Diabetes susceptibility of BALB/cBOM mice treated with streptozotocin. Inhibition by lethal irradiation and restoration by splenic lymphocytes

International Nuclear Information System (INIS)

Paik, S.G.; Blue, M.L.; Fleischer, N.; Shin, S.

1982-01-01

In genetically susceptible strains of mice, repeated injections of a subdiabetogenic dose of streptozotocin induces the development of progressive insulin-dependent hyperglycemia. We showed previously that host T-cell functions play an obligatory etiologic role in this experimental disease by demonstrating that the athymic nude mouse is resistant to diabetes induction unless its T-cell functions are reconstituted by thymus graft. Here we show that lethal irradiation of euthymic (+/nu) mice of BALB/cBOM background causes selective resistance of the mice to the diabetogenic effects of the multiple low doses of streptozotocin without affecting their sensitivity to a high pharmacologic dose of the toxin. We also show that reconstitution of the irradiated mice with splenic lymphocytes causes the restoration of diabetes susceptibility. Lethally irradiated mice thus represent a useful experimental model for analyzing the host functions involved in the development of this disease. These results provide an additional support for the hypothesis that the induction of diabetes in this model system is mediated by an autoimmune amplification mechanism

The effects of gut commensal bacteria depletion on mice exposed to acute lethal irradiation

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Hou Bing; Xu Zhiwei; Zhang Chenggang

2007-01-01

The prevention and management of bacterial infection are the mainstays of therapies for irradiation victims. However, worries about adverse effects arise from gut commensal flora depletion owing to the broad-spectrum antibiotics treatment. In the present study, we investigated the effects of gut bacteria depletion on the mice receiving total-body irradiation (TBI) at a single dose of 12 Gy. One group of mice was merely exposed to TBI but was free of antibiotic treatment throughout the experiment, while the other two groups of mice were additionally given broad-spectrum antibiotics, either from 2 weeks before or immediately after irradiation. The survival time of each animal in each group was recorded for analysis. Results showed that the mean survival time of mice was longest in the group without antibiotic treatment and shortest in the group treated with broad-spectrum antibiotics from 2 weeks before TBI. In conclusion, our data suggested that depletion of gut commensal bacteria with broad-spectrum antibiotics seemed deleterious for mammals receiving lethal TBI. (author)

The effect of cyclophosphamide and x-irradiation on experimental influenza in mice

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Frankova, V.

1989-01-01

Mice treated with Cyclophosphamide (Cy) shortly before inoculation of influenza A virus exhibited increased mortality and delayed mean time of death. The extrapulmonary dissemination of the infection was observed more often in Cy-treated animals with the titres of virus in different organs substantially higher than in equally infected immunocompetent controls. Although the humoral antibody response was not impaired in Cy-treated mice, they were more susceptible to challenge with a lethal dose of virus than normal animals. In X-irradiated mice, the increased multiplication of virus in lungs and spread of the infection to other organs was observed, with prolonged persistence of virus in lungs and brains as compared to adequate controls, reminding of previous observation in immunocompromised persons, who died in the course of influenza. (author) 1 fig., 4 tabs., 23 refs

Metabolic changes after non-lethal X-irradiation of rats. I

International Nuclear Information System (INIS)

Ahlersova, E.; Ahlers, I.; Slavkovska, E.; Praslicka, M.

1981-01-01

Male rats of the Wistar strain were fasted overnight prior to exposure to single whole-body X-ray dose of 2.39 Gy (250 R). Irradiated and sham-irradiated rats were pair-fed for 5 days, in the following period they were fed ad libitum. The levels of corticosterone and immunoreactive insulin in serum, glucose in blood, glycogen in liver, heart and skeletal muscle were determined 1 and 6 h, 1, 2, 3, 7, 14, 21, 28, and 38 days after irradiation and sham-irradiation. Irradiation of rats resulted, in one hour, in a decrease and, in two days, in an increase in blood glucose level. A marked increase in liver glycogen persisted from 6 h to 21 days after irradiation. The level of glycogen in the skeletal muscle was reduced after 6 h and increased on days 3 and 14. Heart muscle glycogen declined within the first 24 h and rose at 14 days after exposure. The kinetics of changes in the heart and skeletal muscle glycogen following non-lethal irradiation was similar and indicated an overlap of changes produced by fasting with those brought about by irradiation, particularly during the first week. Corticosterone in serum was markedly increased in rats 24 and 72 h after irradiation compared to pair-fed controls. The serum insulin concentration did not change after irradiation, except for a single increase on day 21. Irradiation with non-lethal doses produced changes in the parameters of the carbohydrate metabolism studied, except for serum insulin which reflected the changes in the nutrition regimen upon pair-feeding rather than the effect of ionizing irradiation. (author)

Effects of 6-methyl-uracil upon the phagocytic activity in mice following whole-body X-irradiation or 2,4,6,-triethyleneimino-s-triazine treatment

International Nuclear Information System (INIS)

Raake, W.; Tempel, K.

1977-01-01

1. Phagocytic activity measured by means of the intravasal clearence of a soot dispersion in male NMRI-mice was increased six to ten days after whole-body X-irradiation (640 R) and decreased during the same period after i.v. administration of 2,4,6-triethyleneimino-s-triazine (TEM 2.0 mg/kg). 2. By means of 6-methyl-uracil food admixtures (200 to 400 ppm during 2 or 3 weeks) or by repeated intravenous injections of a N-methyl-D-glucosamine-6-methyluracil complex (62.5 to 250 mg/kg daily during five days), a significant augmentation of the phagocytic index being related to time and dosage was obtained in otherwise untreated mice. Comparable results were seen using cytidine and cytidine-5'-phosphate, whereas guanosine-5'-phosphate remained ineffective. 3. Whilst stimulating effects of 6-methyl-uracil or its N-methyl-D-glucosamine complex on X-irradiated mice were suspended, an increase up to supernormal values of the phagocytic index was produced by the pyrimidine base in animals treated with TEM. In accordance to this the survival rate of lethally X-irradiated mice (960 R) could not be increased; with animals given lethal TEM-doses, however, a significantly increased survival rate was obtained. 4. The present investigations as well as former biochemical analyses confirm the assumption that 6-methyluracil produces its regeneration effects, to some extent at least, by specific pathways influencing the reticuloendothelium. Different results from X-irradiated and TEM-treated mice are referring to the different points of attack of the two noxa. (orig.) [de

Increased haematopoietic stem cell survival in mice injected with tocopherol after X-irradiation

International Nuclear Information System (INIS)

Roy, R.M.; Malick, M.A.; Clark, G.M.

1982-01-01

Tocopherol injection (2.5 mg) immediately after irradiation reduced lethality only during bone-marrow syndrome. Endogenous spleen colony count at 8 days after X-radiation were significantly greater in vitamin-E-injected mice compared to noninjected or vehicle-injected animals; however, 59 Fe incorporation into spleen and bone marrow did not suggest enhanced erythropoietic activity in vitamin-E-injected groups at 2, 4, 8 and 10 days following irradiation. Mitotic index and frequency of micronuclei in marrow at 24 hours post irradiation (3 GY) were unaffected by tocopherol injection. The uptake of tritium from injected 3 H-tocopherol suggests that tocopherol has been accumulated in spleens but not marrows of irradiated animals within a few hours. Also tocopherol has no effect on endogenous spleen colony counts if injected after 5 hours nor is there an effect on the seeding efficiency of exogenous bonemarrow cells injected into recipients receiving tocopherol after irradiation. (orig.) [de

Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis

International Nuclear Information System (INIS)

Hofer, M.; Pospisil, M.; Tkadlecek, L.; Viklicka, S.; Pipalova, I.; Hola, J.

1992-01-01

An impairment was observed of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of the prostaglandin synthesis inhibitors (PGSIs) indomethacin or diclofenac. Morphological examination of the gastrointestinal tract and estimation of the blood loss into its lumen in animals treated with diclofenac did not show serious damage such as hemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation. (author) 2 tabs., 4 figs., 20 refs

Megakaryocytopoiesis and the number of thrombocytes after bone marrow cell transplantation in lethally irradiated mice

International Nuclear Information System (INIS)

Viktora, L.; Hermanova, E.; Zoubkova, M.

1977-01-01

Changes were studied in the number of thrombocytes in the peripheral blood and megakaryocytes in the bone marrow and spleen in lethally irradiated mice after the transplantation of bone marrow cells. It was found that the thrombocytes increased in dependence on time after transplantation with the maximal values around the 20th day. An increased megakaryocytopoiesis was observed not only in the bone marrow but also in the spleen. These ascertainments suggest the importance of the transplantation of bone marrow cells and the role of thrombocytes for the survival of the organism after irradiation. (author)

Metabolic changes after non-lethal X-irradiation of rats. II

International Nuclear Information System (INIS)

Ahlers, I.; Ahlersova, E.; Sedlakova, A.; Praslicka, M.

1981-01-01

Male rats of the Wistar strain were subjected to whole-body X-irradiation with 2.39 Gy (250 R) and after irradiation they were pair-fed with the sham-irradiated control group. One, 6 and 24 h, 2, 3, 7, 14, 21, 28, and 38 days after exposure the animals were sacrificed and examined for serum and some tissue lipids. In the first hours an increase in lipolysis in the white adipose tissue and accumulation of non-esterified fatty acids and triacylglycerols (TG) in the liver predominated; phospholipid level increased in serum and liver and decreased in bone marrow and thymus. The later phase was characterized by hypertriacylglycerolaemia and a transient hypercholesterolaemia; accumulation of TG in bone marrow was the most important change, however. Changes in the lipid composition of the serum and tissues, except for an increase in TG level in thymus, returned to normal levels at the end of the observation period. Pair-feeding provided an equivalent nutritional situation in irradiated and sham-irradiated animals and thus eliminated the non-specific changes caused by different levels of food intake in both groups of animals, especially in the initial period. A sufficiently long observation period is necessary for estimating the kinetics of metabolic changes in rats exposed to non-lethal doses of X-irradiation. (author)

Radioprotection of mice by lactoferrin against irradiation with sublethal X-rays

International Nuclear Information System (INIS)

Nishimura, Yoshikazu; Homma-Takeda, Shino; Kim, Hee-Sun; Kakuta, Izuru

2014-01-01

The influence of a host defense protein, lactoferrin (LF), contained in exocrine secretions such as milk, on radiation disorder was investigated. A total of 25 C3H/He mice in each of two groups were maintained with 0.1% LF-added and LF-free diets, respectively, for one month. The mice were then treated with single whole-body X-ray irradiation at a sublethal dose (6.8 Gy), and the survival rate after irradiation was investigated. The survival rate at 30 d after irradiation was relatively higher in the LF group than in the control group (LF-free), (85 and 62%, respectively). The body weight 15 d after X-ray irradiation was also significantly greater in the LF group than in the control group. The hemoglobin level and hematocrit value were higher in the LF group at 5 d before X-ray irradiation. Another 52 mice underwent whole-body X-ray irradiation at the sublethal dose (6.8 Gy), and then LF was intraperitoneally injected once at 4 mg/animal to half of them. The survival rate in LF-treated mice 30 d after irradiation was 92%, significantly higher than in mice treated with saline (50%) (P = 0.0012). In addition, LF showed hydroxyl radical scavenger activity in vitro. These findings suggest that LF may inhibit radiation damage. (author)

Radioprotective properties of some heterocyclic nitrogenous compounds against changes in hemoglobin concentration and hematocrit value in x-irradiated mice

International Nuclear Information System (INIS)

Rousdhy, H.; Pierotti, T.; Polverelli, M.

1969-01-01

Radioprotective properties of imidazole and benzimidazole have been proved in previous works. In this study, authors try to demonstrate radioprotective action of these compounds in comparison with cysteamine upon the hematopoietic system after lethal X-irradiation. Results show: no drastic variations of hematologic constants (hemoglobin concentration and hematocrit value) after intraperitoneal injection of radioprotective compounds apart certain apparent reactions with the heterocyclic compounds; the better radioprotective action of benzimidazole. Twenty five days after irradiation, hemoglobin concentration and hematocrit of radio protected mice return to normal values. (author) [fr

Effects of ginger extract on testis enzymes of X-ray irradiated mice

International Nuclear Information System (INIS)

Zhao Shuhua; Li Jingshun; Wang Chunhua; Pan Qin; Yang Qiong

2005-01-01

Objective: To research the effects of extract of ginger on testis enzymes of X-ray irradiated mice. Methods: Mice were treated with three different doses of extract of ginger: high dose (9.3 mL·kg -1 ), middle dose (4.7 mL·kg -1 ), and low dose (2.3 mL·kg -1 ). All mice were irradiated once with 2.0 Gy X-ray. At the same time, the negative group (treated with vegetable oil only) and positive one (irradiated as well as extract of ginger groups after treated with vegetable oil) were set up. The changes of activities of enzymes in testes of mice were observed. Results: After irradiated, in the group of high dose the activity of G-6-PD was decreased but the activity of LDH was increased (P 0.05). In every group, SDH had no significant difference (P>0.05). Conclusion: The proper dose of extract of ginger has significant effects on stabilization of testis enzymes of X-ray irradiated mice. (authors)

Changes with age in swimming performance of X-irradiated mice

International Nuclear Information System (INIS)

Norimura, T.; Yoshikawa, I.; Okajima, S.

1980-01-01

The time required to swim 250 cm was determined once weekly for the entire life of fifteen pairs of male dd/K mice. The irradiated group was exposed to a single 224 rad of X-rays at 20 weeks of age. Median survival time (ST 50 ) for the control was 88.9 weeks and that for the irradiated group was 77.4 weeks, and both regression lines relating to death rate and age were parallel. The swimming ability of control mice began to decrease when the mice were 40 weeks of age, after which there was a gradual reduction with age at 0.00646/day. In the irradiated group, the swimming ability decreased from seven weeks after irradiation. The time of 50% reduction of swimming speed (TRS 50 ) for the control was 78.9 weeks and that for the irradiated group was 66.3 weeks, and the slopes of the regression lines relating reduction rate and age were similar. Differences between ST 50 and TRS 50 were 10 weeks in the control and 11 weeks in the irradiated group, respectively. These results indicate that there is no basic difference in the reduction in swimming ability between control and irradiated mice. The X-irradiation may simply mean that the reduction in the swimming ability is displaced to an earlier time with no alteration in the rate of reduction, and that the earlier appearance in the irradiated group is related to premature aging as induced by irradiation. (author)

Effect of local x-irradiation on mice reproduction in two successive generations

International Nuclear Information System (INIS)

Strel'nikova, N.K.; Lisenkova, L.N.

1978-01-01

For an experimental assessment of the biologic effectiveness of a single exposure to local irradiation exposure in simulating the conditions of exposure in X ray studies, an experiment was carried out on white mice. Mice of two successive generations were exposed to local X irradiation in the eye region. The radiation was found to bring about changes in the reproductive function (such as sterility, reduced litter size and fertility of females); these changes being dose-dependent in a nonlinear manner. The biologic effect of irradiation was greater in the second-generation mice

Genetic effects of feeding irradiated wheat to mice

International Nuclear Information System (INIS)

Vijayalaxmi

1976-01-01

The effects of feeding irradiated wheat in mice on bone marrow and testis chromosomes, germ cell numbers and dominant lethal mutations were investigated. Feeding of freshly irradiated wheat resulted in significantly increased incidence of polyploid cells in bone marrow, aneuploid cells in testis, reduction in number of spermatogonia of types A, B and resting primary spermatocytes as well as a higher mutagenic index. Such a response was not observed when mice were fed stored irradiated wheat. Also there was no difference between the mice fed un-irradiated wheat and stored irradiated wheat. (author)

Survival of Lymphatic Cells after X-Irradiation in Mice

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Vos, O. [Medical Biological Laboratory, National Defense Research Organization TNO, Ruswuk, Z.H. (Netherlands)

1967-07-15

Lymphatic tissues are generally classified among the most radiosensitive tissues of the body. The main reason for this is that histologically extensive destruction is found within a few hours after irradiation. We tried to estimate the degree of cellular degeneration by making cell suspensions from lymph nodes and thymus of mice at different times after X-irradiation with 800 R or at 24 h after radiation with different doses. The numbers of normal viable cells we obtained were expressed as percentages of the cells recovered from unirradiated control mice.

Induction of lethal mutations in the x-chromosome of unirradiated Drosophila oocytes after fertilization by irradiated spermatozoa

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Shaposhnikov, M.V.; Zainullin, V.G.

2003-01-01

Full text: In primary study on Drosophila it was found that irradiated male X-chromosomes induce recessive lethals in unirradiated female homologues (Abeleva et al., 1961, Radiobiologya. 1:123-126). The same effects were obtained in Drosophila in some recent investigations. The mechanisms of these effects is unknown. However it may be responsible for low-dose radiation effects as it induce mutations in unirradiated DNA. We assume that this effect may be a result of activation of error prone repair in response to preliminary DNA lesions in irradiated chromosome. In this research we analyse the frequencies of the recessive lethal mutations in the X-chromosome of Drosophila females mated with irradiated Basc males. We used acute irradiation with a dose rate of 10 Gy. For testing our hypothesis we use the mus209 and mei-41 mutant females. Mus209 is a PCNA gene homologue and mei-41 is a homologue of ATM gene. These genes are involved in post-replication DNA repair which may be error prone repair in Drosophila. It was obtained the tendency to decreasing the mutation rate at the mei-41[D5] background and decreasing mutation rate in mus209[B1] background in comparison with wild type strains CS (p<0.05). The obtained results demonstrate the possible role of mus209[B1] and mei-41[D5] genes in the inducing of mutations in the unirradiated X-chromosome in the presence of irradiated homologue

Meiotic chromosomal translocations in male mice induced by X-irradiation

Energy Technology Data Exchange (ETDEWEB)

Savkovic, N.; Pecevski; Vuksanovic, L.; Radivojevic, D.; Alavantic, D.

1983-01-01

The dose-response curve for reciprocal translocations induced by acute exposure of spermatogonial stem cells to X-rays in treated mice and their F-1 sons was examined. Male mice were totally irradiated with doses of 1Gy;5x1Gy and 5Gy. The obtained results show that frequency of the chromosomal translocations in directly treated animals is dose dependent. The percentage of animals irradiated with 1Gy which had the chromosomal translocations was 60, while this percentage in animals irradiated with single and fractionated dose of 5Gy was 100. The frequency of chromosomal translocations varies from 1.5% to 8.0%. Multivalent configurations in F-1 males were observed after exposure to 5Gy only. The incidence of F-1 translocated males was 17.5%.

Functional and morphological recovery of the T-cell compartment in lethally irradiated and reconstituted mice

International Nuclear Information System (INIS)

Kraal, G.; Hilst, B. van der; Boden, D.

1979-01-01

The recovery of the T-cell compartment in mice after lethal irradiation and reconstitution was studied using functional and morphological parameters. T-helper cell activity, determined by the direct SRBC-plaque-forming cell (PFC) response, recovered in a similar fashion as T-memory function which was studied by adoptive transfer of carrier-primed cells. Both functions returned to control levels in 2.5 to 3 months. Using immunoperoxidase staining of frozen sections with anti-T cell serum, the morphological recovery of the T-cell dependent areas in the white pulp of the spleen could be studied and compared with the functional recovery. (author)

Time-effect relationship of immunological adaptive response induced by low dose X-irradiation in mice

International Nuclear Information System (INIS)

Zhao Yong; Gong Shouliang; Liu Shuzheng

1995-01-01

Kunming mice irradiated with whole-body X-rays were used to observe time-effect relationship of immunological adaptive response induced by ionizing radiation. The results showed that pre-irradiation dose of 75 mGy X-rays with the intervals of 6-48 h between pre-irradiation and challenge irradiation could induce immunological adaptive response in the spontaneous proliferation of thymocytes and the responses of splenocytes to Con A and LPS in mice at 18-24 h after challenge irradiation with 1.5-2.0 Gy X-rays

Interplay of thymus and bone marrow regeneration in x-irradiated mice

International Nuclear Information System (INIS)

Hiesche, K.-D.

1975-01-01

aim of the prepresent investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed. (author)

Interplay of thymus and bone marrow regeneration in x-irradiated mice

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Hiesche, K D

1975-01-01

The aim of the present investigation was to study the modifying effects of bone marrow cells on regeneration, after X-irradiation, of thymus and bone marrow cell populations. Data are presented which indicate that the cellular composition of the thymus and, in particular, the frequency of the stem cells in the organ at the time of radiation exposure determines thymic regeneration for about two weeks after irradiation. After this period, regeneration depends on new precursors from the bone marrow which have previously seeded the thymus. In contrast to the thymus, cellular restoration of the bone marrow is already initially dependent on the number of protected or transplanted marrow cells. Two phases in the recovery of thymic PHA-reactivity after irradiation were observed: one initial phase which is independent on the number of the available bone marrow cells, and a subsequent phase during which PHA-reactivity is slightly increased in mice irradiated with partly protected bone marrow in comparison to in total body irradiated animals. During the entire observation period, PHA-reactivity remains at a low level not exeeding 50 % of that in untreated mice. In contrast the thymus is fully repopulated with regard to the number of nonreactive cells. Alternative pathways of thymocyte development within the thymus are discussed. Bone marrow X cells were shown to be as sensitive to in vitro treatment with a specific H-2 antiserum as were lymphocytes from normal bone marrow. This finding was teken to indicate that the X cells represent a particular lymphoid cell type. A xenogeneic rabbit-anti-mouse embryo antiserum was more toxic to pre-irradiated bone marrow, with high proportion of X cells, than to bone marrow from untreated mice, using in vitro cytotoxicity test. A possible embryonic character of the X cells is discussed.

B-lymphocyte differentiation in lethally irradiated and reconstituted mice. II. Recovery of humoral immune responsiveness

International Nuclear Information System (INIS)

Rozing, J.; Brons, N.H.C.; Benner, R.

1977-01-01

The recovery of humoral immune responsiveness was studied in lethally irradiated, fetal liver-reconstituted mice. By means of both membrane fluorescence and antibody formation to sheep red blood cells (SRBC) as a functional assay, the rate of recovery of the compartments of B and T lymphocytes was determined in various lymphoid organs. The recovery of the immunoglobulin-positive (B) cell compartment after irradiation and reconstitution started in the spleen. This organ was also found to be the first in which the recovery of the B-cell population was completed. The interval between the recovery of the B-cell population in the spleen and that in the other organs tested was found to increase when the irradiated mice were reconstituted with spleen colony cells instead of fetal liver cells. This proved to be caused by the number and nature of the reconstituting hemopoietic stem cells. The immunoglobulin-positive (B) cells were found to appear before SRBC-reactive B cells could be demonstrated in spleen, lymph nodes, and Peyer's patches. The appearance of T lymphocytes in the various lymphoid organs required even more time. By means of cell transfer experiments, a sequential appearance of the precursors of anti-SRBC IgM-, IgG-, and IgA-plaque-forming cells could be demonstrated in spleen, bone marrow, lymph nodes, and Peyer's patches

Aberrations of holokinetic chromosomes and associated lethality after X-irradiation of meiotic stages in Tetranychus urticae Koch (acari, tetranychidae)

International Nuclear Information System (INIS)

Tempelaar, M.J.

1979-01-01

Chromosomes of the holokinetic organization type were irradiated with X-rays in various stages of meiosis in unfertillized eggs of Tetranychus urticae Koch. Visible cytological aberrations, lethality and sterility were investigated in subsequent generations. Chromosome fragments are the most frequently occuring light-microscopically visible chromosome aberrations; bridges are not formed. Contrary to expectations, the presence of fragments appears to be positively correlated with the occurrence of lethality; loss of fragments, missegregation and the measure of damage of the broken chromosome parts are involved. In contrast with monokinetic chromosomes the earliest lethality occurs only after about 10 divisions. The ratios between different embryonic lethality types (early vs. late) differ depending on the stage irradiated: in more compact chromatin, more serious damage (i.e. more early lethality syndromes) is induced than in less compact chromatin. In the progeny of the surviving males, neither translocations nor independent fragments are found; indirect evidence indicated the occasional presence of inversions. The presumtive inversions are induced more frequently in a chromatin-compact stage (metaphase I) than in a less compact one (telophase I). (Auth.)

Long-term effect of whole-body X-irradiation on cell-mediated immune reaction in mice

International Nuclear Information System (INIS)

Norimura, Toshiyuki; Tsuchiya, Takehiko

1989-01-01

Age-related change in immunological activity was examined at 10 to 91 weeks following whole-body irradiation by determining the specific anti-tumor cell-mediated immunity in host mice induced and/or enhanced by local irradiation to transplanted tumor. Median survival time of the non-irradiated C3H/He female mice was 98.6 weeks while the median life-span of the mice exposed to two and four Gy of 250 kVp X-rays at the age of 10-12 weeks was shortened by 14.9 and 23.4 weeks, respectively. The rate of tumor reduction within two weeks after local irradiation to tumor and the growth inhibitory activitiy of spleen cells from tumor irradiated mice were reduced in a dose-dependent manner when assessed 10 weeks after whole-body irradiation, but recovered to the near-complete level of the non-irradiated controls within a few months, then gradually decreased with normal aging. These results suggest that the age-dependent decline of this immunological activity apears earlier in the irradiated mice as a result of whole-body X-irradiation at a young age, suggesting accelerated aging of the immune system. (author)

Effect of restricted access to food on metabolic changes in lethally X-irradiated rats. I

International Nuclear Information System (INIS)

Toropila, M.; Ahlers, I.; Ahlersova, E.; Praslicka, M.

1982-01-01

Differences in the reaction of glucose in blood and in that of glycogen in liver in animals with free access to food and in those with restricted food intake to lethal irradiation by X-rays were studied. SPF bred male rats of the Wistar strain were fed by common laboratory diet and by tap water ad libitum (AL group) or food was accessible to them (in unlimited amounts) only in the period between 09.00 a. m. and 11.00 a. m. (meal-fed group, MF), all under standard laboratory conditions. After more than three weeks of adaptation to the nutrition patterns and 22 h after the last food intake, animals of both groups were irradiated with a single whole-body 14.35 Gy dose of X-rays and/or sham irradiated, respectively. Glucose concentration in blood was increased in both groups during the experiment; terminal hyperglycaemia was more expressed in the MF group. Due to the high initial glycogen concentration in the liver of MF irradiated animals the accumulation of glycogen was substantially lower and started later than in irradiated AL animals. (author)

Whole-body X-irradiation of mice accelerates polyploidization of hepatocytes

International Nuclear Information System (INIS)

Shima, A.; Egami, N.

1985-01-01

Male C57BL/6 mice were whole-body irradiated with 4.75 gy of X-rays at the age of 2 months and killed at 2, 6, 12 and 19 months after irradiation. The percentage survival began to decline earlier and faster in the irradiated group than the controls up to 19 months after exposure when the study was terminated. The nuclear DNA content of individual hepatocytes was measured by a Feulgen-DNA microfluorometric method, and hepatocytes were classified into various ploidy classes. In the irradiated mice, the degree of polyploidization was significantly higher than the controls by 2 months after exposure and steadily increased up to 6 months after exposure. Thereafter, however, a slow return to the control level was found up to 19 months after irradiation. These results appear to support a hypothesis that radiation accelerates the ageing process as judged from hepatocyte polyploidization. (author)

Relationship between X-ray irradiation and chromosomal damage in bone marrow tissue of mice

International Nuclear Information System (INIS)

Chaubey, R.C.; George, K.P.; Sundaram, K.

1976-01-01

X-ray induced chromosomal damage in bone-marrow tissue of male mice was studied using micronucleus technique. Dose response relationship was evaluated. Male Swiss mice received whole body x-ray irradiation at different doses from 25-1000 rads. Animals were sacrificed at the end of 24 hours, bone-marrow smears were made and stained in May-Grunwald-Giemsa. The preparatians were scored for the following types of aberrations: micronuclei in young erythocytes-polychromatic cells and in the mature erythrocytes-normechromatic cells. A dose dependent increase in the frequency of micronuclei in polychromatic cells up to a dose of 100 rads was observed. In addition the effect of post-irradiation duration on the frequency of micronuclei in polychromatic and normochromatic cells were studied. Male Swiss mice were exposed to 200 rads x-rays and were then sacrificed at different time intervals after irradiation and bone-marrow preparations were made and scored. Maximum polychromatic cells with micronuclei were observed in 24 hours post-irradiated animals, thereafter a decrease in the frequency of polychromatic cells with micronuclei was observed in 40 hours post irradiated animals. (author

Protective effect of alkali extract of Huangmo (AEHM) on immunological function in X-irradiated mice

International Nuclear Information System (INIS)

Ye Fei; Wu Congmei; Su Shijie; Cao Ruimin

1996-01-01

The male mice were given ip AEHM 5 mg/kg, wt/d before irradiation with 2.0 Gy X-rays for 3 days, and the changes of several immunological indexes were observed 24 h after X-irradiation. The results showed that AEHM significantly increased the numbers of splenocytes and thymocytes, the reaction of splenocytes to ConA and the spontaneous proliferation of thymocytes in irradiated mice, and decreased the fall of spleen and thymus. In addition, a tendency of the increases in the above indexes in the intact mice treated with AEHM was observed. Meanwhile, AEHM possessed similar radioprotective effect on immunological functions to polysaccharides of Ginseng. The results suggest that AEHM has not only a radioprotective effect on immunological functions in the irradiated mice, but also an enhancing effect on the defence functions in the intact mice. It is very hopeful that AEHM acted as immune-enhanced drug should be used in the clinic

The effect of thymus cells on bone marrow transplants into sublethally irradiated mice

International Nuclear Information System (INIS)

Kruszewski, J.A.; Szcylik, C.; Wiktor-Jedrzejczak, W.

1984-01-01

Bone marrow cells formed similar numbers of 10-days spleen colonies in sublethally (6 Gy) irradiated C57B1/6 mice as in lethally (7.5 Gy) irradiated mice i.e. approximately 20 per 10 5 cells. Numbers of 10 day endogenous spleen colonies in sublethally irradiated mice (0.2 to 0.6 per spleen) did not differ significantly from the numbers in lethally irradiated mice. Yet, transplants of 10 7 coisogenic marrow cells into sublethally irradiated mice resulted in predominantly endogenous recovery of granulocyte system as evidenced by utilization of ''beige'' marker for transplanted cells. Nevertheless, transplanted cells engrafted into sublethally irradiated mice were present in their hemopoietic tissues throughout the observation period of 2 months never exceeding 5 to 10% of cells. Thymus cells stimulated endogenous and exogenous spleen colony formation as well as endogenous granulopoietic recovery. Additionally, they increased both the frequency and absolute numbers of graft-derived granulocytic cells in hemopoietic organs of transplanted mice. They failed, however, to essentially change the quantitative relationships between endogenous and exogenous hemopoietic recovery. These results may suggest that spleen colony studies are not suitable for prediction of events following bone marrow transplant into sublethally irradiated mice. Simultaneously, they have strengthened the necessity for appropriate conditioning of recipients of marrow transplants. (orig.) [de

Frequencies of aneuploidy and dominant lethal mutations in young female mice induced by low dose γ-rays

International Nuclear Information System (INIS)

Yao Suyan; Zhang Chaoyang; Dai Lianlian; Gao Changwen

1991-01-01

Relationship between aneuploidy, dominant lethal mutations and doses in young feral mice induced by low dose γ-rays was examined. The results suggest that the frequencies of aneuploidy of embryos increased at 0.15 Gy, but increases at over 0.50 Gy after irradiation in groups. The frequencies of aneuploidy and dominant lethal mutations increased with increasing doses and fitted linear relationship. This dose-response relationship of trisomic was not significant. The frequency of dominant lethal mutations induced by 60 Co γ irradiation is 5.59%. The effect of dominant lethal mutation is higher than that of the aneuploidy

Poly(ADP-ribose) metabolism in X-irradiated Chinese hamster cells: its relation to repair of potentially lethal damage

International Nuclear Information System (INIS)

Ben-Hur, E.; Elkind, M.M.

1984-01-01

Nicotinamide-adenine dinucleotide (NAD + ) is the substrate used by cells in poly(ADP-ribose) synthesis. X-irradiation of log-phase Chinese hamster cells caused a rapid decrease in NAD + levels which was linearly dependent on radiation dose. The activity of ADP-ribosyl transferase (ADPRT) also increased linearly with radiation dose. The decrease of NAD + was slower, and the increase in ADPRT activity was less pronounced, in a radiation sensitive line, V79-AL162/S-10. An inhibitor of ADPRT, m-aminobenzamide, largely prevented the depletion of cellular NAD + and reduced the rate at which ADPRT activity disappeared during post-irradiation incubation. Post-irradiation treatment with hypertonic buffer or with medium containing D 2 O-which inhibit repair of radiation-induced potentially lethal damage-enhanced the depletion of NAD + and prevented the reduction in ADPRT activity following irradiation. The characteristics of the effects of treatment with hypertonic buffer on NAD + metabolism were qualitatively similar to the effects that such treatment has on radiation-induced cell killing. These results suggest that poly(ADP-ribose) synthesis after irradiation plays a role in the repair of potentially lethal damage. (author)

Reproductive-phase and interphase lethal cell damage after irradiation and treatment with cytostatics

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Hagemann, G.

1979-01-01

After X-ray irradiation of manual cells, two lethal fractions occur due to reproductive and interphase death under low and high radiation doses. The damage kinetics on which this fact is based is compared with hypothetical tumour frequencies and leucemia induction caused in experiments. The reproductive-lethal damage can be manifested by means of colony size spectrometry, with the median colony size class differences (MCD) serving as measure for the damage found. The simultaneous effects of the cytostatics BLEOMYCIN or ICRF 159 and X-rays on reproductive lethal and interphase-lethal damage are measured by means of MCD and survival fraction, and the additive and intensifying effect' is judged with the help of suitably defined terms. This shows that the clinically used ICRF 159 has an additive effect on interphase-lethal and a sub-additive effect on reproductive-lethal cell damage. Thus, favourable results may be expected for the electivity factor in fractionated irradiation and with regard to delayed damage in healthy tissue. (orig.) 891 MG/orig. 892 RDG [de

Lethal effect after whole-body irradiation on mouse with various photon radiations

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Kohda, Shizuo

1976-01-01

The dependence of mortality on the quality of radiation was investigated in ICR mice after wholebody irradiation with 200 kV x-ray, 60 Co γ-ray, or 10 MV x-ray. With respect to the 30 day mortality, LD 50 values were estimated as 606 rad for 200 kV x-ray and as 713 rad both for 60 Co γ-ray and for 10 MV x-ray. Hence, the value of relative biological effectiveness (RBE) to that for 200 kV x-ray was 0.850, while the value decreased with increasing the mortality rate. The value extrapolated to 100% mortality was estimated as 0.6. These results were valid for either 7 or 8 week mice, but the life span of 7 week mice after the irradiation was 3 days shorter than that of 8 week mice. These findings resulted in following conclusions: 1) There are no qualitative differences between 10 MV x-ray and 60 Co γ-ray irradiations. 2) The biological effects after 10 MV x-ray and 60 Co γ-ray irradiations are reduced with increased killing rate, compared with that after 200 kV x-ray irradiations. (Evans, J.)

Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr. ) Karst after X-ray irradiation in mice

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Hsu, H.Y.; Lian, S.L.; Lin, C.C. (Kaohsiung Medical College (Taiwan))

1990-01-01

Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X-ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasn't significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiation exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05).

Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr.) Karst after X-ray irradiation in mice

International Nuclear Information System (INIS)

Hsu, H.Y.; Lian, S.L.; Lin, C.C.

1990-01-01

Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X-ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasn't significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiation exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05)

Effects of AET, MEA, or 5-HT treatment before X-irradiation of pregnant C57B mice

International Nuclear Information System (INIS)

Mazur, L.

1985-01-01

C57B mice were either whole body X-irradiated with a dose of 200 R or, 15 minutes before X-radiation injected with AET, MEA, or 5-HT, in a dose of 40 mg/kg of body weight, on the first day of gestation. Uterine contents were examined on the nineteenth day of pregnancy. The number of corpora lutea was assumed as 100% and the percentage values of live and dead foetuses, resorptions, and non-implanted embryos were calculated. The percentage ratio of females with live foetuses in the uterus, in relation to the total number of those with a vaginal plug was also determined. X-irradiation of pregnant mice influenced the embryonic survival. As compared with controls, in only X-irradiated mice a lower percentage value of live foetuses and higher percentage values of non-implanted embryos and resorptions were found. One dead foetus was only observed in X-irradiated females. Percentage value of X-irradiated females with live foetuses was lower than that of control ones. High mortality of embryos occurred more often before than after the implantation of blastocysts. The percentage value of non-implanted embryos was higher than that of resorptions. AET, MEA, and 5-HT when injected to mice before their X-irradiation acted as radioprotectors. The strongest radioprotective effect was obtained following AET administration, intermediate after 5-HT treatment and the weakest one when MEA was injected. (orig.) [de

A reliable method for reconstituting thymectomized, lethally irradiated guinea pigs with bone marrow cells

International Nuclear Information System (INIS)

Terata, N.; Tanio, Y.; Zbar, B.

1984-01-01

The authors developed a reliable method for reconstituting thymectomized, lethally irradiated guinea pigs. Injection of 2.5-10 x 10 7 syngeneic bone marrow cells into adult thymectomized, lethally irradiated guinea pigs produced survival of 46-100% of treated animals. Gentamycin sulfate (5 mg/kg of body weight) for 10 days was required for optimal results. Acidified drinking water (pH 2.5) appeared to be required for optimal results. Thymectomized, lethally irradiated, bone marrow reconstituted ('B') guinea pigs had impaired ability to develop delayed cutaneous hypersensitivity to mycobacterial antigens and cutaneous basophil hypersensitivity to keyhole limpet hemocyanin; proliferative responses to phytohemagglutinin were impaired. (Auth.)

Interaction of radiation, Dihydroxyanthraquinone, and Adriamycin on the induction of acute lethality in mice

International Nuclear Information System (INIS)

Kimler, B.F.; Cox, G.G.; Reddy, E.K.

1984-01-01

The acute lethality induced by combinations of radiation, Dihydroxyanthraquinone (DHAQ), and Adriamycin (ADR) was investigated in mice. Whole-body irradiation produced acute lethality, with an LD-50/30 of approximately 6.5 Gy. ADR and DHAQ produced LD-50/30's of 14 and 4 mg/kg, respectively. When 10 mg/kg doses were fractionated into 5 x 2 mg/kg daily doses, both drugs were equally or more efficient at producing mortality, 90% by day 30. When 4 Gy radiation was combined with 5 mg/kg ADR or 5 mg/kg DHAQ, a response no greater than that produced by drug alone was obtained. However, when 5 mg/kg ADR was administered concomitantly with 5 mg/kg DHAQ, there was a less-than-additive induction of lethality, resulting in only 21% mortality by day 20. ADR and DHAQ (at doses of 5 mg/kg) were combined but with a 1 day interval between drugs, the protective effect was lost and animals died earlier than after either agent alone. At present, no definite explanation is available for this unusual protective effect of ADR against acute lethality induced by DHAQ

Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

Energy Technology Data Exchange (ETDEWEB)

Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Li, Zhiguo [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Chao, Nelson J. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Department of Immunology, Duke University Medical Center, Durham, North Carolina (United States); Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Chen, Benny J., E-mail: chen0032@mc.duke.edu [Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States)

2013-03-15

Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.

Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

International Nuclear Information System (INIS)

Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S.; Li, Zhiguo; Chao, Nelson J.; Chen, Benny J.

2013-01-01

Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells

The analysis of the defense mechanism against indigenous bacterial translocation in X-irradiated mice

International Nuclear Information System (INIS)

Kobayashi, Toshiya; Ohmori, Toshihiro; Yanai, Minoru; Kawanishi, Gosei; Mitsuyama, Masao; Nomoto, Kikuo.

1991-01-01

The defense mechanism against indigenous bacterial translocation was studied using a model of endogenous infection in X-irradiated mice. All mice irradiated with 9 Gy died from day 8 to day 15 after irradiation. The death of mice was observed in parallel with the appearance of bacteria from day 7 in various organs, and the causative agent was identified to be Escherichia coli, an indigenous bacterium translocating from the intestine. Decrease in the number of blood leukocytes, peritoneal cells and lymphocytes in Peyer's patches or mesenteric lymph nodes was observed as early as 1 day after irradiation with 6 or 9 Gy. The mitogenic response of lymphocytes from various lymphoid tissues was severely affected as well. The impairment of these parameters for host defense reached the peak 3 days after irradiation and there was no recovery. However, in vivo bacterial activity of Kupffer cells in mice irradiated with 9 Gy was maintained in a normal level for a longer period. It was suggested that Kupffer cells play an important role in the defense against indigenous bacteria translocating from the intenstine in mice. (author)

Entire litters developed from transferred eggs in whole body x-irradiated female mice

International Nuclear Information System (INIS)

Lin, T.P.

1980-01-01

The sensitivity of mouse eggs to sublethal x-irradiation was determined in vitro and in vivo with regard to the development of donor litters in foster mothers. One thousand seven hundred fifty-eight unfertilized eggs of agouti dark-eyed donor mice were transferred into 293 unirradiated or x-irradiated, mated female pink-eyed mice. Two hundred thirty-nine recipients became pregnant; of these 35 produced litters containing solely dark-eyed fetuses. Sublethal doses of x-radiation administered to donor eggs in vitro before transferring into unirradiated recipients did not influence significantly the number of litters of exclusively dark-eyed fetuses produced. However, recipients irradiated by 250 roentgens (r) produced more solely dark-eyed litters than did those irradiated with 100 r. In 21 pregnant females irradiated by 100 r, only 3 (14%) developed solely dark-eyed fetuses as compared to 22 pregnant females irradiated by 250 r, of which 13 (59%) developed solely dark-eyed fetuses, all from unirradiated, transferred eggs. Of another group of 22 pregnant females which received 250 r body irradiation and subsequently received eggs also irradiated by 250 r, only 7 (32%) produced litters of dark-eyed fetuses. No one female of these three groups carried native fetuses. Such radiation-induced infertility resulting from damage of native eggs rather than loss of mother's ability to carry a pregnancy, is frequently remedied by egg transfer

Life-shortening and carcinogenesis in mice irradiated neonatally with x rays

International Nuclear Information System (INIS)

Sasaki, S.; Kasuga, T.

