Akio A. Awa

Increased somatic cell mutant frequency in atomic bomb survivors.

Frequencies of mutant T-cells in peripheral blood, which are deficient in hypoxanthine guanine phosphoribosyltransferase (HPRT) activity, were determined for atomic bomb survivors by direct clonal assay using a previously reported method (Hakoda et al., 1987). Results from 30 exposed survivors (more than 1 rad exposed) and 17 age- and sex-matched controls (less than 1 rad exposed) were analyzed. The mean mutant frequency (Mf) in the exposed (5.2 X 10(-6); range 0.8-14.4 X 10(-6)) was significantly higher than in controls (3.4 X 10(-6); range 1.3-9.3 X 10(-6)), which was not attributable to a difference in non-mutant cell-cloning efficiencies between the 2 groups, which were virtually identical. An initial analysis of the data did not reveal a significant correlation between individual Mfs and individual radiation dose estimates when the latter were defined by the original, tentative estimates (T65D), even though there was a significant positive correlation of Mfs with individual frequency of lymphocytes bearing chromosome aberrations. However, reanalysis using the newer revised individual dose estimates (DS86) for 27 exposed survivors and 17 controls did reveal a significant but shallow positive correlation between T-cell Mf values and individual exposure doses. These results indicate that HPRT mutation in vivo in human T-cells could be detected in these survivors 40 years after the presumed mutational event.

Interlaboratory Comparison of the Dicentric Chromosome Assay for Radiation Biodosimetry in Mass Casualty Events

Abstract Wilkins, R. C., Romm, H., Kao, T-C., Awa, A. A., Yoshida, M. A., Livingston, G. K., Jenkins, M. S., Oestreicher, U., Pellmar, T. C. and Prasanna, P. G. S. Interlaboratory Comparison of the Dicentric Chromosome Assay for Radiation Biodosimetry in Mass Casualty Events. Radiat. Res. 169, 551–560 (2008). This interlaboratory comparison validates the dicentric chromosome assay for assessing radiation dose in mass casualty accidents and identifies the advantages and limitations of an international biodosimetry network. The assays validity and accuracy were determined among five laboratories following the International Organization for Standardization guidelines. Blood samples irradiated at the Armed Forces Radiobiology Research Institute were shipped to all laboratories, which constructed individual radiation calibration curves and assessed the dose to dose-blinded samples. Each laboratory constructed a dose–effect calibration curve for the yield of dicentrics for 60Co γ rays in the 0 to 5-Gy range, using the maximum likelihood linear-quadratic model, Y = c + αD + βD2. For all laboratories, the estimated coefficients of the fitted curves were within the 99.7% confidence intervals (CIs), but the observed dicentric yields differed. When each laboratory assessed radiation doses to four dose-blinded blood samples by comparing the observed dicentric yield with the laboratorys own calibration curve, the estimates were accurate in all laboratories at all doses. For all laboratories, actual doses were within the 99.75% CI for the assessed dose. Across the dose range, the error in the estimated doses, compared to the physical doses, ranged from 15% underestimation to 15% overestimation.

Biological Dosimetry by the Triage Dicentric Chromosome Assay: Potential Implications for Treatment of Acute Radiation Syndrome in Radiological Mass Casualties

Abstract Biological dosimetry is an essential tool for estimating radiation dose. The dicentric chromosome assay (DCA) is currently the tool of choice. Because the assay is labor-intensive and time-consuming, strategies are needed to increase throughput for use in radiation mass casualty incidents. One such strategy is to truncate metaphase spread analysis for triage dose estimates by scoring 50 or fewer metaphases, compared to a routine analysis of 500 to 1000 metaphases, and to increase throughput using a large group of scorers in a biodosimetry network. Previously, the National Institutes for Allergies and Infectious Diseases (NIAID) and the Armed Forces Radiobiology Research Institute (AFRRI) sponsored a double-blinded interlaboratory comparison among five established international cytogenetic biodosimetry laboratories to determine the variability in calibration curves and in dose measurements in unknown, irradiated samples. In the present study, we further analyzed the published data from this previous study to investigate how the number of metaphase spreads influences dose prediction accuracy and how this information could be of value in the triage and management of people at risk for the acute radiation syndrome (ARS). Although, as expected, accuracy decreased with lower numbers of metaphase spreads analyzed, predicted doses by the laboratories were in good agreement and were judged to be adequate to guide diagnosis and treatment of ARS. These results demonstrate that for rapid triage, a network of cytogenetic biodosimetry laboratories can accurately assess doses even with a lower number of scored metaphases.

