Shoichiro Fujita

Effect of Recent Changes in Atomic Bomb Survivor Dosimetry on Cancer Mortality Risk Estimates

Abstract Preston, D. L., Pierce, D. A., Shimizu, Y., Cullings, H. M., Fujita, S., Funamoto, S. and Kodama, K. Effect of Recent Changes in Atomic Bomb Survivor Dosimetry on Cancer Mortality Risk Estimates. Radiat. Res. 162, 377–389 (2004). The Radiation Effects Research Foundation has recently implemented a new dosimetry system, DS02, to replace the previous system, DS86. This paper assesses the effect of the change on risk estimates for radiation-related solid cancer and leukemia mortality. The changes in dose estimates were smaller than many had anticipated, with the primary systematic change being an increase of about 10% in γ-ray estimates for both cities. In particular, an anticipated large increase of the neutron component in Hiroshima for low-dose survivors did not materialize. However, DS02 improves on DS86 in many details, including the specifics of the radiation released by the bombs and the effects of shielding by structures and terrain. The data used here extend the last reported follow-up for solid cancers by 3 years, with a total of 10,085 deaths, and extends the follow-up for leukemia by 10 years, with a total of 296 deaths. For both solid cancer and leukemia, estimated age–time patterns and sex difference are virtually unchanged by the dosimetry revision. The estimates of solid-cancer radiation risk per sievert and the curvilinear dose response for leukemia are both decreased by about 8% by the dosimetry revision, due to the increase in the γ-ray dose estimates. The apparent shape of the dose response is virtually unchanged by the dosimetry revision, but for solid cancers, the additional 3 years of follow-up has some effect. In particular, there is for the first time a statistically significant upward curvature for solid cancer on the restricted dose range 0–2 Sv. However, the low-dose slope of a linear-quadratic fit to that dose range should probably not be relied on for risk estimation, since that is substantially smaller than the linear slopes on ranges 0–1 Sv, 0–0.5 Sv, and 0– 0.25 Sv. Although it was anticipated that the new dosimetry system might reduce some apparent dose overestimates for Nagasaki factory workers, this did not materialize, and factory workers have significantly lower risk estimates. Whether or not one makes allowance for this, there is no statistically significant city difference in the estimated cancer risk.

Studies of the Mortality of A-Bomb Survivors: 9. Mortality, 1950-1985: Part 1. Comparison of Risk Coefficients for Site-Specific Cancer Mortality Based on the DS86 and T65DR Shielded Kerma and Organ Doses

As a result of the reassessment of the A-bomb dosimetry, new (DS86) doses were calculated in 1986. In this paper, site-specific estimates of cancer mortality in the years 1950-1985, based on these new doses, are compared with those using the T65DR doses. The subjects of the study are 75,991 members of the Life Span Study sample for whom DS86 doses have been calculated. This reevaluation of the exposures does not change the list of radiation-related cancers. Most differences in dose response between Hiroshima and Nagasaki are no longer significant with the DS86 doses. The dose-response curve is closer to linear with the DS86 than the T65DR doses even for leukemia in the entire dose range, though, statistically, many other models cannot be excluded. However, in the low-dose range, the risk of leukemia remains nonlinear. Assuming a linear model at an RBE of 1, and using organ-absorbed doses, the risk coefficients derived from the two dosimetries are very similar, whereas those based on shielded kerma are about 40% higher with the new dosimetry. If RBE values larger than 1 are assumed, the disparity between the two dosimetries increases because the neutron dose is much greater in the T65DR. At an RBE of 10, for the five specific cancers, i.e., female breast, colon, leukemia, lung, and stomach, the increase in excess number of deaths per 10(4) PYSv under the DS86 varies from 12% (colon) to 133% (female breast). The magnitude of the effects of such modifiers of radiation-induced cancer as age at time of bomb and sex do not differ between the two dose systems.

Studies of the mortality of A-bomb survivors. 8. Cancer mortality, 1950-1982.

This study extends an earlier one by 4 years (1979-1982) and includes mortality data on 11,393 additional Nagasaki survivors. Significant dose responses are observed for leukemia, multiple myeloma, and cancers of the lung, female breast, stomach, colon, esophagus, and urinary tract. Due to diagnostic difficulties, results for liver and ovarian cancers, while suggestive of significant dose responses, do not provide convincing evidence for radiogenic effects. No significant dose responses are seen for cancers of the gallbladder, prostate, rectum, pancreas, or uterus, or for lymphoma. For solid tumors, largely due to sex-specific differences in the background rates, the relative risk of radiation-induced mortality is greater for women than for men. For nonleukemic cancers the relative risk seen in those who were young when exposed has decreased with time, while the smaller risks for those who were older at exposure have tended to increase. While the absolute excess risks of radiation-induced mortality due to nonleukemic cancer have increased with time for all age-at-exposure groups, both excess and relative risks of leukemia have generally decreased with time. For leukemia, the rate of decrease in risk and the initial level of risk are inversely related to age at exposure.

Frequency of mutant T lymphocytes defective in the expression of the T-cell antigen receptor gene among radiation-exposed people

The frequency of mutant T lymphocytes defective in T-cell receptor gene (alpha or beta) expression was measured using the 2-color flow cytometric technique. Results for a total of 203 atomic bomb survivors, 78 of whom were proximally exposed (DS86 doses of greater than or equal to 1.5 Gy) and 125 of whom were distally exposed (DS86 dose of less than 0.005 Gy), showed that the mutant frequency was significantly higher in males than in females. No significant dose effects were observed. In contrast, a significant increase of mutant frequency was observed for 6 patients treated with Thorotrast, a contrast medium containing thorium-232 formerly used for radioligands. In addition, thyroid disease patients treated with 131I showed a dose-related increase of mutant frequency. It was suggested that the present T-cell receptor mutation assay has a unique characteristic as a biological dosimeter for measurement of recent exposures to genotoxic agents.