1981-01-01

The characteristics of life-shortening and carcinogenesis were investigated in x-irradiated neonatal B6WFr mice. Animals were irradiated with 24 hr after birth and allowed to complete their normal life span. Mean life span was shortened linearly with doses at a rate of 9.1% per 100 R for females and 9.8% for males. The spectrum of neoplastic diseases was apparently modulated by x irradiation, showing neonatal B6WFr mice to be highly susceptible to the induction of thymic lymphoma, liver tumor, and pituitary tumor. The dose-response relationship for thymice lymphoma could be described by a linear-quadratic model, and linearity could be rejected. Thymic lymphoma developed after a short latent period, resulting in death between 100 and 450 days of age. Liver and pituitary tumors increased with increasing dose up to 400 R and decreased thereafter. The latent period for liver tumor development was apparently shortened with increasing doses. Pituitary tumor developed in excess only in females after a long latent period

Effects of mecobalamin on testicular dysfunction induced by X-ray irradiation in mice

International Nuclear Information System (INIS)

Oshio, Shigeru; Yazaki, Tsunetada; Umeda, Takashi; Ozaki, Satoru; Ohkawa, Isao; Tajima, Tetsuya; Yamada, Takeshi; Mohri, Hideo.

1991-01-01

Experimental testicular dysfunction was produced by X-ray irradiation to the testes in mice. Mecobalamin (CH 3 -B 12 ) was orally administered at a daily dose of 0.01, 0.1 or 1 mg/kg six times a week for 8 weeks from the next day after the irradiation. The control mice received physiological saline in the same manner. On 4th- and 6th-week after the irradiation, the weights of testes and epididymides were decreased, although those of the body and accessory sex glands (seminal vesicle, coagulating gland and prostate) were nearly equal to those of non-irradiated mice. At the same time, the diameter of seminiferous tubules decreased and sperm parameters (sperm count, sperm motility and sperm abnormality) deteriorated. When CH 3 -B 12 (1 mg/kg) was administered, the diameter of seminiferous tubules increased and sperm parameters improved as compared to those of the control. The results indicate that CH 3 -B 12 improved the experimental testicular dysfunction in mice induced by the irradiation. These results suggest that CH 3 -B 12 might accelerate testicular function. (author)

The protective effect of Royal Jelly against the hemopoiesis dysfunction in X-irradiated mice

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Emori, Yutaka; Oka, Hideki; Ohya, Osamu; Tamaki, Hajime; Hayashi, Yoshiro [Zeria Pharmaceutical Co., Ltd., Konan, Saitama (Japan). Central Research Laboratories; Nomoto, Kikuo

1998-02-01

The protective effect of Royal Jelly (RJ) against the hemopoietic dysfunction in whole body X-irradiated C57BL/6 mice was investigated. When RJ (1.0 g/kg, po or 0.5 g/kg, ip) was administered every day beginning two weeks before X-irradiation (10 Gy), a significant increase in the number of leukocytes and erythrocytes was observed in mice treated with RJ, as compared with X-irradiated control. In addition, the number of colony forming units in culture (CFU-C) of bone marrow cells or splenocytes was significantly increased in mice treated with RJ. Therefore, when granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) in peripheral blood was measured by ELISA kit, a significant increase in the amount of GM-CSF and IL-3 was observed. These results suggest that the protective effect of RJ against hemopoietic dysfunction could be expressed through an increase in the number of hemopoietic stem cells by the induction of hemopoietic factor such as GM-CSF and IL-3. (author)

Changes in activities of adaptive liver enzymes in rats after non-lethal x-irradiation

International Nuclear Information System (INIS)

Toropila, M.; Ahlersova, E.; Ahlers, I.; Benova, K.

1998-01-01

The effect of a single dose of whole-body X-irradiation of 2.39 Gy (250 R) on the activities of selected adaptive rat liver enzymes and blood serum corticosterone concentrations was followed for a period of 28 days. Rats of Wistar strain SPF breeding (VELAZ Prague) were used. Both irradiated and control animals were fed in pairs with the same amount of feed as was consumed by irradiated animals in the pilot experiment. The feed intake of irradiated animals decreased significantly until the fourth day. During the rest of the experimental period no significant differences were recorded in feed intake between the experimental and control groups. The activity of tyrosine aminotransferase (TAT) in the liver of irradiated animals increased, with the exception of the initial period. Similar changes were recorded in the activity of tryptophane-2-3 dioxygenase (TO). A significant increase on the third day and a significant decrease from the seventh day after irradiation was recorded in the activity of aspartate aminotransferase (AST). Similar changes were observed with alanine aminotransferase (ALT). It is necessary to stress that the activity of this enzyme decreased also on the first day after irradiation. Until the third day there was a marked increase of serum corticosterone in the irradiated animals. The results point not only towards significant changes to the parameters observed, caused by a non-lethal irradiation dose, but also towards the importance of the nutritional regime, so-called paired feeding

Effect of single and fractionated x-irradiation on maze learning ability of mice

International Nuclear Information System (INIS)

Aoyama, Takashi; Norimura, Toshiyuki; Nakamura, Takeshi; Yoshikawa, Isao

1976-01-01

Fifty-six-day-old male ddk mice at the starting of the investigation were used as subjects through the experiment for 64 weeks. After 15 days' preliminary training, and 16 times of weekly trial training using complete maze, 15 mice received a single 224 rads of x-rays (S group), another 15 mice received two 112 rads spaced two weeks apart (F group) and another 15 mice were sham-irradiated (Control group). Then those mice were tested on the multiple T-maze with nine-choice points and change of performance was observed in terms of errorchoices by giving one test trial a week. We introduced the concept of ''confusional trials'' as an index for surmising to what extent mice failed to exhibit good maze learning habits. In the results, the F group showed significantly worse performance than the two other groups at early stages, opposite to it the S group exhibited the same, but at late stages after irradiation. The worse performance of F group should be considered to be due to the psychological after-effect to fractionated irradiation and that for S group could be assumed to be due to the acceleration of aging by the irradiation. (auth.)

Late radiation effects in animals surviving lethal irradiation

Energy Technology Data Exchange (ETDEWEB)

Dimitrov, L A

1974-01-01

Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergency of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine disintegrations. Some of the described late radiation effects were also observed in biological controls as features of ageing. After application of radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival till 30th day, DNA and protein metabolism, immune reactions) of the lethally irradiated animals.

Hemopoiesis in bone marrow of lethally irradiated mice

International Nuclear Information System (INIS)

Viktora, L.; Zoubkova, M.; Urbankova, J.

1976-01-01

A percentual representation of individual types of cells and their share of the restoration of hemopoiesis in bone marrow was observed on the 9th, 12th, 16th and 20th days following transplantation of bone marrow cells to letally irradiated mice. Myelopoiesis was ascertained which on the 20th day after transplantation became the dominant constituent and reached peak level around the 16th day after transplantation. The examination further showed that with regard to the period of irradiation and transplantation the erythropoiesis in bone marrow culminates on the 9th day after the transplantation and that normal values are quickly restored. On the 2ath day myelopoiesis and lymphopoiesis come close to values in normal bone marrow

Thyroid and pancreatic hormones in lethally irradiated rats

International Nuclear Information System (INIS)

Ahlersova, E.; Ahlers, I.; Praslicka, M.

1985-01-01

The concentrations of thyroxine, triiodothyronine and reverse triiodothyronine, glucagon and insulin in the serum or plasma were determined by radioimmunoassay in male rats of the Wistar strain 1, 6, 24, 48 and 72 hours after irradiation with 14.35 Gy (1500R) of X-rays. The irradiated and sham-irradiated rats were starved till examination. The concentrations of thyroxine and triiodothyronine dropped 6 hours after irradiation as compared with controls, the concentration of thyroxine also dropped after 72 hours. The level of reverse triiodothyronine in irradiated rats increased in the terminal period. The level of insulin dropped 24 hours after irradiation, at 72 hours it was higher than that in controls. The concentration of glucagon in irradiated rats increased in the terminal phase of radiation disease. The results document the diverse reaction of hormones in lethally irradiated rats and contribute to a deeper recognition of metabolic imbalance in the course of radiation disease. (author)

Late radiation effects in animals surviving lethal irradiation

International Nuclear Information System (INIS)

Dimitrov, L.A.

1974-01-01

Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergence of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine desintegrations which lead to a disturbed supply of the vessels and afterwards to their sclerosis. Some of the described late radiation effects were also observed in biological controls as festures of ageing while in irradiated animals they were manifested in an earlier period. After application of optimal amounts radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival

Induction of dominant lethal mutations by gamma irradiation of Gallus domesticus spermatozoa

Energy Technology Data Exchange (ETDEWEB)

Baumgartner, J; Grom, A; Csuka, J; Kindlova, L [Poultry Research Institute, Ivanka pri Dunaji (Czechoslovakia)

1977-01-01

Mixed semen of Gallus domesticus cocks was gamma irradiated in vitro with exposures of 500, 1000, 2000, and 3000 R at the exposure rate of 5.86 Rs/sup -1/. After the irradiation the semen was applied to experimental and control layer hens, the embryonic mortality in F/sub 1/ was observed, the total number of incubated eggs was 3344. Irradiation with 500 R had a favourable influence on embryonic vitality, the exposures 1000, 2000, and 3000 R resulted in increased embryonic mortality, for 2100 R a 50% mortality of offspring was found. Induced dominant lethality was manifest during embryonic and oviduct development. The frequency of induced dominant lethality for exposures used was 19.2, 9.9, 48.3, and 69.1%, the values of mutation rate were 0.087, 0.104, 0.659, and 1.174. The mutation rate had a linear course, the value of the lethal hit per gamete for 1 R was 1.04x10/sup -4/.

Induction of dominant lethal mutations by gamma irradiation of Gallus domesticus spermatozoa

International Nuclear Information System (INIS)

Baumgartner, J.; Grom, A.; Csuka, J.; Kindlova, L.

1977-01-01

Mixed semen of Gallus domesticus cocks was gamma irradiated in vitro with exposures of 500, 1000, 2000 and 3000 R at the exposure rate of 5.86 Rs -1 . After the irradiation the semen was applied to experimental and control layer hens, the embryonic mortality in F 1 was observed, the total number of incubated eggs was 3344. Irradiation with 500 R had a favourable influence on embryonic vitality, the exposures 1000, 2000 and 3000 R resulted in increased embryonic mortality, for 2100 R a 50% mortality of offspring was found. Induced dominant lethality was manifest during embryonic and oviduct development. The frequency of induced dominant lethality for exposures used was 19.2, 9.9, 48.3, and 69.1%, the values of mutation rate were 0.087, 0.104, 0.659, and 1.174. The mutation rate had linear course, the value of the lethal hit per gamete for 1 R was 1.04x10 -4 . (author)

Vitamin E-deficiency did not exacerbate partial skin reactions in mice locally irradiated with X-rays

International Nuclear Information System (INIS)

Chi, C.; Hayashi, Daisuke; Nemoto, Masato; Nyui, Minako; Anzai, Kazunori; Urano, Shiro

2011-01-01

We previously showed that free radicals and oxidative stress are involved in radiation-induced skin reactions. Since vitamin E (VE) is a particularly important lipophilic antioxidant, VE-deficient mice were used to examine its effects on radiation-induced skin damage. The VE content of the skin was reduced to one fourth of levels of normal mice. Neither the time of onset nor the extent of the reactions quantified with a scoring system differed between normal and VE-deficient mice after local X-irradiation (50 Gy). Similarly, there was no difference in the levels of the ascorbyl radical between the groups, although they were higher in irradiated skin than non-irradiated skin. X-irradiation increased the amount of Bax protein in the skin of normal mice both in the latent and acute inflammatory stages, time- and dose-dependently. The increase was associated with an increase in cytochrome c in the cytosolic fraction, indicating that apoptosis was also promoted by the irradiation. The increase in Bax protein correlated well with the thickness of the skin. Although a deficiency in VE should lower resistance to free radicals in the mitochondrial membrane and thus enhance radiation-induced Bax expression and apoptosis, it actually attenuated the increase in Bax protein caused by irradiation. (author)

Accumulation of lipid peroxidation products in eye structures of mice subjected to whole-body X-irradiation

International Nuclear Information System (INIS)

Sakina, N.L.; Dontsov, A.E.; Afanas'ev, G.G.; Ostrovskij, M.A.; Pelevina, I.I.

1990-01-01

In studying the effect of whole-body X-irradiation on the accumulation of lipid peroxidation products (conjugated dienes, TBA-active products, and Sciff bases) in retina and retinal pigmented epithelium of pigmented and nonpigmented mice it was shown that irradiation of dark-pigmented mice does not cause even a slight accumulation of lipid peroxidation products as compared to that in the controls. Albino mice exhibited a marked increase in the level of lipid peroxidation products which was manifested soon after irradiation and persisted for at least 3 months after irradiation. Melanine is suggested to participate in protecting eye structures against pro-oxidizing action of ionizing radiation

Immuno-enhancement in tumor-bearing mice induced by whole body X-irradiation with 75 mGy

International Nuclear Information System (INIS)

Zhang Ying; Li Xiuyi; Gong Shouliang; Liu Shuzheng

2000-01-01

Objective: In present study the authors observed the effect of whole body irradiation (WBI) with 75 mGy X-rays on the immune function of tumor-bearing mice. Methods: Lewis lung carcinoma cells were implanted into the right thigh muscle of C57BL/6J mice. Ten days after tumor implantation, the tumor-bearing mice were administrated with 75 mGy X-rays WBI, then the mice were sacrificed 18 h after irradiation to detect the immune parameters including the spontaneous proliferation of thymocytes, the proliferative response of splenocytes to ConA and LPS, the cytotoxic activities of specific cytotoxic lymphocytes (CTL) and natural killer cells (NK), as well as lymphokine activated killer cells (LAK) in spleen. The methods the authors used were 3 H-TdR incorporation or release assay. Results: the immune parameters of exposed tumor-bearing mice were much higher than those of sham-irradiated tumor-bearing mice (P<0.01). Conclusion: These results suggested that low dose radiation (LDR) could enhance the immune function of tumor-bearing mice, which might be of practical significance in the prevention and therapy of cancer

Modulation of haemopoietic radiation response of mice by diclofenac in fractionated treatment

International Nuclear Information System (INIS)

Hofer, M.; Pospisil, M.; Pipalova, I.; Hola, J.

1996-01-01

The effects were studied of diclofenac, an inhibitor of prostaglandin synthesis, on the acute radiation syndrome elicited in mice by fractionated irradiation. Several hematological parameters were evaluated in mice irradiated with 5x 2 Gy and 3x, 4x, or 5x 3 Gy (intervals between fractions 24 h) from a 60 Co gamma source. The animals were treated with diclofenac either before each fraction or only once before the last fraction. The survival of mice was recorded after the irradiation regimen of 5x 3 Gy followed by a ''top-up'' dose of 3.5 Gy given 24 h after the last radiation fraction. Statistically significant enhancement of the endogenous spleen colony and of leukopoiesis was found in mice treated with diclofenac repeatedly, as compared with both saline-treated irradiated controls and animals administered a single diclofenac dose, if a sublethal total radiation dose had been accumulated. However, following accumulation of a lethal radiation dose, slightly impaired survival was observed in mice given diclofenac. It follows from the results that diclofenac is a suitable drug for enhancing leukopoisesis impaired by sublethal fractionated irradiation. Nevertheless, the undesirable side effects of this drug affect adversely the survival of the experimental animals following a lethal accumulated radiation dose. 3 tabs., 3 figs.,32 refs

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

Science.gov (United States)

Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

2005-04-01

Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

The effect of whole body or total-head x irradiation of the metallophilic cells in the mice spleen

International Nuclear Information System (INIS)

Sasaki, Osamu; Matsueda, Yasutoshi; Mizuguchi, Hiroshi; Moriguchi, Kenzo; Ogata, Kunitoshi; Sugie, Tsuneto

1984-01-01

The purpose of this paper is to clarify morphological changes of the reticuloendothelial cells in the spleen following X-irradiation by Katsura's silver impregnation method. The animals used in this experiment were ddN female mice weighing 20 to 25g. The mice were given X-irradiation to the total-head (1,500R) or whole body (300R). The metallophilic cells in the spleen of control mice were of the small foamy type in the follicle, the large stellate type in the marginal metallophils, the small branching type in the marginal zone and the small foamy or round type in the red pulp, respectively. The metallophilic cells decreased immediately after whole body irradiation and the number of cells returned to normal in from 10 to 14 days. On the other hand, the number of the metallophilic cells in the follicle and the perifollicular region increased immediately after total-head X-irradiation. This state continued for several days. In the marginal zone and red pulp, the number of amoebian type cells appeared from 24 hours after irradiation and the number of cells in total-head irradiation group were more clearly distinguishable than in the whole body irradiated group. (author)

Protective properties of plasma of burnt and irradiated rats against lethal effect of endotoxins in vivo

Energy Technology Data Exchange (ETDEWEB)

Budagov, R S; Chureyeva, L N

1984-10-01

The purpose of this work was to estimate protective properties of plasma in disease with increased endotoxemia. Burns and acute radiation sickness were used as models of suppression of physiological mechanisms of detoxication. Experiments were performed on male Wistar rats and mice, which received 3rd degree burns over 15% of the body surface, whole body gamma irradiation at 7.5 Gr or both. At 3 hours, 3, 7 and 12 days after the exposure the animals were decapitated and blood collected. The irradiated mice received 0.2 ml endotoxin intraperitoneally, 1.0 ml freshly prepared rat plasma, then the lethality of the mice in 24 hours was observed. It was found that the plasma of intact rats was capable of decreasing the lethal effects of S. typhimurium and E. coli endotoxins in vivo in mice. Deep skin burns, acute radiation sickness and the combined effects of radiation and thermal injury did not change this phenomenon. The plasma of the experimental rats retained the protective properties at various periods of time after the thermal, radiation and combined exposures. The functioning of the humoral detoxication mechanism is radioresistant, indirectly indicating the nonimmunoglobulin nature of endotoxin inactivators. 19 references.

Inhibition of potential lethal damage repair and related gene expression after carbon-ion beam irradiation to human lung cancer grown in nude mice

International Nuclear Information System (INIS)

Yashiro, Tomoyasu; Fujisawa, Takehiko; Koyama-Saegusa, Kumiko; Imai, Takashi; Miyamoto, Tadaaki

2007-01-01

Using cultured and nude mouse tumor cells (IA) derived from a human lung cancer, we previously demonstrated their radiosensitivity by focusing attention on the dynamics of tumor clonogens and the early and rapid survival recovery (potential lethal damage repair: PLD repair) occurring after X-ray irradiation. To the authors' knowledge, this is the first study demonstrating gene expression in association with PLD repair after carbon-ion beam or X-ray irradiation to cancer cells. In this study we tried to detect the mechanism of DNA damage and repair of the clonogens after X-ray or carbon-ion beam irradiation. At first, colony assay method was performed after irradiation of 12 Gy of X-ray or 5 Gy of carbon-ion beam to compare the time dependent cell survival of the IA cells after each irradiation pass. Second, to search the genes causing PLD repair after irradiation of X-ray or carbon-ion beam, we evaluated gene expressions by using semi-quantitative RT-PCR with the selected 34 genes reportedly related to DNA repair. The intervals from the irradiation were 0, 6, 12 and 24 hr for colony assay method, and 0, 3, 18 hr for RT-PCR method. From the result of survival assays, significant PLD repair was not observed in carbon-ion beam as compared to X-ray irradiation. The results of RT-PCR were as follows. The gene showing significantly higher expressions after X-ray irradiation than after carbon-ion beam irradiation was PCNA. The genes showing significantly lower expressions after X-ray irradiation rather than after carbon-ion beam irradiation were RAD50, BRCA1, MRE11A, XRCC3, CHEK1, MLH1, CCNB1, CCNB2 and LIG4. We conclude that PCNA could be a likely candidate gene for PLD repair. (author)

Abnormal sensitivity of diploid skin fibroblasts from a family with Gardner's syndrome to the lethal effects of X-irradiation, ultraviolet light and mitomycin-C

International Nuclear Information System (INIS)

Little, J.B.; Nove, J.; Weichselbaum, R.R.

1980-01-01

Skin fibroblasts isolated from two members of the same family with the cancer-prone disease Gardner's Syndrome (intestinal polyposis, colon cancer, bone and soft tissue tumors) showed enhanced sensitivity to the lethal effects of X-irradiation, ultraviolet light and mitomycin-C. These cells showed no liquid-holding type recovery following UV-irradiation of confluent cultures, but were normal in their capacity for UV-induced unscheduled DNA synthesis. UV survival was not influenced by post-irradiation incubation with caffeine. (orig.)

Studies on the mutagenic and cytogenetic effects of irradiated wheat in mice

International Nuclear Information System (INIS)

Reddy, P.P.; Reddi, O.S.; Ebenezer, D.N.; Naidu, N.V.; Goud, S.N.

1978-01-01

A series of experiments were conducted to test the mutagenic and cytogenetic potentials of freshly and stored irradiated wheat in mice. In the first series, the effects of feeding of CBA mice for 8 weeks with the diet containing 60% of wheat freshly irradiated ( 3 H/He mice were undertaken. Feeding of both freshly and stored irradiated wheat showed neither an increase in dominant lethals and chromosomal aberrations nor a reduction in germ cells. In another series, the reproductive performance of the CBA females fed stored irradiated (75 krad) wheat was investigated and it was observed that the average total number of litters and the litter size did not vary from those of the females fed unirradiated wheat. (author)

Terminal deoxynucleotidyl transferase activity in the regenerating thymus of X-irradiated mice

International Nuclear Information System (INIS)

Daculsi, R.; Astier, T.; Legrand, E.; Duplan, J.F.

1982-01-01

The distribution of terminal deoyxnucleotidyl transferase (TdT) enzyme activity (EU per 10 8 cells) between peaks I and II was followed for a period of 42 days in regenerating thymus of lethally irradiated (9 Gy) C3H mice restored with 10 6 (C3H x AKR) F1 bone marrow cells. The detection of Thy-1.1 and Thy-1.2 surface antigens allowed for the discrimination between host and donor cells, and the main subpopulations of thymic cells were characterized by their sensitivity to H-2sup(k) antiserum and to dexamethazone. Two peaks of TdT activity could be detected on phosphocellulose chromatographic separation. The distribution of TdT activity between these two peaks was followed during the two periods of thymic endo- and exoregeneration. Peak I TdT activity was closely correlated with the variation in the percentage of the high H-2 population. Peak II activity was mostly related to low H-2 cells. The per cell content of both peak I and peak II activities exceeded the norm in rapidly expanding populations. Finally between days 10 and 14 the TdT activity of the endoregenerating population was apparently not different from that of the exoregenerating population between days 14 and 22. (Auth.)

Adaptive response of spermatogenic cell apoptosis selectively induced by low dose X-ray irradiation in mice

International Nuclear Information System (INIS)

Liu Guangwei; Dong Lihua; Liu Yang; Lv Zhe; Liu Shuchun; Gong Shouliang

2003-01-01

Objective: The adaptive response of spermatogenic cell apoptosis induced by whole-body X-ray irradiation at low doses was studied in mice. Methods: Kunming male mice were irradiated with an inductive dose (D1:75 mGy) and/or a challenging dose (D2:1.0, 2.0 or 3.0 Gy). Different kinds of spermatogenic cells were separated using density gradient centrifugation and their apoptotic percentages were analysed using flow cytometry (FCM). Results: When the mice were irradiated with D1 6 h before irradiation with D2, the apoptotic percentages of the spermatogonia and spermatocytes declined rapidly as compared with those in the groups irradiated with D2 only, and those of spermatids and spermatozoa showed no significant changes. When the interval times between D1 and D2 was 3, 6, 12 or 24 h, the apoptotic percentages in spermatogonia and spermatocytes reduced early, significantly and continued for a longer duration after smaller D2(1.0 and 2.0 Gy) irradiation, while the apoptotic percentages did not change after larger D2(3.0 Gy) irradiation. Conclusion: The adaptive response of apoptosis in spermatogonia and spermatocytes could be selectively induced by low dose X-ray irradiation. The adaptive response could be closely related to the D2 dose and interval time between D1 and D2

Protective effect of zinc against lethality of the irradiated mice

International Nuclear Information System (INIS)

Matsubara, J.; Inada, T.; Machida, K.

1982-01-01

The effects of adding 1000 ppm Zn in the drinking water 10 days before gamma irradiation (562 - 1000 rad) of mice were studied. The mice which had received zinc had a lower mortality rate and a longer survival time compared to the controls. The LD 50 of gamma radiation was 690 rad in the control group and 770 rad in the zinc group. Zinc added to the culture medium of human melanoma cells did not shown any change in radiosensitivity; thus the radioprotective effect of zinc appears to work at the whole body level. (U.K.)

Peculiarities of morphofunctional state of adenohypophysis in lethally irradiated recipients after bone marrow transplantation

International Nuclear Information System (INIS)

Tsutsaeva, A.A.; Glushko, T.A.; Shatilova, L.E.; Tupchienko, G.S.

1992-01-01

The effect of lethal irradiation and transplantation of syngenic bone marrow on the morphofunctional state of hypophysis at various stages of the posttransplantation period has been studied for 3 months using 100 linear male mice of 1 F 1 (CBAXC 57 B) line. The experiments conducted have shown that bone marrow transplantation reduces the intensity of the negative effect of irradiation on hypophysis and facililitates normalization of its histological structure. There was a correlation between changes in the number of secretory cells in the anterior lobe of the hypophysis and the level of corticosterone in irradiated and bone-marrow-protected animals

Arrest of irradiated G1, S, or G2 cells at mitosis using nocodazole promotes repair of potentially lethal damage

International Nuclear Information System (INIS)

Iliakis, G.; Nuesse, M.

1984-01-01

The ability of synchronized Ehrlich ascites tumor cells, irradiated in G1, S, and G2 phases, to repair potentially lethal damage when arrested at mitosis by using 0.4 μg/ml nocodazole, a specific inhibitor of microtubule polymerization, has been studied. Cells irradiated in these phases were found to repair potentially lethal damage at mitosis. The extent of this repair was similar to that observed for cells irradiated at the same stages in the cell cycle but allowed to repair potentially lethal damage by incubating in balanced salt solution for 6 hr after X irradiation

X-irradiation of mice in the early fetal period. Pt. 2

International Nuclear Information System (INIS)

Kriegel, H.; Weber, L.; Schmahl, W.

1979-01-01

Pregnant NMRI mice were X-irradiated with 50, 100 and 200 R, respectively, on the twelfth gestational day. The brains of their offspring were weighed and examined for acetylcholinesterase and Na,K-ATPase activities from birth until the 64th postnatal day. The postnatal brain weights were influenced by the prenatal irradiation in a dose-dependent manner. At birth the brains of the treated animals weighed less than those of the controls. After a limited period of restitution (postnatal days 3 to 10), weights fell again, as compared to the controls, and persisted at subnormal levels. This was assumed to be a sequel of surplus neuron cell formation and their speedy degradation as soon as neuronal function had been established. The curves of the activites (per gram of brain tissue) of acetylcholinesterase as well as Na,K-ATPase showed oscillating compensatory responses to the prenatal irradiation. Activities were preferentially found at supernormal levels, the oscillation lasting as long as the restitution period of the brain weights. With the 50 R and 100 R groups, enzyme activities were steadily above the control levels from the 16th until the 48th day after birth. On the 64th postnatal day all enzyme activities but one (200 R, Na,K-ATPase) had returned to the control levels. Oscillating responses to prenatal X-irradiation have been described for the DNA-synthesis in livers and brains of mice during the first three postnatal weeks. From this perspective, our results are discussed as the outcome of radiation-induced alterations in genome activity. (orig.) [de

X-rays and photocarcinogenesis in hairless mice.

Science.gov (United States)

Lerche, Catharina M; Philipsen, Peter A; Wulf, Hans Christian

2013-08-01

It is well known that excessive X-ray radiation can cause non-melanoma skin cancers. With the increased incidence of sun-related skin cancer there is a need to investigate the combination of sunlight and X-rays. Immunocompetent C3.Cg/TifBomTac mice (n = 298) were divided into 12 groups. Mice were irradiated with 12, 29 or 50 kV X-rays. The mice received a total dose of 45 Gy. They were irradiated with 3 SED simulated solar radiation (SSR) either before or after irradiation with X-rays. The groups irradiated with X-rays alone, 0, 3, 9 and 10 mice (0, 12, 29 and 50 kV, respectively) developed squamous cell carcinoma. In the groups irradiated with SSR after X-rays the development of tumours was significantly faster in the 50 kV group than in the corresponding control group (175 vs. 194 days, p X-ray radiation the development of tumours was significantly faster in the 29 and the 50 kV groups than in the corresponding control group (175 vs. 202 days, p X-ray radiation alone is a weak carcinogen in hairless mice. There is an added carcinogenic effect if X-ray radiation is given on prior sun-exposed skin or if the skin is sun-exposed after X-rays. We still believe that X-ray radiation is a safe and effective therapy for various dermatological diseases but caution should be observed if a patient has severely sun-damaged skin or has a high-risk sun behaviour.

Biochemical aspects of the immunomodular action in irradiated survival mice with 60C gama irradiation

International Nuclear Information System (INIS)

Garcia Agudo, N.L. del M. de.

1983-01-01

The radioprotective action of Calmetti-Guerin bacillus (BCG), Corynebacterium parvum, Escherichia coli Lipopolysccharides (LPS) and peptone proteose was evaluated. A single injection of the macrophage activiting agents prior to 60 Co whole-body irradiation increased the survival rate of mice in the lethal dose range. (L.M.J.) [pt

Quantitative changes in the arterial blood gases of mice following localized irradiation of the lungs

International Nuclear Information System (INIS)

Siemann, D.W.; Hill, R.P.

1983-01-01

The arterial pH and partial pressures of oxygen (PaO 2 ) and carbon dioxide (PaCO 2 ) were evaluated in LAF1 mice 15 and 38 weeks after localized irradiation of the animals' thoraxes. Graded radiation doses of 900 to 1200 rad were administered. These doses resulted in 0 to 100% lethality by 26 weeks (180 days) after irradiation. At 15 weeks after treatment mice receiving radiation doses which would subsequently result in lethality (by 180 days) exhibited significant reductions in their PaO 2 and elevations in their PaCO 2 values, respectively. However, there was no clear dose-response relationship between blood gas values and radiation dose, which may reflect the animals' ability to compensate for their poor blood gas exchange by an increased breathing frequency. At 38 weeks after irradiation the blood gas values were abnormal in mice from groups which had normal blood gas values at Week 15 (and no fatalities by Week 26) but in which animal deaths had occurred between Weeks 26 and 38. These data therfore indicated (i) that abnormal blood gas values occurred in the mice prior to fatalities resulting from the acute radiation pneumonitis syndrome and (ii) that mice surviving the initial radiation pneumonitis phase could still succumb to progressive pulmonary toxicity which was reflected by the increasing levels of animal lethality and altered blood gas tensions at the later times

Lack of effect on the chromosomal non-disjunction in aged female mice after low dose x-irradiation

Energy Technology Data Exchange (ETDEWEB)

Strausmanis, R; Hendrikson, I B; Holmberg, M; Roennbaeck, C [Research Inst. of National Defence, Sundbyberg (Sweden). Dept. 4

1978-02-01

Karyotypes were determined in 1064 embryos of aged C57/BL mothers. The virgin female mice were irradiated with 0, 4, 8 or 16 R of X-rays, respectively, and placed with young untreated males 5 days after irradiation. 10.5-days old embryos were recovered from the uterus. Aneuploid embryos classified as alive (heart beats observed at the dissection) were 1 monosomic in the control group (496 embryos) and 2 trisomics in the irradiated group (568 embryos). The number of aneuploid embryos classified as dead was 4 trisomic cases in the control group and 3 trisomics in the irradiated group. The data indicate that trisomic embryos are not uncommon in the mouse but are eliminated in post-implantation death. In contrast to the results of Yamamoto et al. the present data do not demonstrate an increased frequency of chromosome abnormalities in embryos of aged mice X-irradiated before mating as compared to non-irradiated ones.

Lack of effect on the chromosomal non-disjunction in aged female mice after low dose x-irradiation

International Nuclear Information System (INIS)

Strausmanis, R.; Hendrikson, I.-B.; Holmberg, M.; Roennbaeck, C.

1978-01-01

Karyotypes were determined in 1064 embryos of aged C57/BL mothers. The virgin female mice were irradiated with 0, 4, 8 or 16 R of X-rays, respectively, and placed with young untreated males 5 days after irradiation. 10.5-days old embryos were recovered from the uterus. Aneuploid embryos classified as alive (heart beats observed at the dissection) were 1 monosomic in the control group (496 embryos) and 2 trisomics in the irradiated group (568 embryos). The number of aneuploid embryos classified as dead was 4 trisomic cases in the control group and 3 trisomics in the irradiated group. The data indicate that trisomic embryos are not uncommon in the mouse but are eliminated in post-implantation death. In contrast to the results of Yamamoto et al. the present data do not demonstrate an increased frequency of chromosome abnormalities in embryos of aged mice X-irradiated before mating as compared to non-irradiated ones

The effects of radiation dose-rate and quality on the induction of dominant lethals in mouse spermatids

International Nuclear Information System (INIS)

Searle, A.G.; Beechey, G.V.

1981-01-01

Hybrid male mice were given 3 Gy (300 rad) doses of X- or γ-irradiation at dose-rates of either 0.6 or 0.002 Gy/min for each radiation. Germ-cells treated as spermatids were tested for dominant lethality. Effects on spermatogonia were evaluated by studying testis-weight, sperm-count and sperm abnormalities. The rate of induction of dominant lethal mutations was 2.1 times as high after acute X-irradiation as after protracted γ-irradiation. Most of this difference resulted from the change in radiation quality, since the relative effectiveness of X- versus γ-irradiation was 1.9 at low and 1.6 at high dose rates. For each radiation, however, fewer dominant lethals were induced at low dose-rates than at high (low/high ratios of 0.8 and 0.9 respectively) although differences did not reach a significant level. There were no statistically significant effects of dose rate on testis-weight of sperm-count in the X-ray series, but there were significantly less severe effects on both with protraction of the γ-irradiation. Evidence for effects of radiation quality on these characters was conflicting. Frequencies of abnormal spermatozoa were markedly increased 7 weeks after irradiation but there were no consistent effects of radiation intensity or quality. (orig.)

Effect of x-irradiation on cell kinetics of esophageal membrane cells in mice

International Nuclear Information System (INIS)

Ando, Koichi; Tsunemoto, Hiroshi; Urano, Muneyasu; Koike, Sachiko

1977-01-01

Effect of x-irradiation on the cell kinetics of esophageal membrane cells was studied in C3Hf/He male mice. Experimental methods include; counting the number of basal and superficial cells, and pulse or continuous labelling by tritiated thymidine. Esophageal area was irradiated with 1000 rad of 200 kVp x-rays and cell kinetics were studied on the 5th post-irradiation day. Autoradiography revealed the shortening of the cell cycle time, specifically in G- and G- phases. Numbers of basal cells and of superficial cells were found to increase for 5 days after irradiation. Continuous labelling experiments using infusion technique demonstrated than growth fraction of irradiated basal cells was 1.0 as well as that of non-irradiated cells. It was of interest that the migration time, i.e., the time required for labelled cells to migrate from basal cell layer to superficial cell layer, was shortened approximately 1/3 of that of non-irradiated control after irradiation. Diurnal variation was observed not only in normal basal cells but also in irradiated ones, and the rate of increase of labelling index after continuous labelling was independent of the time when the labelling was started. (auth.)

Effect of x irradiation on cell kinetics of esophageal membrane cells in mice

Energy Technology Data Exchange (ETDEWEB)

Ando, K; Tsunemoto, H; Urano, M; Koike, S [National Inst. of Radiological Sciences, Chiba (Japan)

1977-05-01

Effect of x irradiation on the cell kinetics of esophageal membrane cells was studied in C3Hf/He male mice. Experimental methods include; counting the number of basal and superficial cells, and pulse or continuous labelling by tritiated thymidine. Esophageal area was irradiated with 1000 rad of 200 kVp x rays and cell kinetics were studied on the 5th post-irradiation day. Autoradiography revealed the shortening of the cell cycle time, specifically in G- and G- phases. Numbers of basal cells and of superficial cells were found to increase for 5 days after irradiation. Continuous labelling experiments using infusion technique demonstrated than growth fraction of irradiated basal cells was 1.0 as well as that of non-irradiated cells. It was of interest that the migration time, i.e., the time required for labelled cells to migrate from basal cell layer to superficial cell layer, was shortened approximately 1/3 of that of non-irradiated control after irradiation. Diurnal variation was observed not only in normal basal cells but also in irradiated ones, and the rate of increase of labelling index after continuous labelling was independent of the time when the labelling was started.

Influence of thorax irradiation on the survival of mice with spontaneous or artificial lung metastases from a transplantable mammary adenocarcinoma

International Nuclear Information System (INIS)

Wondergem, J.; Haveman, J.; van der Schueren, E.

1985-01-01

The effect of thorax irradiation on lung metastases, either occurring spontaneously from a primary mammary adenocarcinoma (M8013X) transplanted on the leg or artificially induced by intravenous injection of tumor cells was studied. Increasing the interval between the moment at which lung metastases are supposed to originate and the thorax irradiation resulted in a rapid decrease of the effectiveness of this treatment in preventing the development of lung metastases. Increasing the radiation dose led to an increased number of cures; however, an increased number of mice dying of lethal lung damage was also observed. Irradiation of the lungs of mice with 5 or 10 Gy, 24 hours, 7 days or 14 days prior to i.v. injection with tumor cells, did not significantly increase the number of mice with lung metastases. Immunological resistance against the tumor played a role in our experiments with both spontaneous and artificial lung metastases

Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

International Nuclear Information System (INIS)

Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Majima, Takashi; Seki, Shuhji; Matsushita, Yoshitaro; Saitoh, Daizoh

2010-01-01

While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome. (author)

Differences in the acute intestinal syndrome after partial and total abdominal irradiation in mice

International Nuclear Information System (INIS)

Dewit, L.; Oussoren, Y.; Bartelink, H.; Stewart, F.A.

1985-01-01

The acute intestinal syndrome in mice was analysed after partial (PAI) and total abdominal irradiation (TAI). The LDsub(50/15) was significantly higher after PAI (16.3 Gy) than after TAI(14.3 Gy). The dose-response curve for maximal weight loss also showed a shift of 1.8-2 Gy to higher doses after PAI compared with TAI. The X-ray survival curve for duodenal crypt cells was shifted by only 0.6 Gy for PAI and TAI. In order to assess the possible role of radiation-induced leucopenia and the influence of irradiating the spleen (shielded with PAI), lethality, weight loss and blood leucocyte counts were compared after PAI and TAI in splenectomized and non-splenectomized mice. No major difference in leucopenia was found between the different treatment groups, whereas the differences in lethality and weight loss between PAI and TAI remained the same. Shielding the spleen in the partial abdominal field therefore did not contribute to the difference in LDsub(50/15). These findings imply that the increased LDsub(50/15) after PAI compared with TAI was mainly due to shielding of a small part of the bowel (about 13 per cent of the abdominal area). (author)

Models for pulmonary lethality and morbidity after irradiation from internal and external sources

International Nuclear Information System (INIS)

Scott, B.R.; Filipy, R.E.; Hahn, E.F.

1989-05-01

This report provides a hazard-function model for estimating the risk of death from radiation pneumonitis and/or pulmonary fibrosis following a light-water nuclear power accident. A similar model is also provided for estimating the prevalence of respiratory functional morbidity among those that survive death from acute effects. Hazard-function models for lethality and for morbidity were constructed using the cumulative hazard estimator H, which is related to the risk estimator R through the equation R = 1-exp(-H). The estimator H can be calculated using information provided in the report. The method of calculation depends on the exposure scenario. In general, the total normalized dose X for lethality or for morbidity is calculated. For lethality, X = 1 corresponds to a median lethal dose (LD 50 ); for morbidity, X = 1 corresponds to a median effective dose (ED 50 ). H is related to X by the equation H = 1n(2)X/sup V/, where V depends on the type of radiation (or radiations) involved. Contributions to X can arise from each of two main modes of exposure: (1) brief exposure of the lung, at a relatively high dose rate, to mainly external gammas, followed by (2) chronic internal alpha, and/or beta, and/or gamma irradiation of the lung. Equations are provided for calculating the contributions to X from both modes of exposure. 73 refs., 16 figs., 2 tabs

Shielding of the abdominal region during X-irradiation: Effect on haemopoietic stem cells

International Nuclear Information System (INIS)

Vavrova, J.; Petyrek, P.

1984-01-01

The shielding of the abdominal region during X-irradiation is important for two reasons: 1) it prevents the development of the gastrointestinal syndrome following higher radiation doses; 2) it prevents the development of the lethal form of the bone marrow syndrome by shielding a portion of the spinal column bone marrow and the spleen. The dose reduction factor in partial irradiated mice compared to whole-body irradiated mice was 2.6. 15 mins after irradiation with the dose of 10 Gy, the number of spleen colony-forming cells (CFU-S) decreased in the femoral bone marrow of both the group receiving whole-body irradiation and the group having the abdominal region shielded. This decrease persisted in both groups for five hours after irradiation. 48 hours after whole-body irradiation, the number of CFU-S in the femoral bone marrow of the unshielded animals decreased almost to zero values. In shielded group, a statistically significant increase in the number of CFU-S in the femur was observed at 48 hours. At 120 hours, the number of CFU-S in so irradiated mice was at the level of the unirradiated group. In the spleen a great decrease in the number of CFU-S was caused by whole-body irradiation of mice as early as 15 mins after irradiation and the low-levels were recorded until the death of animals. In the shielded group, a statistically signifjcant decrease in the number of CFU-S was observed 15 mins after irradiation, which may have been due to the abscopal effect of irradiation. After a transient recovery 2 hours after irradiation, a significant decrease in the number of CFU-S in the spleens was observed in the subsequent interval from five to 120 hours after irradiation. (author)

Long-term feeding studies in mice fed a diet containing irradiated fish. I

International Nuclear Information System (INIS)

Petten, L.E. van; Calkins, J.E.; McConnell, R.F.; Gottschalk, H.M.; Elias, P.S.

