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.     

Effect of recent changes in atomic bomb survivor dosimetry on cancer mortality risk estimates

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 gamma-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 gamma-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.     

Allowance for random dose estimation errors in atomic bomb survivor studies: a revision

Allowing for imprecision of radiation dose estimates for A-bomb survivors followed up by the Radiation Effects Research Foundation can be improved through recent statistical methodology. Since the entire RERF dosimetry system has recently been revised, it is timely to reconsider this. We have found that the dosimetry revision itself does not warrant changes in these methods but that the new methodology does. In addition to assumptions regarding the form and magnitude of dose estimation errors, previous and current methods involve the apparent distribution of true doses in the cohort. New formulas give results conveniently and explicitly in terms of these inputs. Further, it is now possible to use assumptions about two components of the dose errors, referred to in the statistical literature as "classical" and "Berkson-type". There are indirect statistical indications, involving non-cancer biological effects, that errors may be somewhat larger than assumed before, in line with recommendations made here. Inevitably, methods must rely on uncertain assumptions about the magnitude of dose errors, and it is comforting to find that, within the range of plausibility, eventual cancer risk estimates are not very sensitive to these.     

Risk estimation for fast neutrons with regard to solid cancer.

In the absence of epidemiological information on the effects of neutrons, their cancer mortality risk coefficient is currently taken as the product of two low-dose extrapolations: the nominal risk coefficient for photons and the presumed maximum relative biological effectiveness of neutrons. This approach is unnecessary. Since linearity in dose is assumed for neutrons at low to moderate effect levels, the risk coefficient can be derived in terms of the excess risk from epidemiological observations at an intermediate dose of gamma rays and an assumed value, R(1), of the neutron RBE relative to this reference dose of gamma rays. Application of this procedure to the A-bomb data requires accounting for the effect of the neutron dose component, which, according to the current dosimetry system, DS86, amounts on average to 11 mGy in the two cities at a total dose of 1 Gy. With R(1) tentatively set to 20 or 50, it is concluded that the neutrons have caused 18% or 35%, respectively, of the total effect at 1 Gy. The excess relative risk (ERR) for neutrons then lies between 8 per Gy and 16 per Gy. Translating these values into risk coefficients in terms of the effective dose, E, requires accounting for the gamma-ray component produced by the neutron field in the human body, which will require a separate analysis. The risk estimate for neutrons will remain essentially unaffected by the current reassessment of the neutron doses in Hiroshima, because the doses are unlikely to change much at the reference dose of 1 Gy.     

Neutron versus Á-ray risk estimates

While it is recognized that neutrons contributed to the excess cancer incidence and mortality among the atomic bomb survivors in Hiroshima, there is no possibility to deduce the magnitude of this contribution from the data. This remains true even if the neutron doses in the dosimetry system DS86 are corrected upwards in line with recent neutron activation measurements. In spite of this fact, important information can be obtained in the form of an inverse relation of the risk coefficients for γ-rays and neutrons. Such an interrelation must apply because the observed excess incidence or mortality is made up of a γ-ray and a neutron component; increased attribution to neutrons decreases the attribution to photons. Computations with the uncorrected and the corrected DS86 are performed for the mortality and the incidence of solid tumors combined. They refer to doses up to 2 Gy and employ the constant relative risk model and a linear-quadratic dose dependence with variable ratio – the neutron relative biological effectiveness (RBE) at low doses – of the linear component for neutrons and γ-rays. In line with past analyses, no quadratic component is obtained with the uncorrected DS86, but it is seen, even in these calculations, that the assumption of increased neutron RBEs does not translate into proportional increases of the risk coefficients of neutrons, because it leads to substantially reduced risk estimates for γ-rays. Calculations with the corrected dosimetry bring out this reciprocity even more clearly. High values of the neutron RBE reduce – in line with recent suggestions by Rossi and Zaider – the risk estimates for γ-rays substantially. Even a purely quadratic dose relation for γ-rays is consistent with the data; it requires no major increase of the nominal risk coefficients for neutrons over the currently assumed values. The cancer data from Hiroshima can still provide `prudent' risk estimates for photons, but with the corrected DS86, they do not prove that there is a linear component in the dose dependence for photons. Received: 20 January 1997 / Accepted in revised form: 14 March 1997     