Residual 60Co activity in steel samples exposed to the Hiroshima atomic-bomb neutrons

Residual 60Co radioactivity produced by the neutrons from the Hiroshima atomic bomb has been measured by means of gamma-ray spectrometry for seven steel samples located up to 1,800 m slant range and one control sample obtained at 4.5 km from the hypocenter. After removing the main constituent of iron ions from the steel sample by the solvent extraction method, nickel and cobalt were chemically separated by the ion exchange process. Gamma-ray measurements were performed with a low background well-type germanium detector. Derived specific activities 60Co:Co were compared with previous measurements and with the calculation based on the neutron fluence of current dosimetry system DS86. It has been shown that a systematic discrepancy exists between the measured and calculated activity. The calculated-to-measured ratios for 60Co are consistent with those of 152Eu and 36Cl activity.

Development of a mouse model for studying in vivo T-cell receptor mutations

An experimental system was established to study in vivo T-cell receptor alpha beta (TCR) mutations in murine CD4+ T-lymphocytes. The frequency of TCR-defective mutant T-cells that have the CD3-4+ surface phenotype, was measured using two-color flow cytometry of splenic T-cells passed through nylon wool. The spontaneous TCR mutant frequency (MF) in BALB/c mice (2.3 x 10(-4)) was significantly lower than the frequencies of C57BL/6 (4.0 x 10(-4)) and C3H/He (4.2 x 10(-4)) mice. The general trend of the TCR MF started to increase at 3 days after whole-body X-irradiation, reached a peak level at 2-3 weeks, and then gradually decreased with a half-life of about 2 weeks. To analyze how the dose responses for each strain of mouse differed 2 weeks after X-irradiation, the TCR MF dose responses were fitted to a linear-quadratic or a quadratic curve. The coefficients of the quadratic terms in both models for BALB/c mice were significantly higher than those for the other two strains. These findings suggest that some genetic factor(s) may control the susceptibility of somatic genes to both spontaneous and radiation-induced mutagenesis. Establishing an animal model for in vivo TCR mutations will contribute to the clarification of certain unresolved aspects of TCR mutagenesis in humans and will further advance knowledge of screening for environmental mutagens.

Prevalence of skin neoplasms among the atomic bomb survivors.

About 7,000 atomic bomb (A-bomb) survivors from Hiroshima and Nagasaki who participate in the Radiation Effects Research Foundation (RERF) Adult Health Study (AHS) were examined to define the relationship between skin neoplasms and exposure to ionizing radiation. Careful clinical inspection of the skin was undertaken to detect not only skin cancer but precancerous lesions such as senile keratosis. Five cases of basal cell carcinoma, five cases of senile keratosis and one case of Bowens disease were confirmed histologically among 5955 A-bomb survivors for whom Dosimetry System 1986 (DS86) dose estimates are available. The relationship between the combined prevalence of skin cancer and precancerous lesions and DS86 dose was examined together with other factors that might affect skin neoplasms including occupational exposure to ultraviolet (UV) rays, age, sex and city. The prevalence of basal cell carcinoma and senile keratosis increased as the DS86 dose increased. The prevalence of skin cancer and senile keratosis among persons engaged in work involving frequent exposure to UV rays was higher than among those who were not engaged in such work. Sex and city were not significantly related to those skin diseases. Odds ratios of skin neoplasm for a 1-Gy dose, occupational exposure to UV rays and age at time of examination (in 10-year increments) are 1.7, 5.9 and 1.9, respectively.

Application of Generalized Estimating Equations to a Study of In vitro Radiation Sensitivity

We describe an application of the generalized estimating equation (GEE) method (Liang and Zeger, 1986, Biometrika 73, 13-22) for regression analysis of correlated Poisson data from a split-plot design with a small number of experimental units. As an alternative to the use of an arbitrarily chosen working correlation matrix, we demonstrate the use of GEE with a reasonable model for the true covariance structure among repeated observations within individuals. We show that, under such a split-plot design with large clusters, the asymptotic relative efficiency of GEE with simple (independence or exchangeable) working correlation matrices is rather low. We conclude by summarizing issues and needs for further work concerning efficiency of the GEE parameter estimates in practice.

The effect of changes in dosimetry on cancer mortality risk estimates in atomic bomb survivors

In the spring of 1986 the Radiation Effects Research Foundation (RERF) received a new atomic bomb dosimetry system. This report presents the comparisons of leukemia and nonleukemia cancer mortality risk estimates under the old and new dosimetries. In terms of total kerma (essentially whole-body γ plus neutron exposure), risk estimates for both classes of cancer are 75-85% higher with the new dosimetry. This and other summary comparisons allow for possible nonlinearity at high estimated doses. Changes are also considered in relation to organ doses and assumptions about the relative biological effectiveness (RBE) of neutrons. Without regard to RBE, the risk estimates for total organ dose are essentially unchanged by the dosimetry revision. However, with increasing assumed values of RBE, the estimated low-LET risk decreases much less rapidly under the new dosimetry, due to the smaller neutron component. Thus at an assumed constant RBE of 10, for example, the effect of the dosimetry revision is to increase or...

Atomic bomb induced 152Eu: reconciliation of discrepancy between measurements and calculation.

In order to resolve the discrepancy between the measured and calculated 152Eu activity induced by the atomic bomb at Hiroshima, extremely low background gamma-ray spectrometry was performed for 17 granite samples collected from 134 m to more than 3 km from the hypocenter. Measurements agreed well with theoretical calculations based on DS02 up to 1.4 km from hypocenter.