1980-01-01

A wholesomeness feeding study was carried out in mice fed equal amounts of cod or redfish, comprising 45% of the diet. Three groups of animals received either irradiated [1.75 kGy (175 krad)] fish, non-irradiated fish or stock ration. A 90-day subchronic study, a multigeneration reproduction, a dominant lethality and a teratology study were carried out together with an 80-week oncogenic study on the F 1 generation. No adverse effects were noted on growth, reproduction and litter behaviour, in relation to dominant lethality, teratogenicity or oncogenicity. (Auth.)

Effects of feeding lactobacillus GG on lethal irradiation in mice

International Nuclear Information System (INIS)

Dong, M.Y.; Chang, T.W.; Gorbach, S.L.

1987-01-01

Mice exposed to 1400 rads of total body irradiation experienced 80%-100% mortality in 2 wk. Bacteremia was demonstrated in all dead animals. Feeding Lactobacillus GG strain reduced Pseudomonas bacteremia and prolonged survival time in animals colonized with this organism. In animals not colonized with Pseudomonas, feeding Lactobacillus GG also produced some reduction in early deaths, and there was less Gram-negative bacteremia in these animals compared with controls

Migration inhibition of immune mouse spleen cells by serum from x-irradiated tumor-bearing mice

International Nuclear Information System (INIS)

Moroson, H.

1978-01-01

Tumor-specific antigens of the chemically induced MC 429 mouse fibrosarcoma were detected in a 3 M KCl extract of tumor by the inhibition of migration of specifically immune spleen cells. Using this assay with serum from tumor-bearing mice no tumor antigen was detected in serum of mice bearing small tumors, unless the tumor was exposed to local x irradiation (3000 R) 1 day prior to collection of serum. It was concluded that local x irradiation of tumor caused increased concentration of tumor antigen in the serum. When the tumor was allowed to grow extremely large, with necrosis, then host serum did cause migration inhibition of both nonimmune and immune spleen cells. This migration-inhibition effect was not associated with tumor antigen, but with a nonspecific serum factor

Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice

International Nuclear Information System (INIS)

Yasui, Hironobu; Inanami, Osamu; Asanuma, Taketoshi; Iizuka, Daisuke; Nakajima, Takayuki; Kon, Yasuhiro; Matsuda, Akira; Kuwabara, Mikinori

2007-01-01

Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth

Alternative types of duodenal ulcer induced in mice by partial X irradiation of the thorax

International Nuclear Information System (INIS)

Michalowski, A.; Uehara, S.; Yin, W.B.; Burgin, J.; Silvester, J.A.

1983-01-01

The present study extends our earlier observations on gastrointestinal pathology in thorax-irradiated female CFLP mice. It shows that exposure of the lower mediastinum to single doses of 14-30 Gy X rays results in the formation of the proximal duodenal ulcer accompanied frequently by erosion of the antral gastric mucosa. X irradiation of the lateral thoracic fields is responsible for single ulcers in the proximity of duodenal papilla, often associated with a circumscribed area of degeneration of the fundic mucosa of the stomach. In view of the small amount of radiation received by the subdiaphragmatic parts of the alimentary tract, these gastro-duodenal lesions represent abscopal effects of thoracic irradiation

Prenatal deaths and external malformations caused by x-irradiation during the preimplantation period of ddy mice

International Nuclear Information System (INIS)

Ro, Hee Jeong; Choi, Ihl Bhong; Gu, Yeun Wha

1998-01-01

To evaluate the effects of x-irradiation on prenatal deaths, i.e., preimplantation deaths. embryonic deaths, and fetal deaths, and on external malformations in precompacted preimplantation ddy mice. Pregnant mice (n=85), obtained by limiting the mating time to from 6 to 9 A.M., were segregated into 11 groups, The first five groups (n=26) were irradiated with X-ray doses of 0.1, 0.5, 0.75, 1.5, and 3 Gy, respectively, at 24 h post conception (p.c.) of the preimplantation period. The second five (n=27) groups were irradiated at the same X-ray doses, respectively, but at 48 h p.c. of the preimplantation period. The last group (n=32) was the control group. The uterine contents were examined on the 18th day of gestation for prenatal deaths and external malformations. 1) A statistically significant increase in preimplantation deaths with increasing dose was observed in the experimental groups irradiated at 24 h p.c. and in the groups irradiated at 48 h p.c., as compared to the control group. The threshold dose was close to 0.05 Gy and 0.075 Gy for the irradiations at 24 h p.c. and 48 h p.c. respectively. 2) A statistically significant increase in embryonic deaths with increasing dose was observed in all irradiation groups, except the group irradiated with a dose of 0,1 Gy at 48 h p.c.. 3) No fetal deaths were found in any experimental group. 4) In the experimental groups irradiated at 24 h p.c., anomalies increased with statistical significance, as compared with the control group: 2 exencephalies, 2 open eyelids,' 3 anophthalmias, 2 cleft palates. 2 gastroschisis, 1 abdominal wall defect. 1 leg defect, and 2 short tail anomalies; the threshold dose for external malformations was close to 0.2 Gy at 24 h p.c.. In the groups irradiated at 48 h p.c., 1 open eyelid and 2 short tail anomalies were observed, but there was no statistical significance in those malformations. The results of this study reveal that x-irradiation of precompacted preimplantation ddy mice causes not

Therapeutic effects of the joint administration of magnesium aspartate and adenosine monophosphate in gamma-irradiated mice

International Nuclear Information System (INIS)

Pospisil, M.; Netikova, J.; Pipalova, I.; Kozubik, A.

1990-01-01

The joint administration of magnesium aspartate and adenosine monophosphate, injected on days 1 to 4 post radiation, has been found to exert stimulatory effects on the recovery of hemopoietic functions in sublethally gamma-irradiated mice. These therapeutical effects were enhanced in animals protected by peroral administration of cystamine. The treatment scheme used did not modify survival of lethally irradiated mice. The therapeutic effects of magnesium aspartate and adenosine monophosphate in sublethally irradiated mice are explained by the stimulatory action of these drugs on the cell adenylate cyclase system, which influences the erythropoietic functions. (author)

Some biochemical characteristics of a toxic substance isolated from organs of lethally irradiated animals in the course of the intestinal syndrome

Energy Technology Data Exchange (ETDEWEB)

Meter, J D; Sirota, N S [Tsentral' nyj Nauchno-Issledovatel' skij Rentgeno-Radiologicheskij Inst., Leningrad (USSR)

1976-05-01

A toxic substance isolated from organs of lethally irradiated (1300 rads) animals in the period when intestinal syndrome has developed is classified according to the parameters under study (namely, the molecular weight, UV-absorption curve, extinction coefficient, specific monosaccharides, the presence and percentage of KDA, etc.) as lipopolysaccharide of Escherichia coli, the main inhabitant of the gastroenteric tract of mice. That endotoxins (sensitivity to which is increased in this period of radiation sickness) are detected in the blood and organs of lethally irradiated animals, might indicate their participation in the pathogenesis of the intestinal syndrome.

Some biochemical characteristics of a toxic substance isolated from organs of lethally irradiated animals in the course of the intestinal syndrome

International Nuclear Information System (INIS)

Meter, J.D.; Sirota, N.S.

1976-01-01

A toxic substance isolated from organs of lethally irradiated (1300 rads) animals in the period when intestinal syndrome has developed is classified according to the parameters under study (namely, the molecular weight, UV-absorption curve, extinction coefficient, specific monosaccharides, the presence and percentage of KDA, etc.) as lipopolysaccharide of Escherichia coli, the main inhabitant of the gastroenteric tract of mice. That endotoxins (sensitivity to which is increased in this period of radiation sickness) are detected in the blood and organs of lethally irradiated animals, might indicate their participation in the pathogenesis of the intestinal syndrome

Homogeneous immunoglobulins in the serum of irradiated and bone marrow reconstituted mice: the role of thymus and spleen

International Nuclear Information System (INIS)

Mink, J.G.; Radl, J.; Berg, P. van den; Muiswinkel, W.B. van; Oosterom, R. van.

1979-01-01

The influence of thymectomy and splenectomy on the frequency and class distribution of homogeneous immunoglobulins (H-Ig) in serum was studied in lethally irradiated (DBA/2 x C57B1/Rij)F 1 mice reconstituted with syngeneic bone marrow. During four follow-up periods in the first 9 months after transplantation, the sham-operated controls and splenectomized animals developed transient H-Ig in an average frequency of 14.2 and 15.7% respectively. There were no marked differences in the incidence of H-Ig within these two groups. In contrast, thymectomized mice and mice both thymectomized and splenectomized showed H-Ig in much higher frequencies (average percentages 31.6 and 36.5 respectively). The highest frequency of H-Ig was observed between 1.5 and 3.5 months after transplantation. H-Ig of the IgG1 and IgG2 subclasses were most frequent in all groups during the first 3.5 months. Later, H-Ig belonging to the IgM class also appeared in somewhat higher numbers. H-Ig of the IgA class was a very rare finding at any time. These results indicate that the presence of the thymus, but not necessarily of the spleen, is an important factor in the regulation of the immunoglobulin heterogeneity during the reconstitution of the immune system in lethally irradiated and bone marrow reconstituted mice. (author)

Thermo-radiosensitivity of the granulocyte and macrophage precursor cells of mice. II. - X irradiation effects and influence of hyperthermia on the radiosensitivity

International Nuclear Information System (INIS)

Bueren, J.A.; Nieto, M.

1983-01-01

The effects of the X-irradiation on the viability of the granulocyte-macrophage precursors, has been determined by means of the agar diffusion chamber culture technique. The results show the high radiosensitivity of these cells, with survival parameter similar to those previously reported in the literature about different granulocyte-macrophage precursors. When a hyperthermic treatment is performed prior to the X-irradiation, a radiosensitization phenomenon is observed due to the synergism existent between hyperthermia and X rays on the lethality of the precursors. (Authors) 37 refs

Amelioration of radiation damage to haemopoiesis by Ivastimul, given after irradiation to mice protected by peroral cystamine

International Nuclear Information System (INIS)

Vacek, A.; Rotkovska, D.; Bartonickova, A.; Kautska, J.

1992-01-01

Combined radioprotection by preirradiation peroral cystamine and postirradiation Ivastimul administration was examined in sublethally and lethally whole-body gamma-irradiated mice. Enhancement of haemopoietic recovery and increased survival of irradiated mice was demonstrated for a single dose of Ivastimul administered after irradiation. The ameliorative influence of combined radioprotection may be explained by haemopoietic stem cell protection by cystamine and haemopoietic stimulation mediated by Ivastimul. (author) 2 tabs., 3 figs., 20 refs

The enhancing effect of fractionated whole-body x-irradiation on replication of endogenous leukemia viruses in BALB/c mice

International Nuclear Information System (INIS)

Takamori, Yasuhiko; Okumoto, Masaaki; Iwai, Mineko; Iwai, Yoshiaki

1976-01-01

The incidence of leukemia, changes in the tissue weight of spleen and thymus, and the expression of endogenous viruses were examined with BALB/c mice following 4 weekly fractionated whole-body x-irradiation of 170 R each, starting at 4 weeks of age. The leukemia incidence was quite low for the unirradiated controls, while 60% of the irradiated male mice developed thymic lymphoma. The virus-positive cells appeared earlier in the spleen than in the thymus and bone marrow, and increased with aging. The time of appearance of virus-positive cells in these tissues was remarkably promoted by the fractionated x-irradiation, and its frequency was also enhanced. (auth.)

Action of caffeine on x-irradiated HeLa cells. VII. Evidence that caffeine enhances expression of potentially lethal radiation damage

International Nuclear Information System (INIS)

Beetham, K.L.; Tolmach, L.J.

1984-01-01

HeLa cells irradiated with 2 Gy of 220-kV X rays suffer a 60-70% loss of colony-forming ability which is increased to 90% by postirradiation treatment with 10 mM caffeine for 6 hr. The detailed postirradiation patterns of cell death and sister-cell fusion in such cultures and in cultures in which the colony-forming ability was brought to about the same level by treatment with a larger (4 Gy) X-ray dose alone or by longer (48 hr) treatment with 10 mM caffeine alone were recorded by time-lapse cinemicrography. Because the patterns of cell death and fusion differ radically in irradiated and in caffeine-treated cultures, the response of the additional cells killed by the combined treatment can be identified as X-ray induced rather than caffeine induced. The appearance of cultures after several days of incubation confirms the similarity of the post-treatment patterns of proliferation in cultures suffering enhanced killing to those occurring in cultures treated with larger doses of X rays alone. It is concluded that x rays do not sensitize cells to caffeine, but rather that caffeine enhanced the expression of potentially lethal radiation-induced damage

Protective effect of Asparagus racemosus root extract against lethal total - body electron beam radiation induced damage in Swiss albino mice

International Nuclear Information System (INIS)

Sharmila, K.P.; Bhandary, B. Satheesh Kumar; Suchetha Kumari, N.; Bhat, Vadish S.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.; Fernandes, Ronald

2016-01-01

To investigate the protective effect of Asparagus Racemosus Root ethanolic extract (ARE) in Swiss albino mice against acute lethal total - body Electron beam irradiation. Swiss Albino mice were used for the assessment of radiation induced sickness and 30 day survival analysis. Survival studies were determined using the Kaplan-Meier survival curves. The maximum survival was observed in the experimental mice pretreated with 200 mg/kg.b.wt. of ARE which also reduced the radiation sickness characteristics. This dose was considered as an optimal dose for radioprotection. Treatment of mice with ARE before irradiation delayed the onset of mortality as compared with the untreated irradiated controls. Present findings demonstrate the potential of ARE in mitigating radiation-induced mortality, which may be attributed to its free radical scavenging and increased antioxidant potential

Mammary tumorigenesis in APCmin/+ mice is enhanced by X-irradiation with a characteristic age dependence

International Nuclear Information System (INIS)

Tatsuhiko, Imaoka; Mayumi, Nishimura; Shizuko, Kakinuma; Yoshiya, Shimada; Mieko, Okamoto

2006-01-01

The ApcM min/+ (Min) mouse is a genetically predisposed model of both intestinal and mammary tumorigenesis. We investigated age-related changes in the susceptibility of mice (before, during and after puberty) to radiation-induced mammary tumorigenesis using this model. Female Min and wild-type mice having the C57BL/6J background were irradiated with 2 Gy of X-rays at 2, 5, 7 and 10 weeks and sacrificed at 18 weeks of age. Min mice irradiated at 7 to 10 weeks of age (after puberty) developed mammary tumors with squamous metaplasia, whereas their wild-type litter-mates did not. Interestingly, irradiation of Min mice at 2 to 5 weeks (before and during puberty, respectively) did not induce mammary tumors but rather cystic nodules with metaplasia. The mammary tumors exhibited increased nuclear beta-catenin protein and loss of the wild-type Apc allele. Our results show that susceptibility to radiation-induced mammary tumorigenesis increases after puberty in Min mice, suggesting that the tumorigenic effect of ionizing radiation targets the lobular-alveolar progenitor cells, which increase in number with age and are controlled by beta-catenin signaling. (author)

Free radical scavenging and the expression of potentially lethal damage in X-irradiated repair-deficient Escherichia coli

International Nuclear Information System (INIS)

Billen, D.

1987-01-01

When cells are exposed to ionizing radiation, they suffer lethal damage (LD), potentially lethal damage (PLD), and sublethal damage (SLD). All three forms of damage may be caused by direct or indirect radiation action or by the interaction of indirect radiation products with direct DNA damage. In this report I examine the expression of LD and PLD caused by the indirect action of X rays in isogenic, repair-deficient Escherichia coli. The radiosensitivity of a recA mutant, deficient both in pre- and post replication recombination repair and SOS induction (inducible error-prone repair), was compared to that of a recB mutant which is recombination deficient but SOS proficient and to a previously studied DNA polymerase 1-deficient mutant (polA) which lacks the excision repair pathway. Indirect damage by water radicals (primarily OH radicals) was circumvented by the presence of 2 M glycerol during irradiation. Indirect X-ray damage by water radicals accounts for at least 85% of the PLD found in exposed repair-deficient cells. The DNA polymerase 1-deficient mutant is most sensitive to indirect damage with the order of sensitivity polA1 greater than recB greater than or equal to recA greater than wild type. For the direct effects of X rays the order of sensitivity is recA greater than recB greater than polA1 greater than wild type. The significance of the various repair pathways in mitigating PLD by direct and indirect damage is discussed

Lethal mutation of internal irradiation brown planthopper (Nilaparvita lugens Stal)

International Nuclear Information System (INIS)

Wahid, R.A.

1988-01-01

The moulting IVth of BPH nympha were irradiated internally with radiophosphorous 32-P 1 uCi/ml, 10 uCi/ml, 50 uCi/ml, 100 uCi/ml, and 500 uCi/ml concentrations respectivelly. An observation was carried out to determines heredity of hopper sterilities from the mating groups of R male x N female, R male x R female, and N male x R female. The 32-P concentration below of 50 uCi/ml seemed to be the substerile dose, however, the dominant lethal mutation has been visually shown by R male x R female F1 mating group. The hereditary lines of F1, F2, F3, and F4 of the hopper sterilities wich were indicated by the nympha hatch ability have some significant correlations (r1= -0.77, r2= -0.92, r3= -0.93 and r4= -0.85). Thus, the resesif lethal mutations visually showed by F3 and F4 from all of the 100 uCi/ml and 50 uCi/ml treated groups. (author). 10 refs, 2 figs, 2 tabs

Changes in rat liver and adipose tissue lipogenesis after single lethal X-irradiation: modification by the restricted food intake

International Nuclear Information System (INIS)

Sedlakova, A.; Ahlers, I.; Praslicka, M.

1981-01-01

Male rats of Wistar strain were adapted during a 4-week period to the nutritional regimes of meal feeding (MF) and ad libitum (AL) and were irradiated with the single whole-body lethal X-ray dose 14.35 Gy after 22 h of fasting. Within the intervals 1, 24, 48 and 72 h after irradiation lipogenesis changes in the liver were studied by measuring 1- 14 C-acetate incorporation (74 KBq) in the total lipids, fatty acids and cholesterol, and in the white adipose tissue pieces by measuring U- 14 C-glucose incorporation (74 KBq) in the total lipids, fatty acids and glyceride glycerol. Lipogenesis increased in the liver of the irradiated rats as compared with sham irradiated rats and reached the maximal values at 72 h after irradiation in AL animals and at 48 h after irradiation in MF animals. Lipogenesis in the adipose tissue decreased in the irradiated rats as compared with the sham irradiated ones and continued to decrease with the post-irradiation period. The adaptation to the nutritional regime of meal feeding markedly modified lipogenesis in the liver and the adipose tissue of the irradiated rats. Long-term fasting (before and after irradiation) was supposed to be another modifying factor in the lipogenesis changes. Lipogenesis changes in the liver depended on the MF nutritional regime. (author)

Changes in rat liver and adipose tissue lipogenesis after single lethal X-irradiation: modification by the restricted food intake

Energy Technology Data Exchange (ETDEWEB)

Sedlakova, A; Ahlers, I; Praslicka, M [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie

1981-01-01

Male rats of Wistar strain were adapted during a 4-week period to the nutritional regimes of meal feeding (MF) and ad libitum (AL) and were irradiated with the single whole-body lethal X-ray dose 14.35 Gy after 22 h of fasting. Within the intervals 1, 24, 48 and 72 h after irradiation lipogenesis changes in the liver were studied by measuring 1-/sup 14/C-acetate incorporation (74 KBq) in the total lipids, fatty acids and cholesterol, and in the white adipose tissue pieces by measuring U-/sup 14/C-glucose incorporation (74 KBq) in the total lipids, fatty acids and glyceride glycerol. Lipogenesis increased in the liver of the irradiated rats as compared with sham irradiated rats and reached the maximal values at 72 h after irradiation in AL animals and at 48 h after irradiation in MF animals. Lipogenesis in the adipose tissue decreased in the irradiated rats as compared with the sham irradiated ones and continued to decrease with the post-irradiation period. The adaptation to the nutritional regime of meal feeding markedly modified lipogenesis in the liver and the adipose tissue of the irradiated rats. Long-term fasting (before and after irradiation) was supposed to be another modifying factor in the lipogenesis changes. Lipogenesis changes in the liver depended on the MF nutritional regime.

Immune expulsion of Trichuris muris from resistant mice: suppression by irradiation and restoration by transfer of lymphoid cells

International Nuclear Information System (INIS)

Wakelin, D.; Selby, G.R.

1976-01-01

Lethal irradiation (850 rads of x rays) of mice made resistant to Trichuris muris markedly depressed their ability to expel a challenge infection. Expulsion was restored within 7 to 10 days when MLNC from uninfected mice were transferred on the day of infection, but no significant restoration was evident after transfer of immune serum. Transfer of Bm alone had no restorative effect within 10 days and no synergism was seen when both BM and MLNC were transferred. MLNC from uninfected donors did not restore challenge expulsion when transfer was delayed until day 7 and the mice were killed 3 days later, although MLNC from resistant donors were effective within this time. When irradiated mice were given BM and the challenge infection allowed to continue for 15 days expulsion was restored, as it was when challenge was delayed for 7 days after BM transfer in thymectomized mice. The results confirm that expulsion of T. muris involves both antibody-mediated and lymphoid cell-mediated phases and offer no evidence for the involvement of other cell types. (author)

Influence of paternal 252Cf neutron exposure on abnormal sperm, embryonal lethality, and liver tumorigenesis in the F1 offspring of mice

International Nuclear Information System (INIS)

Watanabe, Hiromitsu; Takahashi, Tadateru; Lee, Juing-Yi

1996-01-01

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with 252 Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) (P 1 generation may be caused by genetic transmission of hepatoma-associated trait (s) induced by 252 Cf neutron irradiation. (author)

Differentiation of strains of yellow fever virus in γ-irradiated mice

International Nuclear Information System (INIS)

Fitzgeorge, R.; Bradish, C.J.

1980-01-01

The mouse sensitized by optimal, sub-lethal γ-irradiation has been used for the differentiation of strains of yellow fever virus and for the resolution of their immunogenicity and pathogenicity as distinct characteristics. For different strains of yellow fever virus, the patterns of antibody-synthesis, regulatory immunity (pre-challenge) and protective immunity (post-challenge) are differentially sensitive to γ-irradiation. These critical differentiations of strains of yellow fever virus in γ-irradiated mice have been compared with those shown in normal athymic and immature mice in order to elucidate the range of quantifiable in vivo characteristics and the course of the virus-host interaction. This is discussed as a basis for the comparisons of the responses of model and principal hosts to vaccines and pathogens. (author)

Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body. gamma. irradiation

Energy Technology Data Exchange (ETDEWEB)

Onoue, M.; Uchida, K.; Yokokura, T.; Takahashi, T.; Mutai, M.

1981-11-01

The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body ..gamma.. irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice.

Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body γ irradiation

International Nuclear Information System (INIS)

Onoue, M.; Uchida, K.; Yokokura, T.; Takahashi, T.; Mutai, M.

1981-01-01

The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body γ irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice

Influence on DNA repair inhibitors on dominant lethal factors after gamma irradiation

International Nuclear Information System (INIS)

Engl, D.

1978-01-01

Experiments were performed in order to test the hypothesis of a correlation between ionizing radiation and DNA repair inhibition under in vivo conditions. In a biometrically planned dominant lethal test on mice, the repair inhibition on the male gametes by butazolidine, TWEEN 80 and vitamin A was studied after gamma irradiation at 20 rad/10 min. No effect was observed in the case of butazolidine and TWEEN 80, whereas the influence of a high concentration of vitamin A (1 million IE/kg) was just at the statistical significancy threshold. (G.G.)

Adaptation and possible attenuation of Theileria parva-infected cells grown in irradiated mice

International Nuclear Information System (INIS)

Irvin, A.D.; Brown, C.G.D.; Stagg, D.A.; Kanhai, G.K.; Kimber, C.D.; Radley, D.E.

1976-01-01

Theileria parva-infected bovine lymphoid cells were taken from 8 cattle immediately after death from East Coast fever (ECF). Cells were inoculated into groups of irradiated Swiss and athymic nude mice. The irradiated mice were exposed to 800 rad doses from a 60 Co source. Cells became established in one group of Swiss mice and 2 groups of athymic mice. Development of cells in mice only occurred if cells concurrently established in culture; when establishment in culture was delayed, cells failed to develop in mice. Cells from one of the isolates in athymic mice were passaged 6 times through further mice. On inoculation of these mouse-passaged cells into cattle, the animals underwent mild reactions and subsequently resisted a lethal ECF challenge. The possibility of vaccinating cattle aginst ECF by means of mouse passaged cells merits further study. (author)

The lethal interaction of x ray and penicillin induced lesions following x-irradiation of Escherichia coli B/r in the presence of hypoxic cell sensitizers

International Nuclear Information System (INIS)

Gillies, N.E.; Obioha, F.I.

1982-01-01

When Escherichia coli B/r were x-irradiated under anoxia in the presence of different electron-affinic sensitizers and then incubated in broth containing penicillin (at a concentration that did not kill unirradiated cells) additional killing of the bacteria occurred provided the sensitizers were of relatively high lipophilicity. The overall effect was to increase the efficiency of these sensitizers. It is concluded that sensitizer-dependent latent radiation lesions(s) are produced in membrane components of the cell envelope that interact with damage caused by penicillin in the peptidoglycan layer and this causes the additional lethality

Late effects of chronic low dose-rate γ-rays irradiation on mice

International Nuclear Information System (INIS)

Tanaka, Satoshi; Sasagawa, Sumiko; Ichinohe, Kazuaki; Matsumoto, Tsuneya; Otsu, Hiroshi; Sato, Fumiaki

2002-01-01

To evaluate late biological effects of chronic low dose-rate radiation, we are conducting two experiments. Experiment 1 - Late effects of chronic low dose-rate g-rays irradiation on SPF mice, using life-span and pathological changes as parameters. Continuous irradiation with g-rays for 400 days was performed using 137 Cs γ-rays at dose-rates of 20 mGy/day, 1 mGy/day and 0.05 mGy/day with accumulated doses equivalent to 8,000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. As of 2002 March 31, 3,999 of the total 4,000 mice have died. Preliminary analyses of data show that 20 mGy/day suggested a shortened life span in both sexes. Partial results show that the most common lethal neoplasms in the pooled data of non-irradiated control and irradiated male mice, in order of frequency, were neoplasms of the lymphohematopoietic system, liver, and lung. In female mice, neoplasms of the lymphohematopoietic system, soft tissue, and endocrine system were common. Experiment 2 - Effects on the progeny of chronic low dose-rate g-ray irradiated SPF mice: pilot study, was started in 1999 and is currently in progress. (author)

Necrostatin-1 rescues mice from lethal irradiation.

Science.gov (United States)

Huang, Zhentai; Epperly, Michael; Watkins, Simon C; Greenberger, Joel S; Kagan, Valerian E; Bayır, Hülya

2016-04-01

There is an emerging need in new medical products that can mitigate and/or treat the short- and long-term consequences of radiation exposure after a radiological or nuclear terroristic event. The direct effects of ionizing radiation are realized primarily via apoptotic death pathways in rapidly proliferating cells within the initial 1-2days after the exposure. However later in the course of the radiation disease necrotic cell death may ensue via direct and indirect pathways from increased generation of pro-inflammatory cytokines. Here we evaluated radiomitigative potential of necrostatin-1 after total body irradiation (TBI) and the contribution of necroptosis to cell death induced by radiation. Circulating TNFα levels were increased starting on d1 after TBI and associated with increased plasmalemma permeability in ileum of irradiated mice. Necrostatin-1 given iv. 48h after 9.5Gy TBI attenuated radiation-induced receptor interacting protein kinase 3 (RIPK3) serine phosphorylation in ileum and improved survival vs. vehicle. Utilizing apoptosis resistant cytochrome c(-/-) cells, we showed that radiation can induce necroptosis, which is attenuated by RNAi knock down of RIPK1 and RIPK3 or by treatment with necrostatin-1 or -1s whereas 1-methyl-L-tryptophan, an indoleamine-2,3-dioxygenase inhibitor, did not exhibit radiomitigative effect. This suggests that the beneficial effect of necrostatin-1 is likely through inhibition of RIPK1-mediated necroptotic pathway. Overall, our data indicate that necroptosis, a form of programmed necrosis, may play a significant role in cell death contributing to radiation disease and mortality. This study provides a proof of principle that necrostatin-1 and perhaps other RIPK1 inhibitors are promising therapeutic agents for radiomitigation after TBI. Copyright © 2016 Elsevier B.V. All rights reserved.

Uptake of carbon monoxide by C3H mice following X irradiation of lung only or total-body irradiation with 60Co

International Nuclear Information System (INIS)

Rappaport, D.S.; Niewoehner, D.E.; Kim, T.H.; Song, C.W.; Levitt, S.H.

1983-01-01

Carbon monoxide uptake (V/sub co/) and ventilation rate (VR) of C3H mice were determined at 14 weeks following either X irradiation of lungs only or total-body irradiation with 60 Co at different dose rates. Following localized X irradiation of lung at 97 /sub c/Gy/min there was a reduction in V/sub co/, which was inversely related to radiation dose, with a small reduction below control levels being detected at 7 Gy, the lowest dose tested. An increase in VR could be detected only at doses of 11 Gy, or more. Another group of animals received 11.5 Gy total-body irradiation at either 26.2 or 4.85 /sub c/Gy/min fllowed by transplantation with syngeneic bone marrow. Following total-body irradiation, V/sub co/ was significantly reduced by about 37% at the higher dose rate and 23% at the lower dose rate. In contrast, a trend toward elevated VR was detected only at the higher dose rate.The results indicate that V/sub co/ is a sensitive indicator of radiation-induced lung injury and that under the experimental conditions used V/sub co/ is a more sensitive indicator of radiation-induced lung injury in C3H mice than VR

Glucorticoids/insulin ratio in irradiated animal blood

International Nuclear Information System (INIS)

Mizina, T.Yu.

1990-01-01

Similar changes in blood levels of immunoreactive insulin (IRI) and glucocorticoids (GC) were observed in rats, mice and dogs after X-irradiation with lethal doses. The use of the blood GC/IRI ratio indices in estimating the functional status of the exposed organism is discussed

Relationship of DNA repair and chromosome aberrations to potentially lethal damage repair in X-irradiated mammalian cells

International Nuclear Information System (INIS)

Fornace, A.J. Jr.; Nagasawa, H.; Little, J.B.

1980-01-01

By the alkaline elution technique, the repair of x-ray-induced DNA single strand breaks and DNA-protein cross-links was investigated in stationary phase, contact-inhibited mouse cells. During the first hour of repair, approximately 90% of x-ray induced single strand breaks were rejoined whereas most of the remaining breaks were rejoined more slowly during the next 5 h. The number of residual non-rejoined single strand breaks was approximately proportional to the x-ray dose at early repair times. DNA-protein cross-links were removed at a slower rate - T 1/2 approximately 10 to 12 h. Cells were subcultured at low density at various times after irradiation and scored for colony survival, and chromosome aberrations in the first mitosis after sub-culture. Both cell lethality and the frequency of chromosome aberrations decreased during the first several hours of repair, reaching a minimum level by 6 h; this decrease correlated temporally with the repair of the slowly rejoining DNA strand breaks. The possible relationship of DNA repair to changes in survival and chromosome aberrations is discussed

Animal experimental model of a graft-versus-host (GVH) reaction after allogenic transplantation of bone marrow in lethally irradiated mice

International Nuclear Information System (INIS)

Schwenke, H.; Muench, S.; Haubold, S.; Weber, B.

1977-01-01

The graft-versus-host (GVH) disease represents a serious still unsolved problem in the human allogenic transplantation of bone marrow. An experimental model of GVH reaction after an allogenic transplantation of bone marrow in the adult mouse has been worked out as a prerequisite for further studies on the therapeutic influence of this syndrome. 3 groups have been formed out of 82 lethally X-irradiated C57 Bl mice. The non-transplanted control group died to a hundred per cent within 12 days. While out of the 2nd group treated with syngenic bone marrow 55 per cent survived from the 22nd day, 30 per cent of the third animal group, allogenicly transplanted with histoincompatible AKR donor marrow developed a chronic GVH syndrome. The following symptoms were observed: retardation, alterations of the skin, diarrhea, edemas of the legs, failing increase of leukocytes in blood and proliferation of lymphocytes in bone marrow of about 60 per cent (18 per cent in syngenically transplanted animals), in lacking proliferation of hematopoiesis. The increase of liver and especially spleen index is not characteristic in comparison with the syngenically transplanted group, since in the latter there is also an increase of the values on account of a strong hematopoetic proliferation. The model is suitable and sufficiently well characterized for the performance of further experimental studies. (author)

Increase of survival of x-irradiated mice by postirradiation injections of a splenic extract prepared from vaccine or endotoxin-treated syngeneic animals

Energy Technology Data Exchange (ETDEWEB)

Tsuneoka, K; Takagi, Y; Shikita, M [National Inst. of Radiological Sciences, Chiba (Japan)

1977-05-01

Spleens of mice which had been treated with E. coli endotoxin or typhoid-paratyphoid vaccine were extracted with isotonic saline. The extract was filtered through an asbestos filter and chromatographed on a Sephadex G-200 column. The fraction which was excluded at around 2.5-void volume (molecular weight, about 20,000) was significantly effective in increasing survival of animals when it was repeatedly injected in mice after x irradiation (600 R). The injection caused an increase of the weight of spleen of the animals with an increased number of endogenous spleen colonies. The result suggests that the life-saving effect of the spleen extract is based on its effect of stimulating repopulation of autochthonous hematopoietic cells in the x-irradiated animals. A similar splenic extract prepared from normal mice had an ambiguous effect on the survival of x-irradiated animals.

Competitive proliferation in the hematopoietic tissues of irradiated hybrid mice engrafted with parental bone marrow and spleen

International Nuclear Information System (INIS)

Muramatsu, S.; Monnot, P.; Duplan, J.F.

1976-01-01

e kinetics of growth and differentiation of hematopoietic stem cells differ markedly according to their origin. A study of the ability of CFU from bone marrow (BM) or spleen to repopulate hemopoietic organs has been carried out in lethally irradiated mice restored with BM cells admixed with spleen cells bearing different chromosomal markers. Hemopoietic cells originating from AKR (40 acbrocentrics) and AKR/T1ALD (36 acrocentrics + 2 metacentrics) mice were engrafted into lethally irradiated (AKR x AKR/T1ALD)F1 or (C3H x AKR/T1ALD)F1 hybrid recipients. Within 10 days, the BM-derived elements outnumbered the spleen-derived population in BM and spleen. This held even when the number of injected spleen-CFU was twice that of BM-CFU. This difference of growth rate subsided within 20 days. The first cells to reappear in the thymus bore the recipient karyotype (endoregeneration); they were later replaced by BM-derived elements but spleen-derived cecells were never present in thymus in the case of competitive engraftment. In contrast, the lymph node cells bore the BM karyotype as well as the spleen karyotype. Injecting the spleen cells 3 days prior to the BM cells partially counterbalanced the overgrowth of the BM-derived elements in the BM and spleen but did not affect the thymic repopulation which remained strictly derived from BM-CFU. When mice were injected only with BM-CFU, or only with spleen-CFU, BM-derived cells were found in the thymus as early as 10-12 days after engraftment, whereas the spleen-derived cells did not appear in the thymus until days 18-20. (author)

Gamma-irradiated scrub typhus immunogens: development of cell-mediated immunity after vaccination of inbred mice

International Nuclear Information System (INIS)

Jerrells, T.R.; Palmer, B.A.; Osterman, J.V.

1983-01-01

Mice immunized with three injections of gamma-irradiated Karp strain of Rickettsia tsutsugamushi were evaluated for the presence of cell-mediated immunity by using delayed-type hypersensitivity, antigen-induced lymphocyte proliferation, and antigen-induced lymphokine production. These animals also were evaluated for levels of circulating antibody after immunization as well as for the presence of rickettsemia after intraperitoneal challenge with viable Karp rickettsiae. After immunization with irradiated Karp rickettsiae, a demonstrable cell-mediated immunity was present as evidenced by delayed-type hypersensitivity responsiveness, lymphocyte proliferation, and production of migration inhibition factor and interferon by immune spleen lymphocytes. Also, a reduction in circulating rickettsiae was seen in mice immunized with irradiated rickettsiae after challenge with 1,000 50% mouse lethal doses of viable, homologous rickettsiae. All responses except antibody titer and reduction of rickettsemia were similar to the responses noted in mice immunized with viable organisms. Antibody levels were lower in mice immunized with irradiated rickettsiae than in mice immunized with viable rickettsiae. Furthermore, mice that were immunized with viable rickettsiae demonstrated markedly lower levels of rickettsemia after intraperitoneal challenge compared with either mice immunized with irradiated rickettsiae or nonimmunized mice

Estimation of mutation rates induced by large doses of gamma, proton and neutron irradiation of the X-chromosome of the nematode Panagrellus redivivus

International Nuclear Information System (INIS)

Denich, K.T.R.; Samoiloff, M.R.

1984-01-01

The radiation-resistant free-living nematode Panagrellus redivivus was used to study mutation rates in oocytes, following gamma, proton and neutron irradiation in the dose range 45-225 grays. γ-Radiation produced approximately 0.001 lethal X-chromosomes per gray over the range tested. Proton or neutron irradiation produced approximately 0.003 lethal X-chromosomes per gray at lower doses, with the mutation rate dropping to 0.001 lethal X-chromosome per gray at the higher doses. These results suggest a dose-dependent mutation-repair system. Cell lethality was also examined. γ-Radiation produced the greatest amount of cell lethality at all doses, while neutron irradiation had no cell lethal effect at any of the doses examined. (orig.)

The effect of low-dose X-irradiation on immune system

International Nuclear Information System (INIS)

Ishii, Keiichiro

1996-01-01

The hypothesis of radiation hormesis has been proposed. To elucidate the hormetic effect on the immune system, we studied the mitogen-induced proliferation of splenocytes of F344/NSlc rat and BALB/c mouse after low-dose X-irradiation. Con A, PHA or LPS-induced proliferation of rat splenocytes prepared at 4 hr after irradiation was augmented with 5 cGy. This augmentation was observed within a few hours after irradiation, being a temporary effect. In case of mice, the proliferation of splenocytes induced by Con A, PHA or LPS was augmented by irradiation with 2.5 cGy. Thus, some phenomena of hormetic effect on the immune system were observed. However, the mechanism of augmentation of immune splenocytes is uncertainty. Therefore, we examined changes in production of LTB 4 and IL-1 being inflammatory mediators. After 5 cGy irradiation the production of LTB 4 of rat splenocyte showed a significant increase. Furthermore, 2.5 cGy irradiation also enhanced, the biological activity of intracellular IL-1 of LPS-stimulated mouse splenocytes. Additionally, to elucidate the stimulative effect on the antitumor immunity by low-dose X-irradiation, we studied the changes in the incidence of thymic lymphoma using AKR mice and of spontaneous metastasis to lung using tumor bearing mice. The incidence of thymic lymphoma was significantly decreased and the life span was significantly prolonged by periodical low-dose X-irradiation in terms of breeding of AKR mice. By an irradiation with 15 cGy, numbers of lung colony in the tumor bearing mice were decreased by 57% relative to the sham-irradiated controls. Then, IL-6 and TNF-α production of tumor bearing mice splenocytes were enhanced. These findings suggest that the low-dose X-irradiation might have caused a light inflammation and might have induced an augmentation of immune splenocytes. Furthermore, these results indicate that an augmentation of the antitumor immunity was induced by low-dose X-irradiation. (author). 127 refs

The effect of low-dose X-irradiation on immune system

Energy Technology Data Exchange (ETDEWEB)

Ishii, Keiichiro [Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab.

1996-06-01

The hypothesis of radiation hormesis has been proposed. To elucidate the hormetic effect on the immune system, we studied the mitogen-induced proliferation of splenocytes of F344/NSlc rat and BALB/c mouse after low-dose X-irradiation. Con A, PHA or LPS-induced proliferation of rat splenocytes prepared at 4 hr after irradiation was augmented with 5 cGy. This augmentation was observed within a few hours after irradiation, being a temporary effect. In case of mice, the proliferation of splenocytes induced by Con A, PHA or LPS was augmented by irradiation with 2.5 cGy. Thus, some phenomena of hormetic effect on the immune system were observed. However, the mechanism of augmentation of immune splenocytes is uncertainty. Therefore, we examined changes in production of LTB{sub 4} and IL-1 being inflammatory mediators. After 5 cGy irradiation the production of LTB{sub 4} of rat splenocyte showed a significant increase. Furthermore, 2.5 cGy irradiation also enhanced, the biological activity of intracellular IL-1 of LPS-stimulated mouse splenocytes. Additionally, to elucidate the stimulative effect on the antitumor immunity by low-dose X-irradiation, we studied the changes in the incidence of thymic lymphoma using AKR mice and of spontaneous metastasis to lung using tumor bearing mice. The incidence of thymic lymphoma was significantly decreased and the life span was significantly prolonged by periodical low-dose X-irradiation in terms of breeding of AKR mice. By an irradiation with 15 cGy, numbers of lung colony in the tumor bearing mice were decreased by 57% relative to the sham-irradiated controls. Then, IL-6 and TNF-{alpha} production of tumor bearing mice splenocytes were enhanced. These findings suggest that the low-dose X-irradiation might have caused a light inflammation and might have induced an augmentation of immune splenocytes. Furthermore, these results indicate that an augmentation of the antitumor immunity was induced by low-dose X-irradiation. 127 refs.

Enzyme release in the skin of mice as an effect of soft X-irradiation

International Nuclear Information System (INIS)

Soltesz, L.

