Diabetes mellitus as a cause for the shortening of the longevity of locally irradiated rats]

A study was made of the development of remote radiation pathology of pancreas in male rats after local irradiation of abdomen with doses of 5, 10 (two fractions of 5 Gy at a 30-day interval) and 15 Gy (three fractions of 5 Gy at a 30-day interval). The clinical and morphological estimates show the dose-dependent development of diabetes mellitus and 1.8-fold shortening of the life span, as compared to biological control.     

Radiation effects on diamine oxidase activities in intestine and plasma of the rat

Diamine oxidase (DAO; EC 1.4.3.6) activity was measured in plasma and in ileal tissue homogenates prepared from male Sprague-Dawley rats euthanized at 1-15 days after acute whole-body irradiation with 14.5-MeV electrons. Animals irradiated with 1 Gy showed no diminution in plasma and ileal DAO activities through Day 13 relative to nonirradiated controls. Animals irradiated with 5, 10, and 12 Gy displayed marked declines in ileal DAO activity, with levels reaching a nadir on Day 3. This was paralleled by a decrease in plasma DAO activity in all three dose groups. Recovery of ileal and plasma DAO levels was later seen as early as Day 4 in animals irradiated with 5- and 10-Gy doses, but animals receiving 12 Gy did not survive beyond Day 3. The relationship between radiation dose and levels of plasma and ileal DAO on Day 3, the time of maximum decrease at all doses, was also investigated. Ileal DAO activity decreased almost linearly between 2 and 8 Gy. Plasma DAO activity closely paralleled the dose dependency of the ileal levels. These data suggest that plasma DAO activity might be useful as a biologic marker of intestinal epithelial injury and recovery after acute radiation exposure.     

Effects of dexamethasone on late radiation injury following partial-body and local organ exposures.

Dexamethasone was evaluated as a treatment for radiation-induced lung, kidney, liver, and spinal cord injuries in rats. One experimental group was partial-body-irradiated (22.5 Gy) with the head, femur, and exteriorized intestine shielded to prevent acute mortality. Other animals received local irradiation to the kidney (20 Gy), liver (25 Gy), or a 1-cm segment of cervical spinal cord (18 to 40 Gy). Following irradiation half of the animals in each radiation group were given drinking water containing 188 micrograms/liter of dexamethasone. Tests were done to assess kidney function (hematocrit, plasma urea nitrogen, ethylenediaminetetraacetic acid clearance), liver function (rose bengal clearance, plasma glutamic oxaloacetic acid transaminase), or spinal cord injury (paralysis). The effectiveness of dexamethasone in preventing radiation injury was tissue specific. Dexamethasone eliminated lethal pleural fluid accumulation after partial-body irradiation and delayed development of kidney dysfunction after local kidney irradiation. As a result, dexamethasone increased the median survival time from 63 to 150 days after partial-body irradiation and from 126 to 175 days after local kidney irradiation. After whole-liver irradiation, development of hepatic functional injury was retarded by dexamethasone treatment but without significantly changing survival time. Dexamethasone had no effect on spinal cord tolerance but significantly shortened the latent period between radiation and paralysis.     

Postradiation death and recovery of duodenal APUD cells in rats

Electron microscopy has revealed death of some of the apudocytes and recovery of the other ones in small intestine of rats after single total body irradiation in sublethal dose (5 Gy) and local fractionated irradiation (35 Gy, 7 Gy X 5) of the abdomen. The ability of EC-cells to form the autophagosomes was found. An absence of uniform reaction of different types of apudocytes to radiation is discussed.     

Protection to glycolysis by a combination of 5-hydroxy-L-tryptophan and 2-aminoethylisothiuronium bromide hydrobromide in lethally irradiated rats.

