Cytogenetic damage in lymphocytes for the purpose of dose reconstruction: a review of three recent radiation accidents

The analysis of chromosomal aberrations in peripheral blood of radiation accident victims is an established method of biological dosimetry. The dose estimate on the basis of an in vitro calibration curve is straightforward when the radiation exposure is homogeneous and the analysis not delayed. In recent years three radiation accidents occurred, where the irradiation or sampling conditions precluded a simple estimation of the dose. During the Georgian accident soldiers carried in their pockets small sources of 137Cs leading to partial and protracted body exposures. During the Tokai-mura accident, three employees involved in the process of 235U enrichment were exposed to very high doses of gamma rays and neutrons. During the Bialystok accident, five patients with breast cancer undergoing radiotherapy were exposed to a single dose of electrons which reached about 100 Gy. In the present paper the approaches chosen to estimate, by cytogenetic methods, the doses absorbed by the people involved in the accidents are described.     

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.     

Differential modulation of specific gene expression following high- and low-LET radiations

Experiments were designed to examine the effects of radiation quality on specific gene expression within the first 3 h following radiation exposure in Syrian hamster embryo (SHE) cells. Preliminary work demonstrated the induction of c-fos and alpha-interferon genes following exposure to low-linear-energy-transfer (low-LET) radiations (X rays or gamma rays). More detailed experiments revealed induction of c-fos mRNA within the first 3 h following exposure to either X rays (75 cGy) or gamma rays (90 cGy). We could not detect induction of c-fos following exposure of SHE cells to fission-spectrum neutrons (high-LET) from the JANUS reactor administered at either high (12 cGy/min) or low (0.5 cGy/min) dose rates. Expression of alpha-interferon mRNA was similarly induced by low-LET radiations but only modestly by JANUS neutrons. The induction by gamma rays was dose-dependent, while induction by neutrons was specific for low doses and low dose rates. These experiments demonstrate the differential gene inductive response of cells following exposure to high- and low-LET radiations. These experiments suggest that these different qualities of ionizing radiation may have different mechanisms for inducing many of the cellular consequences of radiation exposure, such as cell survival and cell transformation.     

Lack of adaptive response of gamma radiation for protection against neutron-induced teratogenesis

BACKGROUND: Although there are some reports on neutron teratology, there is little information on the adaptive response of gamma radiation for protection against neutron‐induced teratogenesis. This study examined whether or not a low dose of gamma radiation can induce an adaptive response in mouse fetuses exposed to a subsequent dose of neutrons in vivo. METHODS: Pregnant ICR mice were exposed to a priming dose of 0.3 Gy (0.9 Gy/min) of gamma rays on day 10.5 of gestation and challenged with 0.8 Gy (0.94 Gy/minute) of neutrons 24 hlater. The mice were sacrificed on day 18.5 of gestation. The fetuses were examined for mortality, growth retardation, and other morphologic abnormalities. RESULTS: The tail length in the 0.3 Gy of gamma rays + 0.8 Gy of neutrons group was significantly shorter than in the 0.8 Gy of neutrons group. Although there was no significant difference compared with the 0.8 Gy of neutrons group, the number of live fetuses in the 0.3 Gy of gamma rays +0.8 Gy of neutrons group was lower. There was no evidence of primed exposure‐related reductions in the malformed fetuses. Although there was no significant difference compared with the unprimed group, the number of malformed offspring in the primed group was higher. Furthermore, the incidence of kinked tail and adactyly was significantly higher in the primed mice than in the unprimed mice. CONCLUSIONS: Overall, this study shows that exposure to 0.3 Gy of gamma rays failed to induce an adaptive response of fetogenesis to a neutron challenge dose. Birth Defects Res (Part B) 83:502‐506, 2008. © 2008 Wiley‐Liss, Inc.     

