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Title: Monitoring exposure to atomic bomb radiation by somatic mutation

Abstract

Atomic bomb survivors are a population suitable for studying the relationship between somatic mutation and cancer risk because their exposure doses are relatively well known and their dose responses in terms of cancer risk have also been thoroughly studied. An analysis has been made of erythrocyte glycophorin A (GPA) gene mutations in 1,226 atomic bomb survivors in Hiroshima and Nagasaki. The GPA mutation frequency (Mf) increased slightly but significantly with age at the time of measurement and with the number of cigarettes smoked. After adjustment for the effect of smoking, the Mf was significantly higher in males than in females and higher in Hiroshima than in Nagasaki. All of these characteristics of the background GPA Mf were in accord with those of solid tumor incidence obtained from an earlier epidemiological study of A-bomb survivors. Analysis of the dose effect on Mf revealed the doubling dose to be about 1.20 Sv and the minimum dose for detection of a significant increase to be about 0.24 Sv. No significant dose effect for difference in sex, city, or age at the time of bombing was observed. Interestingly, the doubling dose for the GPA Mf approximated that for solid cancer incidence (1.59 Sv). Andmore » the minimum dose for detection was not inconsistent with the data for solid cancer incidence. The dose effect was significantly higher in those diagnosed with cancer before or after measurement than in those without a history of cancer. These findings are consistent with the hypothesis that somatic mutations are the main cause of excess cancer risk from radiation exposure. 27 refs., 2 figs.« less

Authors:
; ;  [1]
  1. Radiation Effects Research Foundation, Hiroshima (Japan) [and others
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
569216
Report Number(s):
CONF-950879-
Journal ID: EVHPAZ; ISSN 0091-6765; TRN: 98:003565
Resource Type:
Journal Article
Resource Relation:
Journal Name: Environmental Health Perspectives; Journal Volume: 104; Journal Issue: Suppl.3; Conference: 2. international conference on environmental mutagens in human populations, Prague (Czech Republic), 20-25 Aug 1995; Other Information: PBD: May 1996
Country of Publication:
United States
Language:
English
Subject:
56 BIOLOGY AND MEDICINE, APPLIED STUDIES; 55 BIOLOGY AND MEDICINE, BASIC STUDIES; A-BOMB SURVIVORS; GENE MUTATIONS; HIROSHIMA; MUTATION FREQUENCY; NAGASAKI; SOMATIC MUTATIONS; RADIATION MONITORING; RADIATION DOSES; GENETIC RADIATION EFFECTS; BIOLOGICAL RADIATION EFFECTS; DOSE-RESPONSE RELATIONSHIPS; NEOPLASMS; HEREDITARY DISEASES; RISK ASSESSMENT; GENES; TOBACCO SMOKES; SEX DEPENDENCE; RADIATION DOSE DISTRIBUTIONS; SOMATIC CELLS

