Life Span Study (LSS) population at the Radiation Effects Research Foundation (RERF) revealed that 1,670 (1.4%) of the LSS participants received radiation treatments before 1984. The data on therapeutic radiation doses are indispensable for studying the relationship between radiation treatments and subsequent cancer occurrences. In this study, the radiation treatments were reproduced experimentally to determine the scattered radiation doses. The experiments were conducted using a female human phantom and various radiation sources, including a medium-voltage X-ray machine and a (60)Co gamma-ray source. Doses were measured using thermoluminescence dosimetry and ionization chambers. Radiation doses were determined for the salivary glands, thyroid gland, breast, lung, stomach, colon, ovary and active bone marrow. The results have been used for documenting the organ doses received by patients in previous surveys. The contribution of therapeutic irradiation to the occurrence of chromosome aberrations was studied using data on doses to active bone marrow from both radiation treatments and atomic bomb exposures in 26 RERF Adult Health Study participants. The results suggest that radiation treatments contributed to a large part of their frequencies of stable-type chromosome aberrations. The therapeutic radiation doses determined in the present study are available for investigating the effects of therapeutic irradiation on the subsequent primary cancers among atomic bomb survivors who received radiation treatments.

Chromosome Aberrations↗
PubMed2002

Multistage models and the incidence of cancer in the cohort of atomic bomb survivors.

The analyses in this paper show that a number of biologically based models describe cancer incidence among the A-bomb survivors equally well. However, these different models can predict very different temporal patterns of risk after irradiation. No evidence was found to support the previous claim of Pierce and Mendelsohn that excess cancer risks for the solid tumors depend only upon attained age and not on age at exposure or time since exposure. Although the A-bomb survivor cohort is the largest epidemiological data set for the study of radiation and cancer, it is not large enough to discriminate among various possible carcinogenic mechanisms. Unfortunately for hypothesis generation, the data appear to be consistent with a number of different mechanistic interpretations of the role of radiation in carcinogenesis.

Adult↗
PubMed2004

Noncancer disease incidence in atomic bomb survivors, 1958-1998.

We examined the relationships between the incidence of noncancer diseases and atomic bomb radiation dose using the longitudinal data for about 10,000 Adult Health Study (AHS) participants during 1958-1998. The current report updates the analysis we presented in 1993 with 12 additional years of follow-up. In addition to the statistically significant positive linear dose-response relationships detected previously for the incidence of thyroid disease (P < 0.0001), chronic liver disease and cirrhosis (P = 0.001), and uterine myoma (P < 0.00001), we also found a significant positive dose response for cataract (P = 0.026), a negative linear dose-response relationship for glaucoma (P = 0.025), and significant quadratic dose-response relationships for hypertension (P = 0.028) and for myocardial infarction among survivors exposed at less than 40 years of age (P = 0.049). Significant radiation effects for calculus of the kidney and ureter were evident for men but not for women (test of heterogeneity by sex: P = 0.007). Accounting for smoking and drinking did not alter the results. Radiation effects for cataract, glaucoma, hypertension, and calculus of the kidney and ureter in men are new findings. These results attest to the need for continued follow-up of the aging A-bomb survivors to fully elucidate the effects of radiation exposure on the occurrence of noncancer diseases.

Adolescent↗