No lengthening of life span in mice continuously exposed to gamma rays at very low dose rates

Late effects of continuous exposure to ionizing radiation are potential hazards to workers in radiation facilities as well as to the general public. Recently, low-dose-rate and low-dose effects have become a serious concern. Using a total of 4000 mice, we studied the late biological effects of chronic exposure to low-dose-rate radiation as assayed by life span. Two thousand male and 2000 female 8-week-old specific-pathogen-free (SPF) B6C3F1 mice were randomly divided into four groups (one nonirradiated control and three irradiated). Irradiation was carried out for approximately 400 days using (137)Cs gamma rays at dose rates of 21 mGy day(-1), 1.1 mGy day(-1) and 0.05 mGy day(-1) with total doses equivalent to 8000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept under SPF conditions until they died spontaneously. Statistical analyses showed that the life spans of mice of both sexes irradiated with 21 mGy day(-1) (P < 0.0001) and of females irradiated with 1.1 mGy day(-1) (P < 0.05) were significantly shorter than those of the control group. Our results show no evidence of lengthened life span in mice continuously exposed to very low dose rates of gamma rays.     

Bystander-type effects mediated by long-lived inflammatory signaling in irradiated bone marrow

Radiation-induced bystander and abscopal effects, in which DNA damage is produced in nonirradiated cells as a consequence of communication with irradiated cells, indicate mechanisms of inducing damage and cell death additional to the conventional model of deposition of energy in the cell nucleus at the time of irradiation. In this study we show that signals generated in vivo in the bone marrow of mice irradiated with 4 Gy γ rays 18 h to 15 months previously are able to induce DNA damage and apoptosis in nonirradiated bone marrow cells but that comparable signals are not detected at earlier times postirradiation or at doses below 100 mGy. Bone marrow cells of both CBA/Ca and C57BL/6 genotypes exhibit responses to signals produced by either irradiated CBA/Ca or C57BL/6 mice, and the responses are mediated by the cytokines FasL and TNF-α converging on a COX-2-dependent pathway. The findings are consistent with indirect inflammatory signaling induced as a response to the initial radiation damage rather than to direct signaling between irradiated and nonirradiated cells. The findings also demonstrate the importance of studying tissue responses when considering the mechanisms underlying the consequences of radiation exposures.     

Cell death (apoptosis) in mouse intestine after continuous irradiation with gamma rays and with beta rays from tritiated water

Apoptosis is a pattern of cell death involving nuclear pycnosis, cytoplasmic condensation, and karyorrhexis. Apoptosis induced by continuous irradiation with gamma rays (externally given by a 137Cs source) or with beta rays (from tritiated water injected ip) was quantified in the crypts of two portions of mouse bowel, the small intestine and descending colon. The time-course change in the incidence of apoptosis after each type of radiation could be explained on the basis of the innate circadian rhythm of the cells susceptible to apoptotic death and of the excretion of tritiated water (HTO) from the body. For 6-h continuous gamma irradiation at various dose rates (0.6-480 mGy/h) and for 6 h after injection of HTO of various radioactivities (0.15-150 GBq per kg body wt), the relationships between dose and incidence of apoptosis were obtained. Survival curves were then constructed from the curves for dose vs incidence of apoptosis. For the calculation of the absorbed dose from HTO, the water content both of the mouse body and of the cells was assumed to be 70%. One megabecquerel of HTO per mouse (i.e., 40 MBq/kg body wt) gave a dose rate of 0.131 mGy/h. The mean lethal doses (D0) were calculated for gamma rays and HTO, and relative biological effectiveness values of HTO relative to gamma rays were obtained. The D0 values for continuous irradiation with gamma rays were 210 mGy for small intestine and 380 mGy for descending colon, and the respective values for HTO were 130 and 280 mGy, indicating the high radiosensitivity of target cells for apoptotic death. The relative biological effectiveness of HTO relative to 137Cs gamma rays for cell killing in both the small intestine and the descending colon in the mouse was 1.4-2.1.     