Citation Formats

Akiyama, Mitoshi, Kyoizumi, Seishi, and Kusunoki, Yoichiro. Monitoring exposure to atomic bomb radiation by somatic mutation. United States: N. p., 1996. Web. doi:10.2307/3432811.
Akiyama, Mitoshi, Kyoizumi, Seishi, & Kusunoki, Yoichiro. Monitoring exposure to atomic bomb radiation by somatic mutation. United States. doi:10.2307/3432811.
Akiyama, Mitoshi, Kyoizumi, Seishi, and Kusunoki, Yoichiro. 1996. "Monitoring exposure to atomic bomb radiation by somatic mutation". United States. doi:10.2307/3432811.
@article{osti_569216,
title = {Monitoring exposure to atomic bomb radiation by somatic mutation},
author = {Akiyama, Mitoshi and Kyoizumi, Seishi and Kusunoki, Yoichiro},
abstractNote = {Atomic bomb survivors are a population suitable for studying the relationship between somatic mutation and cancer risk because their exposure doses are relatively well known and their dose responses in terms of cancer risk have also been thoroughly studied. An analysis has been made of erythrocyte glycophorin A (GPA) gene mutations in 1,226 atomic bomb survivors in Hiroshima and Nagasaki. The GPA mutation frequency (Mf) increased slightly but significantly with age at the time of measurement and with the number of cigarettes smoked. After adjustment for the effect of smoking, the Mf was significantly higher in males than in females and higher in Hiroshima than in Nagasaki. All of these characteristics of the background GPA Mf were in accord with those of solid tumor incidence obtained from an earlier epidemiological study of A-bomb survivors. Analysis of the dose effect on Mf revealed the doubling dose to be about 1.20 Sv and the minimum dose for detection of a significant increase to be about 0.24 Sv. No significant dose effect for difference in sex, city, or age at the time of bombing was observed. Interestingly, the doubling dose for the GPA Mf approximated that for solid cancer incidence (1.59 Sv). And the minimum dose for detection was not inconsistent with the data for solid cancer incidence. The dose effect was significantly higher in those diagnosed with cancer before or after measurement than in those without a history of cancer. These findings are consistent with the hypothesis that somatic mutations are the main cause of excess cancer risk from radiation exposure. 27 refs., 2 figs.},
doi = {10.2307/3432811},
journal = {Environmental Health Perspectives},
number = Suppl.3,
volume = 104,
place = {United States},
year = 1996,
month = 5
}
  • To clarify the relationship between somatic cell mutations and radiation exposure, the frequency of hemizygous mutant erythrocytes at the glycophorin A (GPA) locus was measured by flow cytometry for 1,226 heterozygous atomic bomb (A-bomb) survivors in HIroshima and Nagasaki. For statistical analysis, both GPA mutant frequency and radiation dose were log-transformed to normalize skewed distributions of these variables. The GPA mutant frequency increased slightly but significantly with age at testing and with the number of cigarettes smoked. Also, mutant frequency was significantly higher in males than in females even with adjustment for smoking and was higher to Hiroshima than inmore » Nagasaki. These characteristics of background GPA mutant frequency are qualitatively similar to those of background solid cancer incidence or mortality obtained from previous epidemiological studies of survivors. An analysis of the mutant frequency dose response using a descriptive model showed that the doubling dose is about 1.20 Sv [95% confidence interval (CI): 0.95-1.56], whereas the minimum dose for detecting a significant increase in mutant frequency is about 0.24 Sv (95% CI: 0.041-0.51). No significant effects of sex, city or age at the time of exposure on the dose response were detected. Interestingly, the doubling dose of the GPA mutant frequency was similar to that of solid cancer incidence in A-bomb survivors. This observation is in line with the hypothesis that radiation-induced somatic cell mutations are the major cause of excess cancer risk after radiation. 49 refs., 6 figs., 2 tabs.« less
  • On September 1987 a highly radioactive Cesium-137 source was removed from its protective housing in an abandoned radiotherapy clinic in Goiania, Brazil. Subsequently the source was ruptured and for several days many people were exposed, both externally and internally, to significant levels of ionizing radiation of Cesium-137. More than 50 people received doses up to 7 Gy. Because of its mutagenic and carcinogenic effects, the genetic health of the accident victims has been the subject of continuous studies. The detection and characterization of somatic cell mutation occurring in vivo in humans have been made possible by the development of themore » selection assay of 6-thioguanine-resistant T lymphocytes from the peripheral blood. The mutants are selected by their ability to survive, proliferate, and form colonies in the presence of the purine analogue 6-thioguanine. Studies were performed on individuals with doses ranging from 1 to 7 Gy in the three years following the accident. Those expected had high mutation frequencies. The averages of mutant frequencies during those three years are 28 x 10{sup -6} (1990), 19 x 10{sup -6} (1991) and 11 x 10{sup -6} (1992). We thus also demonstrate that the hprt T-cell assay has a por long term memory. The data also show a positive correlation with age, and a negative correlation with plating efficiency as expected.« less
  • Current lung cancer risk estimates after exposure to low-linear energy transfer radiation such as X rays are based on studies of people exposed to such radiation at high dose rates, for example the atomic bomb survivors. Radiobiology and animal experiments suggest that risks from exposure at low to moderate dose rates, for example medical diagnostic procedures, may be overestimated by such risk models, but data for humans to examine this issue are limited. In this paper we report on lung cancer mortality between 1950 and 1987 in a cohort of 64,172 Canadian tuberculosis patients, of whom 39% were exposed tomore » highly fractionated multiple chest fluoroscopies leading to a mean lung radiation dose of 1.02 Sv received at moderate dose rates. These data have been used to estimate the excess relative risk per sievert of lung cancer mortality, and this is compared directly to estimates derived from 75,991 atomic bomb survivors. Based on 1,178 lung cancer deaths in the fluoroscopy study, there was no evidence of any positive association between risk and dose, with the relative risk at 1 Sv being 1.00 (95% confidence interval 0.94, 1.07), which contrasts with that based on the atomic bomb survivors, 1.60 (1.27, 1.99). The difference in effect between the two studies almost certainly did not arise by chance (P = 0.0001). This study provides strong support from data for humans for a substantial fractionation/dose-rate effect for low-linear energy transfer radiation and lung cancer risk. This implies that lung cancer risk from exposures to such radiation at present-day dose rates is likely to be lower than would be predicted by current radiation risk models based on studies of high-dose-rate exposures. 25 refs., 8 tabs.« less