1976-01-01

The shaved skin of 7-8 week old male mice was irradiated locally on the back by doses of 100, 500, 1000, 2000 or 4000 R of soft X-ray. The enzyme activity of the washing solution and of the homogenate of the removed skin, the nitrogen content and the incorporation of 3 H-thymidine were measured immediately after irradiation or 1,2,4,8,16 hours later. The activity of lysosomal enzymes (acid phosphatase, beta-glucuronidase, cathepsine D) increased in the washing solution, whereas in the homogenate no significant change was observed. The maximal values were measured on the second day after irradiation with 1000 R. Tha activity of alkaline phosphatase and leucinaminopeptidase (non-lysosomal enzymes) did not change. Neither was any change observed in the nitrogen content of the skin. The incorporation of 3 H-thymidine considerably decreased. It can be concluded that small doses (500-1000 R) of local X-irradiation damage the membrane of lysosoms and lead to a release of cell destructing enzymes. (L.E.)

The effect of a single lethal X-irradiation exposure on the activity of lipoprotein lipase in the tissues of the rat

International Nuclear Information System (INIS)

Sedlakova, A.; Ahlers, I.; Praslicka, M.

1979-01-01

Wistar male rats, both fed and fasting for 16 h prior to irradiation, were exposed to a single lethal X-ray dose of 387 mC/kg (1500R). The activity of lipoprotein lipase in white adipose (epididymal) tissue and heart muscle and the concentration of serum triglycerides were determined at 1, 6, 24, 48, and 72 h after irradiation. In the early time periods, at 1 and 6 h after exposure, the activity of lipoprotein lipase decreased in adipose tissue and increased in heart muscle of the irradiated fed rats; in fasting rats it decreased in heart muscle at 1 h after exposure. The concentration of serum triglycerides increased at 1 h and decreased at 6 h after exposure in fed rats. In these rats, alterations in serum triglycerides correlated with changes in lipoprotein lipase activity in adipose tissue. Alterations observed at the later time periods were more dependent on the time interval between irradiation and the analysis. Lipoprotein lipase activity increased with time after irradiation up to the maximal values at 72 h. Fasting prior to and after irradiation substantially modified the response of animals to radiation. (author)

A single dose of an inhibitor of cyclooxygenase 2, meloxicam, administered shortly after irradiation increases survival of lethally irradiated mice

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Weiterová, Lenka

2011-01-01

Roč. 176, č. 2 (2011), s. 269-272 ISSN 0033-7587 R&D Projects: GA ČR(CZ) GA305/08/0158 Grant - others:GA ČR(CZ) GAP303/11/0128 Program:GA Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : cyclooxygenase-2 inhibition * lethal irradiation * survival Subject RIV: BO - Biophysics Impact factor: 2.684, year: 2011

Mammary tumorigenesis in APC{sup min/+} mice is enhanced by X-irradiation with a characteristic age dependence

Energy Technology Data Exchange (ETDEWEB)

Tatsuhiko, Imaoka; Mayumi, Nishimura; Shizuko, Kakinuma; Yoshiya, Shimada [National Institute of Radiological Sciences, Experimental Radiobiology for Children' s Health Research Group, Research, Center for Radiation Protection (Japan); Mieko, Okamoto [Tokyo Metropolitan Institute of Medical Science (Japan)

2006-07-01

The ApcM{sup min/+} (Min) mouse is a genetically predisposed model of both intestinal and mammary tumorigenesis. We investigated age-related changes in the susceptibility of mice (before, during and after puberty) to radiation-induced mammary tumorigenesis using this model. Female Min and wild-type mice having the C57BL/6J background were irradiated with 2 Gy of X-rays at 2, 5, 7 and 10 weeks and sacrificed at 18 weeks of age. Min mice irradiated at 7 to 10 weeks of age (after puberty) developed mammary tumors with squamous metaplasia, whereas their wild-type litter-mates did not. Interestingly, irradiation of Min mice at 2 to 5 weeks (before and during puberty, respectively) did not induce mammary tumors but rather cystic nodules with metaplasia. The mammary tumors exhibited increased nuclear beta-catenin protein and loss of the wild-type Apc allele. Our results show that susceptibility to radiation-induced mammary tumorigenesis increases after puberty in Min mice, suggesting that the tumorigenic effect of ionizing radiation targets the lobular-alveolar progenitor cells, which increase in number with age and are controlled by beta-catenin signaling. (author)

High incidence of acute myeloid leukemia in SJL/J mice after X-irradiation and corticosteroids

International Nuclear Information System (INIS)

Resnitzky, P.; Estrov, Z.; Hebrew Univ., Jerusalem; Haran-Ghera, N.

1985-01-01

SJL/J mice which developed a high incidence of spontaneous reticulum cell neoplasms, developed a low rate incidence (20-25%) of myeloid leukemia (ML) after X-irradiation. The possible effect of adrenal steroid imbalance to radiation-induced ML in SJL/J mice was tested. Intact and thymectomized animals were exposed to a single dose of 300 r whole body irradiation and treated with either hydrocortisone acetate, prednisone, metyrapone and adrenocorticotropin as coleukemogenic agents. Hydrocortisone and prednisone exerted a marked coleukemogenic effect, increasing the ML incidence to a similar rate of about 50-70%, at a mean latent period of 300 days. Prominent leukemic infiltration were observed in the bone marrow, spleen, lymph nodes and liver of the leukemic animals. Results of cytological and histological studies, including cytochemistry and ultrastructure, were all consistent with the diagnosis of acute myeloid leukemia (AML). Since AML is the type of human secondary leukemia which appears increasingly in patients treat with alkylating drugs and/or irradiation and corticosteroids for Hodgkin's disease or other neoplastic diseases, the experimental model of AML induced in SJL/J mice could be used for elucidation of mechanisms of leukemogenesis in secondary leukemia. (author)

High incidence of acute myeloid leukemia in SJL/J mice after X-irradiation and corticosteroids

Energy Technology Data Exchange (ETDEWEB)

Resnitzky, P; Estrov, Z; Haran-Ghera, N

1985-01-01

SJL/J mice which developed a high incidence of spontaneous reticulum cell neoplasms, developed a low rate incidence (20-25%) of myeloid leukemia (ML) after X-irradiation. The possible effect of adrenal steroid imbalance to radiation-induced ML in SJL/J mice was tested. Intact and thymectomized animals were exposed to a single dose of 300 r whole body irradiation and treated with either hydrocortisone acetate, prednisone, metyrapone and adrenocorticotropin as coleukemogenic agents. Hydrocortisone and prednisone exerted a marked coleukemogenic effect, increasing the ML incidence to a similar rate of about 50-70%, at a mean latent period of 300 days. Prominent leukemic infiltration were observed in the bone marrow, spleen, lymph nodes and liver of the leukemic animals. Results of cytological and histological studies, including cytochemistry and ultrastructure, were all consistent with the diagnosis of acute myeloid leukemia (AML). Since AML is the type of human secondary leukemia which appears increasingly in patients treat with alkylating drugs and/or irradiation and corticosteroids for Hodgkin's disease or other neoplastic diseases, the experimental model of AML induced in SJL/J mice could be used for elucidation of mechanisms of leukemogenesis in secondary leukemia.

Indirect effects are involved in the production of potentially lethal damage in X irradiated escherichia coli

International Nuclear Information System (INIS)

Billen, D.

1985-01-01

When living cells are exposed to low LET radiation, 60 to 70% of the resulting lethality is said to be due to indirect effects. Using the OH radical scavengers: glycerol n-butanol, t-butanol, and NO/sub 2//sup -/. The authors observed that a radiosensitive E. coli K-12 mutant (W 3110 thy/sup -/ polAl/sup -/) lacking DNA polymerase 1 displays a markedly enhanced radioresistance when exposed to X rays in the presence of these chemicals. The extent of protection afforded by these chemicals correlated with their OH radical scavenging ability over the limited range of concentrations of the chemicals studied. (Only non-toxic concentrations of the chemicals were used). The presence of 2M glycerol during irradiation of the PolAl/sup -/ cells results in a survival level higher than that seen for the unprotected parent strain (W 3110 thy polA/sup +/)

Repair of potentially lethal and sublethal radiation damage in x-irradiated ascites tumor cells

International Nuclear Information System (INIS)

Tsuboi, Atsushi; Okamoto, Mieko; Tsuchiya, Takehiko.

1985-01-01

The ability of cells to repair cellular radiation damage during the growth of TMT-3 ascites tumor and the effect of host reaction on the repair ability were examined by using an in vitro assay of cell clonogenicity after in situ irradiation of tumor cells. In single-dose experiments, the repair of potentially lethal radiation damage (PLD) was observed in stationary phase cells (12-day tumor) of the unirradiated host, but not in exponential phase cells (3-day tumor) of the unirradiated host animals. However, if previously irradiated host animals were used, even the exponentially growing tumor cells showed repair of PLD. In two-dose experiments, the ability to repair sublethal radiation damage (SLD) in exponential phase tumor cells was less than that of stationary phase cells in the unirradiated host. In the pre-irradiated host, the extent of the repair in exponential phase cells was somewhat enhanced. These results suggest that irradiation of host animals might suppress a factor that inhibits repair, resulting in enhancement of the repair capability of tumor cells. (author)

Restoring efficiency of hemopoietic cell transplantation in a mouse lethally irradiated by a total exposure to X rays; L'efficacite restauratrice de la greffe de cellules hemopoietiques chez la souris letalement irradiee par une exposition totale aux rayons X

Energy Technology Data Exchange (ETDEWEB)

Doria, Gino

1959-10-15

This research thesis reports the study of possibility of treatments (or restoration) of a mouse which has been submitted to a lethal dose of X rays. More particularly, the author compared the restoring efficiency of bone marrow and fetal liver injected in a mouse which had been lethally irradiated by a total exposure to X rays. He also studied the functional status of the hemopoietic graft, and the emergence of the secondary disease in mice which had been as well lethally irradiated and then restored by injection of bone marrow and fetal liver. The author then addressed the influence of the induction of immune tolerance of the host with respect to the donor on the survival of a mouse lethally irradiated and restored by homologue bone marrow [French] Des resultats des recherches que nous avons conduites permettent, dans les limites de nos conditions experimentales, d'eclaircir certains aspects du probleme de la restauration des animaux irradies par la greffe de cellules hemopoietiques. On peut admettre que la moelle osseuse de 30 jours est 2 fois plus efficace que le foie foetal de 16 jours, pour ce qui concerne la survie 30 jours; ceci aussi bien en cas de restauration isologue que homologue. En outre, le foie foetal de 16 jours permet une survie d'environ 50 pc plus elevee que les foies foetaux de 13 ou 19 jours; ceci en cas de restauration isologue. On a aussi montre que les degres de capacite restauratrice des differents tissus hemopoietiques dependent du nombre de cellules souches, progenitrices des granulocytes polynucleaires. Nous avons mis en evidence, en cas de restauration par la moelle osseuse homologue, que la presence d'un greffon hemopoietique fonctionnel est necessaire et suffisante pour l'apparition de la maladie secondaire et que celle-ci est une cause suffisante et non necessaire de la mortalite tardive. La constatation experimentale que la viabilite du greffon est une cause suffisante et non necessaire de la mortalite tardive en est la preuve

Production of humoral factors that stimulate spleen colony-forming units in mice irradiated with moderate doses of X rays

International Nuclear Information System (INIS)

Grande, T.; Gonzalez, J.; Tejero, C.; Maganto, G.; Bueren, J.A.

1990-01-01

The production of humoral factors that stimulate spleen colony-forming units (CFU-S) has been studied in irradiated mice using an in vivo diffusion chamber assay. The experiments show that a significant release of factors that stimulate CFU-S takes place in the first few days after irradiation with moderate doses of 1.5 or 5 Gy. In contrast, the release of significant amounts of these humoral factors was not seen in animals irradiated with either low (0.75 Gy) or high (10 Gy) doses of X rays. The correlation observed between the production of factors that stimulate the CFU-S and the hemopoietic regeneration kinetics of the irradiated mice suggests that these factors represent part of the physiological regulators controlling the proliferation of CFU-S

Effects of nutritional status on gastric secretion and composition in X-irradiated rat

International Nuclear Information System (INIS)

D'Souza, D.W.; Vakil, U.K.; Sreenivasan, A.

1974-01-01

Whole body x-irradiation of the rat with a sub-lethal (400 r) or lethal (800 r) dose causes a marked depression in secretion and composition of gastric juice with a maximum drop of the 8th day. Similarly, pepsin and gastricsin activities also decline progressively, being lowest on the 8th day post-irradiation. Radiation exposure of the rat also results in a sudden rise in serum and tissue histamine levels which occurs on the 1st day, and returns to normal on the 3rd day post-irradiation. The nutritional status of the animal appears to influence recovery from radiation injury. Rats fed adequate diets with respect to protein and vitamin A prior to irradiation (400 r) recover earlier from radiation injury than deficient animals. The above biochemical changes are associated with gross and severe degeneration of stomach cells in the x-irradiated rat. (author)

Abrogation of genetically controlled resistance of mice to Treponema pallidum by irradiation

International Nuclear Information System (INIS)

Klein, J.R.; Monjan, A.A.; Hardy, P.H. Jr.; Cole, G.A.

1980-01-01

On intradermal infection, transient primary lesions, characteristic of those seen in naturally acquired human syphilis, can be produced regularly in some strains of mice but not others, indicating a genetic basis for host susceptibility. However strains of mice which normally fail to develop lesions, do so after exposure to ionising radiation. Here the importance of an intact immune system in the outcome of local infection is illustrated by the use of radiation-induced immunosuppression. The mice were exposed to lethal doses of total body irradiation from a 137 Ce source (137 rad per min), 850-1,050 rad depending on mouse strain. (UK)

Induction of dominant lethals in male mice treated as embryos with 35S

International Nuclear Information System (INIS)

Reddy, K.S.; Reddy, P.P.; Reddy, O.S.

1980-01-01

Pregnant female mice were injected (ip) with 20 μCi of 35 S or 0.5 ml of saline (control) on 3.5 day of gestation. The animals were allowed to litter and the (CBA female x C 3 H/He male) F 1 males treated as embryos were tested at maturity (8-10 weeks) for dominant lethal incidence. Each male was mated to 3 untreated virgin females for a period of 3 weeks. The pregnant animals were killed at mid gestation and the uterine contents and corpora lutea were examined. There was a significant increase in the frequency of dominant lethals both at pre- and post-implantation stages in the treated group when compared to controls. As a result a significant increase in dead implantations/female and reduction in live implantations/female were noticed in the treated group. Thus the results clearly delineate the genetic effects of sulfur-35 in mice. (auth.)

Inhibitory effects of prior low-dose X-ray irradiation on carbon tetrachloride-induced hepatopathy in acatalasemic mice

International Nuclear Information System (INIS)

Yamaoka, Kiyonori; Kataoka, Takahiro; Taguchi, Takehito; Wang, Da-Hong; Mori, Shuji; Hanamoto, Katsumi; Kira, Shohei; Nomura, Takaharu

2004-01-01

The catalase activities in blood and organs of the acatalasemic (C3H/AnLCs b Cs b ) mouse of C3H strain are lower than those of the normal (C3H/AnLCs a Cs a ) mouse. We examined the effects of prior low-dose (0.5 Gy) X-ray irradiation, which reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in the acatalasemic or normal mice. The acatalasemic mice showed a significantly lower catalase activity and a significantly higher glutathione peroxidase activity compared with those in the normal mice. Moreover, low-dose irradiation increased the catalase activity in the acatalasemic mouse liver to a level similar to that of the normal mouse liver. Pathological examinations and analyses of blood glutamic oxaloacetic and glutamic pyruvic transaminase activity and lipid peroxide levels showed that carbon tetrachloride induced hepatopathy was inhibited by low-dose irradiation. These findings may indicate that the free radical reaction induced by the lack of catalase and the administration of carbon tetrachloride is more properly neutralized by high glutathione peroxidase activity and low-dose irradiation in the acatalasemic mouse liver. (author)

Enhanced lethal effect of combined ACNU with x-ray on cultured HeLaS3 cells

International Nuclear Information System (INIS)

Kanazawa, Haruyuki; Miyamoto, Tadaaki

1983-01-01

The combined effects of ACNU and X-irradiation on cultured HeLaS 3 cells were investigated. Pretreatment with either ACNU or X-ray induced a substantial reduction in shoulder width the D 0 value of the dose-response curve for the other agent, given later was unchanged. ACNU did not inhibit the recovery of sublethal damage (SLD) induced by X-ray when this treatment preceded the spilit-dose experiment. Our results indicate that some cell damage induced by each agent is transmissible to the progeny of the surviving cells and that the interaction of ACNU and X-irradiation was lethal to the cells. (author)

Pluripotent stem cells with normal or reduced self renewal survive lethal irradiation

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Brecher, G.; Neben, S.; Yee, M.; Bullis, J.; Cronkite, E.P.

1988-01-01

Transfusion with 10,000 or 20,000 marrow cells resulted in 30+ days survival of 15%-50% of mice exposed to an Ld90 or LD100 or radiation. The use of congenic mice with alloenzyme markers permitted the identification of host and donor cells in the peripheral blood of transfused animals. Donor cells were present initially in all hosts. Between 55% and 92% of the animals became 100% host type by 12-24 weeks after transfusion in three separate experiments. To explore whether the temporary repopulation by donor cells was due to short-lived stem cells, the marrows of several primary hosts were transfused into secondary, lethally irradiated hosts. Some of the retransplanted primary donor and host cells persisted only temporarily. It is suggested that some of the donor stem cells in both the primary and secondary hosts had an intrinsically shortened life span

γ-irradiation-induced mortality: protective effect of protease inhibitors in chickens and mice

International Nuclear Information System (INIS)

Palladino, M.A.; Galton, J.E.; Troll, W.; Thorbecke, G.J.

1982-01-01

Chickens (Gallus domesticus) were protected from the acute γ-irradiation-induced mortality (within 24 hours) by the proteolytic enzyme inhibitors, soy-bean trypsin inhibitor (SBTI), lima bean inhibitor (LBTI), antipain, α-N-benzoyl-L-arginine ethyl ester HCl (BAEE), trasylol, and leupeptin. Several other enzyme inhibitors, p-tosyl-L-arginine methyl ester HCl (TAME), α-tosyl-lysyl-chloromethyl ketone HCl (TLCK) and epsilon-amino caproic acid (EACA), did not protect. EACA even increased the mortality caused by γ-irradiation. The pattern of protective enzyme inhibitors suggests involvement of a kallikrein-like enzyme. SBTI and antipain also protected against low range lethal γ-irradiation exposures, 690 R in BALB/c and 880 R in SJL/J mice. It is suggested that enhanced vascular permeability, which in chickens is known to be the cause of the irradiation mortality during the first 24 hours, may also contribute to the mortality in mice during the first week after irradiation. (author)

Chemical and radiation induced late dominant lethal effects in mice

International Nuclear Information System (INIS)

Favor, J.; Crenshaw, J.W. Jr.; Soares, E.R.

1978-01-01

Although theoretically expected, experimental data to date have not shown dominant lethal expression to occur throughout the developmental period. Specifically, late post-implantation effects have not been demonstrated. The authors routinely use an experimental technique in which parental females mated to mutagenically treated males are allowed to give birth and wean their litter, and their uterine horns are then inspected for uterine scars indicative of live and dead embryos. In a number of experiments in which males were mutagenically treated with either chemicals or X-irradiation, a discrepancy was observed between the number of live embryos as determined by the scar technique and the number of live observed at birth, suggesting the possibility of embryonic losses at a late stage in development. Initial analyses showed that mutagenic treatment increased the percentage of these late losses. These differences were statistically significant in 2 of 3 analyses. Factors affecting statistical significance and an understanding of dominant lethal mutations are discussed. (Auth.)

High incidence of hydrocephalus following prenatal exposure to X-irradiation at early gestational stage in mice

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Aolad, H.; Inouye, Minoru; Hayasaka, Shizu; Darmanto, W.; Murata, Yoshiharu

1998-01-01

Hydrocephalus is one of the severe brain anomalies. Several causes of congenital hydrocephalus have been reported and, it is known that radiation is one of those. The current study was designed to obtain postnatally viable hydrocephalic offspring at a high incidence following X-radiation. This finding will be helpful to elucidate the mechanism of congenital hydrocephalus caused by X-radiation. Twenty pregnant Slc:ICR mice, 5 in each group, were exposed to X-irradiation at a dose of 1.0 Gy on gestational days 7 (G7), G8, G9 or G10. The incidence of hydrocephalus was high in the group exposed on G7. An additional 21 pregnant mice were then exposed to a dose of 1.2 Gy, 1.3 Gy, 1.4 Gy or 1.5 Gy X-radiation on G7. The highest incidence of hydrocephalic offspring was found following exposure to 1.4 Gy X-radiation. (author)

Action of caffeine on x-irradiated HeLa cells. V. Identity of the sector of cells that expresses potentially lethal damage in G1 and G2

International Nuclear Information System (INIS)

Beetham, K.L.; Tolmach, L.J.

1982-01-01

When HeLa S3 cells are irradiated in early G 1 with 4 Gy of 220-kV x rays and are then incubated in growth medium containing up to 5 mM caffeine, survival is reduced (as reported previously), reaching a concentration-dependent plateau. Cell killing presumably occurs as a result of the fixation of a portion of the potentially lethal damage the cells contain. These cells respond to continued treatment with caffeine at concentrations greater than 2 mM during S, but less so than during G 1 . When they reach G 2 arrest, however, extensive cell killing again occurs (reported previously), presumably also the result of potentially lethal damage fixation. G 1 -irradiated cultures that are treated with caffeine either continuously at a concentration in the range 1 to 5 mM, or at 10 mM for 8 hr and subsequently with the low concentration, achieve the same survival level in G 2 , provided that the potentially lethal damage is not repaired during G 1 and S. Repair seems to be completely inhibited in the presence of 3 to 4 mM caffeine. The results indicate that fixation of potentially lethal damage occurs in the same sector of cells in G 1 and G 2 , suggesting that the same cellular lesion gives rise to cell killing in the two phases

The effect of postirradiation application of aspartic acid salts on hemopoietic recovery in sublethally X-irradiated mice

International Nuclear Information System (INIS)

Pospisil, M.; Netikova, J.; Vasku, J.; Urbanek, E.

1979-01-01

The effect of aspartic acid salts, especially of K and Mg aspartates, on certain hematological changes in the peripheral blood and hemopoietic organs of sublethally X-irratiated male mice of the strain C57Bl/10 was investigated. Salts of aspartic acid were administered in tap water after irradiation. A favorable effect of aspartic acid salts on erythropoietic recovery and on regeneration of thymus weight was found during the first two weeks after irradiation. (orig.) [de

Lethal Zika Virus Disease Models in Young and Older Interferon α/β Receptor Knock Out Mice

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Andrea Marzi

2018-04-01

Full Text Available The common small animal disease models for Zika virus (ZIKV are mice lacking the interferon responses, but infection of interferon receptor α/β knock out (IFNAR−/− mice is not uniformly lethal particularly in older animals. Here we sought to advance this model in regard to lethality for future countermeasure efficacy testing against more recent ZIKV strains from the Asian lineage, preferably the American sublineage. We first infected IFNAR−/− mice subcutaneously with the contemporary ZIKV-Paraiba strain resulting in predominantly neurological disease with ~50% lethality. Infection with ZIKV-Paraiba by different routes established a uniformly lethal model only in young mice (4-week old upon intraperitoneal infection. However, intraperitoneal inoculation of ZIKV-French Polynesia resulted in uniform lethality in older IFNAR−/− mice (10–12-weeks old. In conclusion, we have established uniformly lethal mouse disease models for efficacy testing of antivirals and vaccines against recent ZIKV strains representing the Asian lineage.

The anti-tumor effect of ACNU and x-irradiation on mouse glioma

International Nuclear Information System (INIS)

Nakagawa, Hidemitsu; Hori, Masaharu; Hasegawa, Hiroshi; Mogami, Heitaro; Hayakawa, Toru.

1979-01-01

Anti-tumor activities of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and x-irradiation on methylcholanthrene induced glioma in C 57 BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and x-irradiation in M phase. As to the combined therapy of ACNU and x-irradiation, the anti-tumor effect was most remarkable when the cells were treated by x-irradiation in the G 2 , M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and x-irradiation on the cells in G 1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and x-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local x-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or x-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of x-ray was remarkably effective. Evidence obtained indicated that the combination therapy of ACNU and x-irradiation have synergistic anti-tumor effect on experimental mouse glioma. (author)

Prenatal effects of ancestral irradiation in inbred mice

International Nuclear Information System (INIS)

Sprackling, L.E.S.

1975-01-01

Mice from 13 inbred strains (S, Z, E, Bab, BaB, BrR, C, K, N, Q, G, CFW, CF1) received continuous cobalt 60 irradiation at low dose rates for varying numbers of consecutive generations. Some Bab and BaB mice had received continuous irradiation for from 24 to 31 generations and the other mice had up to six generations of continuous irradiation in their ancestry. At weaning, the mice were removed from the irradiation room and were mated within strains either to sibs or nonsibs. Ancestral and direct irradiation doses were calculated. The ancestral dose was the effective accumulated dose to the progeny of the mated mice. The direct dose was the amount of irradiation received by any mated female from her conception to her weaning. Each irradiated or control female was scored as fertile or sterile and in utero litter counts were made in pregnant females that were dissected past the tenth day of pregnancy; the sum of moles, dead embryos, and live embryos was the total in utero litter size. A ratio of the living embryos to the total number of embryos in utero was determined for each litter. An increase in ancestral or direct irradiation dose significantly decreased fertility in 11 of the 13 strains. The fertility curves for the pooled data were sigmoid in the area of the doses below those that caused complete sterility. Among the controls, there were significant strain differences in total litter size and in the ratio. Strain X--Y plots, with ancestral or direct doses plotted against total litter size or ratio, revealed the tendency for litter size to decrease as dose increased. The only trend shown for ratio was for the litters with ratios of 0.50 or less to appear more frequently among the irradiated mice. The few corpora lutea counts revealed nothing of significance. Generally, there was a definite trend toward fewer mice alive in utero among the irradiated mice

Characteristics of histocompatibility barriers in congenis strains of mice. III. Passive enhancement of skin allografts in x-irradiated hosts

International Nuclear Information System (INIS)

Cantrell, J.L.; Kaliss, N.; Hildemann, W.H.

1975-01-01

Passive immunological enhancement of skin allografts was investigated in three donor-host combinations of congenic mice disparate at non-H-2 loci. Serum against the graft donor was derived from mice that had received donor strain lymphoid cells as neonates, and thereby were rendered specifically tolerant of a skin allograft. We refer to this serum as ''allograft-tolerant'' serum. Each strain combination was chosen to provide only two non-H-2 histoincompatibilities present in the donor and absent in the host. The differences are categorized as immunogenetically strong, moderate, or weak, on the basis of skin allograft survival times. With passively administered allograft-tolerant serum, significantly prolonged graft survivals were noted for the weakest combination only. Combined treatment with sublethal x-irradiation and allograft-tolerant serum significantly prolonged graft survival in both the moderate and weak combinations, with the largest effect present in the weakest disparity. A hyperimmune alloantiserum (produced in adults) directed against the graft donor prolonged allograft survival in the strongest disparity when given in combination with irradiation. In this combination, graft survival time was increased in hosts exposed to x-ray alone, but joint treatment with x-ray and the alloantiserum gave the largest increment. In contrast, combined treatment with the serum and an antithymocyte alloantiserum did not affect graft survival times. Treatment with both radiation and antithymocyte serum did not prolong graft survival beyond that in mice given only x-radiation. Immunological enhancement with central inhibition is assumed as the mechanism underlying prolonged graft survival, and it is suggested that a population of thymus-derived killer cells, sensitive to x-irradiation, is required for normal graft rejection. (U.S.)

Protein Oxidation in the Lungs of C57BL/6J Mice Following X-Irradiation

Science.gov (United States)

Barshishat-Kupper, Michal; McCart, Elizabeth A.; Freedy, James G.; Tipton, Ashlee J.; Nagy, Vitaly; Kim, Sung-Yop; Landauer, Michael R.; Mueller, Gregory P.; Day, Regina M.

2015-01-01

Damage to normal lung tissue is a limiting factor when ionizing radiation is used in clinical applications. In addition, radiation pneumonitis and fibrosis are a major cause of mortality following accidental radiation exposure in humans. Although clinical symptoms may not develop for months after radiation exposure, immediate events induced by radiation are believed to generate molecular and cellular cascades that proceed during a clinical latent period. Oxidative damage to DNA is considered a primary cause of radiation injury to cells. DNA can be repaired by highly efficient mechanisms while repair of oxidized proteins is limited. Oxidized proteins are often destined for degradation. We examined protein oxidation following 17 Gy (0.6 Gy/min) thoracic X-irradiation in C57BL/6J mice. Seventeen Gy thoracic irradiation resulted in 100% mortality of mice within 127–189 days postirradiation. Necropsy findings indicated that pneumonitis and pulmonary fibrosis were the leading cause of mortality. We investigated the oxidation of lung proteins at 24 h postirradiation following 17 Gy thoracic irradiation using 2-D gel electrophoresis and OxyBlot for the detection of protein carbonylation. Seven carbonylated proteins were identified using mass spectrometry: serum albumin, selenium binding protein-1, alpha antitrypsin, cytoplasmic actin-1, carbonic anhydrase-2, peroxiredoxin-6, and apolipoprotein A1. The carbonylation status of carbonic anhydrase-2, selenium binding protein, and peroxiredoxin-6 was higher in control lung tissue. Apolipoprotein A1 and serum albumin carbonylation were increased following X-irradiation, as confirmed by OxyBlot immunoprecipitation and Western blotting. Our findings indicate that the profile of specific protein oxidation in the lung is altered following radiation exposure. PMID:28248270

Hippophae leaf extract (SBL-1) countered radiation induced dysbiosis in jejunum of total body 60Cobalt gamma - irradiated mice

International Nuclear Information System (INIS)

Beniwal, C.S.; Madhu Bala

2014-01-01

Single dose of SBL-1 administered at the rate 30 mg/kg body weight (b.w.) 30 min prior to whole body 60 Co-gamma-irradiation at lethal dose (10 Gy), rendered >90% survival in comparison to zero survival in the non-SBL-1 treated 60 Co-gamma-irradiated (10 Gy) mice population (J Herbs Spices Med Plants, 2009; 15(2): 203-215). Present study investigated the effect of SBL-1 on jejunal microbiota in lethally irradiated mice. Study was performed with inbred Swiss albino Strain 'A' male mice (age 9 weeks) weighing 28±2 g. The animals were maintained under controlled environment at 26±2℃; 12 h light/dark cycle and offered standard animal food (Golden feed, Delhi) as well as tap water ad libitum. Metagenomic DNA was extracted, purified and quantified from jejunum of the mice. Universal primers (27f and 1492r) were used to amplify the 16S rRNA DNA from the metagenomic DNA. Amplicons were sequenced, vector contamination and chimeras were removed. The sequences (GenBank Accession No: KF681283 to KF681351) were taxonomically classified by using Sequence Match program, Ribosomal Database Project as well as by nucleotide-BLAST (E-value: 10, database: 16S rRNA gene sequences, Bacteria and Archea). Phylogenetic Tree was prepared using MEGA 5.2 package, using maximum likelihood algorithm after sequence alignment by MUSCLE. Thermus aquaticus was used as out-group to construct rooted tree. Branch stability was assessed by bootstrap analysis. Untreated animals and the animals treated with SBL-1 had 100% Lactobacillus; 60 Co gamma-irradiated animals had 55% Cohaesibacter (Alphaproteobacteria); 27% Mycoplasma (Tenericutes) and only 18% Lactobacillus; animals treated with SBL-1 prior to irradiation had 89% Lactobacillus and 11% Clostridium. This study demonstrated that treatment with SBL-1 at radioprotective doses before total body irradiation with lethal dose (10 Gy) countered the jejunal dysbiosis. (author)

Radioprotection conferred by dextran sulfate given before irradiation in mice

International Nuclear Information System (INIS)

Ross, W.M.; Peeke, J.

1986-01-01

Dextran sulfate (DS) has been observed to cause mobilization (fivefold) of hemopoietic stem cells (HSC) and leukocytes, primarily lymphocytes, into the peripheral blood of mice within 2-3 h after intraperitoneal (i.p.) injection. This effect was dose dependent and was prolonged for several hours when the high-molecular-weight version DS500 (500,000 daltons) was used. When DS500 was given 1-3 days before irradiation, hemopoietic recovery was markedly enhanced. Postirradiation injection was ineffective. By ten days after irradiation (7.0 Gy), the number of endogenous spleen colonies (CFUs) and the splenic mass were much larger if DS pretreatment had been given. This effect was dependent on the dose of DS500 and on the time administered, 60 mg/kg producing a maximal effect when given three days before irradiation. DS500 caused a transient anaphylactoid shock, however, in most mice--mild at low doses but potentially lethal at doses above 40 mg/kg (10% mortality within 1-3 days after 60 mg/kg). The following results were obtained with 50 mg/kg, a compromise dose causing minimal mortality (3%) given three days before irradiation. Reticulocyte reappearance was earlier in irradiated mice given DS500, indicating earlier erythropoietic recovery. Some of these reticulocytes were resistant to lysing agents, so their appearance could be detected using the Coulter electronic cell counter, as well as in stained blood smears. The 30-day mortality due to bone marrow failure after irradiation was significantly decreased in DS-treated mice below 9.5 Gy, and the LD50/30 was increased by 0.5 Gy. This study shows that dextran sulfate exerts a radioprotective influence on the hemopoietic system and hence survival when administered prophylactically

Biological properties and response to x-rays of first-generation transplants of spontaneous mammary carcinomas in C3H mice.

Science.gov (United States)

Fowler, J F; Sheldon, P W; Begg, A C; Hill, S A; Smith, A M

1975-05-01

First-generation transplants of spontaneous mouse mammary carcinomas have been used extensively for radiobiological investigations of fractionated irradiation schedules, r.b.e. of fast neutrons and effectiveness of radiosensitizers, as reported elsewhere. The present work investigates the growth characteristics of the tumours; the criteria for the choice of end-points used in the definition of 'local control' of irradiated tumours; the reason for a decrease of 30 per cent in X-ray dose required to control tumours in females as compared with male mice; the proportion of hypoxic cells and its variation with time (reoxygenation) after a single dose of 1500 rad of X-rays; and the repair capacity of tumour cells within 24 hours after a substantial first dose of X-rays. Evidence is presented that the male-female difference was due to a higher proportion of hypoxic cells in tumours in male than in female mice. The repair of sub-lethal injury in tumour cells made hypoxic was slightly less than in skin made hypoxic but not significantly so. In the two-dose experiments on clamped tumours, no evidence of induced synchrony was found.

Repair of membrane damage in X-irradiated E. coli

International Nuclear Information System (INIS)

Gillies, N.E.; Ratnajothi, N.H.; Hewamanna, R.; Obioha, F.I.

1984-01-01

When E. coli B/r or E. coli K12 AB1157 were X-irradiated in the presence of oxygen and incubated immediately after irradiation in broth containing penicillin in concentration that on its own was not lethal to unirradiated bacteria, substantial additional killing was caused. When treatment with penicillin was delayed for increasing times after irradiation the additional killing became progressively less. These results were interpreted as demonstrating the repair or removal of oxygen-dependent radiation-induced lesions in the bacterial membranes. Removal of these lesions was inhibited by incubation of the irradiated bacteria at low temperature before treatment with penicillin or by exposing the cells to a non-lethal concentration of toluene before irradiation. These observations suggest that an enzymatic repair process may be involved in the removal of the membrane lesions. The fatty acid mutant E. coli K 1060 proved exceptional in that some additional killing by penicillin was detectable after anaerobic as well as aerobic irradiation. This points to the importance of membrane composition in the development of those radiation lesions that are brought to light by penicillin treatment. (author)

Survival of irradiated mice treated with WR-151327, synthetic trehalose dicorynomycolate, or ofloxacin

Science.gov (United States)

Ledney, G. D.; Elliott, T. B.; Landauer, M. R.; Vigneulle, R. M.; Henderson, P. L.; Harding, R. A.; Tom, S. P.

1994-10-01

Spaceflight personnel need treatment options that would enhance survival from radiation and would not disrupt task performance. Doses of prophylactic or therapeutic agents known to induce significant short-term (30-day) survival with minimal behavioral (locomotor) changes were used for 180-day survival studies. In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD10) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and γ-rays (n/γ = 1) or 60Co γ-rays. In therapy studies, groups of mice received either S-TDCM, the antimicrobial ofloxacin, or S-TDCM plus ofloxacin after irradiation. For WR-151327 treated-mice, survival at 180 days for n/γ = 1 and γ-irradiated mice was 90% and 92%, respectively; for S-TDCM (protection), 57% and 78%, respectively; for S-TDCM (therapy), 20% and 25%, respectively; for ofloxacin, 38% and 5%, respectively; for S-TDCM combined with ofloxacin, 30% and 30%, respectively; and for saline, 8% and 5%, respectively. Ofloxacin or combined ofloxacin and S-TDCM increased survival from the gram-negative bacterial sepsis that predominated in n/γ = 1) irradiated mice. The efficacies of the treatments depended on radiation quality, treatment agent and its mode of use, and microflora of the host.

Autologous monoclonal antibodies recognize tumour-associated antigens in X-irradiated C57BL/6 mice

Energy Technology Data Exchange (ETDEWEB)

Artus, A; Guillemain, B; Legrand, E; Astier-Gin, T; Mamoun, R; Duplan, J -F

1986-09-01

X-irradiation of C57BL/6 mice induces thymic lymphosarcomas which sometimes contain retroviruses which upon injection into normal mice mimic the effect of the irradiation. We examined whether specific antigenicities, viral or cellular, were expressed by tumour cells that could be recognized by antibodies from the irradiated animals. We developed monoclonal antibodies (MAbs) using splenocytes of the diseased animal. The reactivity of such MAbs towards thymoma cell lines established in vitro was investigated by means of an ELISA. At least 10 antibody specificities were detected on the 13 tumours investigated, allowing separation of the MAbs into three classes: (i) those recognizing the autologous tumour, heterologous tumours as well as normal thymic tissue, (ii) those specific for the autologous tumour, and (iii) those specific for one tumour, but not ones of autologous origin. The last two classes corresponded to specific tumour-associated antigens. Our panel of MAbs defined each tumour by the particular pattern of antigens harboured. It is striking that most of the antigens were present in the normal thymus and that only two tumours had additional antigenicities. Additionally, quantitative variations were observed in the levels of expression of these antigens.

Evolution of glycaemia in the blood of mice in the presence or absence of imidazole

International Nuclear Information System (INIS)

Polverelli, M.; Teoule, R.

1969-01-01

With respect to the radioprotective properties of the heterocyclic compound, imidazole, the authors followed the action of this product on blood sugar levels of mice X irradiated with a lethal dose. The main results of this work are: probably a hypo-glycemic action of the imidazole; an abolishment of the post-irradiation hyperglycemia by imidazole; an appreciably difference between male and female towards irradiation. (author) [fr

Enhancement of the effect of X-irradiation against cultured human glioblastoma cells by pretreatment with ACNU

Energy Technology Data Exchange (ETDEWEB)

Mashiyama, Shoji; Katakura, Ryuichi; Takahashi, Kou; Kitahara, Masakazu; Suzuki, Jiro [Tohoku Univ., Sendai (Japan). Inst. of Brain Diseases; Sasaki, Takehito

1989-12-01

Human glioblastoma A-7 (GB A-7) cells can apparently recover from potentially lethal X-irradiation. The authors, using a colony-forming assay, studied the influence of pretreatment with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) on the effectiveness of X-irradiation against GB A-7 cells grown in monolayers and as multicellular spheroids. Pre-exposure to ACNU inhibited the recovery of irradiated GB A-7 cells. In monolayer cells, the combination treatment was most effective when ACNU was applied 2 to 8 hours prior to irradiation, and the larger the X-ray dose, the more potent the effect. ACNU pretreatment was more effective against large spheroids (enhancement ratio 1.86) than against small ones (1.34). Large spheroids showed necrosis, whereas small ones did not. Isobolographic analysis disclosed that the effect of combining X-irradiation and ACNU is within an additive envelope at the surviving fraction of 10{sup -2}, while supra-additive at the surviving fraction of 10{sup -3}. These results suggest that the potency of X-irradiation is augmented by ACNU pretreatment through an interactive mechanism. Further, suppression of recovery from X-ray induced potentially lethal damage was influenced by the presence of necrosis. (author).

Enhancement of the effect of X-irradiation against cultured human glioblastoma cells by pretreatment with ACNU

International Nuclear Information System (INIS)

Mashiyama, Shoji; Katakura, Ryuichi; Takahashi, Kou; Kitahara, Masakazu; Suzuki, Jiro; Sasaki, Takehito.

1989-01-01

Human glioblastoma A-7 (GB A-7) cells can apparently recover from potentially lethal X-irradiation. The authors, using a colony-forming assay, studied the influence of pretreatment with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) on the effectiveness of X-irradiation against GB A-7 cells grown in monolayers and as multicellular spheroids. Pre-exposure to ACNU inhibited the recovery of irradiated GB A-7 cells. In monolayer cells, the combination treatment was most effective when ACNU was applied 2 to 8 hours prior to irradiation, and the larger the X-ray dose, the more potent the effect. ACNU pretreatment was more effective against large spheroids (enhancement ratio 1.86) than against small ones (1.34). Large spheroids showed necrosis, whereas small ones did not. Isobolographic analysis disclosed that the effect of combining X-irradiation and ACNU is within an additive envelope at the surviving fraction of 10 -2 , while supra-additive at the surviving fraction of 10 -3 . These results suggest that the potency of X-irradiation is augmented by ACNU pretreatment through an interactive mechanism. Further, suppression of recovery from X-ray induced potentially lethal damage was influenced by the presence of necrosis. (author)

Dominant lethal and ovarian effects of plutonium-239 in female mice

International Nuclear Information System (INIS)

Searle, A.G.; Beechey, C.V.; Green, D.; Howells, G.R.

