Myeloid leukemia in male RFM mice following irradiation with fission spectrum neutrons or gamma rays

The induction of myeloid leukemia following fission neutron irradiation was examined over the 0-80 rad dose range. Over this dose range the dose response could be described by the linear regression equation: y = 0.94 + 0.18X. A comparison of these data with data obtained following gamma irradiation from this study and a previous study indicated that the relative biological effectiveness for myeloid leukemia induction was 2.8. These results appear to be compatible with those reported by other investigators.     

Analysis of primate head irradiation with 55-MeV protons.

The distribution of the dose to the head of a primate phantom due to 55-MeV proton irradiation was calculated using a clinical radiotherapy treatment planning system, with anatomic definition through computerized tomography scans. Dose profiles, isodose distributions, and differential and integral dose-volume histograms are used to describe the probable proton dose to the brain of rhesus monkeys, irradiated over two decades ago, in which brain tumors have now developed. The dose analysis shows that 59% of the brain received a dose in excess of the reference surface dose, and that portions of the brain received doses greater than 300% of the reference surface dose. The regions of high dose are illustrated in isodose distributions. This information may be useful in evaluating potential tumor induction following radiation exposure.     

Short- and long-term effects of whole-body irradiation with fission neutrons or X rays on the thymus in CBA mice

Young adult (6 weeks old) female CBA mice were exposed to whole-body irradiation with either 2.5-Gy fast fission neutrons of 1 MeV mean energy or 6.0-Gy 300 kVp X rays at centerline dose rates of 0.1 and 0.3 Gy/min, respectively. The weight of spleen and animal and the weight, cellularity, and histological structure of the thymus were studied at different times after irradiation. Thymic recovery after whole-body irradiation showed a biphasic pattern with minima at 5 and 21 days after irradiation and peaks of regeneration at Days 14 and 42 after X irradiation or at Days 14 and 70 after neutron irradiation. After the second phase of recovery, a marked decrease in relative thymus weight and cellularity was observed, which lasted up to at least 250 days after irradiation. Splenic recovery showed a monophasic pattern with an overshoot on Day 21 after irradiation. After neutron irradiation a late decrease in relative spleen and animal weight was observed. The observed late effects on thymus and spleen weight and thymus cellularity are discussed in terms of a persistent defect in the bone marrow.     

The remote effects of radiation after hypofractionated irradiation with protons of Ehrlich ascites carcinoma in mice

This work focuses on the study of remote effects (duration of remission, recurrence rate, and average lifespan) in mice with Ehrlich ascites carcinoma exposed to oligofractionated irradiation with a pencil scanning beam of protons depending on the volume of the tissue being irradiated and the interval between dose fractions. The results show higher antitumor efficacy and a considerable increase in the average life span of mice after hypofractionated irradiation with a pencil scanning beam of protons at a total dose of 60 Gy of the gross tumor volume compared with the planning target volume.     

Early cell repair of the lung and the intestine in mice, after irradiation by fast neutrons and gamma rays

Lung tolerance is assessed from LD50 at 180 days after thoracic irradiation, in mice, with d(50) + Be neutrons and 60Co gamma rays. Early intestinal tolerance is assessed from LD50 at 7 days after abdominal irradiation. Additional dose (Dr) to reach LD50 when a single dose Ds is split into 2 equal fractions Di separated by different time intervals "i", is determined (Dr = 2Di - Ds), Dr is larger after gamma than after neutron irradiation, for lung and intestine. After thoracic irradiation with gamma rays, Dr reaches 3.36, 4.38, 5.12 and 5.37 Gy for "i" = 2, 6, 12 and 24 hours respectively; after neutron irradiation, Dr reaches 0.66, 0.9, 1.29, 1.95 and 1.50 Gy for "i" = 1, 2, 4, 12 and 24 hours. Dr is smaller for intestine; after abdominal irradiation with gamma rays, it reaches 1.99, 2.59, 2.74, 3.11, 3.34, 4.44 and 4.56 Gy for "i" = 1, 2, 3.5, 8, 12, 18 and 24 hours; after neutron irradiation, it reaches 0.13, 0.45, 0.42 and 1.33 Gy for "i" = 1.5, 3.5, 5.5 and 24 hours. After gamma irradiation, early repair is complete after 3.5 hours for intestine and needs 12 hours for lung.     