Relative biological effectiveness and tolerance dose of fission neutrons in canine skin for a potential combination of neutron capture therapy and fast-neutron therapy

To investigate the potential efficacy of fission neutrons from a fast-neutron reactor for the treatment of radioresistant tumors, the relative biological effectiveness (RBE) and tolerance dose of fission neutrons in canine skin were determined. The forelimbs of 34 healthy mongrel dogs received a single dose of fission neutrons (5.6, 6.8, 8.2, 9.6 or 11 Gy) or 137Cs gamma rays (10, 15, 20, 25 or 30 Gy). Based on observations of radiodermatitis for each radiation, the single-fraction RBE of fission neutrons in the sixth month was calculated as approximately 3. The tolerance doses of fission neutrons and gamma rays, defined as the highest doses giving no moist desquamation on the irradiated skin in the recovery phase, were estimated as 7.6 Gy and 20 Gy, respectively. The tolerance dose of 7.6 Gy of fission neutrons included 5.0 Gy of fast neutrons possessing high anti-tumor effects and 1.4 x 10(12) n/cm2 of thermal neutrons, which could be applicable to neutron capture therapy (NCT). The combination of fast-neutron therapy and NCT using a fast-neutron reactor might be useful for the treatment of radioresistant tumors.     

Evidence for similarities between radiation damage expressed by beta-araA and damage involved in the interaction effect observed after exposure of V79 cells to mixed neutrons and gamma radiation

Plateau-phase V79 cells were exposed sequentially to fast neutrons and gamma rays. A dose-dependent reduction in the shoulder width of the gamma-ray survival curve was observed after preexposure of cells to neutrons. A similar effect was demonstrated on the neutron survival curve when cells were preirradiated with gamma rays. Treatment of cells with 150 microM beta-araA after either gamma or neutron irradiation reduced primarily the shoulder of the survival curve. When beta-araA was given to the cells after exposure to mixed radiation modalities, survival curves similar to those observed after exposure to a single radiation modality and treatment with beta-araA were obtained. The kinetics of loss of the interaction observed after exposure of cells to gamma rays following neutron irradiation was similar to the kinetics of loss of sensitivity to beta-araA (T1/2 = 1 h) measured by delaying drug administration after exposure to gamma rays. The results suggest that the PLD expressed by beta-araA is at least partly involved in the interactive effect observed after combined exposure of plateau-phase V79 cells to neutrons and gamma rays.     

Dose-response modeling of life shortening in a retrospective analysis of the combined data from the JANUS program at Argonne National Laboratory

Life shortening was investigated in both sexes of the B6CF1 (C57BL/6 x BALB/c) mouse exposed to fission neutrons and 60Co gamma rays. Three basic exposure patterns for both neutrons and gamma rays were compared: single exposures, 24 equal once-weekly exposures, and 60 equal once-weekly exposures. Ten different dose-response models were fitted to the data for animals exposed to neutrons. The response variable used for all dose-response modeling was mean after-survival. A simple linear model adequately described the response to neutrons for females and males at doses less than or equal to 80 cGy. At higher neutron dose levels a linear-quadratic equation was required to describe the life-shortening response. An effect of exposure pattern was observed prior to the detection of curvature in the dose response for neutrons and emerged as a potentially significant factor at neutron doses in the range of 40-60 cGy. Augmentation of neutron injury with dose protraction was observed in both sexes and began at doses as low as 60 cGy. The life-shortening response for all animals exposed to gamma rays (22-1918 cGy) was linear and inversely dependent upon the protraction period (1 day, 24 weeks, 60 weeks). Depending on the exposure pattern used for the gamma-ray baseline, relative biological effectiveness (RBE) values ranged from 6 to 43. Augmentation, because it occurred only at higher levels of neutron exposure, had no influence on the estimation of RBEm.     