Cancer risk estimates for gamma-rays with regard to organ-specific doses

Part I of this study presented an analysis of the solid cancer mortality data for 1950-1997 from the Japanese life-span study of the A-bomb survivors to assess the cancer risk for gamma-rays in terms of the organ-specific dose for all solid cancers combined. Compared to earlier analyses, considerably more curvature in the dose-effect relation is indicated by these computations, which now suggests a dose and dose-rate effectiveness factor of about 2. The computations are extended here in order to explore the site-specific solid cancer risks for various organs. A computational method has been developed whereby the site-specific cancer risks are all simultaneously computed with global age and gender effect modifiers. This provides a more parsimonious representation with fewer parameters and avoids the large relative standard errors which would otherwise result. The sensitivity of site-specific risks to the choices of the neutron RBE is examined. The site-specific risk estimates are quite sensitive to the neutron RBE for the least shielded organs such as the breast, bladder and oesophagus. For the deeper lying organs, such as the gallbladder, pancreas and uterus, the impact of the neutrons is much lower. With an assumed neutron RBE of 35, which is in line with results on low neutron doses in major past studies on rodents and which corresponds approximately to the current ICRP radiation weighting factor for neutrons, the neutrons appear to contribute about 40% of the observed excess cancer risk in the breast, i.e. the organ that is closest to the body surface. However, this neutron contribution fraction is only about 10% for deeper lying organs, such as the colon.     

Lung carcinomas in Sprague-Dawley rats after exposure to low doses of radon daughters, fission neutrons, or gamma rays

The effectiveness of radon-daughter inhalation and irradiation with fission neutrons and gamma rays in the induction of lung carcinomas in Sprague-Dawley rats at low doses is compared. Earlier reports which compared radon-daughter inhalations and neutron irradiations over a wider range of doses were based on dosimetry for the radon-daughter inhalations which has recently been found to be faulty. In the present analysis, low-dose experiments were designed to derive revised equivalence ratios between radon-daughter exposures, and fission neutron or gamma irradiations. The equivalence is approximately 15 working level months (WLM) of radon daughters to 10 mGy of neutrons (the earlier value was 30 WLM to 10 mGy). The relative biological effectiveness (RBE) of neutrons is 50 or more at a gamma-ray dose of 1 Gy. In these experiments with low doses and exposures, the lifetime incidences can be estimated from the raw incidences, while the derivation of the time dependence of the prevalence is essential for the estimation of RBE values and equivalence ratios.     

Neutron relative biological effectiveness for solid cancer incidence in the Japanese A-bomb survivors: an analysis considering the degree of independent effects from γ-ray and neutron absorbed doses with hierarchical partitioning

It has generally been assumed that the neutron and γ-ray absorbed doses in the data from the life span study (LSS) of the Japanese A-bomb survivors are too highly correlated for an independent separation of the all solid cancer risks due to neutrons and due to γ-rays. However, with the release of the most recent data for all solid cancer incidence and the increased statistical power over previous datasets, it is instructive to consider alternatives to the usual approaches. Simple excess relative risk (ERR) models for radiation-induced solid cancer incidence fitted to the LSS epidemiological data have been applied with neutron and γ-ray absorbed doses as separate explanatory covariables. A simple evaluation of the degree of independent effects from γ-ray and neutron absorbed doses on the all solid cancer risk with the hierarchical partitioning (HP) technique is presented here. The degree of multi-collinearity between the γ-ray and neutron absorbed doses has also been considered. The results show that, whereas the partial correlation between the neutron and γ-ray colon absorbed doses may be considered to be high at 0.74, this value is just below the level beyond which remedial action, such as adding the doses together, is usually recommended. The resulting variance inflation factor is 2.2. Applying HP indicates that just under half of the drop in deviance resulting from adding the γ-ray and neutron absorbed doses to the baseline risk model comes from the joint effects of the neutrons and γ-rays—leaving a substantial proportion of this deviance drop accounted for by individual effects of the neutrons and γ-rays. The average ERR/Gy γ-ray absorbed dose and the ERR/Gy neutron absorbed dose that have been obtained here directly for the first time, agree well with previous indirect estimates. The average relative biological effectiveness (RBE) of neutrons relative to γ-rays, calculated directly from fit parameters to the all solid cancer ERR model with both colon absorbed dose covariables, is 65 (95 %CI: 11; 170). Therefore, although the 95 % CI is quite wide, reference to the colon doses with a neutron weighting of 10 may not be optimal as the basis for the determination of all solid cancer risks. Further investigations into the neutron RBE are required, ideally based on the LSS data with organ-specific neutron and γ-ray absorbed doses for all organs rather than the RBE weighted absorbed doses currently provided. The HP method is also suggested for use in other epidemiological cohort analyses that involve correlated explanatory covariables.     