Radioprotective action of extracellular adenosine on bone marrow cells in mice exposed to gamma rays as assayed by the micronucleus test

The frequency of micronucleated polychromatic erythrocytes (PCEs) in mouse bone marrow was assessed after administration of dipyridamole and/or adenosine monophosphate (AMP) to nonirradiated mice or to mice irradiated 15 min later with a sublethal dose of 6.5 Gy gamma rays. In nonirradiated mice, the administration of the drugs increased the frequency of micronucleated PCEs significantly (by 108%). In contrast, in irradiated mice, the number of radiation-induced micronucleated PCEs was significantly decreased if the mice had been pretreated with dipyridamole or AMP alone (by 24% after administration of each of the compounds) and in particular after administration of the drugs in combination (by 36%).     

Seventeen-year mortality experience of proton radiation in Macaca mulatta

This is an interim report on the lifetime study of chronic mortality and its causes under investigation in 31 control (20 males, 11 females) and 217 survivors (124 males, 93 females) of an acute 90-day experiment in rhesus monkeys. Single acute whole-body exposures were made using 32-, 55-, 138-, 400-, and 2300-MeV protons in 1964-1965. Doses ranged from 25 to 800 rad and dose rates from 12.5 and 100 rad per minute. Tissue depths of partially penetrating 32- and 55-MeV particles were approximately 1 and approximately 2.5 cm, respectively, and depth doses at the respective distances were 115 and 122% of surface doses. Protons with energies greater than or equal to 138 MeV were totally penetrating and the depth doses were essentially homogenous. For pooled data: (1) mortality was significantly higher (P less than 0.01) in irradiated animals (48%) than in controls (19%); (2) mortality in animals exposed to partially penetrating 55-MeV protons (53%) was essentially similar to those given totally penetrating 138- (53%), 400- (49%), and 2300-MeV (44%) exposures; (3) proton energies and doses that were effective in producing life shortening were greater than or equal to 55 MeV and greater than or equal to 360-400 rad, respectively; (4) death rates for irradiated animals compared to controls began to increase after approximately 8 years, approximately 2 years, and approximately 1 year for those exposed to 360-400, 500-650, and 800 rad, respectively; (5) of the nine probable causes of death reported, the leading causes were primary infections in both irradiated (31%) and control (50%) animals, endometriosis (25% vs 0%, respectively), neoplasms (17% vs 0%), and organ degeneration (17% vs 33%); and (6) if endometriosis is included with the neoplastic group, deaths from all forms of neoplasms would be 42% in irradiated animals.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chromosome aberration frequencies and chromosome instability in mice after long-term exposure to low-dose-rate gamma-irradiation

Chronological changes of chromosome aberration rates related to accumulated doses in chronically exposed humans and animals at a low-dose-rate have not been well studied. C3H female specific pathogen-free mice (8 weeks of age) were chronically irradiated. Chromosome aberration rate in mouse splenocytes after long-term exposure to low-dose-rate (LDR) gamma-rays was serially determined by conventional Giemsa method. Incidence of dicentrics and centric rings increased almost linearly up to 8000 mGy following irradiation for about 400 days at a LDR of 20 mGy/day. Clear dose-rate effects were observed in the chromosome aberration frequencies between dose rates of 20 mGy/day and 200 Gy/day. Furthermore, the frequencies of complex aberrations increased as accumulated doses increased in LDR irradiation. This trend was also observed for the incidences of micronuclei and trisomies of chromosomes 5, 13 and 18 in splenocytes, detected by micronucleus assay and metaphase fluorescence in situ hybridization (FISH) method, respectively. Incidences of 2-4 micronuclei and trisomy increased in mouse splenocytes after irradiation of 8000 mGy at a LDR of 20 mGy/day. These complex chromosome aberrations and numerical chromosome aberrations seem to be induced indirectly after radiation exposure and thus the results indicate that continuous gamma-ray irradiation for 400 days at LDR of 20 mGy/day induced chromosomal instability in mice. These results are important to evaluate the biological effects of long-term exposure to LDR radiation in humans.     