Stable intrachromosomal biomarkers of past exposure to densely ionizing radiation in several chromosomes of exposed individuals

A multicolor banding (mBAND) fluorescence in situ hybridization technique was used to investigate the presence inhuman populations of a stable biomarker-intrachromosomal chromosome aberrations-of past exposure to high-LET radiation. Peripheral blood lymphocytes were taken from healthy Russian nuclear workers occupationally exposed from 1949 onward to either plutonium, gamma rays or both. Metaphase spreads were produced and chromosomes 1 and 2 were hybridized with mBAND FISH probes and scored for intra-chromosomal aberrations. A large yield of intrachromosomal aberrations was observed in both chromosomes of the individuals exposed to high doses of plutonium, whereas there was no significant increase over the (low) background control rate in the population who were exposed to high doses of gamma rays.Interchromosome aberration yields were similar in both the high plutonium and the high gamma-ray groups. These results for chromosome 1 and 2 confirm and extend data published previously for chromosome 5. Intrachromosomal aberrations thus represent a potential biomarker for past exposure to high-LET radiations such as alpha particles and neutrons and could possibly be used as a biodosimeter to estimate both the dose and type of radiation exposure in previously exposed populations.     

Relative biological effectiveness of 144 keV neutrons in producing dicentric chromosomes in human lymphocytes compared with 60Co gamma rays under head-to-head conditions

The RBE for neutrons was assessed in a head-to-head experiment in which cultures of lymphocytes from the same male donor were irradiated simultaneously with 144 keV neutrons and with 60Co gamma rays as the reference radiation and evaluated using matched time, culture conditions, and the end point of chromosomal aberrations to avoid potential confounding factors that would influence the outcome of the experiment. In addition, the irradiation time was held constant at 2 h for the high-dose groups for both radiation types, which resulted in rather low dose rates. For the induction of dicentric chromosomes, the exposure to the 144 keV neutrons was found to be almost equally as effective (yield coefficient alpha(dic) = 0.786 +/- 0.066 dicentrics per cell per gray) as that found previously for irradiation with monoenergetic neutrons at 565 keV (alpha(dic) = 0.813 +/- 0.052 dicentrics per cell per gray) under comparable exposure and culture conditions (Radiat. Res. 154, 307-312, 2000). However, the values of the maximum low-dose RBE (RBE(m)) relative to 60Co gamma rays that were determined in the present and previous studies show an insignificant but conspicuous difference: 57.0 +/- 18.8 and 76.0 +/- 29.5, respectively. This difference is mainly due to the difference in the alpha(dic) value of the 60Co gamma rays, the reference radiation, which was 0.0138 +/- 0.0044 Gy(-1) in the present study and 0.0107 +/- 0.0041 Gy(-1) in the previous study. In the present experiment, irradiations with 144 keV neutrons and 60Co gamma rays were both performed at 21 degrees C, while in the earlier experiment irradiations with 565 keV neutrons were performed at 21 degrees C and the corresponding reference irradiation with gamma rays was performed at 37 degrees C. However, the temperature difference between 21 degrees C and 37 degrees C has a minor influence on the yield of chromosomal alterations and hence RBE values. The large cubic PMMA phantom that was used for the gamma irradiations in the present study results in a larger dose contribution from Compton-scattered photons compared to the mini-phantom used in the earlier experiments. The contribution of these scattered photons may explain the large value of alpha(dic) for gamma irradiation in the present study. These results indicate that the yield coefficient alpha(dic) for 144 keV neutrons is similar to the one for 565 keV neutrons, and that modification of the alpha(dic) value of the low-LET reference radiation, due to changes in the experimental conditions, can influence the RBE(m). Consequently, alpha(dic) values cannot be shared between cytogenetic laboratories for the purpose of assessment of RBM(m) without verification of the comparability of the experimental conditions.     