Rate of glycolysis in vivo at different time intervals following 8 Gy [LD100(30)] whole body gamma radiation (WBGR) was evaluated by estimating liver glycogen, blood sugar, serum lactic dehydrogenase (LDH) and blood lactic acid concentration in adult male Sprague Dawley rats. Within 1 hr of radiation exposure, a significant fall in liver glycogen was observed in rats fed food and water ad libitum. The glycogen content increased after 24 hr and had returned to control level on 7th day after radiation exposure. Blood sugar, serum LDH and blood lactate levels increased significantly as compared to non irradiated controls. Pretreatment with 5-hydroxy-L-tryptophan (5-HTP; 100 mg/kg) + 2-aminoethylisothiuronium bromide hydrobromide (AET; 20 mg/kg) ip 30 min before 8 Gy WBGR, modified these values and restored them to normal level on 7th day post-irradiation.     

Effects of gamma-irradiation on the infectivity and chromosome aberration of Clonorchis sinensis

Effects of gamma irradiation on the worm survival and chromosomal aberration of Clonorchis sinensis were studied. The metacercariae irradiated with various amounts of gamma radiation (ranging from 5 Gy to 50 Gy) were fed to rats, and the effects were compared with those of non-irradiated controls. Recovery rates of adult worms in irradiated groups were reduced gradually as increasing of the irradiation doses. No worm was recovered from rats which were fed with 50 Gy irradiated metacercariae. The chromosome number was 2n = 56 in all worms from all experimental groups. However, the groups irradiated with 20 Gy, 25 Gy or 30 Gy showed variations in the chromosome number, depending on different cells in the same individual. Radiation doses used in this study did not appear to induce chromosome aberrations, however, irradiation with 30 Gy showed slightly reduced chromosome size.     

Peculiarities of dephosphorylation reaction catalyzed by purified protein tyrosine phosphatase CD45 from thymocytes of intact and exposed to ionising radiation rats

This paper is devoted to analysis of parameters of catalytical activity of CD45, the major transmembrane proteintyrosine phosphatase (PTP-ase) of the lymphocytes, isolated from plasma membranes of thymocytes of control and 0.5 Gy irradiated rats. CD45 catalytic features were evaluated using 0.2 mM sodium vanadate as the inhibitor and paranitrophenylphosphate (1-8 mM) and phosphotyrosine (1-6 mM) as, respectively, nonspecific and specific substrates. With the former, irradiation was shown to cause a decrease in Vmax but an increase in affinity. With phosphotyrosine both Vmax and affinity decreased. These data suggest that the exposure to radiation causes an increase in non-specific enzyme activity with a decrease in the ability to dephosphorylate the specific substrate. A study of cooperativity parameters shows that cooperativity between two phosphatase domains increased after irradiation. An analysis of the inhibitor kinetics showed that radiation caused a change of competitive inhibition by mixed one.     

Langerhans cell number and morphology in mouse footpad epidermis after X irradiation

Effects of 250-kV X rays on epidermal Langerhans cells were studied in CBA/CaH mice. One group received 20 Gy to the feet, another 8 Gy to the whole body, and a third both the 8 Gy whole-body and a 12 Gy local dose to the feet. Mice from each group and controls were sacrificed at intervals from 1 to 64 days later. ATPase-positive cells in sheets of footpad epidermis were counted by light microscopy. The density of Langerhans cells in controls was 1515 +/- 36/mm2 (mean +/- SE; n = 34). By 3 days after irradiation they became rounded and less dendritic and numbers gradually reached a nadir by 10 days, at 18% of controls after 20 Gy and 57% of controls after 8 Gy. Some of the remainder exhibited bizarre morphology and ultrastructural abnormalities. After local irradiation of the feet Langerhans cell numbers recovered rapidly between 14 and 16 days, although their distribution was uneven until 30 days after irradiation. Repopulation was delayed after an 8 Gy whole-body dose by at least 3 weeks. These results demonstrate that high local doses of X rays substantially but transiently deplete the epidermal Langerhans cell population and support the hypothesis that functional hemopoietic tissue is required for extensive Langerhans cell replenishment.     