Low doses of very low-dose-rate low-LET radiation suppress radiation-induced neoplastic transformation in vitro and induce an adaptive response

The purpose of this study was to determine whether adaptation against neoplastic transformation could be induced by exposure to very low-dose-rate low-LET radiation. HeLa x skin fibroblast human hybrid cells were irradiated with approximately 30 kVp photons from an array of (125)I seeds. The initial dose rate was 4 mGy/day. Cell samples were taken at four intervals at various times over a period of 88 days and assayed for neoplastic transformation and the presence of reactive oxygen species (ROS). The dose rate at the end of this treatment period was 1.4 mGy/day. Transformation frequencies and ROS levels were compared to those of parallel unirradiated controls. At the end of 3 months and an accumulated dose of 216 mGy, cells treated with very low-dose-rate radiation were exposed to a high-dose-rate 3-Gy challenge dose of (137)Cs gamma rays, and the effects compared with the effect of 3 Gy on a parallel culture of previously unirradiated cells. Cells exposed to very low-dose-rate radiation exhibited a trend toward a reduction in neoplastic transformation frequency compared to the unirradiated controls. This reduction seemed to diminish with time, indicating that the dose rate, rather than accumulated dose, may be the more important factor in eliciting an adaptive response. This pattern was in general paralleled by a reduction of ROS present in the irradiated cultures compared to controls. The very low-dose-rate-treated cells were less sensitive to the high challenge dose than unirradiated controls, suggesting the induction of an adaptive response. Since there was a suggestion of a dose-rate threshold for induction suppression, a second experiment was run with a fresh batch of cells at an initial dose rate of 1 mGy/day. These cells were allowed to accumulate 40 mGy over 46 days (average dose rate=0.87 mGy/day), and there was no evidence for suppression of transformation frequency compared to parallel unirradiated controls. It is concluded that doses of less than 100 mGy delivered at very low dose rates in the range 1 to 4 mGy/day can induce an adaptive response against neoplastic transformation in vitro. When the dose rate drops below approximately 1 mGy/day, this suppression is apparently lost, suggesting a possible dose-rate-dependent threshold for this process.     

Low-dose studies of bystander cell killing with targeted soft X rays

The Gray Cancer Institute ultrasoft X-ray microprobe was used to quantify the bystander response of individual V79 cells exposed to a focused carbon K-shell (278 eV) X-ray beam. The ultrasoft X-ray microprobe is designed to precisely assess the biological response of individual cells irradiated in vitro with a very fine beam of low-energy photons. Characteristic CK X rays are generated by a focused beam of 10 keV electrons striking a graphite target. Circular diffraction gratings (i.e. zone plates) are then employed to focus the X-ray beam into a spot with a radius of 0.25 microm at the sample position. Using this microbeam technology, the correlation between the irradiated cells and their nonirradiated neighbors can be examined critically. The survival response of V79 cells irradiated with a CK X-ray beam was measured in the 0-2-Gy dose range. The response when all cells were irradiated was compared to that obtained when only a single cell was exposed. The cell survival data exhibit a linear-quadratic response when all cells were targeted (with evidence for hypersensitivity at low doses). When only a single cell was targeted within the population, 10% cell killing was measured. In contrast to the binary bystander behavior reported by many other investigations, the effect detected was initially dependent on dose (<200 mGy) and then reached a plateau (>200 mGy). In the low-dose region (<200 mGy), the response after irradiation of a single cell was not significantly different from that when all cells were exposed to radiation. Damaged cells were distributed uniformly over the area of the dish scanned (approximately 25 mm2). However, critical analysis of the distance of the damaged, unirradiated cells from other damaged cells revealed the presence of clusters of damaged cells produced under bystander conditions.     

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.     

Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts

The dose response for adaption to radiation at low doses was compared in normal human fibroblasts (AG1522) exposed to either (60)Co gamma rays or (3)H beta particles. Cells were grown in culture to confluence and exposed at either 37 degrees C or 0 degrees C to (3)H beta-particle or (60)Co gamma-ray adapting doses ranging from 0.1 mGy to 500 mGy. These cells, and unexposed control cells, were allowed to adapt during a fixed 3-h, 37 degrees C incubation prior to a 4-Gy challenge dose of (60)Co gamma rays. Adaption was assessed by measuring micronucleus frequency in cytokinesis-blocked, binucleate cells. No adaption was detected in cells exposed to (60)Co gamma radiation at 37 degrees C after a dose of 0.1 mGy given at a low dose rate or to 500 mGy given at a high dose rate. However, low-dose-rate exposure (1-3 mGy/min) to any dose between 1 and 500 mGy from either radiation, delivered at either temperature, caused cells to adapt and reduced the micronucleus frequency that resulted from the subsequent 4-Gy exposure. Within this dose range, the magnitude of the reduction was the same, regardless of the dose or radiation type. These results demonstrate that doses as low as (on average) about one track per cell (1 mGy) produce the same maximum adaptive response as do doses that deposit many tracks per cell, and that the two radiations were not different in this regard. Exposure at a temperature where metabolic processes, including DNA repair, were inactive (0 degrees C) did not alter the result, indicating that the adaptive response is not sensitive to changes in the accumulation of DNA damage within this range. The results also show that the RBE for low doses of tritium beta-particle radiation is 1, using adaption as the end point.     

