Low dose of the gamma acute radiation syndrome (1.5 Gy) does not significantly alter either cognitive behavior or dopaminergic and serotoninergic metabolism.

The aim of this study was to evaluate the early-delayed effects of a low dose of the gamma acute radiation syndrome (1.5 Gy) on memory and on dopaminergic and serotoninergic metabolism in Swiss albino CD1 mice, of various ages (6, 10 and 20 weeks). At different times after irradiation (from 24 hr to three months), the mice were trained in a single-trial passive avoidance task and tested for retention either 24 hr or 5 days later. Their performance was compared to that of mice that were sham-irradiated. At the end of the behavioral test (days 3, 9, 30 and 93), the concentrations of dopamine (DA) and serotonin (5HT) and their metabolites were determined in hippocampus, anterior cortex and striatum of mice irradiated at the age of six weeks. No significant behavioral effect was observed whichever the age of the animals or the delay of observation. On the contrary at the moderate dose of 4.5 Gy we observed a significant memory deficit 9 days after the exposure. Considering the neurochemical study, in the striatum or in the frontal cortex, no significant modification was observed whichever the delay or the molecule. In the hippocampus slight modifications were noted: an increase (+144%, p = 0.002) in DA level on day 3 after exposure, and a decrease (-27%, p = 0.028) of 5HT level on day 30 post-irradiation. These modifications were only transient and not associated to modifications of the catabolites. This study demonstrates that total-body exposure to gamma radiation at low dose seems to induce only slight effects on the central nervous system.     

Dominant lethal effect of 60Co gamma radiation in Biomphalaria glabrata (SAY, 1818)

The dominant lethal effects of gamma radiation of 60Co in the snail Biomphalaria glabrata were studied. Three groups of 13 wild-type snails were irradiated with single doses of 2.5; 10 and 20 Gy. Crossings were carried out at intervals of 7, 17, 23, 30 and 36 days after irradiation. The dominant lethal effect was observed only at the first crossing occurring 7 days after irradiation with 2.5 Gy. With 10 and 20 Gy, the induction of lethal mutations was detected at 7, 17 and 23 days after irradiation; a dose-response effect was observed. The effect was stronger 7 days after irradiation, decreasing in the succeeding crossings up to 30 days. Cell-killing effects on germ cells were detected in the crossings at 23 days and 30 days after irradiation with 20 Gy. After 36 days, frequencies of malformations resumed background levels; crossing rates partially recovered. These results show that gamma radiation affected all the stages of spermatogenesis. Germ cells at later phases were more sensitive to the mutagenic effect of radiation and the cell killing effects were observed on the youngest cells. This response was similar to the highly homogeneous pattern observed in widely different species and allowed us to estimate some parameters of spermatogenesis in B. glabrata.     

Effect of Pseudomonas contamination or antibiotic decontamination of the GI tract on acute radiation lethality after neutron or gamma irradiation

The influence of antibiotic decontamination of Pseudomonas contamination of the GI tract prior to whole-body neutron or gamma irradiation was studied. It was observed that for fission neutron doses greater than 5.5 Gy, cyclotron-produced neutron doses greater than 6.7 Gy, and 137Cs gamma-ray doses greater than 14.4 Gy, the median survival time of untreated rats was relatively constant at 4.2 to 4.5 days, indicating death was due to intestinal injury. Within the dose range of 3.5 to 5.5 Gy of fission neutrons, 4.9 to 6.7 Gy of cyclotron-produced neutrons, and 9.6 to 14.4 Gy of gamma rays, median survival time of these animals was inversely related to dose and varied from 12 to 4.6 days. This change in survival time with dose reflects a transition in the mechanisms of acute radiation death from pure hematopoietic, to a combination of intestinal and hematopoietic, to pure intestinal death. Decontamination of the GI tract with antibiotics prior to irradiation increased median survival time 1 to 5 days in this transitional dose range. Contamination of the intestinal flora with Pseudomonas aeruginosa prior to irradiation reduced median survival time 1 to 5 days in the same radiation dose range. Pseudomonas-contaminated animals irradiated within this transitional dose range had maximum concentrations of total bacteria and Pseudomonas in their livers at the time of death. However, liver bacteria concentration was usually higher in gamma-irradiated animals, due to a smaller contribution of hematopoietic injury in neutron-irradiated animals. The effects of both decontamination of the GI tract and Pseudomonas contamination of the GI tract were negligible in the range of doses in which median survival time was dose independent, i.e., in the pure "intestinal death" dose range. Finally, despite the marked changes in survival time produced by decontamination or Pseudomonas contamination in the "transitional dose range," these treatments had little effect on ultimate survival after irradiation as measured by the LD50/5 day and the LD50/30 day end points. The implications of these results with respect to treatment of acute radiation injury after whole-body irradiation are discussed.     