Early biological effects of whole body irradiation on rat lungs

Summary The influence of whole-body irradiation (WBI) with 4, 8 and 15 Gyionizing radiation upon some biochemical indices in the brochoalveolar lavage fluid (BALF) of rat lungs was studied. It was established that lactate dehydrogenase (LDH), alkaline phosphatase, (APH) and acid phosphatase (AcPH) activities show a dose-dependent decrease on the day 1 and day 5 after the irradiation. A similar trend was observed in the total protein content on the day 1. Angiotensin converting enzyme (ACE) activity was increased on the day 1 in the groups irradiated with 8 Gy and 15 Gy in comparison with the controls (190,2% and 187,5%, respectively). It was concluded that WBI decreass LDH, APH and AcPH levels in the lung cells, which secrete them into bronchoalveolar spaces. An irradiation with 8 Gy and 15 Gy WBI provokes an early damage on cytoplasmic membranes of the endothelial cells in lung capillars. It was considered that the bronchoalveolar lavage can find a more wide application for evaluation of the biological effect of ionizing radiation in lungs.     

Antioxidant tolerance of kidney after irradiation

Different doses of irradiation were performed in which group 1 (non-irradiated), group 2 (8 Gy/single dose/whole body) and group 3 (15 Gy/single dose/whole body) were formed of guinea pigs. After 24 hr of radiation exposure the levels of lipid peroxidation product, malondialdehyde, (MDA), glutathione (GSH) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured in the whole kidney. The MDA content increased in animals irradiated with 8 and 15 Gy. And group 3 showed an increase the level of MDA. GSH contents of kidney in group 2 and 3 increased. The activity of SOD decreased markedly in group 3 when compared with control group. The activity of GSH-Px decreased significantly in group 2 and group 3 in comparison to controls. It may be concluded that a high dose of ionizing irradiation cause excessive oxidative stress in kidney.     

The dynamics of the rats higher nervous activity disturbances after total influence of electrons and gamma-rays in doses 5-100 Gy

The dynamics of using of stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after total influence of high energy electrons and of gamma-rays in doses 5-100 Gy were investigated. The quality structure of higher nervous activity disturbances after the influence of these kinds of ionizing radiation was identical. Therefore the tendency to disturbances aggravating after the electron radiation influence in the periods of the initial depression and of relatively normalization was revealed, especially after the irradiation in dose 50 Gy. The effective compensation of the functional disturbances in the central nervous system at the first 5-10 min after irradiation was after influence of electron radiation in doses about 30 Gy and after the influence of gamma-radiation in doses about 50 Gy. The irradiation of rats in doses 10 Gy and 5 Gy caused qualitative different dynamics of radiation disturbances in rats higher nervous activity. The differences in rats higher nervous activity after influence of electron and of gamma-radiation in these doses did not manifest distinctly.     

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.     

核辐射对大深度快速上浮脱险致减压病大鼠相关指标的影响*

目的: 探讨不同剂量核暴露后不同时间对大深度快速上浮脱险致减压病大鼠模型的发病率、死亡率及损伤指标的影响。方法: 80只SD雄性大鼠,随机分成空白对照组、脱险对照组和6个干预组(4 Gy辐射后4 h脱险、6 Gy辐射后4 h脱险、12 Gy辐射后4 h脱险、4 Gy辐射后8 h脱险、6 Gy辐射后8 h脱险、12 Gy辐射8 h后脱险),每组10只。干预组动物先采用不同剂量γ射线外照射(4、6、12 Gy),再进行大深度快速上浮脱险实验(最大加压深度150 m),分析大鼠肺W/D、脾指数及血浆IL-1β的变化。结果: 与脱险对照组比较,核辐射后脱险大鼠的减压病发病率及死亡率明显上升。4 Gy、6 Gy照射4 h后上浮脱险的大鼠发病率和死亡率较照射8 h后高。12 Gy辐射后4 h及8 h脱险大鼠的减压病的发病率及死亡率均比低剂量照射组明显增高,死亡率尤其明显。和发病率及死亡率的变化相一致,肺组织湿/干比、肺组织病理损伤程度、脾指数下降也表现同样的变化趋势:较低剂量(4 Gy、6 Gy)辐射后4 h改变明显,8 h改变不明显,而高剂量(12 Gy)辐射后4、8 h均变化明显。和空白对照组及脱险对照组相比较,各辐射后脱险组的血浆IL-1β浓度均显著上升。结论: 核辐射引起放射性肺损伤、免疫功能下降及血浆炎症因子浓度升高,会增加大鼠快速上浮脱险致减压病的风险。     