Effect of continuous irradiation with a very low dose of gamma rays on life span and the immune system in SJL mice prone to B-cell lymphoma

Ionizing radiation has been shown to have dose- and dose-rate-dependent carcinogenic effects on the hematopoietic and lymphoreticular systems. We report here that continuous exposure to a low dose of gamma rays influences the course of spontaneous B-cell lymphoma in SJL mice. We studied the biological effects of 10 cGy year(-1) gamma rays on the life span of 560 4-week-old SJL/J female mice and on various parameters of the cell-mediated immune response. Life span was slightly prolonged. The mean survival was 397 days for controls and 417 days for irradiated mice that died with lymphoma (P = 0.34). In lymph nodes and spleen, lower percentages of CD4+ and CD8+ T cells were observed in irradiated mice before 32 weeks. Interestingly, the percentages of CD49+ NK cells were increased in the spleens of irradiated mice at 28 weeks (0.61 +/- 0.08% compared to 0.43 +/- 0.12% in controls, P = 0.01) and at 32 weeks (0.62 +/- 0.24% compared to 0.33 +/- 0.09%, P = 0.02), while NK cell activity remained unchanged in exposed mice. These results provide further support for the absence of harmful effects of a continuous very low dose of radiation on life span and incidence of lymphoma in SJL mice.     

Effects of carbon-ion radiation on the postnatal development of mice and on the yield of white spots in the mid-ventrum and tail tips

Pregnant female C57BL/10JHir mice were irradiated whole-body at 9 days of gestation with a single acute dose of carbon-ion radiation. The average linear energy transfer (LET) of the carbon ions was 50 keV/microm within a spread-out Bragg peak (SOBP). The effects were studied by scoring changes in the postnatal development of the mice as well as in the pigmentation of the cutaneous coats and tail tips of their offspring 22 days after birth. The percentage of live births was reduced in mice exposed to carbon ions at doses greater than 0.5 Gy. The survival to day 22 was also reduced in mice exposed to carbon ions at doses greater than 0.75 Gy. Moreover, the body weight at day 22 was reduced in mice exposed to carbon ions at doses greater than 0.1 Gy. A comparison of the survival to day 22 after exposure to carbon ions with our previous results for 60Co gamma rays indicated that carbon ions were twice as effective as gamma rays. White spots were found in the mid-ventrum as well as in the tail tips of offspring exposed to carbon ions in utero. The frequency and the size of the white spots in the mid-ventrum and in the tail tips increased as the dose increased. Carbon ions appear to be slightly more effective than the gamma rays used in our previous study. In the ventral white spots, no melanocytes were observed in the epidermis, dermis and hair follicles. These results indicate that prenatal exposure to carbon ions has a greater effect on the postnatal development and survival of mice than does exposure to gamma rays, and that the relative biological effectiveness is greater than that for effects on melanocyte development.     