Thymus repair compared with hemopoiesis repair in spleen after protracted irradiation

Mature female mice of ICR strain were irradiated from the source 60Co with a daily dose rate of 5 Gy till total accumulated dose of 10 Gy for 2 days. Animals were examined in various intervals within 42 days after irradiation. The results obtained that protracted irradiation will induce a massive injury to hemopoiesis. The first repair processes occurred in thymus and were characterized by two phases. The first repair wave peaked about the day 10 and the second about the day 30 after irradiation. The repair processes observed in the red pulp of the spleen reached their highest intensity approximately between the days 14-16 after irradiation.     

Hyperresponsiveness of residual thyroid lobe of hemithyroidectomised rat to thyrotropin

The effects of hemithyroidectomy and thyrotropin administration on rat thyroid gland function were studied in adult male rats. Immediately after surgery or sham operation rats were treated daily with 0.12 IU of bovine thyrotropin (TSH) for 3 or 5 days. In control rats TSH dose applied resulted in an increase in serum T4 level at day 5 of experiment. Serum thyroxine concentration markedly decreased in sham operated and hemithyroidectomised rats, an effect observed at days 3 and 5 of experiment. TSH administration had no effect on serum T4 concentration in sham operated rats while in hemithyroidectomised animals such a treatment resulted in a marked increase in serum T4 level, a phenomenon observed in both time intervals studied. The reasons for hemithyroidectomy-induced hyperresponsiveness of rat thyroid residual lobe to thyrotropin are unknown.     

Specific effect of attenuated strain of Francisella tularensis on the development of radiation induced lesions in experimental animals and effictiveness of antibacterial therapy for lesions induced by radiation combined with virulemt strain of the bacteria

For study of the effects of whole-body gamma-radiation (1 and 4 Gy) on the response of the body to administration of vaccines and virulent strains of tularemia 206 outbred white mice were used. The results of the study shown that the administration of attenuated bacterial cells in 5 days after exposure to radiation (1 and 4 Gy) caused more severe post-radiation effects and the increase in the number of died animals. The severity of the disease was less if mice were vaccinated in 26 days after irradiation (4 Gy). The treatment of tularemia in irradiated mice twith Riphampicin (daily peroral administration, 5 mg/mouse, duration of treatment--7 days) administered in 4 hours after infection was effective and caused high survival of affected mice. The results show effectiveness of the riphampicin treatment of tularemia in the animals exposed to sublethal dose of radiation.     

Effect of gamma-irradiation on some biological activities of the larval stage of the khapra beetle, Trogoderma granarium Everts (Col., Dermestidae)