Metallothionein induction as a potent means of radiation protection in mice

A striking resistance to lethal damage from a single dose of 6-8 Gy of X rays has been found in mice which had received various pretreatments to induce metallothionein (MT) synthesis in the liver prior to irradiation. Mice were injected with manganese (10 mg Mn/kg) or cadmium (3 mg Cd/kg) salt subcutaneously, or a patch of dorsal skin (2 X 2 cm2) was excised 1 or 2 days prior to irradiation. The increased tolerance of these mice to radiation was established by a marked decrease of mortality rate, an increase of mean survival time, a reduction of weight loss, and a smaller decrease in the number of leukocytes as compared with the control group. The LD50/30 for control mice was 6.3 Gy, while the corresponding values for the groups pretreated with Mn, Cd, and skin excision were 7.5, 7.7, and 7.9 Gy, respectively. The normal level of MT in mouse liver was approximately 25 micrograms/g tissue. This level increased 2.5- to 3-fold 24 h after 6.3 Gy irradiation. The MT levels of mice pretreated with Cd, Mn, and skin excision were increased 8-, 5-, and 7-fold, respectively, prior to irradiation as compared with the preirradiation control. These results indicate that the induction of MT in mouse liver is a significant factor in the mechanism of protection against radiation.     

Nitric oxide produced by inducible nitric oxide synthase is associated with mammary tumorigenesis in irradiated rats.

This study evaluated whether nitric oxide (NO) derived from nitric oxide synthase (NOS) induced by radiation is associated with tumorigenesis in the mammary glands. When rats were exposed to whole-body irradiation with gamma-rays (1.5 Gy) immediately after weaning and then treated with diethylstilbestrol, as an irradiated control, the tumor incidence (85%) was increased 7.6-fold in comparison with that (11.1%) of the non-irradiated control. The tumor incidence declined to 28.6% in the rats injected intraperitoneally with phenyl-N-tert-butylnitrone (PBN, 160 mg/kg), an inhibitor of inducible NOS (iNOS) expression and also a spin trapping agent, 30 min before irradiation. Also, the tumor incidence (25%) in rats orally administered with N-(3-(aminomethyl)-benzyl)-acetamide (1400W, 2.3+/-0.1 mg/day), a highly selective inhibitor of iNOS, dissolved in drinking water for 3 days after the irradiation was less than one-third of that in the irradiated control. On treatment with PBN or 1400W, no adenocarcinoma developed. Many of the mammary tumors that developed in the irradiated rats were positive for the estrogen receptor (ER). In contrast, ER was not detected in the tumors yielded from irradiated rats administered with PBN or 1400W. These results indicate that iNOS-derived NO may participate in the formation of estrogen-dependent mammary adenocarcinomas following radiation.     

Protection to testicular activity by a combination of 5-hydroxy L-tryptophan with a thiol compound in whole body gamma irradiated rats

Radiation induced changes in testicular activity were studied by estimating sialic acid content in plasma and testis and 17-ketosteroids in 24 hr urine samples of male Sprague Dawley rats following 8 Gy whole body gamma ray exposure with and without pretreatment with 2-aminoethylisothiuronium bromide hydrobromide (AET) or with a combination of 5-hydroxy L-tryptophan (5-HTP) and AET. Combination of 5-HTP with AET or AET alone in optimum radioprotecting dose has significantly modified the radiation damage to the testis.     