New models for evaluation of radiation-induced lifetime cancer risk and its uncertainty employed in the UNSCEAR 2006 report

Generalized relative and absolute risk models are fitted to the latest Japanese atomic bomb survivor solid cancer and leukemia mortality data (through 2000), with the latest (DS02) dosimetry, by classical (regression calibration) and Bayesian techniques, taking account of errors in dose estimates and other uncertainties. Linear-quadratic and linear-quadratic-exponential models are fitted and used to assess risks for contemporary populations of China, Japan, Puerto Rico, the U.S. and the UK. Many of these models are the same as or very similar to models used in the UNSCEAR 2006 report. For a test dose of 0.1 Sv, the solid cancer mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 5.4% Sv(-1) [90% Bayesian credible interval (BCI) 3.1, 8.0]. At 0.1 Sv, leukemia mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 0.50% Sv(-1) (90% BCI 0.11, 0.97). Risk estimates varied little between populations; at 0.1 Sv the central estimates ranged from 3.7 to 5.4% Sv(-1) for solid cancers and from 0.4 to 0.6% Sv(-1) for leukemia. Analyses using regression calibration techniques yield central estimates of risk very similar to those for the Bayesian approach. The central estimates of population risk were similar for the generalized absolute risk model and the relative risk model. Linear-quadratic-exponential models predict lower risks (at least at low test doses) and appear to fit as well, although for other (theoretical) reasons we favor the simpler linear-quadratic models.     

Cancer risk estimates for gamma-rays with regard to organ-specific doses

A previous analysis of the solid cancer mortality data for 1950-1990 from the Japanese life-span study of the A-bomb survivors has assessed the solid cancer risk coefficients for gamma-rays in terms of the low dose risk coefficient ERR/Gy, i.e. the initial slope of the ERR vs. dose relation, and also in terms of the more precisely estimated intermediate dose risk coefficient, ERR(D1)/D1, for a reference dose, D1, which was chosen to be 1 Gy. The computations were performed for tentatively assumed values 20-50 of the neutron RBE against the reference dose and in terms of organ-averaged doses, rather than the traditionally applied colon doses. The resulting risk estimate for a dose of 1 Gy was about half as large as the most recent UNSCEAR estimate. The present assessment repeats the earlier analysis with two major extensions. It parallels computations based on organ-average doses with computations based on organ-specific doses and it updates the previous results by using the cancer mortality data for 1950-1997 which have recently been made available. With an assumed neutron RBE of 35, the resulting intermediate dose estimate of the lifetime attributable risk (LAR) for solid cancer mortality for a working population (ages 25-65 years) is 0.059/Gy with the attained-age model, and 0.044/Gy with the age-at-exposure model. For a population of all ages, 0.055/Gy is obtained with the attained-age model and 0.073/Gy with the age-at-exposure model. These values are up to about 20% higher than those obtained in the previous analysis with the 1950-1990 data. However, considerably more curvature in the dose-effect relation is now supported by the computations. A dose and dose-rate reduction factor DDREF=2 is now much more in line with the data than before. With this factor the LAR for a working population is--averaged over the age-at-exposure and the age-attained model--equal to 0.026/Gy. This is only half as large as the current ICRP estimate which is also based on the assumption DDREF=2.     

Risk coefficient for gamma-rays with regard to solid cancer

A previous investigation has uncoupled the solid cancer risk coefficient for neutrons from the low dose estimates of the relative biological effectiveness (RBE) of neutrons and the photon risk coefficient, and has related it to two more tangible quantities, the excess relative risk (ERR1) due to an intermediate reference dose D1 = 1 Gy of gamma-rays and the RBE of neutrons, R1, against this reference dose. With tentatively assumed RBE values between 20 and 50 and in terms of organ-averaged doses--rather than the usually invoked colon doses--the neutron risk factor was seen to be in general agreement with the current risk estimate of the International Commission on Radiation Protection (ICRP). The present assessment of the risk coefficient for gamma-rays incorporates--in terms of the unchanged A-bomb dosimetry system, DS86--this treatment of the neutrons, but is otherwise largely analogous to the evaluation of the A-bomb data for the ICRP report and for the recent report of the United Nations Scientific Committee on the effects of ionizing radiation, UNSCEAR. The resulting central estimate of the lifetime attributable risk (LAR) for solid cancer mortality is 0.043/Gy for a working population (ages 25-65), and is nearly the same whether the age at exposure or the attained age model is used for risk projection. For a population of all ages 0.042/Gy is obtained with the attained age model and 0.068/Gy with the age at exposure model. The values do not include a dose and dose rate effectiveness factor (DDREF), and they are only half as large as the new UNSCEAR estimates of 0.082/Gy (attained age model and all ages) and 0.13/Gy (age at exposure model and all ages). The difference is only partly due to the more explicit treatment of the neutrons. It reflects also the fact that UNSCEAR has converted ERR into LAR in a way that differs from the ICRP procedure, and that it has summed the overall risk coefficient for solid tumor mortality and incidence from separate estimates for eight solid tumor categories, whereas the present study employs a combined computation for all solid tumors and uses the ICRP procedure for the conversion of ERR into LAR. The appendix gives results for the solid cancer incidence data.     