Peripheral lymphocyte response to PHA and T cell population among atomic bomb survivors

The percentage of T lymphocytes of atomic bomb survivors showed no change as a function of age or exposure dose. The percentage of T cells was slightly lower in malignant-tumor patients than in the control group, but was significantly higher in the group with chromosomal aberrations than in the control group. The percentages of phytohemagglutinin (PHA)-induced transformation of peripheral lymphocytes decreased significantly with age in the 0 rad control group and the 200+ rad exposure group, particularly so in the latter. The malignant-tumor group also showed lower percentages of PHA-induced transformation than the control group. The percentages of PHA-induced transformation of lymphocytes of the chromosomal-aberration group were significantly depressed as compared with that of the control group.

An Estimate of the Magnitude of Random Errors in the DS86 Dosimetry from Data on Chromosome Aberrations and Severe Epilation

An analysis of the proportion of cells with chromosome aberrations in cultured blood lymphocytes from A-bomb survivors in Hiroshima and Nagasaki reveals that the dose-response relationship using DS86 assigned dose is significantly steeper in the subsample of individuals who reported severe epilation after the bombings than in those who did not report severe epilation. This effect is due either to random errors in the DS86 dose assignments or to individual differences in sensitivity to radiation, or to both. In this paper, working within a class of dosimetry error models, we estimate the magnitude of random dosimetry errors which would be required to account for all of the difference in the observed dose response between people who did and did not report severe epilation under the assumption that random dosimetry error is the only cause of the effect. We conclude that random dosimetry errors in the range 45 to 50% of true dose are necessary to explain completely the difference in dose response between the two epilation groups. We discuss evidence that the contribution of individual differences in radiation sensitivity to the observed epilation effect is likely to be small, so that random dosimetry errors may be the major cause of this effect.

Dose-response analyses among atomic bomb survivors exposed to low-level radiation.

An analysis of the dose response within the low-dose range (as here defined, doses of less than 50 cGy (50 rad) was conducted among A-bomb survivors in the ABCC-RERF cohort in an attempt to detect the phenomenon of radiation hormesis, if it is present. These studies include as endpoints cancer mortality, cancer incidence, the frequency of cells with chromosomal aberrations, the phytohemagglutinin response of peripheral lymphocytes and the frequency of mental retardation among survivors exposed in utero. In general, the dose response for these indices of radiation damage varied among comparison groups within the low-dose range, but failed to suggest the existence of radiation hormesis.

Organ Doses from Radiation Therapy in Atomic Bomb Survivors

Abstract Kato, K., Antoku, S., Kodama, K., Kawamura, S., Fujita, Y., Komatsu, K. and Awa, A. A. Organ Doses from Radiation Therapy in Atomic Bomb Survivors. Radiat. Res. 155, 783–793 (2001). 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 60Co γ-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.

Cytogenetic Reconstruction of Gamma-Ray Doses Delivered to Atomic Bomb Survivors: Dealing with Wide Distributions of Photon Energies and Contributions from Hematopoietic Stem/Progenitor Cells

Retrospective estimation of the doses received by atomic bomb (A-bomb) survivors by cytogenetic methods has been hindered by two factors: One is that the photon energies released from the bomb were widely distributed, and since the aberration yield varies depending on the energy, the use of monoenergetic 60Co gamma radiation to construct a calibration curve may bias the estimate. The second problem is the increasing proportion of newly formed lymphocytes entering into the lymphocyte pool with increasing time intervals since the exposures. These new cells are derived from irradiated precursor/stem cells whose radiosensitivity may differ from that of blood lymphocytes. To overcome these problems, radiation doses to tooth enamel were estimated using the electron spin resonance (ESR; or EPR, electron paramagnetic resonance) method and compared with the cytogenetically estimated doses from the same survivors. The ESR method is only weakly dependent on the photon energy and independent of the years elapsed since an exposure. Both ESR and cytogenetic doses were estimated from 107 survivors. The latter estimates were made by assuming that although a part of the cells examined could be lymphoid stem or precursor cells at the time of exposure, all the cells had the same radiosensitivity as blood lymphocytes, and that the A-bomb gamma-ray spectrum was the same as that of the 60Co gamma rays. Subsequently, ESR and cytogenetic endpoints were used to estimate the kerma doses using individual DS02R1 information on shielding conditions. The results showed that the two sets of kerma doses were in close agreement, indicating that perhaps no correction is needed in estimating atomic bomb gamma-ray doses from the cytogenetically estimated 60Co gamma-ray equivalent doses. The present results will make it possible to directly compare cytogenetic doses with the physically estimated doses of the survivors, which would pave the way for testing whether or not there are any systematic trends or factors affecting physically estimated doses.