Development of radiation injuries and recovery processes in the hematopoietic tissue of mice after repeated exposure to fast neutrons and gamma-irradiation

A study was made of the number of CFUs and karyocytes in thigh bone and the concentration of functional cells in the peripheral blood of mice subjected to fast neutron- and gamma-irradiation four times at a 60-day interval (210 cGy per fraction). The regenerating potential decreased and the half-recovery time T1/2 increased in the haemopoietic tissue as the number of fractions and total absorbed dose increased. The dependence of T1/2 on the equivalent radiation dose was as follows: T1/2 = T1/2(0)e0.0009D.     

Characteristics of chromatin breakdown in the rat thymus after exposure to fast neutrons and gamma rays

A comparative study was made of the radiobiological aftereffects of the action of fast neutrons and gamma-rays on lymphoid tissues of rat thymus with a reference to a biochemical criterion of the interphase death of lymphocytes, i.e. the formation of polydeoxynucleotides (PDN). It was shown that the increase in the chromatin degradation was a function of dose of neutron- and gamma-radiation (up to 4 Gy). The dynamics of the PDN formation was similar with both types of radiation, but 4-6 h after neutron irradiation chromatin degradation was higher more pronounced. The RBE of neutrons varied from 3 to 2 with a radiation dose varying from 0.25 to 4 Gy.     

Mitigation of lung injury after accidental exposure to radiation

There is a serious need to develop effective mitigators against accidental radiation exposures. In radiation accidents, many people may receive nonuniform whole-body or partial-body irradiation. The lung is one of the more radiosensitive organs, demonstrating pneumonitis and fibrosis that are believed to develop at least partially because of radiation-induced chronic inflammation. Here we addressed the crucial questions of how damage to the lung can be mitigated and whether the response is affected by irradiation to the rest of the body. We examined the widely used dietary supplement genistein given at two dietary levels (750 or 3750 mg/kg) to Fischer rats irradiated with 12 Gy to the lung or 8 Gy to the lung + 4 Gy to the whole body excluding the head and tail (whole torso). We found that genistein had promising mitigating effects on oxidative damage, pneumonitis and fibrosis even at late times (36 weeks) when drug treatment was initiated 1 week after irradiation and stopped at 28 weeks postirradiation. The higher dose of genistein showed no greater beneficial effect. Combined lung and whole-torso irradiation caused more lung-related severe morbidity resulting in euthanasia of the animals than lung irradiation alone.     

Patterns of postradiation recovery of the spermatogenic epithelium in rodents and man

On the basis of the data reported in the literature a model is proposed describing the kinetics of the post-irradiation recovery of the main spermatogenous epithelium populations. In studying the spermatogenous epithelium structure of rodents and comparing the experimental and theoretical curves the parameters necessary for the kinetics estimations have been quantitated and their specific variations analysed. From these the parameters have been obtained and the kinetic curves shaped with a reference to human spermatogenous epithelium.     

Induction of minisatellite mutations in the mouse germline by low-dose chronic exposure to gamma-radiation and fission neutrons

Germline mutation induction at mouse minisatellite loci by paternal low-dose (0.125-1 Gy) exposure to chronic (1.66 x 10(-4) Gy min(-1)) low-linear energy transfer (low-LET) gamma-irradiation and high-LET fission neutrons (0.003 Gy min(-1)) was studied at pre-meiotic stages of spermatogenesis. Both types of radiation produced linear dose-response curves for mutation of the paternal allele. In contrast to previous results using higher doses, the pattern of induction of minisatellite mutation after chronic gamma-irradiation was similar to acute (0.5 Gy min(-1)) exposure to X-rays, indicating that the elevated mutation rate was independent of the ability of the cell to repair damage induced immediately or over a period of up to 100 h. Chronic exposure to fission neutrons was more effective than acute or chronic low-LET exposure (relative biological effectiveness, RBE=3.36). The data also provide strong support for the previous conclusion that increases in minisatellite mutation rate are not caused by radiation-induced DNA damage at minisatellite loci themselves, but rather from damage induced by ionising radiation elsewhere in the genome/cell.     

Preimplantation growth delay and micronucleus formation after in vivo exposure of mouse zygotes to fast neutrons.