谷氨酰胺对低剂量电离辐射损害的保护作用

观察小剂量电离辐射条件下大鼠补充谷氨酰胺(Gln)对体内谷胱甘肽(GSH)代谢的影响。SD雄性大鼠受照射后经饲料补充2%Gln。照射源为60Co;剂量率6×10-2Gy/h,1h/d,5d/周,累积剂量1.5Gy。与对照组相比,受照射大鼠睾丸重量降低,精子畸变率增高,肝脏GSH含量降低,外周血白细胞计数降低,血清Gln及Glu+Gln含量降低,差异具有显著性,补充Gln则与对照组无明显差异。表明小剂量电离辐射导致大鼠出现可逆性损害,机体的Gln需求有所增加,补充Gln对大鼠的GSH代谢有一定益处。     

Radioprotective potential of histamine on rat small intestine and uterus

The aim of this study was to improve knowledge about histamine radioprotective potential investigating its effect on reducing ionising radiation-induced injury and genotoxic damage on the rat small intestine and uterus. Forty 10-week-old male and 40 female Sprague-Dawley rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a dose of whole-body Cesium-137 irradiation. Three days after irradiation animals were sacrificed and tissues were removed, fixed, and stained with haematoxylin and eosin, and histological characteristics were evaluated. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate chromosomal damage. Histamine treatment reduced radiation-induced mucosal atrophy, oedema and vascular damage produced by ionising radiation, increasing the number of crypts per circumference (239±12 vs 160±10; P<0.01). This effect was associated with a reduction of radiation-induced intestinal crypts apoptosis. Additionally, histamine decreased the frequency of micronuclei formation and also significantly attenuated 8-OHdG immunoreactivity, a marker of DNA oxidative damage. Furthermore, radiation induced flattening of the endometrial surface, depletion of deep glands and reduced mitosis, effects that were completely blocked by histamine treatment. The expression of a proliferation marker in uterine luminal and glandular cells was markedly stimulated in histamine treated and irradiated rats.The obtained evidences indicate that histamine is a potential candidate as a safe radio-protective agent that might increase the therapeutic index of radiotherapy for intra-abdominal and pelvic cancers. However, its efficacy needs to be carefully investigated in prospective clinical trials.Key words: histamine, ionising radiation, radio-protectors, small intestine, uterus.     

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.     

Radio-protective effects of melatonin against irradiation-induced oxidative damage in rat peripheral blood

During radiotherapy, ionizing irradiation interacts with biological systems to produce free radicals, which attacks various cellular components. The hematopoietic system is well-known to be radiosensitive and its damage may be life-threatening. Melatonin synergistically acts as an immunostimulator and antioxidant. In this study we used a total of 120 rats with 20 rats in each group. Group 1 did not receive melatonin or irradiation (Control group), Group 2 received only 10 mg/kg melatonin (Mel group), Group 3 exposed to dose of 2 Gy irradiation (2 Gy Rad group), Group 4 exposed to 8 Gy irradiation (8 Gy Rad group), Group 5 received 2 Gy irradiation plus 10 mg/kg melatonin (Mel +2 Gy Rad group) and Group 6 received 8 Gy irradiation plus 10 mg/kg melatonin (Mel+8 Gy Rad group). Following exposure to radiation, five rats from each group were sacrificed at 4, 24, 48 and 72 h. Exposure to different doses of irradiation resulted in a dose-dependent decline in the antioxidant enzymes activity and lymphocyte count (LC) and an increase in the nitric oxide (NO) levels of the serum. Pre-treatment with melatonin (10 mg/kg) ameliorates harmful effects of 2 and 8 Gy irradiation by increasing lymphocyte count(LC) as well as antioxidant enzymes activity and decreasing NO levels at all time-points. In conclusion 10 mg/kg melatonin is likely to be a threshold concentration for significant protection against lower dose of 2 Gy gamma irradiation compared to higher dose of 8 Gy. Therefore, it seems that radio-protective effects of melatonin are dose-dependent.