1982-01-01

(C3H x 101)F 1 female mice were injected intravenously with 239 Pu in trisodium citrate, then mated in pairs to strain CBA males, to test for dominant lethality. In the first experiment 10μCi kg -1 and in the second 20μCi kg -1 body mass was injected. Matings were after 6 days in the first experiment (estimated ovarian absorbed dose of 0.1 Gy) and after 3,6 or 12 weeks in the second (estimated ovarian doses of 1.11, 2.45 and 5.91 Gy respectively). No evidence of dominant lethal induction was found in the first experiment, but in the second there was a significant increase over controls in pre-implantation loss in all three series. Post-implantation lethality increased significantly (by 12%) only after 12 weeks' exposure. With the 6- and 12-week exposures (especially the latter) luteal counts fell, fewer females becoming pregnant than in controls. This is attributed to oocyte killing by the α-particles. Histological and autoradiographic investigations showed a marked reduction in ovarian size and follicular numbers with fission-tracks clustered mainly over the medullary stroma. The preimplantation loss may stem from lowered fertilization of oocytes because of their damage, so that the best measure of dominant lethality is that based on post-implantation death. (author)

Effects of x-irradiation on cell kinetics of oral epithelium in mice

International Nuclear Information System (INIS)

Jinnouchi, Kenichi

1982-01-01

The acute radiation effects on the tongue and lip mucosa epithelium were cytokinetically investigated after the local irradiation at the head part of C 3 Hf/He mice with single dose of 516 mC/kg(2000R) of X rays. The microautoradiographic study was performed for these two kinds of oral epithelium at various times after the pulse-labeling with 3 H-thymidine, which followed immediately after the irradiation. The cell kinetics of irradiated as well as unirradiated basal cells were investigated by observing the changes in frequencies of the labeled cells and the labeled mitoses in the epithelium along the time course after irradiation. The results of the analysis of the percent frequencies of mitotic cells as a function of time after the labeling and the irradiation showed that the movement of the labeled cells were blocked at G 2 phase for about 6 hr and that the cell cycle time after the 1st post irradiation mitoses became shorter than that of the unirradiated cells. However, no change was found in the migration rate of the tongue epithelium, i.e., the time required for labeled cells to migrate from basal cell layer to prickle-granular cell layer. On the other hand, only 25% of labeled cells in the lip mucosa epithelium migrated into prickle-granular cell layer until 40 hr after irradiation, and it was hardly observed that the labeled cells moved into mitotic phase. These results suggest that basal cell of the lip mucosa is more radiosensitive than that of the tongue epithelium. (author)

Enhancement of radioprotective effectiveness of adenosine monophosphate by magnesium aspartate in mice

International Nuclear Information System (INIS)

Pospisil, M.; Netikova, J.; Kozubik, A.; Chertkov, K.S.; Ministry of Health, Moscow

1988-01-01

The enhancing effect of magnesium aspartate on the radioprotective effectiveness of adenosine monophosphate (AMP) administered to whole-body gamma-irradiated mice was studied. Male (CBA x C57BL/10)F 1 hybrid mice of a mean body weight of 32 g were used. 5 mg AMP per mouse was injected i.p. 15 min before and 15 min after irradiation; magnesium aspartate (13.3 mg per mouse) was administered s.c. 35 min before irradiation. The benefical effect of the drug combination used was manifested when investigating hematological indices at the recovery phase of sublethally irradiated animals, as well as when observing the survival of lethally irradiated mice. The synergistic radioprotective effects of AMP and magnesium aspartate are explained by the stimulatory action of both these compounds on the cell adenylate cyclase system. (author)

Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

International Nuclear Information System (INIS)

Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

2012-01-01

Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

Associations between tumor types in irradiated BALB/c female mice

International Nuclear Information System (INIS)

Storer, J.B.

1982-01-01

Associations between pairs of 12 different tumor types were estimated for a population of over 3800 irradiated BALB/c female mice. The associations were adjusted for age and radiation dose. Of the 66 pairs of tumor types, 21 showed significant positive or negative associations. Of these, 8 were considered to be spurious, principally because one or both of the tumors was rapidly lethal, leading to an apparent negative association. Six of the remaining 13 significant associations involed tumors of endocrine organs or tumors known to be endocrine related. Six others involved associations between lung, vascular tissue, or reticular tissue tumors, and tumors of endocrine organs. The remaining and highly negative association was between reticulum cell sarcomas and other lymphomas and leukemias. It was concluded that in irradiated female mice of this strain, at least, tumors are not independent and that alterations in host factors (principally endocrine) lead to animals developing both tumors (positive associations) or to one tumor but not the other (negative associations)

Regulation of antibody synthesis in the X-irradiated Mexican axolotl

International Nuclear Information System (INIS)

Charlemagne, J.

1981-01-01

The effects of X-irradiation were studied on the Mexican axolotl antibody synthesis. To reduce the anti-horse red blood cell (HRBC) antibody titers, 150 rd and smaller doses are ineffective, 200-450 rd are increasingly effective, and 700 rd are maximally effective (and lethal). A significant enhancement of the anti-HRBC titers was observed in low doses (50-150 rd X-irradiated animals). This enhancement was also observed when a low X-ray dose was applied only on the thymic areas. In whole body, but thymus area-shielded, 100 rd X-irradiated animals, the anti-HRBC titers were similar to those of the nonirradiated, HRBC-immunized control group. To explain these phenomena, it is suggested that a radiosensitive, adult thymectomy-sensitive and hydrocortisone-sensitive suppressor T cell subpopulation regulates the antibody synthesis in the axolotl. (orig.) [de

Regulation of antibody synthesis in the X-irradiated Mexican axolotl

Energy Technology Data Exchange (ETDEWEB)

Charlemagne, J.

1981-09-01

The effects of X-irradiation were studied on the Mexican axolotl antibody synthesis. To reduce the anti-horse red blood cell (HRBC) antibody titers, 150 rd and smaller doses are ineffective, 200-450 rd are increasingly effective, and 700 rd are maximally effective (and lethal). A significant enhancement of the anti-HRBC titers was observed in low doses (50-150 rd X-irradiated animals). This enhancement was also observed when a low X-ray dose was applied only on the thymic areas. In whole body, but thymus area-shielded, 100 rd X-irradiated animals, the anti-HRBC titers were similar to those of the nonirradiated, HRBC-immunized control group. To explain these phenomena, it is suggested that a radiosensitive, adult thymectomy-sensitive and hydrocortisone-sensitive suppressor T cell subpopulation regulates the antibody synthesis in the axolotl.

Delayed cell death, giant cell formation and chromosome instability induced by X-irradiation in human embryo cells

International Nuclear Information System (INIS)

Roy, K.; Kodama, Seiji; Suzuki, Keiji; Watanabe, Masami

1999-01-01

We studied X-ray-induced delayed cell death, delayed giant cell formation and delayed chromosome aberrations in normal human embryo cells to explore the relationship between initial radiation damage and delayed effect appeared at 14 to 55 population doubling numbers (PDNs) after X-irradiation. The delayed effect was induced in the progeny of X-ray survivors in a dose-dependent manner and recovered with increasing PDNs after X-irradiation. Delayed plating for 24 h post-irradiation reduced both acute and delayed lethal damage, suggesting that potentially lethal damage repair (PLDR) can be effective for relieving the delayed cell death. The chromosome analysis revealed that most of the dicentrics (more than 90%) observed in the progeny of X-ray survivors were not accompanied with fragments, in contrast with those observed in the first mitosis after X-irradiation. The present results indicate that the potentiality of genetic instability is determined during the repair process of initial radiation damage and suggest that the mechanism for formation of delayed chromosome aberrations by radiation might be different from that of direct radiation-induced chromosome aberrations. (author)

Effects of hyperthermia, x-ray irradiation and their combination on ascites tumor cells of mice

International Nuclear Information System (INIS)

Kaneko, Itsuo

1982-01-01

Fibrosarcoma ascites tumor cells (PB8) from NMRI mice were used to investigate cell loss by hyperthermia and/or x-ray irradiation. The tumor cells were labelled by an injection of 125 I-deoxyuridine to the abdominal cavity of the donors 2 days before the physical treatments. The labelled cells, transfered in test tubes, were heated at 44 0 C for 10-20 min and/or irradiated by x-ray at 250-1612 rad, and were transplanted in the recipient abdominal cavity as soon as possible after the treatments. The radioactivity of the tumor cells, as an indicator of cell loss, was measured with a gamma spectrometer. In the irradiated group, the ratio of cell loss increased in a dose-dependent manner, starting from the 4th day after the transplantation to the 9th day. In the heated group, the ratio of cell loss increased in proportion to the heating time, starting without delay after transplantation. In the combination group, the effect of the treatments was more marked than that by each single treatment. In the early stage of this group, cell loss was by heating and then, from the 4th day, the irradiation effect mostly dominated. It is concluded from the above results that cell loss by heating or irradiation is independent and that the effect of the combination is additive. (author)

Influence of X-ray irradiation on metabolic effects of adrenaline

International Nuclear Information System (INIS)

Szyszko, A.

1976-01-01

Effects of X-ray irradiation in the whole-body dose of 650 R on changes in glycogen levels in liver, and in either diaphragm and skeletal muscles, and on blood glucose levels, induced in 10 min by adrenaline, were investigated in starved mice. One day after the exposure, the drops in liver glycogen levels due to starvation were found to be highly reduced by previous irradiation. This resulted in an over dozen-fold relative elevation of liver glycogen content in relation to starved not irradiated mice. The post-irradiation accumulation of liver glycogen was found to disappear after administration of adrenaline. Also in diaphragm and skeletal muscles, the changes in muscle glycogen content, induced by irradiation of starved mice, have turned out to be abolished or even reversed by adrenaline, what reflected in reduction of elevated levels and elevation of those reduced. In starved mice during first three days following irradition, adrenaline was found to be ineffective in increasing blood sugar levels, whereas this its effects was noted in either not irradiated mice or on the fourth day after irradiation. (author)

Reduced repair of potentially lethal radiation damage in glutathione synthetase-deficient human fibroblasts after X-irradiation

International Nuclear Information System (INIS)

Midander, J.; Revesz, L.; Deschavanne, P.J.; Debieu, D.; Malaise, E.P.

1986-01-01

Using a human fibroblast strain deficient in glutathione synthetase and a related proficient control strain, the role of glutathione (GSH) in repair of potentially lethal damage (PLD) has been investigated in determining survival by plating cells immediately or 24 h after irradiation. After oxic or hypoxic irradiation, both cell strains repair radiation-induced damage. However, under hypoxic conditions, the proficient cells repair PLD as well as under oxic conditions while the deficient cells repair less PLD after irradiation under hypoxic than under oxic conditions. Therefore, the oxygen enhancement ratio (o.e.r.) for proficient cells is similar whether the cells are plated immediately or 24 h later (2.0 and 2.13, respectively). In contrast, the o.e.r. for deficient cells is lower when the cells are plated 24 h after irradiation than when they are plated immediately thereafter (1.16 as compared to 1.55). The results indicate that GSH is involved in PLD repair and, in particular, in the repair of damage induced by radiation delivered under hypoxic conditions. (author)

Immunization against Capillaria hepatica: The effects of primary infections, X-irradiated stages, non-embryonated eggs and soluble egg extracts

Energy Technology Data Exchange (ETDEWEB)

Zahner, H.; Schmidt, H.; Laemmler, G.; Geyer, E.

1980-01-01

The worm reproductivity was significantly suppressed in a sublethal challenge infection given 11 days after a primary infection of Mastomys natalensis with 50, 150, 400, and 800 eggs per animal. The administration of 600 X-irradiated (2.2 Krd) embryonated eggs 36 days before challenge as well as an intraperitoneal injection of non-embryonated eggs 12, 10, 8, 6, 4, and 2 days before challenge also reduced significantly the egg production of a weak (50 eggs/animal) infection. No effect was observed on a moderate challenge (300 eggs/animal). The effect was not markedly enhanced by the repeated administration of X-irradiated eggs or by the combination of X-irradiated infective eggs and non-embryonated eggs. Immunization of mice with soluble egg extracts resulted in significant reduction of egg production determined 60 days after challenge. Two hundred and thirty eggs of C. hepatica/g bodyweight proved to be a lethal infection dose for M. natalensis. The animals died between 20 and 35 days after infection. After single infections with 50, 150, 400, or 800 eggs per animal the mortality of Mastomys challenged 36 or 52 days later was reduced to 0-30%. Using X-irradiated embryonated eggs for immunization only repeated administration led to protection in 70 to 80%, of the animals. About 40% of the animals could be protected by the intraperitoneal injection of non-embryonated eggs. If death occurred it was delayed. The combination of X-irradiated stages and eggs did not enhance the protection.

Forecasting of the lethality in cases of nonuniform accidental irradiation (experimental studies at external gamma irradiation of rats)

International Nuclear Information System (INIS)

Ingilizova, K.

1983-01-01

A model is suggested that enables the prediction of death probability for the body (L) within the whole lethality dose range (DL 0 -DL 100 ), on the basis of predetermined physical characteristics: in cases of uneven external wholebody irradiation. Some biological effects of 4 variants of uneven irradiation have been studied, i.e. ventro-dorsal (V-D), dorso-ventral (D-V), cranio-caudal (Cr-Ca) and caudo-cranial (Ca-Cr). The following basic conclusions have been drawn: 1. The study of the biological effects of uneven irradiation, when estimated by the lethality factor, points out the lower efficiency of the former, if compared to even irradiation. 2. The even irradiation lethality in the conducted experiments, according to the ALE data and the postradiation mortality dynamics, is determined basically by the damage of the bloodforming tissue and the animals die of bone marrow syndrome. 3. The uneven irradiation, estimated by the total weight factor, is of lower efficiency than the even one. 4. The radiation-induced hypoplasia of the studied organs is exponential in character. 5. An original model for predicting radiation mortality in cases of uneven irradiation has been constructed. The model gives the possibility of relating the alterations in the index of biological efficiency reduction to the wholebody irradiation factor, as well as to the two systems with highest radiosensitivity: red bone marrow and the small intestine. The model helps determining the numerical value of death probability, depending on the average body irradiation doses and the integral unevenness factors for RBM. (author)

Differentiation of bone marrow cells to functional T lymphocytes following implantation of thymus grafts and thymic stroma in nude and ATxBM mice

International Nuclear Information System (INIS)

Splitter, G.A.; McGuire, T.C.; Davis, W.C.

1977-01-01

Cardiac allografts were used to compare the immunologic capacity of nude mice and adult, thymectomized, lethally irradiated, bone marrow-reconstituted (AT x BM) mice. Neither nude nor AT x BM mice were able to reject cardiac allografts of any party. However, both rejected grafts of any party following implantation of neonatal thymus or thymus from 3-week-old syngeneic mice. Irradiated syngeneic thymus grafts (800 R) were equally effective in restoring host responsiveness against allografts. In contrast, allogeneic thymus grafts restored the capacity to reject second-party heart grafts only in AT x BM mice. Second-party grafts persisted indefintely when placed on nude mice implanted with an allogeneic, unirradiated thymus graft. Third-party grafts transplanted 17 weeks after reconstitution, however, were rejected. Irradiated nude mice given normal littermate bone marrow and simultaneously grafted with second-party thymus and heart allografts also failed to reject their second-party heart grafts. The difference in ultimate capacity to respond between AT x BM and nude mice suggests that a maturational defect exists in the nude mouse environment which impedes development of precursor T lymphocytes

Effects of whole-body x irradiation on the biogenesis of creatine in the rat

International Nuclear Information System (INIS)

Thyagarajan, P.; Vakil, U.K.; Sreenivasan, A.

1977-01-01

Influences of whole-body x irradiation on various aspects of creatine metabolism have been studied. Exposures to sublethal or lethal doses of x radiation results in excessive urinary excretion as well as higher accumulation of creatine in the skeletal muscle of x-irradiated rats. A sudden fall in CPK activity in muscle with a concomitant rise in serum suggests that changes in serum and tissue CPK activity are of an adaptive nature in rats exposed to sublethal doses of x radiation. In vitro studies on creatine synthesis shows that transaminidase and methyl transferase activities in kidneys and liver, respectively, are decreased on the 5th day in the x-irradiated, are decreased on the 5th day in the x-irradiated rat. However, on the 8th day, the enzyme activities are restored to normal

The response of mouse skin to re-irradiation with x-rays or fast neutrons

International Nuclear Information System (INIS)

Tsukiyama, Iwao; Egawa, Sunao; Kumazawa, Akiyoshi; Iino, Yuu.

1986-01-01

Effects of neutrons and x-rays on mouse skin which had been previously irradiated with x-rays were investigated. Two tattoo marks were placed in the hairless legs of mice at intervals of 15 mm. The legs were exposed to various doses of x-ray and neutrons to determine the relative biological effectiveness (RBE) using the contraction of the skin as an index. The RBE was 0.93 - 1.73. The legs of the mice were preexposed to 25 Gy of x-ray, and exposed 4 months later. The contraction of the skin began earlier than after the first irradiation. RBE was 2.18 - 2.47. This RBE was higher than that in untreated mice. These results suggest that previously irradiated normal tissues are much more sensitive to neutrons than to x-rays. (author)

High-energy proton irradiation of C57Bl6 mice under hindlimb unloading

Science.gov (United States)

Mendonca, Marc; Todd, Paul; Orschell, Christie; Chin-Sinex, Helen; Farr, Jonathan; Klein, Susan; Sokol, Paul

2012-07-01

Solar proton events (SPEs) pose substantial risk for crewmembers on deep space missions. It has been shown that low gravity and ionizing radiation both produce transient anemia and immunodeficiencies. We utilized the C57Bl/6 based hindlimb suspension model to investigate the consequences of hindlimb-unloading induced immune suppression on the sensitivity to whole body irradiation with modulated 208 MeV protons. Eight-week old C57Bl/6 female mice were conditioned by hindlimb-unloading. Serial CBC and hematocrit assays by HEMAVET were accumulated for the hindlimb-unloaded mice and parallel control animals subjected to identical conditions without unloading. One week of hindlimb-unloading resulted in a persistent, statistically significant 10% reduction in RBC count and a persistent, statistically significant 35% drop in lymphocyte count. This inhibition is consistent with published observations of low Earth orbit flown mice and with crewmember blood analyses. In our experiments the cell count suppression was sustained for the entire six-week period of observation and persisted for at least 7 days beyond the period of active hindlimb-unloading. C57Bl/6 mice were also irradiated with 208 MeV Spread Out Bragg Peak (SOBP) protons at the Midwest Proton Radiotherapy Institute at the Indiana University Cyclotron Facility. We found that at 8.5 Gy hindlimb-unloaded mice were significantly more radiation sensitive with 35 lethalities out of 51 mice versus 15 out of 45 control (non-suspended) mice within 30 days of receiving 8.5 Gy of SOBP protons (p =0.001). Both control and hindlimb-unloaded stocktickerCBC analyses of 8.5 Gy proton irradiated and control mice by HEMAVET demonstrated severe reductions in WBC counts (Lymphocytes and PMNs) by day 2 post-irradiation, followed a week to ten days later by reductions in platelets, and then reductions in RBCs about 2 weeks post-irradiation. Recovery of all blood components commenced by three weeks post-irradiation. CBC analyses of 8

Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicorynomycolate (S-TDCM)

Energy Technology Data Exchange (ETDEWEB)

Madonna, G.S.; Ledney, G.D.; Moore, M.M.; Elliott, T.B.; Brook, I. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

1991-03-01

Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. We recently showed that injection of synthetic trehalose dicorynomycolate (S-TDCM) significantly augments resistance to infection and increases survival of mice compromised either by whole-body irradiation with gamma radiation or equal mixtures of fission neutron and gamma radiation. In this study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an open wound (15% total body surface area (TBSA)) 1 hr later while anesthetized. Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than mice exposed to radiation alone, and died from natural wound infection and sepsis within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or ofloxacin for 10 days significantly increased survival time compared with untreated irradiated/wounded mice (p less than 0.01). Combination therapy with topical gentamicin cream and systemic oxacillin increased survival from 0% to 100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and systemic gentamicin increased survival compared with antibiotic treatment alone. These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics augments resistance to infection in immunocompromised mice. The data suggest that therapies which combine stimulation of nonspecific host defense mechanisms with antibiotics may increase survival of irradiated patients inflicted with accidental or surgical trauma.

Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicorynomycolate (S-TDCM)

International Nuclear Information System (INIS)

Madonna, G.S.; Ledney, G.D.; Moore, M.M.; Elliott, T.B.; Brook, I.

1991-01-01

Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. We recently showed that injection of synthetic trehalose dicorynomycolate (S-TDCM) significantly augments resistance to infection and increases survival of mice compromised either by whole-body irradiation with gamma radiation or equal mixtures of fission neutron and gamma radiation. In this study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an open wound (15% total body surface area [TBSA]) 1 hr later while anesthetized. Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than mice exposed to radiation alone, and died from natural wound infection and sepsis within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or ofloxacin for 10 days significantly increased survival time compared with untreated irradiated/wounded mice (p less than 0.01). Combination therapy with topical gentamicin cream and systemic oxacillin increased survival from 0% to 100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and systemic gentamicin increased survival compared with antibiotic treatment alone. These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics augments resistance to infection in immunocompromised mice. The data suggest that therapies which combine stimulation of nonspecific host defense mechanisms with antibiotics may increase survival of irradiated patients inflicted with accidental or surgical trauma

Effect of ultraviolet irradiation on mast cell-deficient W/Wv mice

International Nuclear Information System (INIS)

Ikai, K.; Danno, K.; Horio, T.; Narumiya, S.

1985-01-01

The effect of UV irradiation on the skin was investigated in (WB-W/+) X (C57BL/6J-Wv/+)F1-W/Wv mice, which are genetically deficient in tissue mast cells. Their congenic littermates (+/+) and normal albino mice (ICR or BALB/c) were used as controls. Mice were irradiated with 500 mJ/cm2 of UVB and the increment of ear thickness was measured before and 6, 12, and 24 h after irradiation. Ear swelling in W/Wv mice at 12 and 24 h after irradiation was significantly smaller than that in +/+ and ICR mice. In contrast, the number of sunburn cells formed 24 h after UVB irradiation (200 or 500 mJ/cm2) was similar in W/Wv, +/+ and ICR mice. On the other hand, when mice were treated with 8-methoxy-psoralen (0.5%) plus UVA irradiation (4 J/cm2) (topical PUVA), ears of W/Wv and BALB/c mice, which were both white in color, were thickened similarly 72 h after treatment, but less swelling was observed in +/+ mice, which were black in skin color. The amount of prostaglandin D2 (PGD2) in ears, determined by radioimmunoassay specific for PGD2, was elevated 3-fold in +/+ and ICR mice at 3 h after irradiation with 500 mJ/cm2 of UVB in comparison with basal level without irradiation. However, such elevation was not observed in W/Wv mice. These results suggest that mast cells play an important role in UVB-induced inflammation, and PGs from mast cells are responsible at least in part for the development of this reaction. However, neither mast cells nor PGs contribute to the sunburn cell formation and ear swelling response by PUVA treatment

Late vascular effects in irradiated mice brain

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Phillips, T.L.

1982-01-01

The whole brains of mice were irradiated with 250 kVp X-ray at 120 rad min -1 (1.6 mm Cu HVL, TSD 50 cm) and a histological study was done. The dose range of X-irradiation was from 1300 to 2500 rads. i.e., 1300, 1500, 1750, 2000, and 2500 rads. In the microscopic examination, the mice were killed at the regular postirradiation intervals of between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. A histological examination was performed by a morphometric estimation of vascular lesion in which the degree of the damage to the arterial system was scored through whole serial brain sections. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectatic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large artery were observed. Incidence of the fibrinoid necrosis increased dose dependently between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 - 87 weeks and can be used to quantify the vessel injury and a fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis. (author)

[Effect of electromagnetic pulse irradiation on structure and function of Leydig cells in mice].

Science.gov (United States)

Wang, Shui-Ming; Wang, De-Wen; Peng, Rui-Yun; Gao, Ya-Bing; Yang, Yi; Hu, Wen-Hua; Chen, Hao-Yu; Zhang, You-Ren; Gao, Yan

2003-08-01

To explore the effect of electromagnetic pulse (EMP) irradiation on structure and function of Leydig cells in mice. One hundred and fourteen male Kunming mice were randomly divided into irradiated and control group, the former radiated generally by 8 x 10(3) V/m, 2 x 10(4) V/m and 6 x 10(4) V/m EMP respectively five times within two minutes. Pathological changes of Leydig cells were observed by light and electron microscope. Serum testosterone (T), luteinizing hormone (LH) and estradiol (E2) were measured dynamically by radioimmunoassay at 6 h, 1 d, 3 d, 7 d, 14 d and 28 d after irradiation. Main pathological changes were edema and vacuolation, swelling of cytoplasmic mitochondria, reduce of lipid droplets, pale staining of most of lipid droplets, and partial or complete cavitation of lipid droplets in Leydig cells within 28 days after EMP radiation. Compared with normal controls, serum T decreased in all in different degrees within 28 days, and dropped significantly at 6 h-14 d, 6 h-7 d and 1 d-28 d after 8 x 10(3) V/m, 2 x 10(4) V/m and 6 x 10(4) V/m EMP irradiation(P < 0.05 or P < 0.01). EMP irradiation caused no significant changes in serum LH and E2. Leydig cells are among those that are the most susceptible to EMP irradiation. EMP irradiation may cause significant injury in structure and function of Leydig cells in mice, whose earlier and continuous effect is bound to affect sexual function and sperm production.

Safety of dried sambiloto Andrographis paniculata (Burm. F.) nees gamma irradiated based on acute toxicity aspect in mice swiss webster

International Nuclear Information System (INIS)

Ermin Katrin; Susanto; Hendig Winarno

2014-01-01

Andrographis paniculata nees (Family: Acanthaceae) is a medicinal plant commonly cultivated in Asian countries. The purpose of this study was to evaluate the safety of gamma irradiated sambiloto against to animal test (mice) and to support the application of nuclear techniques for radiation pasteurization of sambiloto as health products without changing the properties. In the acute toxicity test was observed the effects of the tested material on behavioral changes, abnormalities in the function of several organs and body weight changes in animal test every day for 2 weeks. The results showed that the ethanol extract of unirradiated and irradiated with dose of 7.5 kGy) sambiloto were not toxic to mice. Lethal Dose 50 (DL 50 ) of ethanol extract from sambiloto unirradiated or irradiated at the dose of 7.5 kGy was > 5000 mg/kg BW. At the highest dose tested 5000 mg/kg BW mice there were no significant toxic effects and no mice that died during the experiment, therefore ethanol extracts of un irradiated and irradiated samples could be declared safe. (author)

Anti-lipopolysaccharide toxin therapy for whole body X-irradiation overdose

Energy Technology Data Exchange (ETDEWEB)

Gaffin, S.L.; Wells, M.; Jordan, J.P.

1985-09-01

Death in humans from ionising radiation overexposure in the 3-8 Gy (300-800 rad) range is in part due to the toxaemia caused by the entry of gram-negative bacteria and/or their lipopolysaccharide toxin (LPS) into the blood circulation through the walls of partially denuded gut. Anti-LPS hyperimmune equine plasma was evaluated for its ability to lower irradiation-induced lethality. Mice were irradiated with 6.3 Gy (630 rad) and six days later received equine Anti-LPS hyperimmune plasma, control plasma or saline. Mortalities in the three groups were 58%, 92% and 79% (p < 0.01) respectively. Thus Anti-LPS may prove useful as an adjunct to conventional therapy in treating radiation sickness.

Anti-lipopolysaccharide toxin therapy for whole body X-irradiation overdose

International Nuclear Information System (INIS)

Gaffin, S.L.; Wells, M.; Jordan, J.P.

1985-01-01

Death in humans from ionising radiation overexposure in the 3-8 Gy (300-800 rad) range is in part due to the toxaemia caused by the entry of gram-negative bacteria and/or their lipopolysaccharide toxin (LPS) into the blood circulation through the walls of partially denuded gut. Anti-LPS hyperimmune equine plasma was evaluated for its ability to lower irradiation-induced lethality. Mice were irradiated with 6.3 Gy (630 rad) and six days later received equine Anti-LPS hyperimmune plasma, control plasma or saline. Mortalities in the three groups were 58%, 92% and 79% (p<0.01) respectively. Thus Anti-LPS may prove useful as an adjunct to conventional therapy in treating radiation sickness. (author)

Synthesis and radioprotective study of novel amino-alkyl dithiocarbamic acid derivatives against γ-irradiation in mice

International Nuclear Information System (INIS)

Hosseinimehr, S. J.; Beiki, D.; Kebriaeezadeh, A.; Khalaj, A.; Pirali Hamedani, M.; Akhlaghpoor, S.; Esmaeili, H.; Barazesh, A. R.

2009-01-01

The aim of this study was to evaluate the radioprotective capacity of some novel amino alkylated dithiocarbamic acid potassium salts against γ-irradiation in mice. Materials and Methods: Eight compounds containing 2-aminoethyl-, 3-aminopropyl-, 4-aminobutyl-, 5-aminopentyl-, 6-aminohexyl-, 7-amino heptyl-, 8-amino octyl and 9-amino nonyl of dithiocarbamate derivatives were prepared. Male NMRI mice were injected intraperitoneally with a geometric progression of doses (300 -1000 mg/kg), through the dose response range for lethal toxicity. To evaluate the radioprotective activity, one-half of the toxic LD 50 of each compound were injected intraperitoneally to groups of twenty mice, 30 minutes prior to γ-irradiation. The treated animals were kept for 30 days, and the lethality was recorded each day. Results: Among Eight compounds of alkyl dithiocarbamic acid derivatives, 5-aminopentyl, 7-amino heptyl, 8-amino octyl and 9-amino nonyl dithiocarbamic acid mono potassium salts are new compounds. All evaluated compounds showed a concentration dependent effect on the survival in mice. The LD 50 values were found to be more than 599 mg/kg. The percentages of 30-day survival of mice for 2-aminoethyl, 7-amino heptyl and 8-amino octyl dithiocarbamic acid derivatives were 7%, 40% and 13.5%, respectively, when injected 30 minutes before γ-irradiation. Other compounds had no radioprotective effects. Statistical analysis showed a significant difference between the treated and control groups for the 7-amino heptyl derivative (p<0.05). Conclusion: Among the compounds investigated in this study, 7-amino heptyl dithiocarbamate derivative showed more radioprotective effects in comparison with the others. Although it seems that the radioprotective effects in these derivatives correlate with the size of the alkyl chain, more experiments are required to support this hypothesis.

Chemical protection against gastrointestinal radiation injury in mice by WR 2822, WR 2823, or WR 109342 after 4 MeV x ray or fission neutron irradiation

International Nuclear Information System (INIS)

Connor, A.M.; Sigdestad, C.P.

1982-01-01

Three compounds were tested for their radioprotective properties against the effects of 4 MeV X rays or fission neutron irradiation. The endpoints tested were lethality, intestinal crypt survival, and DNA synthesizing cellularity. Two of the compounds tested; S-2(4-aminobutylamino) ethylphosphorothioc acid (WR 2822) and the aminopentylamino derivative (WR 109342). All drugs were administered via intraperitoneal injections at their approximately maximum tolerated dose. WR 2822 was shown to have a slight protective effect against X rays and neutrons. The dose modification factor (DMF) for gastrointestinal death (LD/sub 50(6)/) was 1.23 for X rays and 1.51 for neutrons. The assay for intestinal crypt survival produced DMF's of 1.44 (X rays) and 1.4 (neutrons). WR 2823 also showed a protective action in these assays. The DMF for LD/sub 50(6)/ was 1.32 (X rays) and 1.42 (neutrons). WR 109342 was found to be extremely toxic and had no significant protective effects. All three drugs were more toxic and demonstrated less protection in most of these assays than the benchmark radioprotective agent WR 2721, although WR 2822 protected against lethal effects of fission neutrons almost as well as WR 2721. Both WR 2822 and WR 2823 produced greater protection in the crypt survival assays for fission neutron irradiation than WR 2721

Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

Science.gov (United States)

Cacciabue, Marco; García-Núñez, María Soledad; Delgado, Fernando; Currá, Anabella; Marrero, Rubén; Molinari, Paula; Rieder, Elizabeth; Carrillo, Elisa; Gismondi, María Inés

2017-09-01

Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

Types and three-dimensional distribution of neuronal ectopias in the brain of mice prenatally subjected to X-irradiation

Energy Technology Data Exchange (ETDEWEB)

Sun, Xue-Zhi; Takahashi, Sentaro; Kubota, Yoshihisa; Sato, Hiroshi [National Inst. of Radiological Sciences, Chiba (Japan); Cui, Chun; Fukui, Yoshihiro [Tokushima Univ. (Japan). School of Medicine; Inouye, Minoru [Shin Nippon Biomedical Lab., Ltd., Miyanoura, Kagoshima (Japan)

2002-03-01

The types and three-dimensional distribution of neocortical ectopias following prenatal exposure to X-irradiation were studied by a histological examination and computer reconstruction techniques. Pregnant ICR mice were subjected to X-irradiation at a dose of 1.5 Gy on embryonic day 13. The brains from 30-day-old mice were serially sectioned on the frontal plane at 15 {mu}m, stained with HE and observed with a microscope. The image data for the sections were input to a computer, and then reconstructed to three-dimensional brain structures using the Magellan 3.6 program. Sectional images were then drawn on a computer display at 240 {mu}m intervals, and the positions of the different types of neocortical ectopias were marked using color coding. Three types of neocortical ectopias were recognized in the irradiated brains. Neocortical Lay I ectopias were identified as small patches in the caudal occipital cortex, and were located more laterally in the neocortex in caudal sections than in the rostral sections. Periventricular ectopias were located more rostrally than Lay I ectopias, and were found from the most caudal extent of the presumed motor cortex to the most caudal extent of the lateral ventricle. Hippocampal ectopias appeared as continuous linear bands, and were frequently associated with the anterior parts of the periventricular ectopias. (author)

Response of mesenchymal stem cells in mice to 3.5 Gy X-ray irradiation

International Nuclear Information System (INIS)

Su Wenxia; Liu Huimin; Chen Yonghong; Zeng Wen; Liu Wenli; Sun Hanying

2011-01-01

Objective: To investigate the response of mesenchymal stem cells in mice to medium-dose X-ray irradiation in vitro. Methods: The mouse mesenchymal stem cell line C3H10T1/2 was submitted to 3.5 Gy X-ray irradiation. Hoechst33258 staining of adherent cells and Annexin V-FITC staining and flow cytometry analysis of suspension cells were performed respectively to assess cellular apoptosis at 3, 6, 12, 24, 48, 72 h and 1 week after irradiation. SA-β-gal staining was performed to analyze the cellular senescence at 24, 48, 72 h and 1 week after irradiation. The mRNA level of both Fas with its ligand FasL and p53 with its downstream target p21 WAF1 were measured by Real-Time PCR analysis. The expression of Fas protein was determined by immunofluorescence staining. Results: An increased apoptosis was observed at 3 h after irradiation with apoptosis rate 11.72% ± 1.61% (t=9.01, P<0.01), the apoptosis rate reached the peak level at 12 h 20.52% ± 1.96% (t=16.27, P<0.01), and then declined progressively to normal level at 48 h 4.93% ±0.46% (t=2.26, P>0.05). The SA-β-gal positive rate of post-radiation cells at 72 h was 53.33% ± 5.62%, significantly higher than that of normal control 3.24% ± 0.39% (t=17.77, P<0.01). The level of Fas, FasL mRNA was found to be elevated 3 h after irradiation with a peak at 12 h, and no differences were found l week later. The level of Fas protein was observed to reach the peak at 12 h after irradiation. The occurrence of peak level of Fas/FasL mRNA and protein was consistent with that of apoptosis of C3H10T1/2 cell. A transient up-regulation of p53, p21 WAF1 mRNA expression was found at 12 h after irradiation followed by a significant increase later at 72 h after irradiation. The occurrence of the two peaks of p53, p21 WAF1 mRNA expression were coincident with that of cellular apoptosis and senescence, respectively. The levels of p53, p21 WAF1 mRNA in senescence group were significantly higher than those of apoptosis group (t=17.85, 13

Evidence of heritable lethal mutations in progeny of X-irradiated CHO cells by micronucleus count in clon-cells

International Nuclear Information System (INIS)

Hagemann, G.; Kreczik, A.; Treichel, M.

1996-01-01

Low doses of ionizing radiation reduce the growth rates of clones following irradiation of the progenitor cells. Such reductions of clone growth have been proven by means of measurements of clone size distributions. The medians of such distributions can be used to quantify the radiation damage. Prolongations of generation times and cell death as result of heritable lethal mutations have been discussed as causes for the reduction of clone growth. The cell number of a clone of hypotetraploid CHO-cells was compared to the frequency of micronucleated binucleated cells in the same clone using the cytokinesis-block-micronucleus method. The dose dependent reduction of clone sizes is measured by the difference of the medians (after log transformation) of the clone size distributions. At cytochalasin-B concentrations of 1 μg/ml and after an incubation time of 16 h a yield of binucleated cells of about 50% was obtained. Median clone size differences as a measure of clonal radiation damage increased linearly with incubation times of 76, 100, 124, and 240 h following irradiation with 3, 5, 7, and 12 Gy. The frequency of binucleated clone cells with micronuclei strongly increased with decreasing clone size by a factor up to 20 following irradiation with 3, 5, and 7 Gy. The frequency of micronucleated binucleated clone cells was found to be independent of incubation time after irradiation. Radiation induced clone size reductions result from cell losses caused by intraclonal expression of micronuclei which have its origin in heritable lethal mutations. Measurements of clone size distributions can be done automatically. They can serve as predictive test for determination of median cell loss rates of surviving cell clones. (orig./MG) [de

Photoreactivable sector of lethal damage in ultraviolet-irradiated Escherichia coli cells

International Nuclear Information System (INIS)

Balgavy, P.

1976-01-01

The photoreactivable sector of lethal damage in Escherichia coli Bsub(s-1), Escherichia coli B/r Hcr - and Escherichia coli B/r Hcr + cells after ultraviolet irradiation at 254 nm is 0.823 +- 0.004, 0.70 +- 0.01 and 0.53 +- 0.06, respectively, at 99% confidence limits. For the low values of the photoreactivable sector in the B/r Hcr - and B/r Hcr + strains are likely to be responsible dark repair processes which eliminate lethal damage, brought about by pyrimidine dimers, preferably in comparison with lethal damage caused by photoproducts of another type. (author)

The entry of the prothymocyte into the thymus after lethal irradiation and bone marrow transplantation. 2

International Nuclear Information System (INIS)

Mulder, A.H.; Visser, J.W.M.; Zoetelief, J.; Bekkum, D.W. van

1988-01-01

The time of entry of prothymocytes into the thymus after lethal irradiation and bone marrow transplantation (BMT) was determined by exposing the thymus only or the whole body with the thymus shielded to a second irradiation after different intervals. The repopulation of the thymus by donor type cells was determined by a thymus repopulation assay using donor specific markers. Reirradiation of the thymus kills the prothymocytes that have entered the thymus during the interval. It was found that reirradiation of the thymus from 48 hours after BMT onwards increasingly delayed thymus regeneration. This shows that donor prothymocytes do not enter the thymus until about 2 days after BMT and that they continue to do so during at least 3 subsequent days. In the second reirradiation protocol thymus regeneration occurred earlier in the shielded thymus than in thymuses of whole body irradiated mice. Earlier thymus regeneration was not seen in mice that were reirradiated at 24 hours after BMT, but occurred only when irradiation took place at 48 hours and later. These data are consistent with those obtained in the first protocol. The results are in contradiction with results of direct homing experiments, which showed entrance of donor cells within 3 hours after BMT. A functional assay demonstrated that the early appearing cells cannot be prothymocytes. In retransplantation experiments it was shown that the bone marrow may indeed be the initial homing site of prothymocytes. 14 refs.; 5 figs.; 1 table

Stimulatory effect of aminoethylisothiuronium on the immune response and interferogenesis in irradiated mice

Energy Technology Data Exchange (ETDEWEB)

Zheleznikova, G.F.; Ogurtsov, R.P.; Stepanov, A.N. (Tsentral' nyj Nauchno-Issledovatel' skij Rentgeno-Radiologicheskij Inst., Leningrad (USSR))

Aminoethylisothiuronium (AET) stimulated the formation of antibodies against sheep erythrocytes, not against E. coli, in X-irradiated (4 Gy) mice. The serum containing AET-induced interferon had the same effect. AET also promoted the rejection of the allogenic skin graft in mice irradiated with the same dose. In addition, AET and cystaphos stimulated the induction of interferon by the Newcastle disease virus in mice exposed to doses of 4, 5 or 6 Gy.

The effect of X-irradiation on the fertility and the induction of meiotic chromosome rearrangements in mice and their first generation

International Nuclear Information System (INIS)

Savkovic, N.; Pecevski, J.; Maric, N.; Radivojevic, D.

1978-01-01

The effect of whole-body and local irradiation with a dose of 600 X-rays on the induction of chromosomal translocations in Diakinesis-Metaphase I of meiosis in treated and F 1 males and their fertility have been examined. Our results showed the high percentage of mortality in whole-body irradiated mice. The percentage of fertility was 25% in whole-body, and 93,7% in locally irradiated males. The testis weight was also reduced. The percentage of chromosomal translocations in Diakinesis-Metaphase I of meiosis was greater after whole-body than after local irradiation. In F 1 males both types of irradiation induced chromosomal translocations. (orig.) [de

Protection of Escherichia coli cells against the lethal effects of ultraviolet and X-irradiation by prior X-irradiation. A genetic and physiological study

Energy Technology Data Exchange (ETDEWEB)

Smith, K C; Martignoni, K D [Stanford Univ., Calif. (USA). Dept. of Radiology

1976-12-01

When log phase cells of wild-type E.coli K-12 were maintained in growth medium after X-irradiation, they became progressively more resistant to a subsequent exposure to UV or X-radiation. The time to achieve maximum resistance was about 60 min. The uvrB, uvrD, polA and certain exrA strains (W3110 background) also demonstrated this X-ray-induced resistance to subsequent UV or X-irradiation but recA, recB, lex (AB1157 or W3110 backgrounds) and other exrA strains (AB1157 background) did not. The resistance induced in wild-type, uvrB and uvrD cells was characterized by the production or enhancement of a shoulder on the survival curves obtained for the second irradiation, while the resistance induced in the W3110 exrA strains was expressed only as a change in slope. The induction of resistance in the W3110 exrA strain was not inhibited by the presence of chloramphenical, but that in the wild-type cells appeared to be. The production or enhancement of a shoulder on the survival curves of the rec/sup +/ lex/sup +/ exr/sup +/ cells is consistent with the concept of the radiation induction of repair enzymes. Alternative explanations, however, are discussed.