Neutron RBEs and the radiosensitive target for mouse immature oocyte killing

The highly radiosensitive immature oocytes of mice were irradiated in vivo with graded doses of 252Cf fission radiation, 0.43- or 15-MeV neutrons, or 60Co gamma rays. Comparisons of oocyte survival for neutrons and for gamma rays demonstrate that neutron RBEs for the killing of these important cells do not reach the high values (30-50 or more) at low doses observed for several other biological end points. Rather, neutrons differ little in effectiveness from gamma rays in killing these extremely sensitive murine oocytes. For 0.43-MeV neutrons, RBEs obtained from fitted survival curves reach only 1.7 at 0.1 rad. For 15-MeV neutrons, they are not significantly different from 1 at any dose tested (lowest, 4.5 rad). For 252Cf fission neutrons (E = 2.15 MeV), RBEs are intermediate between those for 0.43- and 15-MeV neutrons. For all neutron energies tested, the RBEs are particularly low in the juvenile period, a time when murine immature oocytes are especially radiosensitive. With exposure just prior to birth, however, when these cells are much less easily killed, higher, more usual RBEs are found. The minimum size of the lethality target in mouse immature oocytes, estimated from the inactivation constant for 0.43-MeV neutrons and microdosimetric values, is larger than the nucleus but not larger than the cell. This and related analytical considerations suggest that the hypersensitive target in these particular oocytes is the plasma membrane, a finding which is in excellent accord with results from other experiments using different, contrasting radiations and dose deliveries (accelerated Si14+ ions, gamma rays, and beta rays from 3HOH compared with those from [3H]thymidine).     

Pathology effects at radiation doses below those causing increased mortality

Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.     

A comparison of gamma and neutron irradiation on Raji cells: effects on DNA damage, repair, cell cycle distribution and lethality.

The Comet assay (microgel electrophoresis) was used to study DNA damage in Raji cells, a B-lymphoblastoid cell line, after treatment with different doses of neutrons (0.5 to 16 Gy) or gamma rays (1.4 to 44.8 Gy). A better growth recovery was observed in cells after gamma-ray treatments compared with neutron treatments. The relative biological effectiveness (RBE) of neutron in cell killing was determined to be 2.5. Initially, the number of damaged cells per unit dose was approximately the same after neutron and gamma-ray irradiation. One hour after treatment, however, the number of normal cells per unit dose was much lower for neutrons than for gamma rays, suggesting a more efficient initial repair for gamma rays. Twenty-four hours after treatment, the numbers of damaged cells per unit dose of neutrons or gamma rays were again at comparable level. Cell cycle kinetic studies showed a strong G2/M arrest at equivalent unit dose (neutrons up to 8 Gy; gamma rays up to 5.6 Gy), suggesting a period in cell cycle for DNA repair. However, only cells treated with low doses (up to 2 Gy) seemed to be capable of returning into normal cell cycle within 4 days. For the highest dose of neutrons, decline in the number of normal cells seen at already 3 days after treatment was deeper compared with equivalent unit doses of gamma rays. Our present results support different mechanisms of action by these two irradiations and suggest the generation of locally multiply damaged sites (LMDS) for high linear energy transfer (LET) radiation which are known to be repaired at lower efficiency.     

Nonlinear survival curves for cells of solid tumors after large doses of fast neutrons and gamma rays.

We have previously proposed that survival curves for cells of murine NFSa fibrosarcomas after exposure to fast neutrons might demonstrate curvature when the neutron doses reach a level high enough to cure the fibrosarcomas. We report here that this is the case. Murine NFSa fibrosarcomas growing in the hind legs of syngeneic mice were exposed to either gamma rays or fast neutrons. The tumors were removed and retransplanted into fresh recipients to obtain 50% tumor cell doses, from which the dose-cell survival relationship was constructed. Survival curves showed continuous bending down to 10(-7), and were well fitted using the linear-quadratic model. The alpha and beta values for neutrons were larger than those for gamma rays. When the surviving fractions at experimental TCD50 doses were calculated using these values, comparable figures were obtained for neutrons and gamma rays. The RBEs for neutrons were comparable for the TCD50 and TD50 assays. Neutron RBE was independent of dose within a range of 5-28 Gy. The capacity of the tumors to repair the damage caused by large doses of neutrons was identical to that for small doses of neutrons, indicating that cells retained the capacity to repair neutron damage irrespective of the size of the dose.     

