Masanori Otake

In utero exposure to A-bomb radiation and mental retardation; a reassessment

The prevalence of mental retardation in children exposed in utero to the atomic bombs in Hiroshima and Nagasaki has been re-evaluated in reference to gestational age and tissue dose in the fetus. There was no risk at 0-8 weeks post-conception. The highest risk of forebrain damage occurred at 8-15 weeks of gestational age, the time when the most rapid proliferation of neuronal elements and when most, if not all, neuroblast migration to the cerebral cortex from the proliferative zones is occurring. Overall, the risk is five or more times greater in these weeks than in subsequent ones. In the critical period, damage expressed as the frequency of subsequent mental retardation appears to be linearly related to the dose received by the fetus. A linear model is not equally applicable to radiation-related mental retardation after the 15th week, the observed values suggesting that there a threshold may exist. The data are consistent with a probability of occurrence of mental retardation of 0.40% per cGy or 40% per gray.

Threshold for radiation-related severe mental retardation in prenatally exposed A-bomb survivors: a re-analysis

Significant effects on the developing human brain of exposure to ionizing radiation are seen among individuals exposed in the 8th-25th week after ovulation. These effects, particularly in the highly vulnerable period of 8-15 weeks after ovulation, manifest themselves most dramatically as an increased frequency of severe mental retardation. However, the distribution of cases of severe mental retardation suggests a threshold in the low-dose region. The 95% lower bound of the threshold in those survivors exposed 8-15 weeks after ovulation was zero for the individual data based on the simple linear model, and 0.15 Gy based on the exponential linear model used in our previous report (1987), but the 95% lower bound of the threshold based on all of the data including 21 additional cases with known doses appears to be 0.05 Gy using the maximum likelihood estimates derived from an exponential-linear model. The latter model was selected because it provides the best fit from the standpoint of the stableness and reasonableness of the estimates among the five models applied to the data. When two probably non-radiation-related cases of Downs syndrome are excluded from the 19 mentally retarded cases exposed 8-15 weeks post ovulation, the 95% lower bound of the threshold is in the range of 0.15-0.25 Gy based on the exponential-linear model used in 1987, but is in the range of 0.06-0.31 Gy when the more reasonable and better model applied here is used. For exposure in the 16-25-week period based on the same model, the 95% lower bound of the threshold changed from 0.25 to 0.28 Gy, both with and without inclusion of the two probable non-radiation-related mentally retarded cases; one of these cases was probably familial in origin since there was a retarded sibling, and the other due to infection, since the individual had Japanese B encephalitis at age 4 years.

Radiation-related posterior lenticular opacities in Hiroshima and Nagasaki atomic bomb survivors based on the DS86 dosimetry system

This paper investigates the quantitative relationship of ionizing radiation to the occurrence of posterior lenticular opacities among the survivors of the atomic bombings of Hiroshima and Nagasaki suggested by the DS86 dosimetry system. DS86 doses are available for 1983 (93.4%) of the 2124 atomic bomb survivors analyzed in 1982. The DS86 kerma neutron component for Hiroshima survivors 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. The dose-response relationship has been evaluated as a function of the separately estimated gamma-ray and neutron doses. Among several different dose-response models without and with two thresholds, we have selected as the best model the one with the smallest x2 or the largest log likelihood value associated with the goodness of fit. The best fit is a linear gamma-linear neutron relationship which assumes different thresholds for the two types of radiation. Both gamma and neutron regression coefficients for the best fitting model are positive and highly significant for the estimated DS86 eye organ dose.

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.

Prenatal Exposure to Atomic Radiation and Brain Damage

Abstract Evaluation of data on the frequency of severe mental retardation among prenatally exposed survivors of the atomic bombing of Hiroshima and Nagasaki, and the performance of such survivors on intelligence tests and in school has shown the most striking effects on the developing brain of exposure to ionizing radiation to occur among those individuals exposed in the 8th through the 15th, and the 16th through the 25th week after fertilization. This is true under the earlier T65DR and the newer DS86 systems of dosimetry. Seizure data have also revealed a significant effect of radiation in the 8‐15 week period after fertilization.

The analysis of chromosomally aberrant cells based on beta-binomial distribution

Analysis carried out here generalized on earlier studies of chromosomal aberrations in the populations of Hiroshima and Nagasaki, by allowing extrabinomial variation in aberrant cell counts corresponding to within-subject correlations in cell aberrations. Strong within-subject correlations were detected with corresponding standard errors for the average number of aberrant cells that were often substantially larger than was previously assumed. The extrabinomial variation is accommodated in the analysis in the present report, as described in the section on dose-response models, by using a beta-binomial (beta-B) variance structure. It is emphasized that we have generally satisfactory agreement between the observed and the beta-B fitted frequencies by city-dose category. The chromosomal aberration data considered here are not extensive enough to allow a precise discrimination between competing dose-response models.