Congenital malformations, stillbirths, and early mortality among the children of atomic bomb survivors: a reanalysis

Of all the data sets pertinent to the estimation of the genetic risks to humans following exposure to ionizing radiation, potentially the most informative is that composed of the cohort of children born to atomic bomb survivors. We present here an analysis of the relationship between parental exposure history and untoward pregnancy outcomes within this cohort, using to the fullest extent possible the recently revised estimates of the doses received by their parents, the so-called DS86 doses. Available for study are 70,073 terminations, but DS86 doses have not been or presently cannot be computed on the parents of 14,770. The frequency of untoward pregnancy outcomes, defined as a pregnancy terminating in a child with a major congenital malformation, and/or stillborn, and/or dying in the first 14 days of life, increases with combined (summed) parental dose, albeit not significantly so. Under a standard linear model, when the sample of observations is restricted to those children whose parents have been assigned the newly established DS86 doses (n = 55,303), ignoring concomitant sources of variation and assuming a neutron RBE of 20, the estimated increase per sievert in the predicted frequency of untoward outcomes is 0.00354 (+/- 0.00343). After adjustment for concomitant sources of variation, the estimated increase per sievert in the proportion of such births is 0.00422 (+/- 0.00342) if the neutron RBE is assumed to be 20. A "one-hit" model with appropriate adjustments for extraneous sources of variation results in an almost identical value, namely, 0.00412 (+/- 0.00364). When the sample is extended to include parents lacking the full array of dose parameters necessary to calculate the DS86 dose, but sufficient for an empirical conversion of the previously employed T65DR dose system to its DS86 equivalent, we find under the linear model that the estimated increase per sievert in untoward pregnancy outcomes is some 31% higher than that published previously, 0.00264 (+/- 0.00277), assuming an RBE of 20, after adjustment for extraneous sources of variation. (Since a dose could not be calculated in 367 of the 70,073 outcomes, the n = 69,706). The corresponding value with the one-hit model is 0.00262 (+/- 0.00294).     

Choice of model and uncertainties of the gamma-ray and neutron dosimetry in relation to the chromosome aberrations data in Hiroshima and Nagasaki

Chromosome data pertaining to blood samples from 1,703 survivors of the Hiroshima and Nagasaki A-bombs, were utilized and different models for chromosome aberration dose response investigated. Models applied included those linear or linear-quadratic in equivalent dose. Models in which neutron and gamma doses were treated separately (LQ-L model) were also used, which included either the use of a low-dose limiting value for the relative biological effectiveness (RBE) of neutrons of R(0)=70+/-10 or an RBE value of R(1)=15+/-5 at 1 Gy. The use of R(1) incorporates the assumption that it is much better known than R(0), with much less associated uncertainty. In addition, error-reducing transformations were included which were found to result in a 50% reduction of the standard error associated with one of the model fit parameters which is associated with the proportion of cells with at least one aberration, at 1 Gy gamma dose. Several justifiable modifications to the DS86 doses according to recent nuclear retrospective dosimetry measurements were also investigated. Gamma-dose modifications were based on published thermoluminescence measurements of quartz samples from Hiroshima and on a tentative reduction for Nagasaki factory worker candidates by a factor of 0.6. Neutron doses in Hiroshima were modified to become consistent with recent fast neutron activation data based on copper samples. The applied dose modifications result in an increase in non-linearity of the dose-response curve for Hiroshima, and a corresponding decrease in that for Nagasaki, an effect found to be most pronounced for the LQ-L models investigated. As a result the difference in the dose-response curves observed for both cities based on DS86 doses, is somewhat reduced but cannot be entirely explained by the dose modifications applied. The extent to which the neutrons contribute to chromosome aberration induction in Hiroshima depends significantly on the model used. The LQ-L model including an R(1) value of 15 at 1 Gy which is recommended here, would predict between 10% and 20% of the observed chromosome aberrations to be due to neutrons, at all doses. Because of the good agreement between DS86 predictions and the results of retrospective gamma and neutron dosimetry, the modifications applied here to DS86 doses are relatively small. Consequently, the choices of model and RBE values were found to be the major factors dominating the interpretation of the chromosome data for Hiroshima and Nagasaki, with the dose modifications resulting in a smaller influence.     