Quantitative assessment of the contribution of clustered damage to DNA double-strand breaks induced by 60Co gamma rays and fission neutrons

The induction of DNA strand breaks by fission neutrons was studied in aqueous plasmid (pBR322) DNA under aerobic conditions for a wide range of hydroxyl radical (*OH) scavenger concentrations and was compared to the induction of strand breaks by 6OCo gamma rays. Strand breaks were measured using agarose gel electrophoresis coupled with sensitive 32P-based phosphor imaging. Yields are reported for DNA single-strand breaks (SSBs) and double-strand breaks formed linearly with dose (alphaDSBs). The fraction of alphaDSBs that were dependent on the multiply damaged site (MDS) or clustered damage mechanism was also calculated using a model. G values for SSBs and alphaDSBs declined with increasing *OH scavenging capacity. However, with increasing *OH scavenging capacities, the decrease in yields of strand breaks for fission neutrons was not as pronounced as for gamma rays. The percentage of alphaDSBs for gamma rays was dependent on *OH scavenging capacity, appearing negligible at low scavenging capacities but increasing at higher scavenging capacities. In contrast, fission neutrons induced high percentages of alphaDSBs that were approximately independent of *OH scavenging capacity. The levels of alphaDSBs formed by the MDS mechanism after exposure to fission neutrons are consistent with the expected distinctive features of high-LET energy deposition events and track structure. The results also confirm observations made by others that even for low-LET radiation, the MDS mechanism contributes significantly to DNA damage at cell-like scavenging conditions.     

CHANGED ACTIVITIES OF BRAIN ENZYMES INVOLVED IN NEUROTRANSMITTER METABOLISM IN RATS EXPOSED TO DIFFERENT QUALITIES OF IONIZING RADIATION

—The effect of different qualities of ionizing radiation on the activity of brain enzymes involved in the metabolism of neurotransmitters in specific regions of the brain of rats was investigated. Groups of Sprague-Dawley adult male rats were exposed to approx. 18,000 rads of radiation either rich in neutrons or rich in gamma rays. It was found that, when the animals were exposed to radiation rich in neutrons, monoamine oxidase (MAO) activity was markedly decreased in all brain areas studied. In contrast, a very marked increase in the activity of this enzyme was observed when the animals received the same dose of radiation rich in gamma rays. Relatively minor changes were observed in the activity of choline acetyl transferase (ChAc). Acetylcholinesterase (AChE) activity did not change appreciably.     

The effectiveness of monoenergetic neutrons at 565 keV in producing dicentric chromosomes in human lymphocytes at low doses

The induction of dicentric chromosomes in human lymphocytes from one individual irradiated in vitro with monoenergetic neutrons at 565 keV was examined to provide additional data for an improved evaluation of neutrons with respect to radiation risk in radioprotection. The resulting linear dose-response relationship obtained (0.813 +/- 0.052 dicentrics per cell per gray) over the dose range of 0.0213-0.167 Gy is consistent with published results obtained for irradiation with neutrons from different sources and with different spectra at energies lower than 1000 keV. Comparing this value to previously published "average" dose-response curves obtained by different laboratories for (60)Co gamma rays and orthovoltage X rays resulted in maximum RBEs (RBE(m)) of about 37 +/- 8 and 16 +/- 4, respectively. However, when our neutron data were matched to low-LET dose responses that were constructed several years earlier for lymphocytes from the same individual, higher values of RBE(m) resulted: 76.0 +/- 29.5 for (60)Co gamma rays and 54.2 +/- 18.4 for (137)Cs gamma rays; differentially filtered 220 kV X rays produced values of RBE(m) between 20.3 +/- 2.0 or 37.0 +/- 7. 1. The results highlight the dependence of RBE(m) on the choice of low-LET reference radiation and raise the possibility that differential individual response to low-LET radiations may need to be examined more fully in this context.     