Abstract: The present study was carried out on the larval stage of the khapra beetle, Trogoderma granarium Everts to determine some biological effects of gamma irradiation at levels between 20 to 100 Gy on various aspects of larval behaviour such as number of moults, developmental time, larval growth, starvation and mortality, pupal promptness in addition to larval density. Larval mortality of 92.5% was obtained by treating with 80 Gy and no larva lived after an exposure of 100 Gy or more. With increasing doses from 40 Gy or more, half of the male and female larvae had six moults as compared with three to five moults in the control. The larval duration increased gradually and reached 40.2 days for male larvae and 44.2 days for female ones at a dose of 80 Gy as compared to 25.2 and 28.3 days, respectively, for the control. Larvae irradiated with 60 and 80 Gy did not feed as much as those irradiated at 20 and 40 Gy or the control group. A negative correlation was observed between increasing dosage levels and reduction in the fresh body weight of larvae. The highest larval starvation of 79.8% occurred at 80 Gy and the least (23.8%) at 20 Gy. Pupal promptness seems to be lower at the higher radiation doses. With 40, 60 and 80 Gy, approximately 69.5, 19.6 and 7.5%, respectively, of the larvae succeeded in pupation compared with 94.6% in the control. High doses of radiation seem to enhance the production of males. An increase of larval density enhances the effects of radiation doses to retard the developmental time, to increase larval and pupal mortality and to reduce adult eclosion.     

Circadian rhythms in the incidence of apoptotic cells and number of clonogenic cells in intestinal crypts after radiation using normal and reversed light conditions

Variations in the number of radiation-induced morphologically dead or dying cells (apoptotic cells) in the crypts in the small intestine of the mouse have been studied throughout a 24-h period under a normal light regimen (light on, 07.00-19.00 h; light off, 19.00-07.00 h). A clear circadian rhythm was displayed in the apoptotic incidence 3 or 6 h after irradiation for each gamma-ray dose studied (range 0.14-9.0 Gy). The most prominent circadian rhythm was obtained after 0.5 Gy. The peak time of day for inducing apoptosis was 06.00-09.00 h, and the trough occurred at 18.00-21.00 h. Some mice were also transferred to a room with the light cycle reversed, and were irradiated on different days after the transfer. The apoptosis induced by 0.5 Gy or 9.0 Gy, or the number of surviving crypts (microcolonies) after 11.0 Gy or 13.0 Gy was examined. The transition point for reversal (i.e. the switch time from the normal-light pattern to the reversed-light pattern) of the circadian rhythm in apoptosis (after 0.5 Gy) occurred 7 days after the transfer and the rhythm was reversed by 14 days. The rhythm for crypt survival (i.e. for clonogenic cell radiosensitivity) was disturbed on 1 day and the transition point for reversal occurred 3 days after the transfer. The rhythm became reversed by 7 days. These observations are discussed in relation to the identity of clonogenic cells, (functional) stem cells, proliferating transit cells and the cells sensitive to small doses of radiation (i.e. hypersensitive cells) in the crypt.     

Immune response in mice exposed to low-dose X-rays

The present paper was conducted to evaluate the immunological effect of low dose gamma-irradiation. The splenocytes of mice (C57BL/6N), 24 hours after the irradiation from 0.087 to 0.87 Gy, were incubated with mitogens of T or B lymphocytes, allo-antigen (splenic cells of BALB/c mice) (MLC) or sheep red blood cells (SRBC) 10 days after immunization with the SRBC in vivo, and then their incorporations of 3H-thymidine were measured. On the other hand, this incorporation in the presence of T-cell growth factor (IL-2) in vitro and a drug of AET in vivo was investigated to examine their radioprotective effects. The dose-response relation, i.e. decrease of 3H-thymidine incorporation in function of increase of the irradiation dose, was demonstrated in these immunological examinations except at the dose of 0.087 Gy. More, their incorporation was remarkably promoted by the administration of the T cell growth factor and the drug, therefore, these substances represent the radioprotective effect.     