Gene expression profiles in mouse liver after long-term low-dose-rate irradiation with gamma rays

Changes in gene expression profiles in mouse liver induced by long-term low-dose-rate γ irradiation were examined by microarray analysis. Three groups of male C57BL/6J mice were exposed to whole-body radiation at dose rates of 17-20 mGy/day, 0.86-1.0 mGy/day or 0.042-0.050 mGy/day for 401-485 days with cumulative doses of approximately 8 Gy, 0.4 Gy or 0.02 Gy, respectively. The gene expression levels in the livers of six animals from each exposure group were compared individually with that of pooled sham-irradiated animals. Some genes revealed a large variation in expression levels among individuals within each group, and the number of genes showing common changes in individuals from each group was limited: 20 and 11 genes showed more than 1.5-fold modulation with 17-20 mGy/day and 0.86-1.0 mGy/day, respectively. Three genes showed more than 1.5-fold modulation even at the lowest dose-rate of 0.04-0.05 mGy/day. Most of these genes were down-regulated. RT-PCR analysis confirmed the expression profiles of the majority of these genes. The results indicate that a few genes are modulated in response to very low-dose-rate irradiation. The functional analysis suggests that these genes may influence many processes, including obesity and tumorigenesis.     

Prepulse inhibition of acoustic startle in aromatase knock-out mice: effects of age and gender

Estrogen has been suggested to play a neuromodulatory and neuroprotective role on the brain dopamine system. We used aromatase knockout (ArKO) mice that lack a functional aromatase enzyme and are unable to convert testosterone into estrogen, and assessed prepulse inhibition of acoustic startle, locomotor hyperactivity to amphetamine treatment and rotarod performance. Mice were tested at either 1 month, 4–5 months or 12–18 months of age. In male, but not female ArKO mice, there was an age-related reduction of prepulse inhibition. The 12–18 months old male ArKO mice also showed significantly greater amphetamine-induced hyperactivity. Mice heterozygous for the mutation showed no deficits or were in-between wildtype mice and ArKO mice. We postulate that these data indicate a neuroprotective role of estrogen, particularly in male mice, on ageing of brain mechanisms involved in prepulse inhibition and locomotor activity regulation. It is likely that these brain mechanisms are or include dopaminergic activity.     

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.     

Early changes in the lymphocyte surface membrane of rats after whole-body irradiation with neutrons and gamma rays

Biochemical changes in lymphocyte plasma membranes were studied 3 and 18 h after whole-body exposure of rats to neutrons and gamma-rays at doses from 2 to 6 Gy. It was shown that fast neutrons, with an average energy of 1.5-2.0 MeV, increased the rate of lipid peroxidation more markedly than gamma-rays did. In addition, there was an increase in the number of free aminogroups on the thymocyte surface. Dose- and time-dependent parameters of changes in the aminogroup content on the cellular surface were quantitatively different after the effect of radiation with different LET.     

Effects of small doses of gamma rays on gestation in mice]

Female mice were irradiated with 10 rads of 60Co gamma ray, 7 hours after mating. This low dose induces a decrease in implantation number, and alive foetus number and is followed by a lower number of corpora lutea. These results to seem to show an effect of gamma irradiation on ovary and embryonic development.     

Changes in DNA flexibility after irradiation with gamma rays and neutrons studied with the perturbed angular correlation method

Neutron and gamma irradiation of buffered solutions of calf thymus DNA resulted in changes in the dynamics of the macromolecule. In the low-dose region (0.8-10 cGy of 239Pu-Be neutrons and 0.34-3 Gy of 60Co gamma rays), the flexibility of DNA decreased as indicated by slower rotation of the molecules. Neutrons appeared to be approximately 35 times more effective than 60Co gamma rays. The rotational correlation time, tau C, was measured using the perturbed angular correlation (PAC) method. Its variation appears to follow a linear-exponential behavior. An attempt is made to formulate this behavior as a function of the energy deposited on the macromolecule (radiation dose), the average threshold energy (dose) required to form new lesions, and the available population of intact DNA sites.     

Long-term pathomorphologic changes in the neurons of the rat brain following irradiation with carbon ions and gamma rays

Quantitative and qualitative morphological changes in neurons and glia of rat brain were studied one month after exposure to accelerated carbon ions 4 GeV/nucleon (LET-76 MeV cm2.r-1) and gamma-radiation (137Cs, 0.25 to 4.0 Gy). There were certain peculiarities in the structural changes induced by the effect of carbon ions that possessed a higher relative biological effectiveness.     

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.