Cataract in atomic bomb survivors based on a threshold model and the occurrence of severe epilation

This report re-examines the relationship of radiation dose to the occurrence of cataracts among 1742 atomic bomb survivors seen in the years 1963-1964 for whom the degree of epilation and Dosimetry System 1986 (DS86) doses are known. Of these individuals, 67 had cataracts. A relative risk model with two thresholds, one for the epilation group and the other for the no-epilation group, has been fitted to the data using a binomial odds regression approach and a constant relative biological effectiveness (RBE) for neutrons of 10. Among these models, a linear-linear (L-L) dose-response relationship with two thresholds presents the best fit. Under the L-L threshold model based on DS86 eye organ dose estimates for the epilation and no-epilation groups, the slope estimate for the epilation group was 1.6-2.0 times greater than that for the no-epilation group, but no statistical difference between the two slope estimates was noted. The estimated threshold for the epilation group was 0.86 Sv and 1.54 Sv for the no-epilation group, but again the difference between the two threshold estimates is not statistically significant. When an L-L relative risk model with two thresholds was fitted to the data assuming the dose estimates to be in error by 35%, or when the data were restricted to the 1105 individuals exposed in Japanese houses at distances of less than 2500 m, where the DS86 doses are thought to be most reliable, the results were almost the same as those for the individuals for whom unadjusted DS86 eye organ dose estimates were used.

Radiation-Related Ophthalmological Changes and Aging among Hiroshima and Nagasaki A-Bomb Survivors: A Reanalysis

The relationship of ionizing radiation to the age-related ophthalmological findings of the 1978-1980 ophthalmological examination of A-bomb survivors of Hiroshima and Nagasaki has been reanalyzed using DS86 eye organ dose estimates. The main purpose of this reevaluation was to determine whether age and radiation exposure, as measured using the recently revised dosimetry information (DS86), have an additive, synergistic, or antagonistic effect. The data in this study are limited to axial opacities and posterior subcapsular changes, for which a definite radiation-induced effect has been observed in Hiroshima and Nagasaki A-bomb survivors. The best model fitting for axial opacities gives a significant positive effect for both linear dose and linear age-related regression coefficients and a significant negative effect for an interaction between radiation dose and age. Such a negative interaction implies an antagonistic effect in that the relative risks in relation to radiation exposure doses become smaller with an increase in age. On the other hand, the best-fitting relationship for posterior subcapsular changes suggested a linear-quadratic dose and linear age-related effect. The estimate of the quadratic dose coefficient shows a highly negative correlation with age, but the negative quadratic dose term is extremely small and is of little biological significance.

Evidence of radiation-induced reduction of height and body weight from repeated measurements of adults exposed in childhood to the atomic bombs.

Reduction of growth from exposure to atomic bomb radiation has been examined using individuals under 10 years old at the time of the bombing (ATB) and a growth curve analysis based on measurements of height and weight made in the course of the 4th-7th cycles of the Adult Health Study examinations (1964-1972). As expected, the largest difference in growth to emerge is between males and females. However, a highly significant reduction of growth associated with dose (DS86) was observed among those survivors for whom four repeated measurements of height and weight were available. Longitudinal analysis of a more extended data set (n = 821), using expected values based on simple linear regression models fitted to the three available sets of measurements of height and weight on the 254 individuals with a missing measurement, also indicates a significant radiation-related growth reduction. The possible contribution of such factors as poor nutrition and disruption of normal family life in the years immediately after the war is difficult to evaluate, but the effects of socioeconomic factors on the analysis of these data are discussed.

A longitudinal study of growth and development of stature among prenatally exposed atomic bomb survivors

Growth retardation due to exposure to the atomic bomb has been evaluated using repeated measurements of stature from 10 to 18 years of age. A highly significant growth retardation due to the DS86 uterine dose was observed in all trimesters combined and in the first and second trimesters of pregnancy. In the first trimester, all parameter estimates based on a linear (L) or linear-quadratic (L-Q) dose-response relationship were negative in relation to the DS86 uterine dose. The positive dose estimate in the second trimester is small and close to the control level. Statistically significant difference was determined by a multivariate test statistic examining whether or not a set of two- or three-parameter estimates including a constant term related to an L or L-Q dose-response relationship was different from zero. A radiation-related growth retardation was demonstrable as a longitudinal result of the repeated measurements of stature. The dose effect in the third trimester was not significant under either the L or the L-Q model. The relationship between birth weights and repeated measurements of stature in adolescence is discussed based on the results obtained by a growth curve analysis.