Inhibition of repair of radiation-induced DNA double-strand breaks by nickel and arsenite

The effect of arsenite or nickel on the repair of DNA double-strand breaks (DSBs) was studied in gamma-irradiated Chinese hamster ovary cells using pulsed-field gel electrophoresis. After treatment with nickel chloride or arsenite for 2 h, cells were irradiated with gamma rays at a dose of 40 Gy, and the numbers of DNA DSBs were measured immediately after irradiation as well as at 30 min postirradiation. Both arsenite and nickel(II) inhibited repair of DNA DSBs in a concentration-dependent manner; 0.08 mM arsenite significantly inhibited the rejoining of DSBs, while 76 mM nickel was necessary to observe a clear inhibition. The mean lethal concentrations for the arsenite and nickel(II) treatments were approximately 0.12 and 13 mM, respectively. This indicates that the inhibition of repair by arsenite occurred at a concentration at which appreciable cell survival occurred, but that nickel(II) inhibited repair only at cytotoxic concentrations at which the cells lost their proliferative ability. These novel observations provide insight into the mechanisms underlying the effects of combined exposure to arsenite and ionizing radiation in our environment.     

Advantage of combining NLCQ-1 (NSC 709257) with radiation in treatment of human head and neck xenografts

NLCQ-1 (NSC 709257), a hypoxia-selective cytotoxin that targets DNA through weak intercalation, was investigated for efficacy in combination with single or fractionated radiotherapy of human head and neck xenografts. A staged tumor experiment was performed in tumor-bearing female athymic nude mice that were locally irradiated with or without NLCQ-1. Tumor hypoxia was assessed by immunohistochemistry for pimonidazole adducts in tumors of varying weight. Fractionated radiation, depending on the dose, was administered either once daily for 4 days or once daily for 4 days followed by a 7-day rest and repeat. NLCQ-1 was administered i.p. at 15 mg/kg alone or 45 min before each radiation dose. Hypoxia (1-52%) was detected in all tumors and was positively correlated with tumor size. NLCQ-1 alone resulted in about 10 days of tumor growth delay, measured at sixfold the tumor's original size, without causing toxicity. All combination treatments with NLCQ-1 were more effective than treatments with radiation alone. Radiation at 1 Gy given once daily for 4 days on days 20 and 30 caused 3.5 days of tumor growth delay, whereas in combination with NLCQ-1 it caused 14.5 days of growth delay. Radiation at 5 Gy given in two doses 10 days apart resulted in 3.5 days of tumor growth delay, whereas more than 20 additional days of delay were observed in combination with NLCQ-1. Radiation given as a single dose of 10 Gy resulted in about 7 days of tumor growth delay, whereas in combination with NLCQ-1 about 30 additional days of delay were seen. These results suggest a significant advantage in combining radiation with NLCQ-1 in treatment of human head and neck tumors, which are known to have hypoxic areas.     

Dose-rate effects of mammary tumor development in female Sprague-Dawley rats exposed to X and gamma radiation

Mammary tumour development was followed in two experiments involving a total of 2229 female Sprague-Dawley rats exposed to various doses of X or gamma rays at different dose rates. The data for another 462 rats exposed to tritiated water in one of these experiments were also analyzed. The incidence of adenocarcinomas and fibroadenomas at a given time after exposure increased linearly in proportion to total radiation dose for most groups. However, no significant increase in adenocarcinomas was observed with chronic gamma exposures up to 1.1 Gy, and the increase in fibroadenomas observed with chronic gamma exposures at a dose rate of 0.0076 Gy h-1 up to an accumulated dose of 3.3 Gy was small compared to that observed after acute exposures. The incidence of all mammary tumors increased almost linearly with the log of dose rate in the range 0.0076 to 26.3 Gy h-1 for 3 Gy total dose of gamma rays. The effects of X rays appeared to be less influenced by dose rate than were the effects of gamma rays.     

Characterization of altered absorptive and secretory functions in the rat colon after abdominal irradiation: comparison with the effects of total-body irradiation.