Lung cancer risk in mice: analysis of fractionation effects and neutron RBE with a biologically motivated model

Data from Argonne National Laboratory on lung cancer in 15,975 mice with acute and fractionated exposures to gamma rays and neutrons are analyzed with a biologically motivated model with two rate-limiting steps and clonal expansion. Fractionation effects and effects of radiation quality can be explained well by the estimated kinetic parameters. Both an initiating and a promoting action of neutrons and gamma rays are suggested. While for gamma rays the initiating event is described well with a linear dose-rate dependence, for neutrons a nonlinear term is needed, with less effectiveness at higher dose rates. For the initiating event, the neutron RBE compared to gamma rays is about 10 when the dose rate during each fraction is low. For higher dose rates this RBE decreases strongly. The estimated lifetime relative risk for radiation-induced lung cancers from 1 Gy of acute gamma-ray exposure at an age of 110 days is 1.27 for male mice and 1.53 for female mice. For doses less than 1 Gy, the effectiveness of fractionated exposure to gamma rays compared to acute exposure is between 0.4 and 0.7 in both sexes. For lifetime relative risk, the RBE from acute neutrons at low doses is estimated at about 10 relative to acute gamma-ray exposure. It decreases strongly with dose. For fractionated neutrons, it is lower, down to about 4 for male mice.     

Temporal analysis of a dose-response relationship: leukemia mortality in atomic bomb survivors

A data analysis that incorporates time dependencies is demonstrated for the dose response of leukemia mortality in the atomic bomb survivors. The time dependencies are initially left unspecified and the data on leukemia mortality--up to the end of 1978--are used to infer them. Several findings based on T65 revised doses (T65DR) are obtained. First, it is shown that the fits to the data of time-dependent L (linear in gamma dose)-Q (quadratic in gamma dose)-L (linear in neutron dose), L-L, and Q-L dose-response models are significantly improved (P less than 0.001) by using the corresponding time-dependent dose-response models. Second, it is shown that the increased risk of leukemia mortality due to gamma irradiation decreases in time while the increased risk due to neutron exposure decreases more slowly, if at all, in time. Consequently, relative biological effectiveness (RBE) of neutrons is shown to increase in time (P = 0.002) and the current definition of RBE as a time-independent quantity is therefore challenged. It is demonstrated with time-dependent models that the L-L model has a poor fit (P = 0.01) to the data for the first 7 years of study, but has an adequate fit for the remaining 21 years. In contrast the Q-L model has an adequate fit for the entire follow-up period (P greater than 0.30).     

Comparison of the biological effects of tritium oxide and gamma radiation based on changes in the mass of the rat thymus gland

RBE of tritium oxide (cumulative doses from 0.33 to 14.7 Gy), in comparison with gamma-radiation, amounted to 2-3 as estimated by the thymus mass. As determined by the rate of injury and repair, the RBE values decreased from 4 to 1.4 with dose increasing, and from 6.5 to 1.3, by the periods of half-decrease and half-recovery of the organ mass. The 2-3-fold variations in the RBE values for various parameters of the organ mass changes were registered at low doses, whereas within the range of median and high doses under study, the differences were insignificant.     

A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy

While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.     

Neutron-energy-dependent oncogenic transformation of C3H 10T1/2 mouse cells

The relative biological effectiveness (RBE) of a range of neutron energies relative to 250-kVp X rays has been determined for oncogenic transformation and cell survival in the mouse C3H 10T 1/2 cell line. Monoenergetic neutrons at 0.23, 0.35, 0.45, 0.70, 0.96, 1.96, 5.90, and 13.7 MeV were generated at the Radiological Research Accelerator Facility of the Radiological Research Laboratories, Columbia University, and were used to irradiate asynchronous cells at low absorbed doses from 0.05 to 1.47 Gy. X irradiations covered the range 0.5 to 8 Gy. Over the more than 2-year period of this study, the 31 experiments provided comprehensive information, indicating minimal variability in control material, assuring the validity of comparisons over time. For both survival and transformation, a curvilinear dose response for X rays was contrasted with linear or nearly linear dose responses for the various neutron energies. RBE increased as dose decreased for both end points. Maximal RBE values for transformation ranged from 13 for cells exposed to 5.9-MeV neutrons to 35 for 0.35-MeV neutrons. This study clearly shows that over the range of neutron energies typically seen by nuclear power plant workers and individuals exposed to the atomic bombs in Japan, a wide range of RBE values needs to be considered when evaluating the neutron component of the effective dose. These results are in concordance with the recent proposals in ICRU 40 both to change upward and to vary the quality factor for neutron irradiations.     

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.