Effective dose of A-bomb radiation in Hiroshima and Nagasaki as assessed by chromosomal effectiveness of spectrum energy photons and neutrons

The effective dose of combined spectrum energy neutrons and high energy spectrum γ-rays in A-bomb survivors in Hiroshima and Nagasaki has long been a matter of discussion. The reason is largely due to the paucity of biological data for high energy photons, particularly for those with an energy of tens of MeV. To circumvent this problem, a mathematical formalism was developed for the photon energy dependency of chromosomal effectiveness by reviewing a large number of data sets published in the literature on dicentric chromosome formation in human lymphocytes. The chromosomal effectiveness was expressed by a simple multiparametric function of photon energy, which made it possible to estimate the effective dose of spectrum energy photons and differential evaluation in the field of mixed neutron and γ-ray exposure with an internal reference radiation. The effective dose of reactor-produced spectrum energy neutrons was insensitive to the fine structure of the energy distribution and was accessible by a generalized formula applicable to the A-bomb neutrons. Energy spectra of all sources of A-bomb γ-rays at different tissue depths were simulated by a Monte Carlo calculation applied on an ICRU sphere. Using kerma-weighted chromosomal effectiveness of A-bomb spectrum energy photons, the effective dose of A-bomb neutrons was determined, where the relative biological effectiveness (RBE) of neutrons was expressed by a dose-dependent variable RBE, RBE(γ, D _n), against A-bomb γ-rays as an internal reference radiation. When the newly estimated variable RBE(γ, D _n) was applied to the chromosome data of A-bomb survivors in Hiroshima and Nagasaki, the city difference was completely eliminated. The revised effective dose was about 35% larger in Hiroshima, 19% larger in Nagasaki and 26% larger for the combined cohort compared with that based on a constant RBE of 10. Since the differences are significantly large, the proposed effective dose might have an impact on the magnitude of the risk estimates deduced from the A-bomb survivor cohort.     

Mutation induction and relative biological effectiveness of neutrons in mammalian cells. Experimental observations

The induction of mutation by graded doses of monoenergetic neutrons was examined using the human-hamster hybrid cell system. The AL cells, formed by fusion of human fibroblasts with the gly- A mutant of the Chinese hamster ovary cells, contain the standard set of hamster chromosomes plus a single human chromosome, number 11. These cells contain specific human cell surface antigens that render them sensitive to killing by specific antisera in the presence of complement. Mutant AL cells that have lost the surface markers, however, would survive and give rise to scorable colonies. The cells were irradiated with neutrons produced at the Radiological Research Accelerator Facility of Columbia University. Doses corresponding to low, moderate, and high cytotoxicities and in energies ranging from 0.33 to 14 MeV were used. Neutrons induced a dose-dependent cytotoxicity and mutation frequency in the AL cells. Over the range of doses examined, it was found that the mutagenesis induced by neutrons was energy-dependent and the frequencies were a curvilinear function of dose for both the a1 and a2 antigenic loci examined. In comparison to gamma rays, the relative biological effectiveness (RBE) for cell lethality at the 10% survival level ranged from 5.2 for 0.33 MeV to 1.8 for 14 MeV neutrons. The RBE for mutation induction at the a1 locus, however, ranged from 30 for 0.33 MeV to 4.2 for 14 MeV neutrons at or around the lowest levels of effect examined. Results of the present study demonstrated that neutrons, when measured under conditions which permit detection of a spectrum of gene and chromosomal mutations, in fact, are more efficient mutagens than previously thought.     

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.     

Hiroshima-like neutrons from A-bomb replica: physical basis for their use in biological experiments

The lineal energy distribution and several other dosimetric parameters were measured for the neutrons emitted from a replica of the Hiroshima bomb to determine their usefulness in biological experiments designed to estimate the effectiveness of actual Hiroshima neutrons. The "Little-Boy" replica (LBR) was constructed at the Los Alamos National Laboratory in support of the recent atomic-bomb dose reevaluation and was made of identical materials and had nearly identical dimensions and geometry as the Hiroshima bomb. However, the LBR was operated as a steady-state nuclear reactor, which permitted measurements under controlled conditions. Detailed dosimetric measurements and calculations were made at distances of up to 2.1 m from the center of the LBR uranium core. At these distances, the in-air kerma was approximately 97% from neutrons and kerma rates were shown to be particularly useful for biological experiments (up to approximately 7 Gy/h was possible). Quantitative intercomparisons of neutron energy spectra, lineal energy distributions, and measured cytogenetic results for several fission-neutron sources indicate that Hiroshima and LBR neutrons should be of similar biological effectiveness. Based on these evaluations, and cytogenetic results for LBR neutrons reported in a companion paper (this issue), it is estimated that Hiroshima neutrons were 20 to 30% more effective than the fission neutrons commonly used in radiobiology.     