Mouse zygotes were irradiated with fast neutrons (0.06 to 1.00 Gy) 1 h after conception and examined at various intervals (24 to 100 h after conception) for embryonic development and micronucleus formation. The frequency of micronuclei per cell increased linearly with dose in 2-cell embryos observed at 24 h after conception and in 4-cell and 8-cell embryos at 48 h after conception. Compared with X rays, the relative biological effectiveness of neutrons for the induction of micronuclei per embryo was 2.5 at 24 h after conception and 3.5 at 48 h after conception. Neutron-induced micronucleus formation was accompanied by morphological growth delay and a significant decrease in the number of cells in the embryos. An inverse relationship was found between the number of cells in embryos and the number of micronuclei when observed at 48 h after conception following irradiation with 0.12 to 1.00 Gy and at 78 h after conception following exposure to 0.50 Gy. The effect of neutron irradiation on embryonic development was likely to be mediated by cell death, as suggested by a significantly increased dead cell index in blastocysts following irradiation of zygotes.     

Locomotion and its recovery after spinal injury

Recent advances indicate not only that the spinal cord has great potential for locomotor recovery after lesion but also that locomotor training can optimise this recovery through some form of 'learning'. Improvement of residual function can also be achieved through the use of various drugs and treatments such as spinal grafts. In spinal-cord-injured humans, a number of recent studies have allowed an objective quantification of the improvement of locomotion through various forms of training and stimulation.     

Cytogenetic effects in follicular epithelium of thyroid gland under prolonged exposure to gamma-radiation at low-doses

The forming processes of micronucleated follicular thyrocytes in thyroid gland of mature Wistar rats under exposure to the prolonged low-intensity gamma-radiation with 5 and 50 cGy (dose rates: 25, 400 microGy/h; duration: 55, 80 days) were investigated. The chronic exposure to low-intensity gamma-radiation in both doses invokes the frequency of micronuclated thyrocytes three times higher in comparison with control animals. As a result of the small-sized micronuclei formation prevalence in irradiated group, the average size of micronuclei was 1.4-2 times lower than control values. This phenomenon can be reproduced in model experiments with hemithyroidectomized animals exposured to acute gamma-radiation with 2-4 Gy. The obtained results show high sensitivity of micronucleus test to the early determination of radiation-induced genetic damages in follicular epithelium of thyroid gland.     

The assessment of recovery of the intestine after acute radiation injury

Several aspects of intestinal function and morphology are affected by acute radiation damage, including changes in the activity of proliferative cells in the crypts, immune cell populations, and the transport of various substrates. This study was designed to compare the time course of the recovery of intestinal proliferation, transport, and leukocyte population following radiation injury. Rats received a single dose of 6 Gy to the abdomen from a 137Cs source and were studied 3, 7, and 14 days later. No changes in the passive uptake of L-glucose or D-leucine were observed in the jejunum. Active transport of D-glucose and maximal water uptake were reduced at 3 days but had returned to normal by 7 days, whereas L-leucine uptake required more than 7 days to return to control levels. Mucosal permeability, assessed by an in vivo potential difference technique, remained increased 7 days after irradiation. Ornithine decarboxylase, an indicator of DNA synthetic activity, was elevated following radiation treatment and remained so even after 14 days. By comparison, myeloperoxidase activity, used as a quantitative monitor of granulocyte numbers, was still reduced after 7 days. These data indicate that while certain parameters of gut function may return to normal soon after radiation injury, the recovery of other factors is more prolonged. Thus the return of transport function to normal values post irradiation may be viewed as an adaptive change rather than simply the recovery of the tissue.     

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.     

Quantitative dependence of sheep death on dose and dose rate of external gamma-radiation

The results of experimental studies of sheep death at different dose rates of gamma-radiation have been analyzed. Parameters of a mathematical dependence of animal death on the exposure dose and dose rate have been identified. The evaluation of adequacy of the derived equation has demonstrated that the established relationship correctly describes the experimental data in studied dose rate range.     

Qantitative description of mammalian cell recovery after combined exposure to ionizing radiation with chemical agents

The parameters of recovery of mammalian cells after exposure to ionizing radiation combined with chemical agents were calculated based on a mathematical model of post-radiation recovery. The data presented, in contrast to the previously published results, indicate that the inhibition of the recovery may be due either to the damage or disruption of the process of recovery or the increase in the part of irreversible damages from which the cells are incapable to recover; or both of these processes can be realized simultaneously. It is concluded that the combination of ionizing radiation with chemical agents that inhibit the recovery processes through the formation of irreversible damages or affect the probability of recovery can be a perspective way in terms of finding the most effective means to increase radiosensitivity.