The aim of this work was to determine the alterations in the absorptive and secretory functions of the rat colon after abdominal irradiation and to compare the effects of abdominal and whole-body irradiation. Rats received an abdominal irradiation with 8 to 12 Gy and were studied at 1, 4 and 7 days after exposure. Water and electrolyte absorption was measured in vivo by insertion of an agarose cylinder into the colons of anesthetized rats. In vitro measurements of potential difference, short-circuit current and tissue conductance were performed in Ussing chambers under basal and agonist-stimulated conditions. Most of the changes appeared at 4 days after abdominal irradiation. At this time, a decrease in water and electrolyte absorption in the colon was observed for radiation doses > or = 9 Gy. The response to secretagogues (VIP, 5-HT and forskolin) was attenuated after 10 and 12 Gy. Epithelial integrity, estimated by potential difference and tissue conductance, was altered from 1 to 7 days after 12 Gy abdominal irradiation. These results show that the function of the colon was affected by abdominal irradiation. Comparison with earlier results for total-body irradiation demonstrated a difference of 2 Gy in the radiation dose needed to induce changes in the function of the colon.     

Biological dosimetry: the potential use of radiation-induced apoptosis in human T-lymphocytes

An assay for biological dosimetry based on the induction of apoptosis in human T-lymphocytes is described. Radiation-induced apoptosis was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation. CD4 and CD8 T-lymphocytes were analysed. They were recognized on the basis of their cell-surface antigens. Four parameters were measured for both cell types: cell size, granularity, antigen immunofluorescence and DNA content. Apoptosis was quantified as the fraction of CD4-, or CD8-positive cells with a characteristic reduction of cell size and DNA content. At doses below 1 Gy, levels of radiation-induced apoptosis increased for up to 5 days after irradiation. Optimal dose discrimination was observed 4 days after irradiation, at which time the dose-response curves were linear, with a slope of 8% ± 0.5% per 0.1 Gy. In controlled, dose-response experiments the lowest dose level at which the radiation-induced apoptosis frequency was still significantly above control was 0.05 Gy. After 5 days post-irradiation incubation, intra- and interdonor variations were measured and found to be similar; thus, apoptotic levels depend more on the dose than on the donor. The results demonstrate the potential of this assay as a biological dosimeter. Received: 27 February 1997 / Accepted in revised form: 14 May 1997     

Effects of split-dose X irradiation on rat salivary gland function.

The effect of a single local dose of 15 Gy on salivary gland function in male Albino Wistar rats was compared with the effect of two doses of 7.5 Gy. The intervals chosen were 0-24 h and 1 week. Before and 1-30 days after the last radiation dose, samples of parotid and submandibular saliva were collected simultaneously after stimulation of the glands with pilocarpine. Irradiation with the single dose resulted in an increased lag phase and potassium concentration, and a decreased flow rate and sodium concentration. The rate of secretion of amylase was decreased during Days 1-6, increased at Day 10, and was decreased again at Day 30. With two dose fractions, substantial dose-sparing effects on lag phase, flow rate, and secretion of amylase were observed for both the very early (0-6 days postirradiation) and later (6-30 days postirradiation) effects. These effects were maximal when the interval between the fractions was 6 h. A significant dose-sparing effect on electrolytes was observed for the later effects only, again with a maximum for the 6-h interval. The dose-sparing observed for the very early effects cannot be explained satisfactorily by repair of sublethal damage (SLD), redistribution of cells over the cell cycle, or repopulation of salivary gland tissue between the doses. In contrast to the earlier dose-sparing effects, the split-dose recovery seen for later damage may be attributed, in part, to SLD repair in providing for greater reproductive survival of intercalated ductal cells and enhanced tissue regeneration.     

Growth Hormone Mitigates against Lethal Irradiation and Enhances Hematologic and Immune Recovery in Mice and Nonhuman Primates

Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7.5 Gy and treated post-irradiation with rhGH intravenously at a once daily dose of 20 µg/dose for 35 days. rhGH protected 17 out of 28 mice (60.7%) from lethal irradiation while only 3 out of 28 mice (10.7%) survived in the saline control group. A shorter course of 5 days of rhGH post-irradiation produced similar results. Compared with the saline control group, treatment with rhGH on irradiated BALB/c mice significantly accelerated overall hematopoietic recovery. Specifically, the recovery of total white cells, CD4 and CD8 T cell subsets, B cells, NK cells and especially platelets post radiation exposure were significantly accelerated in the rhGH-treated mice. Moreover, treatment with rhGH increased the frequency of hematopoietic stem/progenitor cells as measured by flow cytometry and colony forming unit assays in bone marrow harvested at day 14 after irradiation, suggesting the effects of rhGH are at the hematopoietic stem/progenitor level. rhGH mediated the hematopoietic effects primarily through their niches. Similar data with rhGH were also observed following 2 Gy sublethal irradiation of nonhuman primates. Our data demonstrate that rhGH promotes hematopoietic engraftment and immune recovery post the exposure of ionizing radiation and mitigates against the mortality from lethal irradiation even when administered after exposure.     

Effects of heavy ion to the primary [correction of rimary] culture of mouse brain cells.

To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05 Gy up to 2.0 Gy. The subsequent biological effects were evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55-200 keV/micrometers) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this report, a result of memory and learning function to adult mice after whole-body and brain local irradiation at carbon ion and iron ion.     

Dependence of the therapeutic effectiveness of interleukin-1beta on the time of the drug administration after irradiation of mice

In experiments on mice F1(CBA x C57BL/6) the dependence of 30th days survival on the time of betaleukin (medicine form of interleukin-1 beta) administering after exposure to 7.5 Gy whole body gamma-irradiation from 137Cs (approximately DL80/30) was studied. Betaleukin was injected subcutaneously in dose 25 mcg/kg 0.2, 1, 3, 6 and 24 h after the exposure. The highest therapeutic effect took place in case of 0.2 h interval, then it dropped but was slightly expressed at 1 h. The hemopoiesis condition was studied in 7 or 9 days after the mice exposure to 6 Gy and betaleukin administering 1 h later in dose 25 or 50 mcg/kg. The positive effect on granulopoiesis beginning from the level of CFU-GM was observed. There were analyzed the reasons of weaker betaleukin effect and shorter period of its effectiveness after exposure in comparison with literature data regarding IL-1.     

Effects of low dose rate (0.003-0.025 Gy/h) chronic X-irradiation on radioresistant and radiosensitive L5178Y mouse lymphoma cells

Cultures of radioresistant (LY-R) and radiosensitive (LY-S) strains of L5178Y mouse lymphoma cells were exposed continuously to X-rays delivered at dose rates ranging from 0.003 to 0.025 Gy/h for up to 35 days. Populations of both strains proliferated actively during the exposure, but the growth rates were reduced in a dose rate-dependent manner. The reduction of growth rate occurred for strain LY-S earlier during the exposure and at lower dose rates than for strain LY-R. The survival (as measured by colony forming ability) of strain LY-R was affected only slightly at all dose rates applied. For strain LY-S, a decrease in the surviving fraction was observed in the initial part of the exposure. This decrease was followed by a plateau and eventually by an increase, in some cases to values close to the control level. The increase in the surviving fraction indicated that the radioresistance of the exposed LY-S cells had increased. This pattern was particularly clear for dose rates greater than 0.014 Gy/h. The pre-irradiated cells exhibited radioresistance when exposed to acute X-radiation after termination of the chronic exposure. The increase in radiation resistance was stable for at least 70 days after termination of the protracted exposure. These results show that mutagenic and/or selective phenomena leading to an increase in radiation resistance of mammalian cells can be caused by protracted exposures to X-rays at dose rates permitting active proliferation.     

Effects of single gamma-irradiation on the activity of ornithine decarboxylase in the thymus and pulmonary tissue]

In studying the dose (0.1-6 Gy) and time (2 h to 180 days) dependence of ornithine decarboxylase activity, it was found that deviations from the control were more pronounced in the thymus than in the pulmonary tissue. The radiation effect was a function of dose and time after irradiation. A nonmonotonous type of the dose-response curve was observed 7 days after irradiation: the radiation effect with a low dose (0.1 Gy) was opposite to that with sublethal doses (1-6 Gy).