Heterogeneous response to X-ray and ultraviolet light irradiations of cultured skin fibroblasts in two families with Gardner's Syndrome

International Nuclear Information System (INIS)

Kinsella, T.J.; Little, J.B.; Nove, J.; Weichselbaum, R.R.; Li, F.P.; Meyer, R.J.; Marchetto, D.J.; Patterson, W.B.

1982-01-01

A heterogeneous response to X-ray and far UV (254 nm) light irradiations was found in cultured skin fibroblast lines from 2 separate families with Gardner's syndrome. When compared to 2 normal control cultures and cultures from 2 patients with nonfamilial colon cancer, cultures from 4 clinically affected members of family 1 showed increased sensitivity to the lethal effects of both X-ray and UV light irradiations. These cells also showed a delayed pattern of X-ray potentially lethal damage repair (PLDR) and absent UV PLDR. In contrast, cultures from 3 members of family 2 (2 of whom were clinically affected) showed a normal response of survival and PLDR to both X-ray and UV light irradiations. Thus increased sensitivity of cultured skin fibroblasts to X-ray and UV light irradiations was not a consistent in vitro finding in patients with Gardner's syndrome. However, in families with Gardner's syndrome who demonstrate in vitro radiosensitivity, additional studies are needed to assess the usefulness of these techniques in detecting affected individuals prior to the development of colon carcinoma and other manifestations

Toxicological and radiological safety of chicken meat irradiated with 7.5 MeV X-rays

Science.gov (United States)

Song, Beom-Seok; Lee, Yunjong; Park, Jong-Heum; Kim, Jae-Kyung; Park, Ha-Young; Kim, Dong-Ho; Kim, Chang-Jong; Kang, Il-Jun

2018-03-01

This study was conducted to evaluate the toxicological and radiological safety of chicken meat that had been irradiated at 30 kGy with 7.5 MeV X-rays. In a sub-chronic toxicity study, ICR mice were fed X-ray-irradiated chicken meat at 2500 mg/kg body weight daily for 90 days, and no mortality or abnormal clinical signs were observed throughout the study period. However, several hematological and serum biochemical parameters of the ICR mice differed significantly from those in the control group; nevertheless, the observed values were all within the normal range for the respective parameters. In addition, no toxicological effects were determined in male or female mice. Furthermore, no differences in gamma-ray spectrometric patterns were detected between the non-irradiated and irradiated samples, indicating that the radioactivity induced by 7.5 MeV X-ray irradiation was below the detection limit. These results tentatively suggest that chicken meat irradiated with 7.5 MeV X-rays would be safe for human consumption in terms of toxicology and radiology.

Suppression of carcinogenesis in mice by adaptive responses to low dose rate irradiation

Energy Technology Data Exchange (ETDEWEB)

Sakai, Kazuo; Iwasaki, Toshiyasu; Hoshi, Yuko; Nomura, Takaharu; Ina, Yasuhiro; Tanooka, Hiroshi [Central Research Institute of Electric Power Industry, Low Dose Radiation Research Center, Komae, Tokyo (Japan)

2003-07-01

Effects of prolonged low-dose-rate irradiation on the process of carcinogenesis were examined in mice treated with chemical carcinogen or irradiated with high doses of X-rays. Female ICR mice, 5 week-old, 35 in each group, were exposed to gamma-rays from a {sup 137}Cs source in the long-term low dose rate irradiation facility at CRIEPI. The dose rate was 2.6 mGy/hr (A), 0.96 mGy/hr (B), or 0.30 mGy/hr (C). Thirty-five days later, the mice were injected into the groin with 0.5 mg of methylcholanthrene (MC) dissolved in olive oil and irradiation was continued. Cumulative tumor incidences after 216 days following MC injection were 89% in group A, 76% in group B, and 94% in group C. That in non-irradiated control group was 94%. The difference in the tumor incidence between the control and position B was statistically significant, indicating the suppressive effect of the low dose rate irradiation on the process of MC-induced carcinogenesis with an optimum dose rate around 1 mGy/hr. In B6C3F1 mice, although the suppression of tumor incidence was not observed, there was a significant delay in tumor appearance in the irradiated mice between 100-150 days after MC injection. A group of 20 female C57BL/6N mice, 5 weeks old, were exposed to gamma-rays at 0.95 mGy/hr for 5 weeks. Then, they were exposed weekly to 1.8 Gy whole body X-irradiation (300 kVp) for consecutive 4 weeks to induce thymic lymphoma. Another group received only the fractionated irradiation. The first mouse died from thymic lymphoma appeared 89 days after the last irradiation in the group received only the fractionated irradiation, while 110 days in the group combined with the low dose rate irradiation. (author)

Studies on the leukemogenic and immunologic effects of radiostrontium (90Sr) and x rays in mice

International Nuclear Information System (INIS)

Ito, K.; Nagao, K.; Kawamura, Y.; Yokoro, K.

1976-01-01

The leukemogenic effect of internal irradiation with radiostrontium ( 90 Sr) was compared with that of external irradiation with x rays in ICR/JCL mice. Immunological, hematological, and cytogenetical changes were also studied during the preleukemic period in mice treated with 90 Sr or with x rays. A single intraperitoneal injection of 1.0 μCi of 90 Sr per gram of body weight resulted in leukemia in 62 percent of the mice. Only one of the 90 Sr-induced leukemias was of thymic origin. The occurrence of the leukemia was not affected by thymectomy. A fractionated whole-body x-irradiation of 680 R induced leukemia in 77 percent of the mice; the majority of the leukemias were of thymic origin. Although x-irradiation over the thymic region was ineffective in eliciting leukemia, a combined treatment of 90 Sr and local x-irradiation of the thymus was effective in inducing thymic lymphomas. The single intraperitoneal administration of 90 Sr caused an enhancement of both direct and indirect splenic plaque-forming cell (PFC) responses to sheep red blood cells, lasting for 35 days after treatment. No changes were observed in delayed-type hypersensitivity to picryl chloride. Thymectomy caused no appreciable effect in these immune responses. The fractionated whole-body x-irradiation rapidly depressed both PFC and delayed-type hypersensitivity responses, which persisted for a long period, especially in thymectomized mice. An abrupt increase of chromosomally aberrant cells in the thymus 60 days after the last x-irradiation was preceded by an increase of aberrant population in the bone marrow. On the other hand, a long-lasting appearance of aberrant population in the bone marrow and lymph nodes was observed in 90 Sr-injected mice

Repair of potentially lethal damage following irradiation with x rays or cyclotron neutrons: response of the EMT-6/UW tumor system treated under various growth conditions in vitro and in vivo

International Nuclear Information System (INIS)

Rasey, J.S.; Nelson, N.J.

1981-01-01

Postirradiation potentially lethal damage (PLD) repair was examined in the EMT-6/UW tumor system under a variety of in vitro and in vivo growth conditions. Following x irradiation, surviving fraction increased in fed and unfed plateau cultures if subculture and plating were delayed; in exponentially growing cultures if they were covered with depleted medium for the first 6 h postirradiation; and in tumors in vivo if excision for preparation of a cell suspension was delayed. Following irradiation with 21.5 meV (d + → Be) neutrons, PLD repair was measurable only in unfed plateau cultures when subculture was delayed and in exponentially growing cells exposed to depleted culture medium immediately after irradiation. In x-irradiated EMT-6/UW cells, the greatest repair capacity and the highest surviving fraction ratios were measured in unfed plateau cultures; the least repair was observed in exponentially growing cells exposed to depleted medium. Thus post-neutron repair was not limited to situations where the amount of repair of photon PLD is large. The demonstration of PLD repair in tumors irradiated in vivo with X rays and the absence of such repair after neutrons could have important implications in radiotherapy if this is a general phenomenon

Adrenaline and serotonin therapeutic effect on the hemopoietic system of irradiated mice

International Nuclear Information System (INIS)

Smirnova, I.B.; Dontsova, G.V.; Rakhmanina, O.N.; Konstantinova, M.M.

1984-01-01

Post-irradiation effect of adrenaline and serotonin on the hemopoietic system of irradiated mice has been studied. The pharmaceuticals were injected subcutaneously 15 minutes before the X-radiation exposure at a dose of 7 Gy or immediately after it. The degree of radiation injury has been estimated from 30-day survival fraction of the animals, cell state of the bone marrow, mass of spleen, cfu quantity in the bone marrow at exo- and endocolonial growth (following implantation of bone marrow cells from mice that had been injected with these drugs to irradiated recipients). Post-irradiation effect of adrenaline turned to be weaker than that of serotonin, the latter increasing the survival rate of irradiated mice to 50%. It is stated that post-irradiation therapeutic effect of adrenaline and serotonin expressed in acceleration of the irradiated hemopoietic tissue repair can be realized under direct effect of drugs on the viable hemopoietic cells, probably, by enchancement of their proliferation

The production of IL-1, IL-3, CSA by bone marrow nuclears during bone marrow haemopoiesis after lethal irradiation and syngenic bone marrow transplantation

International Nuclear Information System (INIS)

Dygaj, A.M.; Buznik, D.V.; Bogdashin, I.V.; Agafonov, V.I.

1994-01-01

The production of haemopoietic factors (IL-1, IL-3, CSA) by adherent and unadherent cells of lethally irradiate CBA mice bone marrow and after syngenic myelokaryocyte transplantation was studied. Radioresistant myelokaryocytes capable to produce haemopoetic factors IL-1, CSA as early as 24 hr after irradiation were found in adherent cell fraction. The synthesis of humoral factors (IL-3, CSA) by unadherent bone marrow elements was realised in a late of experiment (3-6 days) that was connected with forming of functionally valuable cell forms from transplanted or viable stem cells

X irradiation combined with TNF alpha-related apoptosis-inducing ligand (TRAIL) reduces hypoxic regions of human gastric adenocarcinoma xenografts in SCID mice

International Nuclear Information System (INIS)

Takahashi, Momoko; Yasui, Hironobu; Ogura, Aki; Asanuma, Taketoshi; Inanami, Osamu; Kubota, Nobuo; Tsujitani, Michihiko; Kuwabara, Mikinori

2008-01-01

Our previous study showed that X irradiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines under not only normoxia but also hypoxia. X irradiation combined with TNF α-related apoptosis-inducing ligand (TRAIL), which is the ligand of DR5, induced apoptosis in vitro (Takahashi et al., (2007) Journal of Radiation Research, 48: 461-468). In this report, we examined the in vivo antitumor efficacy of X irradiation combined with TRAIL treatment in tumor xenograft models derived from human gastric adenocarcinoma MKN45 and MKN28 cells in severe combined immunodeficiency (SCID) mice. X irradiation combined with TRAIL synergistically suppressed the tumor growth rates in the xenograft models derived from MKN45 and MKN28 cells, which have wild type Tp53 and mutated Tp53, respectively, indicating that the antitumor effects occurred in a Tp53-independent manner. Histological analysis showed that the combination of X irradiation and TRAIL induced caspase-3-dependent apoptotic cell death. Moreover, the immunohistochemical detection of hypoxic regions using the hypoxic marker pimonidazole revealed that caspase-3-dependent apoptosis occurred in the hypoxic regions in the tumors. These results indicated that X irradiation combined with TRAIL may be a useful treatment to reduce tumor growth in not only normoxic but also hypoxic regions. (author)

Preliminary studies on factors controlling the rate of regrowth of heavily x-irradiated rat rhabdomyosarcoma tumors

International Nuclear Information System (INIS)

Tenforde, T.S.; Curtis, S.B.; Woodruff, H.K.; Parks, D.L.; Daniels, S.J.; Crabtree, K.E.; Schilling, W.A.; DeGuzman, R.J.

1977-12-01

Following large single doses of x rays, rat rhabdomyosarcoma tumors exhibit a volume response which characteristically has a swelling phase, a regression phase, a rapid ''initial'' regrowth phase and a slow ''late'' regrowth phase. The preliminary experiments reported here were designed to examine three mechanisms that may underlie the reduction in growth rate occurring in the late regrowth phase; heritable non-lethal cellular damage, host immunity, delayed post-irradiation tissue and vascular damage. Based on retransplantation experiments and studies with immunosuppressed rats, neither heritable non-lethal damage nor host immune factors appear to influence the regrowth rate of tumors receiving radiation doses well below the cure level. After an x-ray dose approaching the cure level, regrowing tumors were observed to have a greatly reduced growth rate, possibly reflecting the presence of heritable non-lethal damage and/or an increased antigenicity of the heavily irradiated tumor cells. Morphometric analysis of histological sections did not reveal statistically significant abnormalities at the cellular level during the late regrowth phase, except for an increase in the percentage of necrotic tissue relative to non-irradiated tumors. The morphological resolution of small blood vessels was not adequate to evaluate delayed vascular damage in regrowing irradiated tumors

Therapy of infections in mice irradiated in mixed neutron/photon fields and inflicted with wound trauma: a review of current work.

Science.gov (United States)

Ledney, G D; Madonna, G S; Elliott, T B; Moore, M M; Jackson, W E

1991-10-01

When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, we developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60[Co sources. Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections. Combined therapy with S-TDCM and ceftriaxone for K. pneumoniae infections in mice exposed to a mixed radiation field or to gamma rays was more effective than single-agent therapy. In all irradiated-wounded mice, single therapy of acquired infections with an antibiotic or S-TDCM did not increase survival. Survival of irradiated-wounded mice after topical application of gentamicin sulfate cream suggested that bacteria colonizing the wound disseminated systemically in untreated irradiated mice, resulting in death from sepsis. In lethal models of acquired infections in irradiated-wounded mice, significant increases in survival were achieved when systemic treatments with S-TDCM or gentamicin were combined with topical treatments of gentamicin cream. Therapies for sepsis in all mice exposed to a mixed field were less effective than in mice exposed to gamma rays. Nonetheless, the data show a principle by which successful therapy may be provided to individuals receiving tissue trauma in conjunction with

Effects of pre-natal X-ray exposure on learning behaviour of mice

International Nuclear Information System (INIS)

Frank, P.; Faber, U.; Budny, T.

1983-01-01

The authors investigated whether prenatal X-raying affects the learning behaviour of mice. For this purpose they irradiated mice of strain C57BL/6Ffm with 130 r at different points of the fetal phase. Unirradiated mice served as controls. The animals underwent two learning test series of 14 days each teaching them optical signs. The results of the test series show a distinctly inferior learning ability in the animals exposed to pre-natal irradiation as compared to unirradiated controls. The extent of the reduction of the learning ability depends on the stage of the pregnancy at the time of X-ray exposure. The greatest difference as compared to non-irradiated mice occurred in the animals irradiated at the earliest stage (13th/14th day of pregnancy). The results of the other test groups (15th/16th and 17th/18th day of pregnancy) exhibited less distinct, but still significant differences to the controls. Exposure at the latest period (17th/18th day) coincided with the smallest difference. (orig./MG) [de

Immunization of mice with gamma-irradiated intramuscularly injected schistosomula of Schistosoma mansoni

International Nuclear Information System (INIS)

Bickle, Q.D.; Taylor, M.G.; Doenhoff, M.J.; Nelson, G.S.

1979-01-01

The parameters involved in the induction of resistance against Schistosoma mansoni by injection of irradiated, artificially transformed schistosomula were studied in mice. Single intramuscular injections of 500 schistosomula exposed to radiation doses in the range 2.3 to 160 krad. resulted in significant protection ( in the range 20 to 50% as assessed by reduced worm burdens) against a challenge infection administered at intervals from 3 to 24 weeks post-vaccination. However, schistosomular irradiated with 20 krad. consistently resulted in better protection than those exposed to either higher or lower radiation doses despite the persistence of stunted adults from the infections irradiated with 2.3 krad. Vaccination with 40 krad. schistosomula resulted in significant protection in terms of reduced worm and tissue egg burdens and increased survival following lethal challenge. Varying the number of irradiated schistosomula, the frequency and route of their administration, the site of challenge and the strain of host all failed to enhance the level of resistance. However, percutaneously applied, irradiated cercariae were found to be more effective in stimulating resistance (60%) than intramuscularly injected, irradiated schistosomula (40%). (author)

Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice

International Nuclear Information System (INIS)

Wang, Bing; Tanaka, Kaoru; Ji, Bin

2014-01-01

The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with 11 C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice. (author)

Effect of experimental immune atrophic gastritis on the induction of gastric carcinoma by x-irradiation in ICR mice

International Nuclear Information System (INIS)

Hirose, Fumio; Watanabe, Hiromitsu; Takeichi, Nobuo; Naito, Yukiko; Inoue, Shozo

1976-01-01

Divided doses of 6,000 or 8,000 rad of x-ray were given to the gastric region of ICR/JCL female mice with immune atrophic gastritis produced by the injection with allogenic stomach antigen. The carcinogenic effect of x-rays for inducing gastric carcinoma was significantly increased by this method. Two points can be presented as its reason. First, the pyloric gland mucosa regenerating from injuries by immunization was exposed to the divided doses of x-rays. Second, the marked requirement of gastrin secretion attributable to severe injuries of parietal cell mass by immunization and local x-irradiation acted as a promoting factor on the induction of gastric carcinoma by x-ray for a long time through the trophic effects on the pyloric gland. (auth.)

Delayed erythropoiesis in irradiated rats grafted with syngeneic marrow: effects of cytotoxic drugs and iron-deficiency anemia

International Nuclear Information System (INIS)

Rodday, P.; Bennett, M.; Vitalle, J.J.

1976-01-01

Erythropoiesis in spleens of lethally irradiated Lewis rats grafted with 4-35 x 10 6 syngeneic marrow cells was inhibited or delayed during the test period of 5 days; this was in marked contrast to observations in irradiated mice. The mechanism of this inhibition was the subject of this study. Pretreatment of recipients 9 days prior to irradiation with the cytotoxic drugs cyclophosphamide (CY), busulfan (BUS), or dimethylmyleran (DMM), or the induction of iron deficiency with anemia in recipients reversed this delayed erythropoiesis. However, neither iron-deficiency anemia nor pretreatment with BUS or DMM affected the ability of irradiated recipients to reject 20 to 50 x 10 6 allogeneic marrow cells. The administration of commercial preparations of erythropoietin to hosts stimulated erythropoiesis moderately. However, proliferation of syngeneic marrow cells was not enhanced when infused into lethally irradiated spontaneous hypertensive (SH) inbred-strain rats which have high levels of endogenous erythropoietin. Finally, plasma from irradiated rats treated with phenylhydrazine to produce severe anemia was rich in erythropoietin but failed to stimulate erythropoiesis in the cell transfer system. Two hypotheses are considered

The effect of X-irradiation on the fertility and on the induction of meiotic chromosome rearrangements in mice and their first generation

International Nuclear Information System (INIS)

Savkovic, N.; Pecevski, J.; Maric, N.; Radivojevic, D.

1980-01-01

The effect of whole-body or local irradiation with X-rays at a dose of 600 R on the induction of chromosomal translocations in the diakinesis metaphase I of the meiosis in treated and F 1 males has been examined along with their fertility. Our results show the high percentage of mortality in whole-body irradiated mice. The percentage of the fertility was 25% in whole-body, and 93.7% in locally irradiated males. The testis weight was also reduced. The percentage of chromosomal translocations in diakinesis, metaphase I, of the meiosis was higher after whole-body irradiation than after local irradiation. In F 1 males both types of irradiation induced chromosomal translocations. (orig.) [de

Protective effects of the fermented milk Kefir on X-ray irradiation-induced intestinal damage in B6C3F1 mice

International Nuclear Information System (INIS)

Teruya, Kiichiro; Nakamichi, Noboru; Shirahata, Sanetaka; Myojin-Maekawa, Yuki; Shimamoto, Fumio; Watanabe, Hiromitsu; Tokumaru, Koichiro; Tokumaru, Sennosuke

2013-01-01

Gastrointestinal damage associated with radiation therapy is currently an inevitable outcome. The protective effect of Kefir was assessed for its usefulness against radiation-induced gastrointestinal damage. A Kefir supernatant was diluted by 2- or 10-fold and administered for 1 week prior to 8 Gray (Gy) X-ray irradiation at a dose rate of 2 Gy/min, with an additional 15d of administration post-irradiation. The survival rate of control mice with normal drinking water dropped to 70% on days 4 through 9 post-irradiation. On the other hand, 100% of mice in the 10- and 2-fold-diluted Kefir groups survived up to day 9 post-irradiation (p<0.05 and p<0.01, respectively). Examinations for crypt regeneration against 8, 10 and 12 Gy irradiation at a dose rate of 4 Gy/min revealed that the crypt number was significantly increased in the mice administered both diluted Kefir solutions (p<0.01 for each). Histological and immunohistochemical examinations revealed that the diluted Kefir solutions protected the crypts from radiation, and promoted crypt regeneration. In addition, lyophilized Kefir powder was found to significantly recover the testis weights (p<0.05), but had no effects on the body and spleen weights, after 8 Gy irradiation. These findings suggest that Kefir could be a promising candidate as a radiation-protective agent. (author)

Clinical and symptomatological study of pigs subjected to a lethal dose of integral gamma irradiation

International Nuclear Information System (INIS)

Vaiman, M.; Guenet, J.-L.; Maas, J.; Nizza, P.

1966-05-01

Results are reported from a clinical and haematological study on a Corsican species of pigs wholly exposed to an approximately lethal dose of γ radiation. The aim of this work was to examine the changes in the irradiation syndrome of irradiation for pigs to make it thus possible to devise further experiments, in particular in the therapeutic field. The dose received was 285 rads (measured as the absorption in the vertical antero-posterior medial plane). Data are presented on cyto-haematological changes in the blood circulating immediately after irradiation, and followed up to death, and changes in the medullary cytology after irradiation. The clinical picture of lethal radiation injury in swine is described. (authors) [fr

Radioprotective properties of tocopherol succinate against ionizing radiation in mice

International Nuclear Information System (INIS)

Singh, V.K.; Singh, P.K.; Wise, S.Y.; Posarac, A.; Fatanmi, O.O.

2013-01-01

Threats of nuclear and other radiologic exposures have been increasing but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. In prior publications we have demonstrated the efficacy of tocopherol succinate (TS) as a promising radiation countermeasure with the potential to protect against lethal doses of ionizing radiation exposure. The aim of this study was to gain further insight regarding how TS protects mice against a lethal dose of radiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of TS, and 24 h later exposed to 60 Co γ-radiation. Intestinal tissues or spleen/thymus were harvested after irradiation and analyzed for CD68-positive inflammatory cells and apoptotic cells by immunostaining of jejunal cross-sections. Comet assay was used to analyze DNA damage in various tissues. Phospho-histone H3 (pH3) and the proliferating cell nuclear antigen (PCNA) were used as mitotic markers for immunostaining jejunal cross-sections. We observed that injecting TS significantly decreased the number of CD68-positive cells, DNA damage and apoptotic cells (bcl-associated X protein (BAX), caspase 3 and cleaved poly (ADP-ribose) polymerase-positive cells) as judged by various apoptotic pathway markers. TS treatment also increased proliferating cells in irradiated mice. Results of this study further support our contention that TS protects mice against lethal doses of ionizing radiation by inhibiting radiation-induced apoptosis and DNA damage while enhancing cell proliferation. (author)

Synergistic induction of tumors in NMRI mice by combined fetal X-irradiation with low doses and ethylnitrosourea administered to juvenile offspring

Energy Technology Data Exchange (ETDEWEB)

Schmahl, W.

1988-08-01

Mice were X-irradiated on day 15 of gestation with 0.2, 0.4, 0.8 or 1.6 Gy. Offspring were reared by their mothers and divided into two subgroups at an age of 21 days, one subgroup receiving a single dose (45 mg/kg) of ethylnitrosourea (ENU). All animals were kept ultimately until 22 months to register the long-term tumor pattern. The carcinogenic effects of ENU alone were also studied in two separate experiments. Prenatal X-irradiation with 1.6 Gy mostly abolished the carcinogenic late effects of ENU, with the exception of an almost constant leucosis incidence and an unchanged lung tumor frequency. Lowering the prenatal X-ray dose to 0.8 Gy resulted in a significantly increased rate of liver tumors and ovary tumors. Synergistic effects on various tissues were observed after both 0.4- and 0.2-Gy fetal X-irradiation treatment in combination with postnatal application of ENU. These effects mainly involved a significant increase in the frequency of leucosis and of tumors of the liver, intestine, uterus and ovaries. The greater-than-additive effect in the case of these tumors suggests that low-level prenatal X-irradiation leads to a lasting sensitivity of some tissues towards a subsequent carcinogenic stimulus.

Comparison of the effects of bisphenol A alone and in a combination with X-irradiation on sperm count and quality in male adult and pubescent mice.

Science.gov (United States)

Dobrzyńska, Małgorzata M; Jankowska-Steifer, Ewa A; Tyrkiel, Ewa J; Gajowik, Aneta; Radzikowska, Joanna; Pachocki, Krzysztof A

2014-11-01

Bisphenol A (BPA) is employed in the manufacturing of epoxy, polyester-styrene, and polycarbonate resins, which are used for the production of baby and water bottles and reusable containers, food and beverage packing, dental fillings and sealants. The study was designed to examine the effects of 8-week exposure (a full cycle of spermatogenesis) to BPA alone and in a combination with X-irradiation on the reproductive organs and germ cells of adult and pubescent male mice. Pzh:Sfis male mice were exposed to BPA (5, 10, and 20 mg/kg) or X-rays (0.05 Gy) or to a combination of both (0.05 Gy + 5 mg/kg bw BPA). The following parameters were examined: sperm count, sperm motility, sperm morphology, and DNA damage in male gametes. Both BPA and X-rays alone diminished sperm quality. BPA exposure significantly reduced sperm count in pubescent males compared to adult mice, with degenerative changes detected in seminiferous epithelium. This may suggest a higher susceptibility of germ cells of younger males to BPA action. Combined BPA with X-ray treatment enhanced the harmful effect induced by BPA alone in male germ cells of adult males, whereas low-dose irradiation showed sometimes protective or additive effects in pubescent mice. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

Transient virus expression during murine leukemia induction by x-irradiation

International Nuclear Information System (INIS)

Haas, M.

1977-01-01

Most x-irradiation-induced thymomas in C57BL/6 mice are virus-free when assayed by immunofluorescence for the gs antigen (gsa) of murine leukemia virus (MuLV). Virus was induced transiently in bone marrow cells and later appeared in thymus cells. Six to 7 weeks post irradiation, thymocytes and bone marrow cells were MuLV gsa-negative and remained negative for the lifetime of most animals, whether or not they contracted overt leukemia. During the period when MuLV gsa-positive bone marrow cells were found, XC-positive syncytia-producing bone marrow cells were also found. Virus information was expressed, therefore, for a limited duration, long before any signs of leukemia in the animal were evident. MuLV gsa-positive thymocytes taken from mice 4 weeks after x-irradiation were cocultivated with a series of indicator cells. B-tropic virus, in addition to a xenotropic virus, was isolated from these cells. Ecotropic virus was not found in normal mouse thymocytes, in irradiated thymocytes a few days after termination of the X-irradiation sequence, or in most primary thymomas. All thymocytes produced only xenotropic virus in the cocultivation assays. Expression of the ecotropic virus was, therefore, transient, as assayed by immunofluorescence, XC syncytia formation, and virus isolation from MuLV gsa-positive thymus cells

The effect of sex differences on induction of intestinal metaplasia in x-ray irradiated rats

International Nuclear Information System (INIS)

Watanabe, Hiromitsu; Takizawa, Shoichi; Terada, Yoritake; Naito, Masashi; Naito, Yukiko

1980-01-01

The effects of sex differences and ovarian resection on induction of intestinal metaplasia in x-ray irradiated mice were discussed. 1,000 rad of x-ray was irradiated to the stomach of female and male mice twice at intervals of 3 days. The range of intestinal metaplasia in male mice was wider than that in female mice. A total of 400 rad was irradiated to the whole body of mice which underwent ovarian resection (group 1), mice which underwent autotransplantation of the ovary after ovarian resection (group 2), and mice which underwent sham-ovarian resection (group 3). The incidence of intestinal metaplasia in the group 1 was significantly higher than that in the group 3. The weight of the uterus decreased gradually in order of the group 3, group 2, and group 1. It was suggested from above-mentioned results that disappearance or lowering of femal sex hormones, that is, male or androphacy, induced intestinal metaplasia. (Tsunoda, M.)

Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival.

Science.gov (United States)

Tinkum, Kelsey L; Stemler, Kristina M; White, Lynn S; Loza, Andrew J; Jeter-Jones, Sabrina; Michalski, Basia M; Kuzmicki, Catherine; Pless, Robert; Stappenbeck, Thaddeus S; Piwnica-Worms, David; Piwnica-Worms, Helen

2015-12-22

Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.

Action of caffeine on x-irradiated HeLa cells. III. enhancement of x-ray-induced killing during G2 arrest

International Nuclear Information System (INIS)

Busse, P.M.; Bose, S.K.; Jones, R.W.; Tolmach, L.J.

1978-01-01

The ability of caffeine to enhance the expression of potentially lethal x-ray damage in HeLa S3 cells was examined as a function of the age of the cells in the generation cycle. Synchronous populations were irradiated at different times after mitotic collection and treated for various intervals with 1 mM caffeiene, which causes negligible killing of unirradiated cells. The response was thereby determined as a function of cell age at both the time of irradiation and the time of exposure to caffeine. The amount of cell killing depends strongly on when in the cycle caffeine is present and only weakly on when the cells are irradiated. If cells are irradiated in early G 1 , caffeine treatment enhances killing for 2 to 3 hr. No additional enhancement is observed until 16 to 17 hr postcollection, corresponding to G 2 ; here they enter a second period of much greater sensitivity. Similarly, fluorodeoxyuridine resynchronized cells irradiated during S and treated with caffeine suffer no enhanced killing until they pass into this sensitive phase in G 2 , approximately 7 hr after release from the fluorodeoxyuridine block. The sensitive period appears to coincide with G 2 arrest. The rate and extent of killing during this period are dependent upon the x-ray dose and the caffeine concentration. In the absence of caffeine, cells irradiated in G 1 lose sensitivity to caffeine in about 9 hr; they do so faster in G 2 . It is concluded that the potentially lethal x-ray damage expressed on treatment with caffeine is retained for many hours in the presence of caffeine and is maximally manifested by G 2 -arrested cells

Kinetics of lymphohematopoiesis and leukemia induction in chronically whole-body irradiated RF/J mice

International Nuclear Information System (INIS)

Cain, G.R.; Stitzel, K.A.; Fox, L.A.; Klein, A.K.; Dyck, J.A.; Shimizu, J.A.; Rosenblatt, L.S.

1982-01-01

Lymphohematopoietic progenitor cell populations (bone marrow CFU-GM, splenic CFU-BL) were quantitated in unirradiated and in chronically irradiated (17.5 R/day for 4 weeks) RF/J mice and control CAF 1 mice. RF/J mice were found capable of making substantial numbers of bone marrow CFU-GM but less so than the control strain CAF 1 . Significant strain differences were also seen in ability to form splinic B lymphocyte progenitor cells (CFU-BL). Unirradiated and irradiated RF mice produced over three times as many CFU-BL as CAF 1 mice. Throughout the period of protracted irradiation, followed by a twelve week recovery period, CFU-BL and CFU-GM were depressed less in the RF strain than the CAF 1 strain. This was due to an overcompensatory regenerative response which surpassed homostatic baseline levels. Despite strain and strain x dose differences in CFU-BL and CFU-GM, no significant strain x dose relationships were seen in circulati leukocyte counts. The increased susceptibility of RF mice to radiation-induced leukemia may be related to either inherent depressed regulatory control or the persistence of progenitor cell compartments. An apparent increased cell turnover rate in both CFU-BL and CFU-GM in RF mice following radiation damage may likewise play a contributory role

Recovery of endo-CFU-S in radio-adaptive survival response in mice

International Nuclear Information System (INIS)

Yonezawa, Morio; Horie, Kiyohito; Kubo, Kihei

2003-01-01

A priming irradiation with 0.45 Gy of X-rays, given 2 weeks prior to the challenging exposures, induces radio-resistance (decrease in bone marrow death rate after mid-lethal irradiations) in mice of C57BL/6 mice. This acquired radio-resistance appeared on day 9 and continued till day 17 after the priming irradiation, with a maximal on days 12-14 and diminished on day 21. The priming irradiation, given 14 days prior to the challenging exposure, increased endogenous spleen colonies on days 12-13 after exposure to 5.0 Gy. Effect of interval time between the priming and the challenging irradiations on the increase in endogenous spleen colonies was also examined. Significant increase of the colonies by the priming irradiation was observed when the interval time was 12-17 and 21 days. The results correspond to the increase of the survival rates on days 12-17 after the challenging irradiations. (author)

Independent occurence of gastric tumor and intestinal metaplasia by x-irradiation

International Nuclear Information System (INIS)

Watanabe, Hiromitsu; Ito, Akihiro

1986-01-01

The selective occurence of gastric tumors and intestinal metaplasias in the stomach by X-irradiation were described both in mice and rats. The appearance of both lesions was greatly influenced by animal's strains in both species and also by the sex in rats. A few gastric tumors were observed in the animals given a high does with spilt into low doses of X-irradiation. The adequate dose for gastric tumorigenesis may be around 20 Gy in mice and 15 Gy in rats. A good relationship between X-ray dose and incidence of gastric tumor was observed in ICR mice. Frequency of intestinal metaplasia by X-irradiation was much higher in rats compared to that in mice. X-ray dose requested for moderate and induction of intestinal metaplasia was decreased with a dose which was induced erosion and gastric tumor. It has been empirically clarified that an elevation of pH value in the gastric juice is one of the principal factors responsible for the development of intestinal metaplasia in the gastric mucosa among the conditions thus for introduced. In this article, we have introduced the relevant examples about intestinal metaplasia without carcinogenic insult, and the relationship between gastric tumor and intestinal metaplasia were described. The intestinal metaplasia was not always observed within or adjacent to neoplastic gastric glands. A combined treatment of X-ray and MNNG was not effective for gastric tumor and frequency of intestinal metaplasia was inversely related to the incidence of gastric tumors. In conclusion, occurrence of gastric tumor and intestinal metaplasia may be independent, and intestinal metaplasia might not be a prerequite for the occurrence of gastric tumor. (author)

Differential replication of foot-and-mouth disease viruses in mice determine lethality

Science.gov (United States)

Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...

Radioprotective effects of chlorogenic acid against mortality induced by gamma irradiation in mice

International Nuclear Information System (INIS)

Seyed Jalal Hosseinimehr; Amirhossein Ahmadi; Shahram Akhlaghpoor; Tehran University of Medical Sciences, Tehran

2007-01-01

Complete text of publication follows. The radioprotective effects of the naturally occurring compound chlorogenic acid has been investigated against mortality induced by gamma irradiation in mice. Chlorogenic acid administrated at single doses of 100, 200 and 400 mg/kg 1 and 24 h prior to lethal dose of gamma irradiation (8.5 Gy). At 30 days after treatment, the percentage of animal survival in each group was: control, 20%; 100 mg/kg, 20% and 15%; 200 mg/kg, 45% and 15%; 400 mg/kg, 25% and 35% for 1 h and 24 h treatment prior gamma irradiation, respectively. Percentage of survival increased in animal treated with this agent at 200 mg/kg at 1 h statistically compared with irradiated alone group. Other doses of chlorogenic acid have not showed any enhanced survival at 1 and 24 h before irradiation. Chlorogenic acid exhibited concentration-dependent activity on 1, 1-diphenyl 2-picrylhydrazyl free radical to show strong antioxidant activity. It appeared that chlorogenic acid with antioxidant activity reduced mortality induced by gamma irradiation.

Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and sustained susceptibility to multiple death receptor signaling pathways.

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Victoria Ifeadi

Full Text Available BACKGROUND: Death receptors (DR of the TNF family function as anti-tumor immune effector molecules. Tumor cells, however, often exhibit DR-signaling resistance. Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack. The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The ability of radiation to modulate the expression of multiple death receptors (Fas/CD95, TRAILR1/DR4, TRAILR2/DR5, TNF-R1 and LTβR was examined in colorectal tumor cells. The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays. The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined. We found that radiation increased surface expression of Fas, DR4 and DR5 but not LTβR or TNF-R1 in these cells. Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation alone exhibited minimal cell death, but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis, but not LTβR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation. Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L and c-FLIP protein expression, this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types. CONCLUSIONS/SIGNIFICANCE: Irradiation of tumor cells can overcome Fas and TRAIL

Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation

International Nuclear Information System (INIS)

Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P.

2006-01-01

The chlorophyllin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin

Loss of ATM kinase activity leads to embryonic lethality in mice

DEFF Research Database (Denmark)

Daniel, J.A.; Pellegrini, M.; Filsuf, D.

2012-01-01

whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice......, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate...

Irradiated mice lose the capacity to 'process' fed antigen for systemic tolerance of delayed-type hypersensitivity

Energy Technology Data Exchange (ETDEWEB)

Bruce, M G; Strobel, S; Hanson, D G; Ferguson, A

1987-12-01

'Intestinal antigen processing' is a function of the gastro-intestinal tract whereby shortly after an animal has been fed an immunogenic protein antigen, such as ovabumin (OVA), a tolerogenic form of the protein is generated and can be detected in the circulation. The effect of damage to the intestinal epithelium on the processing of OVA has been examined in lethally irradiated mice. Irradiated animals were fed 25 mg OVA and their serum collected 1 h later. When this serum was transferred intraperitoneally into naive recipient mice, this did not induce the typical suppression of systemic delayed-type hypersensitivity. Results were similar when the serum donors were at 2 days after irradiation, with crypt hypoplasia, and at 5 days after irradiation when there was reactive crypt hyperplasia. However reconstitution of donors with normal spleen cells immediately after irradiation restored their capacity to generate a tolerogenic form of the antigen. Immunoreactive OVA was detected by ELISA in both tolerizing and non-tolerizing sera, and the immunological properties of these sera were not related to serum levels of OVA after feeding. The results suggest that lymphoid cells may be involved in the phenomenon of antigen processing.

Peripheral motor axons of SOD1(G127X) mutant mice are susceptible to activity-dependent degeneration

DEFF Research Database (Denmark)

Alvarez Herrero, Susana; Calin, A; Graffmo, K S

2013-01-01

-onset, fast-progression SOD1(G127X) mouse model of amyotrophic lateral sclerosis to long-lasting, high-frequency repetitive activity. Tibial nerves were stimulated at ankle in 7 to 8-month-old SOD1(G127X) mice when they were clinically indistinguishable from wild-type (WT) mice. The evoked compound muscle......-concentrations. It is possible that in SOD1(G127X) there is inadequate energy-dependent Na(+)/K(+) pumping, which may lead to a lethal Na(+) overload....

Influence of immunization on serum γ-globulin levels of calves following whole-body X irradiation

International Nuclear Information System (INIS)

Koch, F.; Mehlhorn, G.; Neumeister, K.; Johannsen, U.; Panndorf, H.

1980-01-01

Calves aged 2.5 to 4 months were whole-body X irradiated with mean lethal doses between 1.2 and 1.7 Gy. The effect of different immunization procedures on the irradiation-induced reaction of the serum gamma globulin levels was studied. Immunization 14 and 21 days before irradiation resulted in obvious stimulation gamma globulin production. After parenteral antigen administration the nearly 2 weeks lasting increase of the gamma globulin level rose in the irradiated animals but declined in the sham-irradiated calves. After a lethal dosis of 1.7 Gy there was a decrease of the gamma globulins 3 weeks post irradiation, at the climax of the radiation syndrome. When 1.5 Gy were used the increase of the gamma globulin concentration was observed also after oral administration of the antigen. The response of the irradiated animals in the secondary reaction of the antibody production was most lear after boosting with homologous bacteria. The stimulating effect of the irradiation on the serum globulin levels after immunization prior to irradiation has been attributed to the reaction of the immunoglobulin-producing system to the release of tissue proteins and antigens, respectively

DNA polymerase I is crucial for the repair of potentially lethal damage caused by the indirect effects of X irradiation in Escherichia coli

International Nuclear Information System (INIS)

Billen, D.

1985-01-01

The radiosensitivity of an Escherichia coli mutant deficient in DNA polymerase I was measured in the presence of OH radical scavengers. The extreme X-ray sensitivity of the mutant could be abolished by OH radical scavengers if a sufficiently high level of radioprotector was present. There was a direct correlation between the OH radical scavenging activity of the chemicals tested (NO 2 - , n-butanol, glycerol, t-amyl alcohol, and t-butanol) and their protective ability. The author interprets the data as showing that the indirect actions of X rays (primarily OH radicals) result in major damage to the bacterial DNA which in large part consists of potentially lethal lesions. This potentially lethal damage is repaired through an enzymatic pathway requiring DNA polymerase I. I. In the mutant lacking DNA polymerase I, these potentially lethal lesions are expressed as cell lethality

Effect of X-irradiation on the alanine- and aspartate aminotransferase activity in the liver, kidney and spleen of mice

Energy Technology Data Exchange (ETDEWEB)

Jungowska-Klin, B; Lozinska, M; Wojtaszek, J [Wroclaw Univ. (Poland)

1975-01-01

The alanine- and aspartate aminotransferase (GOT and GPT) activities and the protein content were measured in the liver, kidney and spleen homogenates of mice exposed to a single whole body X-irradiation with a 900 R dose. The assays were performed in 6 h intervals during the first day and 24 h intervals from the 2nd until the 6th day after the exposure. Significant differences in the enzymatic activity were found in the course of 24 h in control animals and a marked increase of this activity was found after irradiation. This may be explained by changes in the permeability of the mitochondrial membrane for enzyme molecules.