The effects of neutrons in Hiroshima. Implications for the risk estimates

Risk estimates for radiation-induced late effects are relevant to various considerations in radiation protection. Most of these considerations relate to small doses for which no excess risk can be seen even in extensive epidemiological studies. Risk coefficients for radiation protection must, therefore, be based on uncertain extrapolation of observations obtained at moderate or high doses. The extrapolation can not be replaced, as yet, by new, more direct information on processes such as radiation-induced genetic instability or adaptive response. While the new findings indicate complexities that may be highly relevant to the effectiveness- or lack of effectiveness- of radiation at low doses, they remain insufficiently understood to permit a decision as to whether dose-effect relations are linear, curvilinear, or have a threshold in dose. In view of these uncertainties radiation-protection regulations are, today, based on the conservative assumption of a linear dose dependence without threshold. This approach assures a sufficient degree of protection, but it may become unreasonably over-conservative, when the cautious hypothesis is treated as proven fact, and when-in addition-the assumed initial slope of the dose relation is not critically evaluated. A reliable evaluation needs to be based on the follow-up of the atom-bomb bomb survivors, and several major aspects of current interest are discussed here. a) Mortality from solid tumours in Hiroshima shows a statistically significant excess at a colon dose of 50 mGy; however, it is likely that this is the result of a bias in assigning causes of death. b) The solid cancer mortality data of the atom-bomb survivors are consistent with linearity in dose, but they can be shown to be equally consistent with a considerable degree of curvature. c) Even with the present dosimetry system, DS86, a substantial part of the effect at small doses in Hiroshima could be due to neutrons. If this is the case, the risk estimates for gamma-rays need to be accordingly decreased. d) Numerous neutron-activation measurements in Hiroshima indicate that the DS86 underestimates the neutron doses. The evidence is, up to now, based only on activation products of low energy neutrons, but efforts are currently underway to determine activation products of high energy neutrons. If these measurements should substantiate the present trend, the cancer data in Hiroshima would cease to be reliable proof of an effect of gamma-rays at low doses. Instead the dose dependence for gamma-rays could be purely quadratic, and any initial slope in the linear-quadratic dependence might well be attributable to neutrons only.     

The relative biological effectiveness of 14.5-MeV neutrons for the induction of gene conversion and mutation in yeast

The relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) were determined in the yeast Saccharomyces cerevisiae for the induction of gene conversion (the product of recombinational repair) and mutation (the product of error prone repair) by 14.5-MeV neutrons in comparison with 60Co gamma rays and 150 KVp X rays. Neutron irradiation in oxic or anoxic conditions induced significantly higher yields of convertants and mutants than sparsely ionizing radiations under the same conditions. RBEs for both gene conversion and mutation under anoxia were significantly higher than under oxic conditions. RBEs for mutant induction under anoxia were lower than the RBEs for gene conversion under the same conditions. The data support the hypothesis that the production of lesions leading to the genetic consequences of gene conversion and mutation differ in their dependence upon LET and the presence of oxygen during irradiation, and therefore the two DNA repair processes which produce these end points recognize, at least in part, different classes of damage.     

DS02 fluence spectra for neutrons and gamma rays at Hiroshima and Nagasaki with fluence-to-kerma coefficients and transmission factors for sample measurements

Fluence spectra at several ground distances in Hiroshima and Nagasaki are provided along with associated fluence-to-kerma coefficients from the Dosimetry System 2002 (DS02). Also included are transmission factors for calculating expected responses of in situ sample measurements of neutron activation products such as ³²P,³⁶Cl,³⁹Ar,⁴¹Ca, ⁶⁰Co,⁶³Ni,¹⁵²Eu, and ¹⁵⁴Eu. The free-in-air (FIA) fluences calculated in 2002 are available for 240 angles, 69 energy groups, 101 ground distances, 5 heights, 4 radiation source components, 2 cities. The DS02 code uses these fluences partitioned to a prompt and delayed portion, collapsed to 58 energy groups and restricted to 97 ground distances. This is because the fluence spectra were required to be in the same format that was used in the older Dosimetry System 1986 (DS86) computer code, of which the DS02 computer code is a modification. The 2002 calculation fluences and the collapsed DS02 code fluences are presented and briefly discussed. A report on DS02, which is available on the website at the Radiation Effects Research Foundation, provides tables and figures of the A-bomb neutron and gamma-ray output used as the sources in the 2002 radiation transport calculations. While figures illustrating the fluence spectra at several ground ranges are presented in the DS02 Report, it does not include any tables of the calculated fluence spectra in the DS02 report. This paper provides, at several standard distances from the hypocenter, the numerical information which is required to translate the FIA neutron fluences given in DS02 to a neutron activation measurement or neutron and gamma-ray soft-tissue dose.