Ovarian tumors not induced by irradiation and gonadotropins in hypogonadal (hpg) mice

Hypogonadal (hpg/hpg) mice deficient in gonadotropin-releasing hormone were used to study gonadotropin involvement in ovarian tumorigenesis following gamma irradiation. In the first experiment, 30-day-old hpg/hpg and normal (+/-) littermate mice were irradiated. The same mice were killed 10-15 mo later, and autopsies were performed. Ovaries of irradiated hpg/hpg mice were devoid of oocytes, but retained follicular structures. Neither mesothelial adenomas nor granulosa cell tumors were observed. In contrast, all irradiated +/- mice formed mesothelial adenomas or granulosa cell tumors, or both. Therefore, oocyte death in the absence of gonadotropins did not initiate ovarian tumorigenesis. In the second experiment, irradiated and nonirradiated hpg/hpg and +/- mice were injected 3 times weekly for 180 days with either low or high doses of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) in combination. Irradiation reduced ovarian mass and markedly reduced ovarian weight increase in response to exogenous gonadotropins. Follicular dissolution and stromal cell hypertrophy were observed in saline-treated and gonadotropin-treated +/- mice that had been irradiated, and in hpg/hpg mice given the high gonadotropin dose. Mesothelial adenoma formation was observed in 100% of saline-treated, 14% of low dose-treated, and 11% of high dose-treated +/- mice. No mesothelial adenomas developed in any hpg/hpg or nonirradiated +/- mice, despite gonadotropin-induced stromal luteinization. These results indicate that, in the absence of gonadotropins, irradiation leads only to the loss of oocytes. The presence of gonadotropins was necessary to promote follicular dissolution and stromal luteinization, but was insufficient to stimulate mesothelial adenoma formation.     

Administration of recombinant human IL11 after supralethal radiation exposure promotes survival in mice: interactive effect with thrombopoietin

In the present study, we evaluated the therapeutic potential of recombinant human IL11 in lethally irradiated C57BL6/J mice exposed to gamma rays. IL11 administered for 5 consecutive days beginning 2 h after total-body irradiation with 8 or 9 Gy 60Co gamma rays resulted in a significant increase in 30-day survival. When IL11 was administered, only a slight improvement in the hematopoietic status (both blood cell counts and progenitor cells) was observed after an 8-Gy exposure, and no improvement in hematopoietic reconstitution was observed after 9 Gy total-body irradiation. The enhancement of fibrinogen in the plasma of irradiated animals suggested the importance of infections in the death of animals. IL11 was able to limit the increase in fibrinogen levels. However, prevention of bacterial infections by antibiotic treatment, although it delayed death, was ineffective in promoting survival either in placebo-treated and IL11-treated mice. IL11 was administered along with thrombopoietin (TPO) or bone marrow transplantation to limit the hematopoietic syndrome, in addition to antibiotic treatment. When IL11 was combined with TPO, a potent stimulator of hematopoiesis, the survival of animals which had been irradiated with 10 Gy 137Cs gamma rays was increased significantly compared to those treated with IL11 or TPO alone. Furthermore, an interactive effect of TPO and IL11 on hematopoietic reconstitution was observed. Similarly, IL11 in combination with bone marrow transplantation enhanced survival after 15 Gy 137Cs gamma rays. These data suggest that the effect of IL11 on the hematopoietic system is only moderate when it is used alone in supralethally irradiated mice but that the effect is improved in the presence of a hematopoietic growth factor or bone marrow transplantation.     

X radiation up-regulates the occurrence and the multiplicity of invasive carcinomas in the intestinal tract of Apc(min/+) mice

X rays are well known to cause genetic damage and to induce many types of carcinomas in humans. The Apc(min/+) mouse, an animal model for human familial adenomatous polyposis (FAP), contains a truncating mutation in the APC gene and spontaneously develops intestinal adenomas. To elucidate the role of X rays in the development of intestinal tumors, we examined the promotion of carcinogenesis in X-irradiated Apc(min/+) mice. Forty out of 77 (52%) X-irradiated Apc(min/+) mice developed adenocarcinomas that invaded the proprial muscle layer of the small intestine; 24 of 44 (55%) were in males, and 16 of 33 (49%) were in females. In contrast, invasive carcinomas were detected in the small intestines of only 13 of 64 (20%) nonirradiated Apc(min/+) mice; nine of 32 (28%) were in males and four of 32 (13%) were in females. These differences between X-irradiated and nonirradiated Apc(min/+) mice in the occurrence of invasive intestinal carcinomas were statistically significant (P < 0.05 for males, P < 0.005 for females). In wild-type mice, invasive carcinomas were not detected in either X-irradiated or nonirradiated mice. Apc(min/+) mice had many polyps in the large intestine with or without X irradiation; there was no difference in the number of polyps between the two groups. Also, invasive carcinomas were not detected in the large intestine with or without irradiation. The occurrence of mammary tumors, which was observed in Apc(min/+) mice, was found to be increased in irradiated Apc(min/+) mice (P < 0.01). Apc(min/+) mice had many polyps in the small and large intestines with or without X irradiation. X-irradiated Apc(min/+) mice had highly invasive carcinomas in the small intestine with multiplicities associated with invasiveness. Our results suggest that X radiation may promote the invasive activity of intestinal tumors in Apc(min/+) mice.     