Influence of conditioned psychological stress on immunological recovery in mice exposed to low-dose x irradiation

International Nuclear Information System (INIS)

Sato, K.; Flood, J.F.; Makinodan, T.

1984-01-01

A study was initiated to determine the effects of psychological stress on the immune response in BALB/c mice recovering from exposure to a low dose of ionizing radiation. Mice were first subjected to conditioning training for 12 days, then exposed to 200 R, subjected to psychological stress for 14 days, and assessed for peak anti-sheep RBC response. The seven treatment groups included two unirradiated groups and five irradiated groups. Mice exposed to 200 R and then subjected to conditioned psychological stress responded less vigorously to antigenic stimulation than those of the other irradiated groups. The psychological stress imposed upon these mice did not influence the antibody-forming capacity of unirradiated mice. These results indicate that a psychological stress which did not affect the immunological activity of unirradiated mice can curtail the immunological recovery of mice exposed to low doses of ionizing radiation

Radiation and chemically induced potentially lethal lesions in noncycling mammalian cells: recovery analysis in terms of x-ray- and ultraviolet-like-systems

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Hahn, G.M.

1975-01-01

Recovery from and fixation of potentially lethal damage after exposure of Chinese hamster cells to uv and to x irradiation were investigated, as was recovery after exposure to chemotherapeutic agents. Recovery after uv radiation has a T/sub 1 / 2 / of about 20 hr; the fraction of cells able to undergo recovery depends upon nutritional factors both before and after exposure. After x irradiation, recovery proceeds with a T/sub 1 / 2 / of approximately 2 hr and is much less influenced by nutritional factors. Fixation after serum stimulation has a T/sub 1 / 2 / of 3 to 4 hr in uv-irradiated cells, a T/sub 1 / 2 / of 30 min in x-irradiated cells. Recovery kinetics after nitrogen mustard and bleomycin exposures mimic those for x-ray exposure; after methyl methane sulfonate the kinetics are mainly uv-like, though with an x-ray-like component. Recovery by cells with BUdR-substituted DNA and irradiated with visible light is primarily x-ray-like, though with a uv-like component. There is no recovery by cells exposed to adriamycin or to 1,3-bis(2-chloroethyl)-1-nitrosourea

Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.

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Mayumi Nakahara

Full Text Available INTRODUCTION: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM. rTM has been approved for the treatment of disseminated intravascular coagulation (DIC in Japan, and is currently undergoing a phase III clinical trial in the United States. METHODS: Histone H3 levels in plasma of healthy volunteers and patients with sepsis and DIC were measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected intravenously with purified histones, and pathological examinations were performed. The protective effects of rTM against histone toxicity were analyzed both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors than in survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding. Platelet depletion protected mice from histone-induced death in the first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might be responsible for death during the early phase. Furthermore, rTM bound to extracellular histones, suppressed histone-induced platelet aggregation, thrombotic occlusion of pulmonary capillaries, and dilatation of the right ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS: Extracellular histones cause massive

The activity of dehydrogenases in the uterus of C57B mice after X-irradiation and serotonin treatment

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Mazur, L.

1978-01-01

In C57B female mice, irradiated with 500 R and/or treated with serotonin (5-hydroxytryptamine), the activity of dehydrogenases in the uterus was studied on the fourth day of pregnancy. The reduction of 2,3,5-triphenyltetrazolium chloride to formazane by the uterine tissue was taken as the measure of such activity. The activity of dehydrogenases in the uterus of irradiated mice was distinctly lower than in non-irradiated controls. This activity was also depressed after serotonin treatment, the level of enzyme activity being dose-dependent. In females injected with serotonin and then irradiated, the activity of dehydrogenases was higher than in those irradiated only. The radioprotective effect was more pronounced in mice injected with serotonin alone on the third day of pregnancy i.e. shortly before irradiation, than in those injected on the second and the third day. (author)

Spontaneous and x-irradiation induced carcinomas of small intestine in Wistar-Furth rats

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Maeura, Y; Kosaki, G; Kitamura, H [Osaka Univ. (Japan). Faculty of Medicine; Nagatomo, T

1980-04-01

Spontaneous carcinoma of the small intestine in Wistar-Furth (WF) rats and carcinoma of the small intestine induced by local x-ray irradiation to the abdomen of WF rats without carcinoma were observed, and x-ray sensitivity of the small intestine mucosa was reported. Out of 19 rats with spontaneous carcinoma of the small intestine, 18 also had carcinoma of the colon, and 4 also had gastric cancer. They already had spontaneous carcinoma of the small intestine within 2 weeks after their birth, and the ratio of female and male was 13 : 6. Histological type of this carcinoma in all 19 rats was highly differentiated adenocarcinoma, and small intestine epithelium around carcinoma presented atypical epithelium. As to mice without carcinoma, x-ray, 1,000 R, 1,500 R, and 2,000 R, was irradiated to the abdomen of Sprague-Dawley (SD) and WF rats. In the irradiation with 1,000 R, carcinogenesis was not found in rats of both strains. In the irradiation with 1,500 R, carcinogenesis was hardly found, but in the irradiation with 2,000 R, carcinoma of small intestine occurred in 5 of 17 rats 15 weeks after the irradiation, 9 of 19 rats 25 weeks after the irradiation, and 9 of 14 rats 35 weeks after the irradiation. Histological type of carcinoma in irradiated rats was highly differentiated adenocarcinoma. The incidence of carcinoma in irradiated rats was higher in WF rats than SD rats through the course after the irradiation, which suggested that x-ray sensitivity of WF rats was higher than that of SD rats. Therefore, carcinoma of the small intestine in irradiated mice seemed to be induced by x-ray.

Prion protein protects mice from lethal infection with influenza A viruses.

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Junji Chida

2018-05-01

Full Text Available The cellular prion protein, designated PrPC, is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues. Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases. However, the physiological functions of PrPC remain largely unknown, particularly in non-neuronal tissues. Here, we show that PrPC is expressed in lung epithelial cells, including alveolar type 1 and 2 cells and bronchiolar Clara cells. Compared with wild-type (WT mice, PrPC-null mice (Prnp0/0 were highly susceptible to influenza A viruses (IAVs, with higher mortality. Infected Prnp0/0 lungs were severely injured, with higher inflammation and higher apoptosis of epithelial cells, and contained higher reactive oxygen species (ROS than control WT lungs. Treatment with a ROS scavenger or an inhibitor of xanthine oxidase (XO, a major ROS-generating enzyme in IAV-infected lungs, rescued Prnp0/0 mice from the lethal infection with IAV. Moreover, Prnp0/0 mice transgenic for PrP with a deletion of the Cu-binding octapeptide repeat (OR region, Tg(PrPΔOR/Prnp0/0 mice, were also highly susceptible to IAV infection. These results indicate that PrPC has a protective role against lethal infection with IAVs through the Cu-binding OR region by reducing ROS in infected lungs. Cu content and the activity of anti-oxidant enzyme Cu/Zn-dependent superoxide dismutase, SOD1, were lower in Prnp0/0 and Tg(PrPΔOR/Prnp0/0 lungs than in WT lungs. It is thus conceivable that PrPC functions to maintain Cu content and regulate SOD1 through the OR region in lungs, thereby reducing ROS in IAV-infected lungs and eventually protecting them from lethal infection with IAVs. Our current results highlight the role of PrPC in protection against IAV infection, and suggest that PrPC might be a novel target molecule for anti-influenza therapeutics.

The effect of ultraviolet radiation on the pathogenesis of Candida albicans in mice

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Denkins, Y.M.

1991-01-01

This dissertation addresses questions concerning the effects of UV radiation on the pathogenesis of opportunistic fungal pathogens such as Candida albicans. UV radiation decreased the survival of Candida-infected mice; however, no correlation was found between suppression of the delayed type hypersensitivity (DTH) response and the course of lethal infection. This suggested that DTH was not protective against lethal disease with this organism. UV radiation also changed the persistence of the organism in the internal organs. UV-irradiated, infected animals had increased numbers of Candida in their kidneys compared to non-irradiated mice. Sensitization prior to UV irradiation aided clearance of the organism from the kidneys of UV-irradiated mice. These data show that UV radiation suppresses cell-mediated immunity to Candida albicans in mice and increases mortality of Candida-infected mice. Moreover, the data suggest that an increase in environmental UV radiation could increase the severity of pathogenic infections

PIXE analysis showed that the preirradiation enhanced recovery of bone marrow elements after challenging irradiation in C57BL/6N Mice

International Nuclear Information System (INIS)

Matsuda, Y.; Yonezawa, M.; Nishiyama, F.

2000-01-01

Priming X-irradiation with 0.3-0.5 Gy induces radio-resistance in C57BL/6 strain of mice 2 weeks afterward. Elements in the bone marrow, sampled 11 days after challenging exposure to 5.0 Gy, were determined by PIXE. The challenging irradiation decreased Mg, P, S, K, Ca and Zn as well as dried bone marrow weight. The pre-irradiation enhanced recovery of these levels, indicating stimulated recovery of the metabolism int he tissue. Fe in both control (without pre-irradiation) and experimental groups increased to about twice the original value, showing elevated hemoglobin synthesis after challenging exposure. In previous studies we have reported that recovery of peripheral blood cell counts after sub-lethal irradiation was enhanced by the pre-irradiation. Further, study on accumulation of p53 and Bax proteins, which lead to apoptotic cell death, revealed that the pre-irradiation significantly suppressed accumulation of these proteins in the spleen after challenging irradiation with 3 Gy. These results and our present study suggest that the pre-irradiation decreased the spleen cell death, and favored re-growth of the spleen cells, resulting in stimulated recovery of metabolism for hematopoiesis in the bone marrow as well as in the spleen after challenging high dose irradiation. Stimulated recovery of Mg, P, S, K, Ca and Zn levels might indicate the importance of these elements in hematopoiesis. (author)

Expression of IL-1β mRNA in mice after whole body X-irradiation

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Nemoto, Kumie; Ishihara, Hiroshi; Tanaka, Izumi; Suzuki, Gen; Tsuneoka, Kazuko; Yoshida, Kazuko; Ohtsu, Hiroshi

1995-01-01

IL-1β is a stimulator of hematopoietic and inflammatory systems, and also acts as a radioprotector. After whole-body exposure to sublethal doses of ionizing radiation, the IL-1β mRNA level in spleen cells increases for a short time prior to regeneration of the spleen. We analyzed spleen cells of C3H/He mice after whole-body irradiation with 3 Gy x-rays to determine the cause of this short-term increase in the transcription level. An increase in the level of the message in spleen cells, found by Northern blot hybridization, reached its peak 5 to 7 days after irradiation. There was a low correlation between the curves of the mRNA level and the ratio of monocyte/macrophage lineage cells; a typical source of the message. Spleen macrophages that produce a large amount of the message were found 7 days after irradiation in an in situ hybridization experiment in which heterogeneous spleen cell populations were used. In contrast, spleen cells had no detectable levels of macrophages rich in IL-1β mRNA before and 17 days after irradiation. Additionally, the population of message-rich cells was 9.4% of the total number of monocytes/macrophages in the spleen. These results suggest that the short-term increase in IL-1β mRNA is a result of the heterogeneous differentiation of a subpopulation of spleen macrophages before regeneration of the spleen. (author)

Oscillations of serum and tissue lipids in rats X-irradiated at different times of day

International Nuclear Information System (INIS)

Ahlers, I.; Ahlersova, E.; Toropila, M.; Smajda, B.; Praslicka, M.

1983-01-01

Young male Wistar rats (mean body mass 200 g) adapted to a 12:12 h light:dark regimen (7 a.m. to 7 p.m., 7 p.m. to 7 a.m.) were X-irradiated at 3-h intervals during one day with doses of 2.39 or 14.25 Gy and were killed 48 or 24 h afterwards. Nonesterified fatty acids were determined in their serum and white and brown adipose tissue, and triacylglycerols, phospholipids and total cholesterol in their serum and liver. The reaction of serum and tissue lipids during the day varied after both non-lethal and lethal irradiation. After non-lethal exposure, most of the curves, as regards their course, the presence of rhythm and their oscillation properties, concurred with the lipid indicator curves in the control series and indicated that the organism's response is dependent on the time of day. Circadian variation of serum and adipose tissue nonesterified fatty acid levels, the liver triacylglycerol concentration and the adrenal cholesterol concentration in lethally irradiated animals showed no significant dependence on the time of application of the stimulus. An analysis of circadian variation of the effectiveness of a stimulus facilitates understanding of the organism's reactivity better than a single examination in the morning. (author)

Stimulation of anti-tumor effect by low-dose irradiation. Pt. 2. The prolongation of life span in AKR mice

International Nuclear Information System (INIS)

Ishii, Keiichiro; Misonoh, Jun; Hosoi, Yoshio; Ono, Tetsuya; Sakamoto, Kiyohiko.

1994-01-01

To elucidate the antileukemic effect of low-dose X-irradiation, we studied the influence of periodical low-dose X-irradiation on survival and tumor incidence of thymus using AKR mice. The findings of the experiments were as follows; (1) The median survival time of control AKR mice was 283±3 days. It of irradiation group of 15 cGy/week and 30cGy was 309±14 days and 316±10 days respectively. The life span was significantly prolonged (p < 0.05 and p < 0.01 respectively by Wilcoxon test) by periodical low-dose X-irradiation in term of breeding. (2) The incidence of thymus tumor which is observed remarkably in control AKR mice was 48.8%. It of irradiation group of 15 cGy/week and 30 cGy/week was 40% and 20% respectively. Inversely, the non-tumor incidence of tymus in control AKR mice was 19.5%. It of irradiation group of 15 cGy/week and 30 cGy/week was 32.5% and 51.4% respectively. The thymic tumor incidence was significantly decreased (p < 0.01 by chi-square test) in irradiation group of 30 cGy/week. (3) The incidence of thymic lymphoma as a death cause in control AKR mice was 80.4%. It of irradiation group of 15 cGy/week and 30cGy/week was 67.5% and 48.6% respectively. The incidence of thymic lymphoma was significantly decreased (p < 0.05 by chi-square test) in irradiation group of 30 cGy/week. (author)

Gastrointestinal decontamination in healthy and lethally irradiated monkeys

International Nuclear Information System (INIS)

Hendriks, W.D.H.

1980-01-01

In periods of extreme immunosuppression, infections which are often life-threatening, frequently occur. In an attempt to prevent such infections in lethally irradiated rhesus monkeys, the animals were subjected to strict reverse isolation prior to irradiation and administrated orally with nonabsorbable antibiotics in order to eliminate their microflora. The antibiotic combination was selected on the basis of a sensitivity test and was added to the liquid food supply. To rapidly achieve a high bactericidal concentration in the intestine, the same antibiotics were additionally given orally for 5 days. The microflora was reduced rapidly; within a few days sterile cultures were obtained. Particularly after discontinuation of the administration of the additional antibiotics were colonizations found. In contrast to colonizations persisting from the first day of treatment on, the first were rather easy to suppress. (Auth.)

New radiation mitigators to reduce bone marrow death of mice by post-irradiation administration

International Nuclear Information System (INIS)

Anzai, Kazunori

2009-01-01

We have found recently that heat-treated mineral yeast preparations and water-soluble analogs of vitamin E are potent radiation mitigator to reduce bone marrow death of mice by post-irradiation administration. When administered immediately after whole-body X-irradiation (7.5 Gy), both Zn-yeast and γ-tocopherol dimethylglycine ester (TDMG) significantly increased the viability of mice from 0% (control) to more than 90% (treated). Zn-yeast did not inhibit the tumor-regulation by γ-rays but even sensitize the radiation effect in mice xenografts of HeLa cells. (author)

Molecular characterization of non-thymic lymphomas in mice exposed to continuous low-dose-rate g-ray irradiation

International Nuclear Information System (INIS)

Takabatake, T.; Fujikawa, K.; Nakamura, S.; Tanaka, S.; Tanaka, I.; Tanaka-Braga III, I.; Sunaga, Y.; Ichinoche, K.; Sato, F.; Tanaka, K.; Matsumoto, T.

2004-01-01

To investigate the effects of continuous low-dose-rate irradiation on life span and neoplasm incidence, SPE B6C3 F1 mice were irradiated with 137Cs-ray at dose-rates of 20, 1 and 0.05 mGy/day with accumulated doses equivalent to 8000, 40 and 20 mGy, respectively. Examination of a total of 3,000 irradiated and 1,000 non-irradiated control mice showed that the life spans of the both sexes irradiated at 20 mGy/day, respectively. Examination of a total of 3,000 irradiated and 1,000 non-irradiated control mice showed that the life spans of the both sexes irradiated at 20 mGy/day were significantly shorter than that of the non-irradiated group. No significant difference in the cause of death and mortality rates was found between the groups. However, non-thymic lymphomas, the most common lethal neoplasm, showed a tendency to develop at an earlier age in mice irradiated with 20 mGy/day, regardless of sex. to obtain clues on the molecular mechanisms underlying the earlier development of non-thymic lymphomas in 20 mGy/day irradiated group, detailed molecular characterizations of non-thymic lymphomas with respect to B-cell or T-cell origin was done by detecting rearrangements in immunoglobulin heavy gene and in T-cell receptor b-and g chain genes by Southem hybridization method. to determine whether the early development of non-thymic lymphomas in 20 mGy/day irradiated group is associated wi the any recurrent chromosomal imbalance such as deletions and amplifications, the genome-wide scanning is also currently in progress by both LOH and array CGH methods. Present data obtained by LOH method show that deletions in parts of chromosomes 11 and 12 were more frequent than in chromosomes 2, 4 and 14 in both the non-irradiated control and 20 mGy/day irradiated groups. this work is supported by grants from Aomori Prefecture, Japan. (Author)

Immunity to Trichinella spiralis in irradiated mice

International Nuclear Information System (INIS)

Wakelin, D.; Wilson, M.M.

1980-01-01

Irradiation prevented the accelerated expulsion of Trichinella spiralis from mice immunized by transfer of immune mesenteric lymph node cells (IMLNC) or by prior infection. Nevertheless, worms in irradiated immune mice were smaller and less fecund than those in controls. In adoptively immunized and irradiated mice expulsion could not be achieved by increasing the numbers of IMLNC transferred, although the effect upon worm length was more severe. Thus IMLNC express a direct, anti-worm immunity which is independent of their role in worm expulsion. IMLNC cause expulsion in irradiated mice only when adequate levels of bone marrow-derived cells are available. The results are discussed in terms of a possible antibody-mediated basis for direct anti-worm immunity. (author)

The protective effects of resveratral on acute radiation injury in mice

International Nuclear Information System (INIS)

Yan Hao; Wang Hui; Zhang Heng

2014-01-01

Objective: To study the protective function of resveratrol on radiation-induced small intestine injury and lethal effect in mice. Methods: Mice were randomly divided into three groups: irradiation (IR) control, IR only, and IR+ resveratrol. 15 mice each group were irradiated on abdomen with 7.2 Gy γ-rays for cell lethal assay and 8 mice each group were irradiated with 6.5 Gy for small intestine injury assay. For the IR+ resveratrol group, the mouse was given resveratrol by intragastric administration 24 h before irradiation and then was fed with resveratrol daily for 5 days. The control and IR alone groups were fed with placebo. After 30 days of IR, mouse survival rate was detected. For small intestine injury experiments, 24 h after IR, the mice were terminated and the small intestines were treated with HE and immunohistochemical staining. Results: Compared with the irradiation group, resveratrol increased mouse survival by 33.3%, decreased apoptosis in intestinal crypt cells (t = 17.35, P < 0.05), and increased Ki67 expression (t = 13.62, P < 0.05). Conclusion: Resveratrol could protect small intestine injury from ionizing irradiation. (authors)

Studies on combination effects of peplomycin and x-ray irradiation

International Nuclear Information System (INIS)

Munenaga, Yasuichi

1984-01-01

In order to study effects and methods of combination of peplomycin (PEP) and x-ray irradiation, inhibitory effects on DNA synthesis were investigated with synchronized cells from the parotid gland of mice treated with isoproterenol (IPR) and inhibitory effects on cell proliferation were investigated with Ehrlich solid tumor cells. PEP had dose-dependent effects on the inhibition of DNA synthesis and on the prolongation of cell cycles in the IPR-treated mouse cells. When 3.0 and 5.0 mg/kg of PEP were combined with 200 rad of x-ray irradiation at the early phase of G 1 , synergistic effects on the inhibition of DNA synthesis were seen. This was most noted in the group with PEP 30 minutes before irradiation. PEP had also dose-dependent inhibitory effects on the proliferation of Ehrlich solid tumor cells. This was increased when x-ray irradiation was combined with PEP. Inhibitory effects on the proliferation of tumor cells were greater when PEP was given before x-ray irradiation than after x-ray irradiation, regardless of the amount. The greatest effect was seen in the group with PEP 30 minutes before irradiation, as well as in the experiment with IPR-treated mouse cells. (Namekawa, K.)

Genotoxicity test of irradiated spice mixture by dominant lethal test

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Barna, J

1986-03-01

Dominant lethal test (DLT) was performed in Sprague Dawley male rats prefed with 25% irradiated spice mixture which was composed of 55% non-pungent ground paprika, 14% black pepper, 9% allspice, 9% coriander, 7% marjoram, 4% cumin, 2% nutmeg. Microbial count of the spice mixture was reduced with 15 kGy from a sup(60)Co source. Control groups received spice-free or untreated spice diet or were administered to cyclophosphamide i.p., respectively. DTL parameters altered significantly in the latter group but neither untreated nor irradiated spice mixture proved to be germ cell mutagens. 24 refs.; 8 figs.

Long-term hematopoietic stem cell damage after external irradiation with X rays

International Nuclear Information System (INIS)

Grande, M.T.; Varas, F.; Bueren, J.A.

1997-01-01

We have investigated the functionality of the lympho-hematopoietic stem cells long-term (9 months) after the irradiation (X rays) of mice at different stages of development, by means of a competitive bone marrow repopulation assay. Our data revealed that a dose of 1 Gy was only capable of inducing significant long-term failures in the functionality of the primitive repopulating cells in mice irradiated at the young-adult stage (12 week-old), but not in mice irradiated at the late stages of foetus development (17 day-old fetuses) nor at the early development of the embryo (4 day-old embryos). The differential generation of long-term stem cell defects as a function of the age was confirmed in mice irradiated with 3 Gy. While no significant effects in the long-term repopulating cells were observed in 4 day-old embryos, significant repopulation deficiencies were observed in this population when mice were irradiated at the 17 day of foetus development, and more markedly at the adult stage of growth. These data offer new evidence about the influence of the developmental stage of the animal on the generation of residual hematopoietic dysfunctions by external irradiation, with particular relevance to the very primitive lympho-hematopoietic stem cells. (author)

Differential androgenesis in gamma irradiated mice

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Kim, Jihyang; Yoon, Yongdal [Hanyang Univ., Seoul (Korea, Republic of); Kim, Jin Kyu [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

2002-07-01

The Leydig cells of the testis account for at least 75% of the total testosterone produced in the normal adult male. Whereas the production of estrogen from androgen is catalyzed by aromatase cytochrome P450, which is found in many tissues, including gonad, brain, adipose tissue, bone, and heart. The gamma-irradiation causes the impairment of spermatogenesis and steroidogenesis in male mice. The present study was performed to analyze changes in testosterone concentrations and expression of steroidogenic enzyme of mice after whole body gamma-irradiation. Eight-week-old male ICR mice were irradiated with 6.5 or 10 Gy. At days 1, 2, 3, 4, and 5 after irradiation, testes were removed and processed for paraffin sections and isolation of mRNA. We calculated the gonad index from body and testis weight, and checked the testis volume. Hormonal analysis was performed by means of radioimmunoassay (RIA) in serum and intratesticular fluid. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression kinetics of the apoptotic gene and the cytochrome P450 aromatase gene after irradiation. In gamma-irradiated mice, the body weight reduced in comparison to that of the control group. Therefore, gonad indices increased. The testosterone concentrations in serum and intratesticular fluid were significantly reduced. RT- PCR data represented that the expression of Fas, Fas ligand, and aromatase cytochrome P450 showed the specific patterns against control groups. These results indicated that gamma- irradiation of adult mice induced the alteration of androgenesis and suggested that might counteract the spermatogenesis.

Determination the lethal dose of ascaris lumbricoides ova by gamma irradiation

International Nuclear Information System (INIS)

Shamma, M.; Al-Adawi, M.; Sharabi, N.

2002-11-01

The lethal gamma irradiation dose of ascaris lumbricoides which collected from Damascus Sewage water Plant was determined. Ascaris lumbricoides ova were treated with several gamma irradiation doses with (0.1, 0.2, 0.3, 0.4,...and 1.5 KGy). No morphological changes were observed on the eggs when directly examined microscopically after irradiation. However after two weeks of incubation at 37 degree centigrade the cell contents of the eggs which irradiated with 0.5 KGy and beyond were fragmented and scattered in the whole eggs and no larvae were observed after eight weeks of incubation. It is concluded that the dose 0.5 my be considered as the dose of choice if sewage water is to be treated by gamma rays. (author)

Determination the lethal dose of ascaris lumbricoides ova by gamma irradiation

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Shamma, M A; Sharabi, N

2002-01-01

The lethal gamma irradiation dose of ascaris lumbricoides which collected from Damascus Sewage water Plant was determined. Ascaris lumbricoides ova were treated with several gamma irradiation doses with (0.1, 0.2, 0.3, 0.4,...and 1.5 KGy). No morphological changes were observed on the eggs when directly examined microscopically after irradiation. However after two weeks of incubation at 37 degree centigrade the cell contents of the eggs which irradiated with 0.5 KGy and beyond were fragmented and scattered in the whole eggs and no larvae were observed after eight weeks of incubation. It is concluded that the dose 0.5 my be considered as the dose of choice if sewage water is to be treated by gamma rays.

Irradiation effects on the tumor and adjacent tissues of brain tumor-bearing mice

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Tsunemoto, Hiroshi; Koike, Sachiko; Furukawa, Shigeo.

1979-01-01

C 3 H mice aged 56 - 70 days, weighing 27 - 37 g were used throughout this experiment. A transplantable fibrosarcoma arising spontaneously from C 3 H mice was used. For experiment, 10 4 tumor cells suspended in 0.025 ml of saline solution were injected into the cerebral hemisphere by a 26 gauge needle with a micrometer syringe under nembutal anesthesia. Whole brain irradiation was performed at 7 days after injection of the tumor cells and the radiation doses were 2,000 and 20,000 rads, respectively. The feature of x-rays were 200 kVp, 20 mA, 0.5 mm Cu + 0.5 mm Al filtration and TSD 20 cm. The dose-rate was 340 - 360 R/min. The articles of this study were as follows: a) Determination of LD 50 values for the mice, tumor-bearing in the brain or non-tumor-bearing; and b) Observation of clinical features and gross autopsy findings of the mice following irradiation. The LD 50 values for 2,000 rad irradiation in the tumor-bearing or non-tumor-bearing mice were 10.9 and 11.4 days, respectively. LD 50 values of 3.7 days and 4.3 days were the results for the tumor-bearing and non-tumor-bearing mice irradiated by 20,000 rad, respectively. On the other hand, the LD 50 value for the control group, i.e. non-irradiated mice, was 6.7 days. At postmortem examinations, gastrointestinal bleeding was observed frequently in mice bearing tumor in the brain. Whole brain irradiation is effective to prolong the life of tumor-bearing mice. However, in some instances, deaths have occurred earlier in tumor-bearing mice compared to the control group. (author)

Effects of irradiation at different dose rates on the onset of type I diabetes in model mice

International Nuclear Information System (INIS)

Nomura, Takashi; Sakai, Kazuo

2003-01-01

We previously demonstrated that low-dose irradiation (0.5 Gy) increased the level of antioxidants and decreased the level of lipid peroxide in normal mice. We also found that 0.5 Gy-irradiation of NOD mice suppressed the onset of type I diabetes. These results were obtained by the irradiation at high dose rate. The aim of the present study is to examine the effects at the low dose rate. The mice were acutely irradiated with 0.5 Gy of X-rays (300 kVp) at 94.2 Gy/hr at 10, 11, 12, 13 or 14 weeks of age, or chronically irradiated with 0.5 Gy of 137 Cs γ-rays at 0.95 mGy/hr starting at 10,11,12,13 or 14 weeks of age. When irradiated at 12th week with the high dose rate X-rays, the onset of diabetes suppressed, and the increase in the specific activity of superoxide dismutase (SOD) in pancreas was observed. On the other hand, the low dose rate γ-rays delivered from 12th week of age to 14th was less effective in the suppression of the incidence of diabetes than the high dose rate X-rays at the 12-14 weeks of age. Furthermore, the significant increase in pancreatic SOD activity was not observed after the low dose irradiation. Splenic macrophage activities of superoxide generation were not affected by the high dose rate irradiation nor the low dose rate irradiation. (author)

Effects of lethal dose of γ-irradiation on intestinal enzymes of the pigeons Columba livia intermedia Strickland

International Nuclear Information System (INIS)

Gadhia, P.K.

1979-01-01

Effect of γ-irradiation with lethal dose (1000 rads) on alkaline phosphatase and glucose-6-phosphatase have been studied in two different regions (duodenum and ileum) of small intestine of pigeons. The enzymes were studied at different intervals like 2, 4, 6 and 8 days after irradiation. The sp. activities of enzyme increased significantly both in duodenum and ileum. However, significant increase in alkaline phosphatase and glucose-6-phosphatase were observed at the 2nd and the 4th days post-irradiation respectively. The increase in enzyme activities may present de novo synthesis of these enzymes after lethal dose of irradiation. The histologic picture revealed that after the 4th day of irradiation, the number of goblet cells increased and after the 6th day crypt-villus system was destroyed completely as compared to sham-irradiated pigeons. (author)

Effects of lethal dose of. gamma. -irradiation on intestinal enzymes of the pigeons Columba livia intermedia Strickland

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Gadhia, P.K. (South Gujarat Univ., Surat (India). Dept. of Biosciences); Shah, V.C. (Gujarat Univ. School of Sciences, Ahmedabad (India))

1979-09-01

Effect of ..gamma..-irradiation with lethal dose (1000 rads) on alkaline phosphatase and glucose-6-phosphatase have been studied in two different regions (duodenum and ileum) of small intestine of pigeons. The enzymes were studied at different intervals like 2, 4, 6 and 8 days after irradiation. The sp. activities of enzyme increased significantly both in duodenum and ileum. However, significant increase in alkaline phosphatase and glucose-6-phosphatase were observed at the 2nd and the 4th days post-irradiation respectively. The increase in enzyme activities may present de novo synthesis of these enzymes after lethal dose of irradiation. The histologic picture revealed that after the 4th day of irradiation, the number of goblet cells increased and after the 6th day crypt-villus system was destroyed completely as compared to sham-irradiated pigeons.

Repair of potentially lethal radiation damage: comparison of neutron and x-ray RBE and implications for radiation therapy

International Nuclear Information System (INIS)

Hall, E.J.; Kraljevic, U.

1976-01-01

Experiments with Chinese hamster cells have shown that neutron irradiation does not result in repair of potentially lethal damage (PLD), i.e., that which can be influenced by changes in environmental conditions following irradiation. Since PLD is presumed to be repaired in tumors but not in normal tissues, this absence of differential sparing of tumor cells relative to normal tissues--a feature characteristic of irradiation with x rays--represents an advantage of neutrons in addition to their reduced oxygen effect. At a given dose, the difference in relative biological effectiveness (RBE) between tumors and normal tissues corresponds to a 5 percent increase in tumor dose with no concomitant increase in dose to normal tissues, which could be significant in cancer therapy

Skin allografts in lethally irradiated animals repopulated with syngeneic hemopoietic cells

International Nuclear Information System (INIS)

Schwadron, R.B.

1983-01-01

Total body irradiation and repopulation with syngeneic hemopoietic cells can be used to induce tolerance to major histocompatibility complex (MHC) mismatched heart and kidney grafts in rats and mice. However, this protocol does not work for MHC mismatched skin grafts in rats or mice. Furthermore, LEW rats that accept WF cardiac allografts after irradiation and repopulation reject subsequent WF skin grafts. Treatment of skin allograft donors with methotrexate prior to grafting onto irradiated and reconstituted mice resulted in doubling of the mean survival time. Analysis of which antigens provoked skin graft rejection by irradiation and reconstituted animals revealed the importance of I region antigens. Cardiac allograft acceptance by irradiated and reconstituted animals is mediated by suppressor cells found in the spleen. Adoptively tolerant LEW rats accepted WF skin grafts in 50% of grafted animals. Analysis of this phenomenon revealed that the adoptive transfer procedure itself was important in achieving skin allograft acceptance by these animals. In general, it seems that the lack of ability of irradiated and reconstituted animals to accept fully MHC disparate skin grafts results from the inability of these animals to suppress lymph node effector cells against I region antigen seen on highly immunogenic allogeneic Langerhans cells in the skin

Effects of fission neutrons and X-rays on the epithelium of the mouse stomach

International Nuclear Information System (INIS)

Kingma-ter Haar, J.M.

1982-07-01

A quantitative study is presented of the effects of whole-body irradiation on the stomach of mice. Two types of ionizing radiation were compared - fast fission neutrons of 1.0 MeV mean energy and 300 kVp X-rays. The effects on the functional cell populations, on gastric secretion and on gastric stem cell populations were studied. These effects have been investigated a) for a neutron dose in the lethal dose-range of 4.0 Gy as a function of time and b) at a post-irradiation interval of 3 weeks as a function of neutron and X-ray dose. (Auth.)

Studies on the transfer of protective immunity with lymphoid cells from mice immune to malaria sporozoites

International Nuclear Information System (INIS)

Verhave, J.P.; Strickland, G.T.; Jaffe, H.A.; Ahmed, A.

1978-01-01

In an effort to understand the mechanisms involved in the protective immunity to malarial sporozoites, an A/J mouse/Plasmodium berghei model was studied. Protective immunity could consistently be adoptively transferred only by using sublethal irradiation of recipients (500 R); a spleen equivalent (100 x 10 6 ) of donor cells from immune syngeneic mice; and a small booster immunization (1 x 10 4 ) of recipients with irradiation-attenuated sporozoites. Recipient animals treated in this manner were protected from lethal challenge with 1 x 10 4 nonattenuated sporozoites. Immune and nonimmune serum and spleen cells from nonimmune animals did not protect recipient mice. Fewer immune spleen cells (50 x 10 6 ) protected some recipients. In vitro treatment of immune spleen cells with anti-theta sera and complement abolished their ability to transfer protection. This preliminary study suggests that protective sporozoite immunity can be transferred with cells, and that it is T cell dependent

Use of gamma irradiated viper venom as the toxoid against viper venom poisoning in mice and rabbits

International Nuclear Information System (INIS)

Hati, A.K.; Mandal, M.; Hati, R.N.; Das, S.

1995-01-01

The present paper deals with detoxification of the crude viper (Vipera russelli) venom by gamma irradiation and its effective immunogenic role in Balb/C mice, used as a toxoid. The successful immunization of rabbits with irradiated viper venom toxoid is also reported. Certain biochemical changes of the venom due to radiation exposure and neutralization capacity of the immune sera against phosphodiesterase and protease activity of the crude viper venom have also been studied. The neutralizing potency of Russell's viper venom (RVV) toxoid anti venom (anti venom raised in rabbits against γ-irradiated RVV toxoid adsorbed on aluminium phosphate), in comparison with a commercial bivalent anti venom (as a standard reference) with reference to haemorrhagic, necrotic and lethal effects of Russell's viper envenomation are reported. 25 refs

Immunomodulatory effects of ultraviolet B irradiation on atopic dermatitis in NC/NGA mice

International Nuclear Information System (INIS)

Yasuko Mutou; Shuji Kojima; Yuko Ibuki

2007-01-01

Complete text of publication follows. Background: Atopic dermatitis (AD) is a common pruritic inflammatory skin disease with severe itching which occurs primarily in childhood. Overexpression of serum IgE are also a characteristic feature in many patient. Furthermore, Th2-type T cell cytokine, such as IL-4, IL-5, and Il-10, are produced in AD lesions. Recently, ultraviolet B (UVB) irradiation may increase according to depletion of the ozone layer. Furthermore, phototherapy is used to treat AD patient, but the mechanism involved is unknown. In this study, we investigated whether UVB irradiation influences atopic dermatitis in the NC/Nga mouse model. Methods: The mice were separated into 3 groups, control, AD-control (immunized with mite antigens), and AD + UVB-irradiated (immunized with mite antigens and UVB irradiation) groups. The mice of the irradiation group were exposed to 1 kJ/m 2 /day twice a week from 6 to 12 weeks of age. Animals of the control and AD-control groups were shaved, but not irradiated. Results: In the AD + UVB-irradiated group, the atopy score, ear thickness, and total IgE were increased in comparison with the AD-control group. On day 40, the levels of IL-4, IL-5, and IL-10 in the spleen lymphocytes were significantly increased compared with the AD-control group, resulting in a marked decrease of the IFN-Γ/IL-4 ratio compared with the AD-control group. In addition, the levels of IL-6, TNF-α, and NO X production by peritoneal macrophages were significantly elevated. Conclusion: These results indicate that UVB irradiation promotes the development of AD-like symptoms in NC/Nga mice, with an increased inflammatory response owing to increases of both IgE and NO X . In addition, systemic immune responses to local UVB were observed. It is possible that upstream proteins involved in IL-4, IL-5, IL-6, IL-10, and TNF-α, and NO X production play roles in the UVB-induced inflammatory responses. Our results also suggest that sunlight may aggravate the

Thermo-radiosensitivity of the granulocyte and macrophage precursor cells of mice. I I . - X- irradiation effects and influence of hyperthermia on the radiosensitivity; Termo-radiosensibilidad del precursor hematopoyetico que origina las series granulocitica y macrofaga de raton. II. - Efectos producidos por la radiacion X e influencia de la hipertermia sobre la radiosensibilidad celular

Energy Technology Data Exchange (ETDEWEB)

Bueren, J A; Nieto, M

1983-07-01

The effects of the X-irradiation on the viability of the granulocyte-macrophage precursors, has been determined by means of the agar diffusion chamber culture technique. The results show the high radiosensitivity of these cells, with survival parameter similar to those previously reported in the literature about different granulocyte-macrophage precursors. When a hyperthermic treatment is performed prior to the X-irradiation, a radiosensitization phenomenon is observed due to the synergism existent between hyperthermia and X rays on the lethality of the precursors. (Authors) 37 refs.

Stem and stromal cell reconstitution of lethally irradiated mice following transplantation of hematopoietic tissue from donors of various ages

International Nuclear Information System (INIS)

Schmidt, C.M.; Doran, G.A.; Crouse, D.A.; Sharp, J.G.

1987-01-01

If the limited life span of hematopoietic tissues in vitro is due to a finite proliferative capacity of individual stem cells, one might expect tissues of young donors to possess a greater proliferative capacity and to contain a larger population of primitive stem cells than those of older donors. To test this hypothesis, we used 12- and 8-day spleen colony formation (CFU-s) to assay more and less primitive stem cell subpopulations of three murine hematopoietic tissues: fetal liver (FL) and weanling (WBM) and adult (ABM) bone marrow. Subsequently, the same assays and a stromal cell assay were performed on the bone marrow from groups of lethally irradiated mice reconstituted with these tissues. Comparison of the CFU-s content of the donor tissues revealed that FL contained a significantly greater proportion of primitive stem cells as evidenced by a (Day 12):(Day 8) CFU-s ratio of 3.0 +/- 1.0 as compared to 0.9 +/- 0.1 for WBM and ABM. In addition, at 21 weeks post-transplantation the CFU-s/femur values of the FL reconstituted group were significantly greater than those of the ABM and WBM reconstituted groups. These results suggest that fetal hematopoietic tissue contains a greater proportion of primitive stem cells and has a greater proliferative potential than hematopoietic tissue from older donors. No differences were seen in stromal cell reconstitution of the three experimental groups. In all cases, assayable fibroblast colony forming cells (CFU-f) remained at 20-40% of control values, even at 21 weeks postreconstitution

Effects of Ru(CO)3Cl-glycinate on the developmental toxicities induced by X-ray and carbon-ion irradiation in zebrafish embryos

Energy Technology Data Exchange (ETDEWEB)

Zhou, Rong [Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000 (China); Song, Jing’e [School/Hospital of stomatology, Lanzhou University, Lanzhou 730000 (China); Si, Jing [Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000 (China); Zhang, Hong, E-mail: zhangh@impcas.ac.cn [Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000 (China); Liu, Bin [School/Hospital of stomatology, Lanzhou University, Lanzhou 730000 (China); Gan, Lu; Zhou, Xin [Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000 (China); and others

2016-11-15

damage, and thus inhibiting the activation of P53 and the mitochondrial apoptotic pathway, leading to the attenuation of cell apoptosis and consequently alleviating X-ray irradiation-induced developmental toxicity at lethal and sub-lethal levels.

Safety evaluation of the ethyl acetate extract on irradiated tea parasite: Acute toxicity study on mice

International Nuclear Information System (INIS)

Hendig Winarno

2011-01-01

Many studies of the pharmacological efficacy of tea parasite and the use of ionizing radiation for decontamination of microbes and extending shelf life have been reported, but there is no information on its safety, such as the acute toxicity. In this study, the acute toxicity of two ethyl acetate extracts from unirradiated and irradiated (irradiation dose of 10 kGy) tea parasites Scurrula atropurpurea on Swiss Webster mice have been examined. The observation was done after the treatment of a single oral dose of ethyl acetate extract in various dose groups, i.e.: control (0 g/kg of mice body weight), D1 (0.625 g/kg), D2 (1.25 g/kg), D3 (2.5 g/kg) D4 (5 g/kg), D5 (10 g/kg) by observing the effect on behavioral response (pharmacological profile), the body weight gains and mortality until the day 14 th . At the last day, the observation of vital organs has also been done. The result showed that no acute toxicity was found in mice treated with a single oral dose of ethyl acetate extract from unirradiated tea parasite and irradiated tea parasite at the dose of 10 kGy. At the dose up to 10 g/kg (equivalent to 77.6 g of extract which administered to human), the normal body weight gains were observed in mice of all dose groups, no mice deaths in any of the dose groups, and no significant change (p > 0.05) in organ weights relative to the body weight i.e.: liver, spleen, kidneys, lung, heart, testes and seminal vesicle (for male), and ovaries and uterus (for female). The approximate lethal doses for male and female mice were determined to be higher than 10 g/kg of mice body weight. It is suggested that the treatment of ethyl acetate extract from unirradiated and irradiated tea parasites until dose up to 10 g/kg of mice body weight was still safe. (author)

Effects of cyclophosphamide and irradiation singly and in combination upon SaI growth in A/J mice

International Nuclear Information System (INIS)

Anderson, R.E.; Williams, W.L.; Tokuda, S.