Life shortening and disease incidence in BALB/c mice following a single d(50)-Be neutron or gamma exposure

Male BALB/c mice, 12 weeks old, were given a single exposure of either 137Cs gamma rays or d(50)-Be neutrons at a dose rate of 3 Gy/min. The animals were kept until death, and causes of death or possible causes of death were ascertained by autopsy and histology. The data were evaluated by competing risk methods. The survival time dose-effect curve for both types of exposure was linear and did not differ significantly (slopes: 55.8 +/- 4.0 days/Gy for neutrons and 46.2 +/- 4.3 days/Gy for gamma rays). The incidence of different diseases also was similar for both groups except that more carcinomas, sarcomas, and myeloid leukemias seemed to occur after neutron exposure and that nonstochastic lung and kidney diseases seemed to arise at lower doses.     

Biological effectiveness of neutrons from Hiroshima bomb replica: results of a collaborative cytogenetic study

The effectiveness of neutrons from a facsimile of the Hiroshima bomb was determined cytogenetically. The "Little-Boy" replica (LBR), assembled at Los Alamos as a controlled nuclear reactor for detailed physical dosimetry, was used. Of special interest, the neutron energy characteristics (including lineal energy) measured 0.74 m from the LBR were remarkably similar to those calculated for the 1945 Hiroshima bomb at 1 to 2 km from the hypocenter, as shown in a companion dosimetric paper (Straume, et al., Radiat. Res. 128, 133-142 (1991)). Thus we examine here the effectiveness of neutrons closely resembling those that the A-bomb survivors received at Hiroshima. Chromosome aberration frequencies were determined in human blood lymphocytes exposed in vitro to graded doses of LBR radiation (97% neutrons, 3% gamma rays). Vials of blood suspended in air at distances up to 2.10 m from the center of the LBR uranium core received doses ranging from 0.02 to 2.92 Gy. The LBR neutrons (E approximately 0.2 MeV) produced 1.18 dicentrics and rings per cell per Gy. They were more effective than the higher-energy fission neutrons (E approximately 1 MeV) commonly used in radiobiology. The maximum RBE (RBEM) of LBR neutrons at low doses is estimated to be 60 to 80 compared to 60Co gamma rays and 22 to 30 compared to 250-kVp X rays. These results provide a quantitative measurement of the biological effectiveness of Hiroshima-like neutrons.     

Conformational properties of DNA after exposure to gamma rays and neutrons

DNA aqueous solutions were irradiated with 0-40 Gy of 60Co gamma rays and 0-1.5 Gy of (Pu-Be) neutrons. Thermal transition spectrophotometry (TTS) was used to trace the changes in the DNA conformation at the above doses. Previous results using the perturbed angular correlation (PAC) method were used to complement to the current analysis. The TTS and PAC methods are two different approaches to the study of the effects of radiation on DNA. Both showed that neutrons are more effective than gamma rays in inducing DNA damage. The TTS method showed that neutrons are 11 +/- 5 times more efficient than gamma rays, while the PAC method had shown this value to be 34 +/- 4. From the current study we deduced that the radiation damage to DNA is not a spontaneous effect but rather is an ensemble of damaging events that occur asynchronously. Any single method selected for the study of such damages can concentrate on only a part of the damage, leading to over- or underestimation of the relative effectiveness of the neutrons.     

A nested case-control study of leukemia mortality and ionizing radiation at the Portsmouth Naval Shipyard

A nested case-control study using conditional logistic regression was conducted to evaluate the exposure-response relationship between external ionizing radiation exposure and leukemia mortality among civilian workers at the Portsmouth Naval Shipyard (PNS), Kittery, Maine. The PNS civilian workers received occupational radiation exposure while performing construction, overhaul, repair and refueling activities on nuclear-powered submarines. The study age-matched 115 leukemia deaths with 460 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992. In addition to radiation doses received in the workplace, a secondary analysis incorporating doses from work-related medical X rays and other occupational radiation exposures was conducted. A significant positive association was found between leukemia mortality and external radiation exposure, adjusting for gender, radiation worker status, and solvent exposure duration (OR = 1.08 at 10 mSv of exposure; 95% CI = 1.01, 1.16). Solvent exposure (including benzene and carbon tetrachloride) was also significantly associated with leukemia mortality adjusting for radiation dose, radiation worker status, and gender. Incorporating doses from work-related medical X rays did not change the estimated leukemia risk per unit of dose.