Effects of 28Si Ions, 56Fe Ions,and Protons on the Induction of Murine Acute Myeloid Leukemia and Hepatocellular Carcinoma

Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n ²⁸Si or 600 MeV/n ⁵⁶Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n ²⁸Si ions, 600 MeV/n ⁵⁶Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with ¹³⁷Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that ²⁸Si or ⁵⁶Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, ²⁸Si or ⁵⁶Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the ²⁸Si and ⁵⁶Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members.     

Radiation-induced micrencephaly in guinea pigs.

The effect of X rays on brain weight of guinea pig pups at birth was studied in 21-day-old embryos exposed in utero to doses of 75 and 100 mGy. When compared to controls and when corrected for body weight, gestation time, litter size, sex, and examiner differences, the brains of irradiated pups weighed approximately 46 mg less than those of controls (P < 0.001) for the 75-mGy group and about 55 mg less for the 100-mGy group. Brains of females weighed 51 mg less than those of males of the same body weight. Dam weight and caging conditions had no observed effect on brain weight.     

The effects of a fractionated gamma irradiation on life shortening and disease incidence in BALB/c mice

BALB/c male mice (12 weeks old) were exposed to a single or fractionated exposure of 137Cs gamma rays. The fractionated dose was split into 10 equal doses delivered at an interval of 1 day. The causes and possible causes of spontaneous death were ascertained by autopsy and histological examination, and the data were treated by competing risk analysis. Life shortening followed a linear dose dependency and was about the same for fractionated (38.1 +/- 3.1 days/Gy) as for single (46.2 +/- 4.3 days/Gy) exposure. Death from tumor disease was enhanced and that from nonstochastic lung and kidney diseases was reduced after fractionated compared to single exposure.     

Activation of antioxidative enzymes induced by low-dose-rate whole-body gamma irradiation: adaptive response in terms of initial DNA damage

An adaptive response induced by long-term low-dose-rate irradiation in mice was evaluated in terms of the amount of DNA damage in the spleen analyzed by a comet assay. C57BL/ 6N female mice were irradiated with 0.5 Gy of (137)Cs gamma rays at 1.2 mGy/h; thereafter, a challenge dose (0.4, 0.8 or 1.6 Gy) at a high dose rate was given. Less DNA damage was observed in the spleen cells of preirradiated mice than in those of mice that received the challenge dose only; an adaptive response in terms of DNA damage was induced by long-term low-dose-rate irradiation in mice. The gene expression of catalase and Mn-SOD was significantly increased in the spleen after 23 days of the low-dose-rate radiation (0.5 Gy). In addition, the enzymatic activity of catalase corresponded to the gene expression level; the increase in the activity was observed at day 23 (0.5 Gy). These results suggested that an enhancement of the antioxidative capacities played an important role in the reduction of initial DNA damage by low-dose-rate radiation.     

The reproductive capacity of male mice protected against the superlethal action of gamma radiation by the administration of a mixture of Archangelica officinalis and Ledum palustre extracts]

Thirty-day old albino mongrel male mice were exposed to gamma radiation (LD90/30) after preventive single injection of a mixture of extracts from Archangelica officinalis and Ledum palustre. One month after irradiation, the survivors were mated to nonirradiated females. Healthy offspring were obtained from 11 out 12 experimental males. The number of mouse pups was 10.2 +/- 0.6 and 7.4 +/- 0.7 in the experimental and nonirradiated groups respectively. The number of both sexes in the posterity of nonirradiated parents was equal, whereas in offspring of experimental groups, the number of female pups was 2.3 times larger than that of males. The experimental posterity was found to be resistant to supralethal radiation doses.