1987-01-01

The effects of various doses of cyclophosphamide and low-dose (15 rads) radiation upon the size of tumors caused by 10(4) Sarcoma I (SaI) cells was determined. In intact A/Jax (A/J) recipients, the effect of the two agents singly and in combination was found to be dependent especially upon the dosage of cyclophosphamide and the time of its administration in relation to tumor inoculation. In cell transfer experiments to adult thymectomized, lethally irradiated, bone-marrow-restored (ATxXBM) mice, the effects of cyclophosphamide and irradiation appeared to be either overlapping (low dosages of cyclophosphamide) or additive (dosages of cyclophosphamide greater than or equal to 50 mg/kg), suggesting that the two agents exert their influence in dissimilar fashion, perhaps by injuring different cell types with the same basic function. The most pronounced conjoint effects are seen when low dosages of cyclophosphamide are given 3 days after the adoptive transfer of spleen cells from mice pretreated with low-dose irradiation. The implications of this observation with respect to immunotherapy are discussed

Interferon synthesis in mouse peritoneal cells damaged by x irradiation

Energy Technology Data Exchange (ETDEWEB)

Szolgay, E; T' alas, M

1976-01-01

NDV-induced interferon of peritoneal cells of irradiated (x-rays, 400 R) and control mice was investigated in vitro. Irradiation or treatment with hydroxyurea (10(-5) M) and mitomycin C (25 microng/ml) did not change interferon synthesis in spite of an 80 to 90% inhibition of 3H-thymidine incorporation. Increased doses of mitomycin C and treatment with actinomycin D and puromycin blocked interferon production. De novo interferon synthesis occurred in cells with damaged replicative activity of DNA caused by irradiation or by treatment with antimetabolites.

Duodenal ulcers as an abscopal effect of thoracic irradiation in mice

International Nuclear Information System (INIS)

Michalowski, A.; Burgin, J.

1982-01-01

Female CFLP mice irradiated to their thorax with either x-rays or fast neutrons developed peptic ulcers within 8 days of exposure. The steep x-ray dose/response curve for induction of duodenal ulcer gave an ED 50 of approximately 14.5 Gu. As little as 6 Gy of fast neutrons was effective in some cases, but the neutron ED 50 exceeded that for x-rays. The ulcers represented an abscopal effect of thoracic irradiation. Scattered radiation as simulated by whole-body x-ray treatment (1 to 5 Gy) caused a dose-dependent decrease in the frequency of duodenal lesions, possibly by decreasing gastric secretion. The greater amount of scattered radiation accompanying fast neutron exposure of the thorax was presumably responsible for the shallower dose/response curve of ulcer induction than that seen with x-rays

Parental resistance of irradiated mice to (CBAXM523)F/sub 1/ lymphocytes: the destiny of transplanted cells, duration of resistance and its specificity

Energy Technology Data Exchange (ETDEWEB)

Kondrat' eva, T K; Fontalin, L N; Nagurskaya, E V; Novikova, T K; Blandova, Z K; Chernousov, A D [Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Ehpidemiologii i Mikrobiologii

1979-05-01

The immunologic reactivity of mouse (CBAxM523)F/sub 1/ lymphocytes to alien antigens (ram erythrocytes) in the organisms of lethally irradiated CBA mice was studied. If the irradiation, cell transfer and antigen test-injection were performed on the same day, the activity of the transplant was suppressed as compared to the syngenic system. If the intervals between these procedures increased to three days the activity of donor cells was recovered. The retransplantation of recipient spleen cells to the irradiated CBA and F/sub 1/ mice demonstrated the viability of the transplanted cells and the absence of their transadaptation to nonsyngenic microenvironment. The resistance of the recipients could be overcome specifically by preliminary injection of F/sub 1/ mouse cells in combination with cyclophosphamide or without it. The results obtained suggest to conclude, that the genetic parental resistance of CBA mice to F/sub 1/ mouse cells is caused by the immunologically competent recipient cells that are inactivated after three days following irradiation. They do not produce a cytotoxic effect on donor cells, but limit temporarily the activity of the latter.

On the recovery of the DNA-synthesis after X-irradiation in the spleen of mice and its modification by the NAD-metabolism

International Nuclear Information System (INIS)

Streffer, C.

1974-01-01

The incorporation of tritium-labelled thymidine into the DNA of mice spleen cells after whole body irradiation with X-rays was measured in order to study the decrease of DNA synthesis is decreased for several hours after irradiation with low doses. Recovery effects become operative after six hours. The radiation effect on the NAD metabolism, known to be related to DNA synthesis, was also investigated. The rate of NAD synthesis is influenced via the extremely radiosensitive metabolic process in the nucleus. Conversely, inhibition of DNA synthesis by injection of NAD enhances the recovery of DNA synthesis after irradiaton. (G.G.)

In vivo radioprotection of mice by 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone; Radicut), a clinical drug

International Nuclear Information System (INIS)

Anzai, Kazunori; Furuse, Masako; Yoshida, Akira; Matsuyama, Azusa; Moritake, Takashi; Ikota, Nobuo; Tsuboi, Koji

2004-01-01

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut) is a brain-protecting agent used clinically to treat acute ischemic stroke with a reaction mechanism of free radical scavenging. Since the initial stage of radiation damage involves the formation of free radicals, edaravone is expected to be effective in preventing lethal damage from ionizing radiation. In the present study, we used mice to examine in vivo the radioprotective effect of edaravone on whole body X-ray irradiation. A solution of edaravone was administered intraperitoneally to C3H mice (male, 10 weeks old), and they were irradiated with a total dose of 8.0 Gy. Edaravone exhibited dose-dependent and injection time-dependent radioprotection. When injected 30 min before the X-ray irradiation, it had the greatest radioprotective effect, whereas an injection after the irradiation showed no protective effect. The LD 50/30 was about 8.8 Gy for edaravone-injected mice and 6.6 Gy for control mice, yielding a DRF for edaravone (450 mg/kg body weight) of 1.3. Edaravone decreased the body temperature transiently about 3-6deg C, but this did not seem to be responsible for the radioprotection. Since the radioprotection was observed only when the reagent was administered before the irradiation, the primary action of edaravone might be the quenching of free radicals with a short lifetime generated by the irradiation. (author)

In vivo radioprotection of mice by 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone; Radicut), a clinical drug

Energy Technology Data Exchange (ETDEWEB)

Anzai, Kazunori; Furuse, Masako; Yoshida, Akira; Matsuyama, Azusa; Moritake, Takashi; Ikota, Nobuo [National Inst. of Radiological Sciences, Chiba (Japan). Research Center for Radiation Safety; Tsuboi, Koji [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

2004-06-01

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; Radicut) is a brain-protecting agent used clinically to treat acute ischemic stroke with a reaction mechanism of free radical scavenging. Since the initial stage of radiation damage involves the formation of free radicals, edaravone is expected to be effective in preventing lethal damage from ionizing radiation. In the present study, we used mice to examine in vivo the radioprotective effect of edaravone on whole body X-ray irradiation. A solution of edaravone was administered intraperitoneally to C3H mice (male, 10 weeks old), and they were irradiated with a total dose of 8.0 Gy. Edaravone exhibited dose-dependent and injection time-dependent radioprotection. When injected 30 min before the X-ray irradiation, it had the greatest radioprotective effect, whereas an injection after the irradiation showed no protective effect. The LD{sub 50/30} was about 8.8 Gy for edaravone-injected mice and 6.6 Gy for control mice, yielding a DRF for edaravone (450 mg/kg body weight) of 1.3. Edaravone decreased the body temperature transiently about 3-6deg C, but this did not seem to be responsible for the radioprotection. Since the radioprotection was observed only when the reagent was administered before the irradiation, the primary action of edaravone might be the quenching of free radicals with a short lifetime generated by the irradiation. (author)

Antibiotic radioprotection of mice exposed to supralethal whole-body irradiation independent of antibacterial activity

International Nuclear Information System (INIS)

Mastromarino, A.; Wilson, R.

1976-01-01

Oral administration of streptomycin, kanamycin, neomycin, or gentamicin to specific pathogen-free C57 x Af mice in their drinking water (4 mg/ml) for 2 weeks before supralethal whole-body irradiation very significantly prolonged their mean survival times (8.2 to 8.9 days vs 6.9 for controls) to values which exceed those reported for germ-free mice (7.3 days). The total fecal concentrations of aerobes and anaerobes were reduced by kanamycin, neomycin, and gentamicin. Streptomycin reduced the anaerobes significantly, but not the aerobes. Unlike germ-free mice, these antibiotic-treated mice did excrete free bile acids, products of bacterial action. Oral antibiotic treatment was ineffective in altering the transit time of the intestinal mucosal cells. Previously reported studies had indicated a correlation between decreased transit time and increased survival after irradiation. No significant correlation between mean survival time after irradiation and mucosal transit time was observed. The data demonstrate that certain antibiotics alter the character of the intestinal bacterial flora and increase protection against supralethal doses of whole-body irradiation. It is concluded that the mechanisms of radioresistance in antibiotic-treated mice and germ-free mice are different and that in both groups radioresistance is the result of more than elimination of postirradiation infection

Study of serotonin effect on the yield of some damages in DNA after ultraviolet and x-ray irradiations

International Nuclear Information System (INIS)

Ivanova, Eh.V.; Frajkin, G.Ya.

1985-01-01

Using thin-layer two-dimensional chromatography serotonin effect on the yield of thymine dimers and appearance of n-glycoside strand breaks in DNA (thymine yield) after ultraviolet and X-ray irradiation is studied. It is shown that bound with DNA serotonin decreases formation of induced by ultraviolet thymine dimers but doesn't affect on the quantity of N-glycoside bond breaks in thymidine residues caused by X radiation. The obtained data are discussed in relation to the problem on mechanisms of realization of serotonin protective effect in the processes of yeast Saccharomyces photoprotection from ultraviolet and X-ray irradiation lethal effect

Participation of lymphocytes in hemopoiesis regeneration under local irradiation of the body

International Nuclear Information System (INIS)

Gol'dberg, E.D.; Dygaj, A.M.

1982-01-01

Lymphocyte participation in regulation of a pool of stem blood-producing cells using a model of local irradiation of bone marrow was studied. Right pelvic limb of BALB/c strain mice was exposed to local X-radiation at a dose of 7.0 Gy. During different periods after the irradiation the animals were killed and the total number of nucleus-containing cells in thymus, spleen, bone marrow from irradiated and screened femurs were counted. Smears of bone marrow were used to calculate myelogram. To study thymocyte effect on postradiation regeneration of hemopoesis, each of thymectomized mice were injected intravenously 4x10 7 viable thymocytes. Processes of the postradiation regeneration of hemopoesis were specially investigated in animals against the background of intraperitoneal injection of antithymocytic heterologous serum. The population of stem blood-producing cells of bone marrow was studied by the method of exogenic cloning in the body of syngenic recipient lethally irradiated (7.5 Gy). It is shown that during the period before active recovery of hemopoesis observed is the selective accumulation of lymphocytes of predominantly thymus origin only in irradiated blood-producing tissue. T lymphocytes stimulated colony-forming activity of bone marrow and accelerated the postradiation regeneration of hemopoesis

Effect of single-dose x irradiation on the growth curves of a human malignant melanoma transplanted into nude mice

International Nuclear Information System (INIS)

Spang-Thomsen, M.; Visfeldt, J.; Nielsen, A.

1981-01-01

A human malignant melanoma transplanted into nude mice was exposed to single-dose x irradiation. Experimental growth data described mathematically according to a transformed Gompertz function were used to determine the effect of irradiation on growth delay, growth rate, and tumor shrinkage. The radiation-induced changes in the histology of the tumors were also described. The results showed that irradiation induced a dose-dependent growth delay; this parameter was therefore found suitable for the assessment of relative therapeutic effect. The treatment also induced a dose-dependent reduction in growth rate during regrowth. As a result of this effect on growth rate, extrapolation of tumor shrinkage to the time of treatment became directly misleading as a measure of the effect of the treatment. From this it can be deduced that in therapeutic studies where treatment induces nonparallel posttherapeutic growth curves, growth delay for various tumors and therapies cannot be compared directly. The transformed Gompertz function proved to be extremely well suited for evaluating these conditions

Influence of X-rays on transgenerational lung tumorigenesis in CBA mice

International Nuclear Information System (INIS)

Kamino, Kenji

2001-01-01

The aim of the present study was to ascertain whether prezygotic exposure of male mice to X-rays increases a carcinogenic risk in the progeny. The testicles of 9-week-old male CBA/J mice were X-ray irradiated (1 Gy or 2 Gy) and the animals were then mated at 1, 3 and 9 weeks after treatment with untreated virgin 12-week-old females of the same strain. The 1-Gy offspring (155 males and 127 females), 2-Gy offspring (111 males and 95 females) and additional control offspring (119 males and 111 females) were kept for life under standard laboratory conditions. The lungs were investigated for development of adenomas and adenocarcinomas. No significantly increased tumour incidences were observed in the 1-Gy and 2-Gy offspring groups compared with the control group. However, with regard to the dignity of the tumours, the ratios of animals with carcinomas to animals with adenomas were slightly increased in both irradiation groups of descendants. Although this phenomenon is not statistically significant, a possibility of enhanced susceptibility to malignant progression of tumours in the offspring through the paternal germ cell X-irradiation should be considered in connection with our previous investigation. (author)

Effects of X-irradiation on some aspects of protein metabolism in the frog, Rana hexadactyla

International Nuclear Information System (INIS)

Rajarami Reddy, G.; Sasira Babu, K.

1980-01-01

Changes in the level of total proteins and protease in brain, muscle and liver tissues of normal and X-irradiated frogs were determined. Low doses of radiation produced an increment in protein level while high doses produced decrement. However, protease activity at all doses exhibited an elevatory trend. Exposure of frogs to lethal doses resulted in increased protease activity and decreased protein content during post-irradiation periods. The results are discussed on the basis of protein destruction and lysosomal damage. (auth.)

Evaluation of freshly irradiated wheat for dominant lethal mutations in Wistar rats

International Nuclear Information System (INIS)

Pawan, S.C.; Aravindakshan, M.; Kumar, N.S.; Subba Rao, V.; Aiyar, A.S.; Sundaram, K.

1977-01-01

Three independent, serially performed experiments involving acute and chronic feeding of freshly irradiated wheat (75 krad, gamma-irradiation) were carried out in Wistar rats. In the first experiment groups of 10 males were given wheat for 1 week; irradiated wheat was consumed by the animals within 24 h of irradiation. In the other two experiments feeding of males was continued for 6 (10 males per group) and 12 (13 males per group) weeks, respectively, and the irradiated wheat was fed within 7 days of irradiation. At the end of each treatment period each male was paired with 3 females for 7 days and sequentially at weekly intervals for 5 or 8 weeks. Females were killed and examined for live and dead implantations and corpora lutea. There were no differences between groups with regard to fertility nor was there any inter-group difference as regards pre- and post-implantation losses whether the rats were fed irradiated or non-irradiated wheat. This suggested that even feeding of freshly irradiated wheat does not induce any dominant lethal mutations in rats

Evaluation of freshly irradiated wheat for dominant lethal mutations in Wistar rats

Energy Technology Data Exchange (ETDEWEB)

Pawan, S C; Aravindakshan, M; Kumar, N S; Subba Rao, V; Aiyar, A S; Sundaram, K [Bhabha Atomic Research Centre, Bombay (India). Bio-medical Group

1977-01-01

Three independent, serially performed experiments involving acute and chronic feeding of freshly irradiated wheat (75 krad, gamma-irradiation) were carried out in Wistar rats. In the first experiment groups of 10 males were given wheat for 1 week; irradiated wheat was consumed by the animals within 24 h of irradiation. In the other two experiments feeding of males was continued for 6 (10 males per group) and 12 (13 males per group) weeks, respectively, and the irradiated wheat was fed within 7 days of irradiation. At the end of each treatment period each male was paired with 3 females for 7 days and sequentially at weekly intervals for 5 or 8 weeks. Females were killed and examined for live and dead implantations and corpora lutea. There were no differences between groups with regard to fertility nor was there any inter-group difference as regards pre- and post-implantation losses whether the rats were fed irradiated or non-irradiated wheat. This suggested that even feeding of freshly irradiated wheat does not induce any dominant lethal mutations in rats.

Migration of bone marrow cells to the thymus in sublethally irradiated mice

International Nuclear Information System (INIS)

Varlet, Andree; Lenaerts, Patrick; Houben-Defresne, M.P.; Boniver, Jacques

1982-01-01

In sublethally irradiated mice, thymus repopulation is due first to the proliferation of surviving thymocytes followed by the multiplication of bone marrow derived prothymocytes. The migration of bone marrow cells to the thymus after a single sublethal whole-body X irradiation was studied by using fluorescein isothiocyanate as a cell marker. Irradiation increases the permissiveness of the thymus to the immigration of bone marrow cells. Furthermore, the post-Rx regenerating bone marrow cells exhibit migration capacities greater than the normal ones. The radiation induced changes in the bone marrow thymus interaction might play an important role in thymus regeneration after sublethal irradiation [fr

CD4+ T lymphocytes injected into severe combined immunodeficient (SCID) mice lead to an inflammatory and lethal bowel disease

DEFF Research Database (Denmark)

Claesson, Mogens Helweg; Rudolphi, A; Kofoed, S

1996-01-01

Transfer of 2 x 10(5) congenic or semiallogenic purified TCR alphabeta+ CD4+ T cells to SCID mice leads to an infiltration of the recipient gut lamina propria and epithelium with a donor-derived CD4+ T cell subset which induces a lethal inflammatory bowel disease (IBD) in the recipients....... In contrast, IBD was not observed in SCID mice transplanted with unfractionated splenic cells. The earliest detectable pathological changes after CD4+ T cell transfer were proliferation and hypertrophy of the entire colonic epithelial layer, including increased mitotic activity, increased expression...... plasma cells were present in the lamina propria of both the small and large intestine. We conclude that low numbers of intraveneously transferred CD4+ T cells induce IBD in SCID mice. In the late stages of CD4+ T cell-induced IBD, the colonic lamina propria becomes infiltrated with macrophages...

Hematologic syndrome in man modeled from mammalian lethality

International Nuclear Information System (INIS)

Jones, T.D.

1981-01-01

Data on acute radiation lethality due to failure of the hematologic system in rats, mice, dogs, swine, monkeys and man are analyzed. Based on the available data, the mortality incidences for 1-100% levels can be computed directly if one has only an estimate of the dose lethal to 50% of the population (LD 50 ) for the mammalian strain and radiation environment of interest. The sole restriction is that the dose profile to the marrow be moderately uniform. If an LD 50 for any exposure situation has been measured, then one can readily scale to any desired situation through implicit-biological and empirical-physical relationships. The LD 50 for man, exposed to an isotropic cloud of photons, and knowledge of the bone-marrow dose profiles readily permit evaluation of the model for other levels of human mortality from different irradiating particles, partial body irradiation and spatially dependent and/or mixed radiation environments. (author)

Sensory dynamics of intense microwave irradiation: A comparative study of aversive behaviors by mice and rats

Energy Technology Data Exchange (ETDEWEB)

Justesen, D.R.

1981-10-01

The results of two experiments are reported, the first on 24 mice and 14 rats, all experimentally naive, that were observed for evidence of adventitious escape from faradic shock or from a potentially lethal, 2450-MHz microwave field in a multi-mode cavity. All of ten rats irradiated at a whole-body-averaged dose rate of 60 mW/g convulsed and expired, presumably from radiation-induced hyperpyrexia. Eight of ten mice irradiated at 60 mW/g survived the four sessions of irradiation, but reliable evidence of escape learning was not observed. The data of the second experiment, which was a pilot study of four rats with an extensive history of exposure to intense but intermittently applied microwave fields, revealed that the animals learned to thermoregulate behaviorally by locomoting in and out of the safe-area circle. A strong relation between dose rate (30, 60, and 120 mW/g) and proportion of time spent in the safe area was observed (r = .97). Post-exposure means of colonic temperature during three sets of sessions under the different rates of energy dosing were highly stable and averaged 39.6 deg C.

Comparative influence of dose rate and radiation nature, on lethality after big mammals irradiation

International Nuclear Information System (INIS)

Destombe, C.; Le Fleche, Ph.; Grasseau, A.; Reynal, A.

1997-01-01

For the same dose and the 30 days lethality as biological criterion, the dose rate influence is more important than the radiation nature on the results of an big mammals total body irradiation. (authors)

The effect of vitamin E on cellular survival after X irradiation of lymphoma cells

International Nuclear Information System (INIS)

Fonck, K.; Kronings, A.W.T.

1978-01-01

Asynchronous cultures of a lymphocytic mouse leukaemic cell line L5178Y were X-irradiated under oxic and hypoxic conditions. The survival curves had almost no shoulder when the cells were grown under normal conditions and then irradiated in the presence of vitamin E, whereas a clear shoulder appeared when the cells were grown and irradiated in a medium supplemented with vitamin E (100 μg/ml). There was no change in the final sensitivity to lethal events in the vitamin E enriched cells. The results suggest that the radioprotective effect of vitamin E depends on its incorporation into the cell membranes. (U.K.)

The population genetics of X-autosome synthetic lethals and steriles.

Science.gov (United States)

Lachance, Joseph; Johnson, Norman A; True, John R

2011-11-01

Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

Mutagenicity studies on alcohol extracts from gamma-irradiated potatoes

International Nuclear Information System (INIS)

Shibuya, Tohru; Murora, Tetsuro; Iwahara, Shigeo; Hashimoto, Koroku; Minegishi, Atsuko.

1982-01-01

Alcohol extracts freshly prepared from gamma-irradiated and unirradiated potatoes were tested for the ability to induce dominant lethals in BDF 1 mice. Male mice were given 0.5 ml of extract twice a day, p.o., for 7 days and then mated with untreated female mice. Female mice were sacrificed on about the 13th day of pregnancy. No significant difference was observed in the number of living inplants between the group treated with extract prepared from unirradiated potatoes and that treated with the extract from 150 Gy (15 krad) irradiated potatoes. (author)

X-Ray-Induced Damage to the Submandibular Salivary Glands in Mice: An Analysis of Strain-Specific Responses

Science.gov (United States)

Kamiya, Mana; Kawase, Tomoyuki; Hayama, Kazuhide; Tsuchimochi, Makoto; Okuda, Kazuhiro; Yoshie, Hiromasa

2015-01-01

Abstract Radiation therapy for head and neck cancers often causes xerostomia (dry mouth) by acutely damaging the salivary glands through the induction of severe acute inflammation. By contrast, the mechanism underlying the X-ray-induced delayed salivary dysfunction is unknown and has attracted increasing attention. To identify and develop a mouse model that distinguishes the delayed from the acute effects, we examined three different mouse strains (C57BL/6, ICR, and ICR-nu/nu) that showed distinct T-cell activities to comparatively analyze their responses to X-ray irradiation. Three strains were irradiated with X-rays (25 Gy), and functional changes of the submandibular glands were examined by determining pilocarpine-induced saliva secretion. Structural changes were evaluated using histopathological and immunohistochemical examinations of CD3, cleaved poly (ADP-ribose) polymerase (PARP), and Bcl-xL. In C57BL/6 mice, the X-ray irradiation induced acute inflammation accompanied by severe inflammatory cell infiltration at 4 days postirradiation, causing substantial destruction and significant dysfunction at 2 weeks. Fibrotic repair was observed at 16 weeks. In ICR-nu/nu mice, the inflammation and organ destruction were much milder than in the other mice strains, but increased apoptotic cells and a significant reduction in salivary secretion were observed at 4 and 8 weeks and beyond, respectively. These results suggest that in C57BL/6 mice, X-ray-induced functional and structural damage to the salivary glands is caused mainly by acute inflammation. By contrast, although neither acute inflammation nor organ destruction was observed in ICR-nu/nu mice, apoptotic cell death preceded the dysfunction in salivary secretion in the later phase. These data suggest that the X-ray-irradiated ICR-nu/nu mouse may be a useful animal model for developing more specific therapeutic methods for the delayed dysfunction of salivary glands. PMID:26309806

Radioprotective effect of RSP-CM on mice irradiated with different doses

International Nuclear Information System (INIS)

Zhang Xia; Yang Rujun; Zhang Xin; Yang Yunfang; Jin Zhijun; Xiang Yingsong

2000-01-01

Objective: To investigate the radioprotective effects of cytokines on hematopoietic impairment of irradiated mice. Methods: Using RSP-CM and LP3-CM respectively originated GM-CSF and G-CSF to treat ICR mice irradiated with different doses of 60 Co γ-rays. The 30-day survival rate of mice, the mean survival days of dead mice were determined and the numbers of peripheral white blood cells and BMC of part of the mice were counted. At the same time, GM clonogenic activity of BM was assayed. Results:RSP-CM could effectively raise 30-day survival rate of mice irradiated with 7.5 Gy. However, LP3-CM had no obvious effect. Judging from the comparative survival ratio, only the RSP-CM treated group showed protective effect on the 8.0 Gy -irradiated mice. The 8.5 Gy-irradiated mice all died within 30 days, indicating that GM-CSF had weak effect on higher dose-irradiated mice. Conclusion: GM-CSF can stimulate the hematopoietic system of irradiated mice, and has dose-effect and time-effect relations. M-CSF used singly has no obvious effect

Late vascular effects of whole brain X-irradiation in the mouse

Energy Technology Data Exchange (ETDEWEB)

Yoshii, Y [Tsukuba Univ., Sakma, Ibaraki (Japan). Inst. of Clinical Medicine; Phillips, T L [California Univ., San Francisco (USA). Dept. of Radiation Oncology

1982-01-01

The whole brains of mice were irradiated with 250kVp X-rays at 120 rads min/sup -1/ (1.6 mm Cu HVL, TSD 50 cm), and a histological study was carried out. The dose range of X-irradiation was from 1,300 to 2,500 rads, i.e., 1,300, 1,500, 1,750, 2,000, and 2,500 rads. Eighty-six mice were used for histological examination. For microscopic examination, the mice were killed at regular postirradiation intervals between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. The brains were removed immediately thereafter, fixed in Bouin's solution, and embedded in paraffin. A histological examination was performed by a morphometric estimation of vascular lesions, in which the degree of the damage to the arterial system was scored in whole serial brain section. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectactic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large arteries, were observed. Dose-dependent incidence of the fibrinoid necrosis increased between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 to 87 weeks, and can be used to quantify the vessel injury, and that fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis.

Late vascular effects of whole brain X-irradiation in the mouse

International Nuclear Information System (INIS)

Yoshii, Y.; Phillips, T.L.

1982-01-01

The whole brains of mice were irradiated with 250kVp X-rays at 120 rads min -1 (1.6 mm Cu HVL, TSD 50 cm), and a histological study was carried out. The dose range of X-irradiation was from 1,300 to 2,500 rads, i.e., 1,300, 1,500, 1,750, 2,000, and 2,500 rads. Eighty-six mice were used for histological examination. For microscopic examination, the mice were killed at regular postirradiation intervals between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. The brains were removed immediately thereafter, fixed in Bouin's solution, and embedded in paraffin. A histological examination was performed by a morphometric estimation of vascular lesions, in which the degree of the damage to the arterial system was scored in whole serial brain section. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectactic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large arteries, were observed. Dose-dependent incidence of the fibrinoid necrosis increased between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 to 87 weeks, and can be used to quantify the vessel injury, and that fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis. (Author)

Effects of x-ray and neutron irradiation on spherical colonies

International Nuclear Information System (INIS)

Aramaki, Ryoji

1980-01-01

Responses of in vitro cultured mammalian cells in spherical colonies to 200 kVp x-rays and D-T neutrons were studied using reproductive capacity as a criterion for survival. Cell lines used were FM3A, L5 and Chinese hamster V79. The spherical colonies exposed to x-rays exhibited two-component survival curves. All cells used were more radio-resistant in spherical colonies than in single cell suspensions. It was suggested that this difference in response was attributable to the presence of hypoxic cells in spherical colonies. Dose-modifying Factor (DMF), the ratios of D 0 of the second slopes of the curves for spherical colonies to those for single cells, were 1.6 for FM3A, 1.8 for L5, and 1.7 for Chinese hamster V79. The hypoxic cell fractions in spherical colonies for FM3A, L5, and Chinese hamster V79, were 0.1, 0.6 and 0.4, respectively, resulting in variations in cell survival in spherical colonies following x-radiation. No significant difference was observed between responses of spherical colonies and single cell suspensions to D-T neutrons. FM3A and Chinese hamster V79 showed two-component survival curves when irradiated with neutrons at 37 0 C, but not at 25 0 C. The repair of potentially lethal and sub-lethal damage was also investigated using FM3A in spherical colonies. No detectable repair of potentially lethal damage was observed for x-rays and D-T neutrons. The effect of neutron fractionation was considerably smaller for spherical colonies as compared to single cells. (author)

Comparative study of the reciprocal translocation rate in spermatocytes after irradiation of newborn and adult mice

International Nuclear Information System (INIS)

Pomerantseva, M.D.

1978-01-01

The yield of reciprocal translocations was investigated in spermatocytes of the CBA male mice irradiated immediately after their brith or after the irradiation of the stem spermatogonia at the age of 3 months. The irradiation doses were 100, 200, 400 R X-rays 300 R gamma-rays 60 Co. The yield of translocations in both groups was the same

Survival of bone marrow-engrafted mice subsequent to protection from lethal radiation by WR 2721

International Nuclear Information System (INIS)

Kinnamon, K.E.; Ketterling, L.L.; Ledney, G.D.; Lorenz, G.B.; Mioduszewski, R.J.; Stampfli, H.F.

1980-01-01

For the first time data are presented for animals treated with bone marrow cells after lethal radiation exposure while protected with WR 2721 (the single radioprotective chemical compound with the highest known dose reduction factor). The LD 50 30 (lethal dose to 50% in 30 days) for mice exposed to whole-body 60 Co radiation was elevated from 824 +- 8 rad in unprotected and untreated mice to (a) 1181 +- 33 rad in animals which received syngeneic bone marrow cells after exposure; (b) 1342 +- 27 rad in animals which received WR 2721 before radiation exposure; and (c) 1608 +- 33 rad in animals receiving both the radioprotective agent before exposure and bone marrow engraftment after exposure

Human umbilical-cord-blood mononucleated cells enhance the survival of lethally irradiated mice. Dosage and the window of time

International Nuclear Information System (INIS)

Kovalenko, Olga A.; Ende, Norman; Azzam, Edouard I.

2013-01-01

The purpose of this study was to evaluate the window of time and dose of human umbilical-cord-blood (HUCB) mononucleated cells necessary for successful treatment of radiation injury in mice. Female A/J mice (27-30 weeks old) were exposed to an absorbed dose of 9-10 Gy of 137 Cs γ-rays delivered acutely to the whole body. They were treated either with 1 × 10 8 or 2 × 10 8 HUCB mononucleated cells at 24-52 h after the irradiation. The antibiotic Levaquin was applied 4 h postirradiation. The increased dose of cord-blood cells resulted in enhanced survival. The enhancement of survival in animals that received 2 × 10 8 HUCB mononucleated cells relative to irradiated but untreated animals was highly significant (P < 0.01). Compared with earlier studies, the increased dose of HUCB mononucleated cells, coupled with early use of an antibiotic, extended the window of time for effective treatment of severe radiation injury from 4 to 24-52 h after exposure. (author)

Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination.

Science.gov (United States)

Betz, U A; Vosshenrich, C A; Rajewsky, K; Müller, W

1996-10-01

The analysis of gene function based on the generation of mutant mice by homologous recombination in embryonic stem cells is limited if gene disruption results in embryonic lethality. Mosaic mice, which contain a certain proportion of mutant cells in all organs, allow lethality to be circumvented and the potential of mutant cells to contribute to different cell lineages to be analyzed. To generate mosaic animals, we used the bacteriophage P1-derived Cre-loxP recombination system, which allows gene alteration by Cre-mediated deletion of loxP-flanked gene segments. We generated nestin-cre transgenic mouse lines, which expressed the Cre recombinase under the control of the rat nestin promoter and its second intron enhancer. In crosses to animals carrying a loxP-flanked target gene, partial deletion of the loxP-flanked allele occurred before day 10.5 post coitum and was detectable in all adult organs examined, including germ-line cells. Using this approach, we generated mosaic mice containing cells deficient in the gamma-chain of the interleukin-2 receptor (IL-2R gamma); in these animals, the IL-2R gamma-deficient cells were underrepresented in the thymus and spleen. Because mice deficient in DNA polymerase beta die perinatally, we studied the effects of DNA polymerase beta deficiency in mosaic animals. We found that some of the mosaic polymerase beta-deficient animals were viable, but were often reduced in size and weight. The fraction of DNA polymerase beta-deficient cells in mosaic embryos decreased during embryonic development, presumably because wild-type cells had a competitive advantage. The nestin-cre transgenic mice can be used to generate mosaic animals in which target genes are mutated by Cre-mediated recombination of loxP-flanked target genes. By using mosaic animals, embryonic lethality can be bypassed and cell lineages for whose development a given target gene is critical can be identified. In the case of DNA polymerase beta, deficient cells are already

A chimera embryo assay reveals a decrease in embryonic cellular proliferation induced by sperm from X-irradiated male mice

International Nuclear Information System (INIS)

Obasaju, M.F.; Wiley, L.M.; Oudiz, D.J.; Raabe, O.; Overstreet, J.W.

1989-01-01

Male mice were divided into three experimental groups and a control group. Mice in the experimental groups received one of three doses of acute X irradiation (1.73, 0.29, and 0.05 Gy) and together with the control unirradiated mice were then mated weekly to unirradiated female mice for a 9-week experimental period. Embryos were recovered from the weekly matings at the four-cell stage and examined by the chimera assay for proliferative disadvantage. Aggregation chimeras were constructed of embryos from female mice mated to irradiated males (experimental embryos) and embryos from females mated to unexposed males (control embryos) and contained either one experimental embryo and one control embryo (heterologous chimera) or two control embryos (control chimera). The control embryo in heterologous chimeras and either embryo in control chimeras were prelabeled with the vital dye fluorescein isothiocyanate (FITC), and the chimeras were cultured for 40 h and viewed under phase-contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution from the FITC-labeled embryo. Experimental and control embryos that were cultured singly were also examined for embryo cell number at the end of the 40-h culture period. In control chimeras, the mean ratio of the unlabeled cells:total chimera cell number (henceforth referred to as ''mean ratio'') was 0.50 with little or no weekly variation over the 9-week experimental period. During Weeks 4-7, the mean ratios of heterologous chimeras differed significantly from the mean ratio of control chimeras with the greatest differences occurring during Week 7 (0.41 for chimeras of 0.05 Gy dose group, 0.40 for chimeras of the 0.29 Gy dose group, and 0.17 for chimeras of the 1.73 Gy dose group)

Sequence-dependent toxicity and small bowel mucosal injury in neonatal mice treated with low doses of 5-azacytidine and X-irradiation at the late organogenesis stage

International Nuclear Information System (INIS)

Schmahl, W.

1983-01-01

A combined treatment of pregnant mice on day 12 of gestation with both azacytidine and X-irradiation in low doses induces sequence-dependent histological effects. These effects, in turn, induce different symptomatic signs if evaluated either prenatally or neonatally. In the azacytidine treatment/X-irradiation sequence the malformations of the fetal forebrain are predominant. Consequently, these dams show a high incidence in the stillbirth rate. Conversely, the X-irradiation/azacytidine treatment schedule leads only to a mild brain hypoplasia, and does not cause an increased stillbirth rate. In these offspring, however, a severe impairment of small bowel epithelial proliferation capacity was found. This is linked to an outstanding neonatal mortality within 48 h after birth. The pathogenesis of these sequence-dependent effects can be attributed to a selective vulnerability of cells in different stages of the generation cycle. This comprises a high degree of cytolethality affecting the S/G 2 -stage cells in azacytidine/X-irradiation treatment and the G 1 /S-stage cells in the reverse combinations (Schmahl 1979). The present observations show the validity of a teratological assay in providing a detailed analysis of the cell kinetic responses after combined noxious influences. (orig.)

Radioprotective properties of some heterocyclic nitrogenous compounds against changes in hemoglobin concentration and hematocrit value in x-irradiated mice; Proprietes radioprotectrices de certains composes heterocycliques azotes sur les variations du taux d'hemoglobine et de la valeur hematocrite chez la souris irradiee

Energy Technology Data Exchange (ETDEWEB)

Rousdhy, H; Pierotti, T; Polverelli, M [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

1969-07-01

Radioprotective properties of imidazole and benzimidazole have been proved in previous works. In this study, authors try to demonstrate radioprotective action of these compounds in comparison with cysteamine upon the hematopoietic system after lethal X-irradiation. Results show: no drastic variations of hematologic constants (hemoglobin concentration and hematocrit value) after intraperitoneal injection of radioprotective compounds apart certain apparent reactions with the heterocyclic compounds; the better radioprotective action of benzimidazole. Twenty five days after irradiation, hemoglobin concentration and hematocrit of radio protected mice return to normal values. (author) [French] Les proprietes radioprotectrices de l'imidazole et du benzimidazole ayant ete demontrees dans de precedents travaux, les auteurs se sont attaches a etudier l'action de ces produits sur le systeme hematopofetique en comparaison avec celle de la cysteamine, apres une irradiation a dose letale. A l'aide des criteres choisis, les resultats demontrent: qu'en dehors de certaines reactions apparentes, succedant a l'injection intraperitoneale des heterocycles azotes, les constantes hematologiques (taux d'hemoglobine et valeur hematocrite) ne sont que legerement modifiees; la superiorite du benzimidazole sur les autres produits utilises. Enfin, le vingt-cinquieme jour apres irradiation, les souris protegees par les heterocycles azotes ont un taux d'hemoglobine et une valeur hematocrite tout a fait normaux. (auteur)

Radiation leukemogenesis in mice: loss of PU.1 on chromosome 2 in CBA and C57BL/6 mice after irradiation with 1 GeV/nucleon 56Fe ions, X rays or gamma rays. Part I. Experimental observations.

Science.gov (United States)

Peng, Yuanlin; Brown, Natalie; Finnon, Rosemary; Warner, Christy L; Liu, Xianan; Genik, Paula C; Callan, Matthew A; Ray, F Andrew; Borak, Thomas B; Badie, Christophe; Bouffler, Simon D; Ullrich, Robert L; Bedford, Joel S; Weil, Michael M

2009-04-01

Since deletion of the PU.1 gene on chromosome 2 is a crucial acute myeloid leukemia (AML) initiating step in the mouse model, we quantified PU.1 deleted cells in the bone marrow of gamma-, X- and 56Fe-ion-irradiated mice at various times postirradiation. Although 56Fe ions were initially some two to three times more effective than X or gamma rays in inducing PU.1 deletions, by 1 month postirradiation, the proportions of cells with PU.1 deletions were similar for the HZE particles and the sparsely ionizing radiations. These results indicate that while 56Fe ions are more effective in inducing PU.1 deletions, they are also more effective in causing collateral damage that removes hit cells from the bone marrow. After X, gamma or 56Fe-ion irradiation, AML-resistant C57BL/6 mice have fewer cells with PU.1 deletions than CBA mice, and those cells do not persist in the bone marrow of the C57B6/6 mice. Our findings suggest that quantification of PU.1 deleted bone marrow cells 1 month postirradiation can be used as surrogate for the incidence of radiation-induced AML measured in large-scale mouse studies. If so, PU.1 loss could be used to systematically assess the potential leukemogenic effects of other ions and energies in the space radiation environment.

Hydrocephalus in mice following X-irradiation at early gestational stage. Possibly due to persistent deceleration of cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Aolad, H.M.; Inouye, Minoru; Darmanto, W.; Hayasaka, Shizu; Murata, Yoshiharu [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

2000-09-01

The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telecephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus. (author)

Hydrocephalus in mice following X-irradiation at early gestational stage. Possibly due to persistent deceleration of cell proliferation

International Nuclear Information System (INIS)

Aolad, H.M.; Inouye, Minoru; Darmanto, W.; Hayasaka, Shizu; Murata, Yoshiharu

2000-01-01

The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telecephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus. (author)

Mechanisms of an increased level of serum iron in gamma-irradiated mice

International Nuclear Information System (INIS)

Xie, Li-hua; Zhang, Xiao-hong; Hu, Xiao-dan; Min, Xuan-yu; Zhou, Qi-fu; Zhang, Hai-qian

2016-01-01

The potential mechanisms underlying the increase in serum iron concentration in gamma-irradiated mice were studied. The gamma irradiation dose used was 4 Gy, and cobalt-60 ( 60 Co) source was used for the irradiation. The dose rate was 0.25 Gy/min. In the serum of irradiated mice, the concentration of ferrous ions decreased, whereas the serum iron concentration increased. The concentration of ferrous ions in irradiated mice returned to normal at 21 day post-exposure. The concentration of reactive oxygen species in irradiated mice increased immediately following irradiation but returned to normal at 7 day post-exposure. Serum iron concentration in gamma-irradiated mice that were pretreated with reduced glutathione was significant lower (p < 0.01) than that in mice exposed to gamma radiation only. However, the serum iron concentration was still higher than that in normal mice (p < 0.01). This change was biphasic, characterized by a maximal decrease phase occurring immediately after gamma irradiation (relative to the irradiated mice) and a recovery plateau observed during the 7th and 21st day post-irradiation, but serum iron recovery was still less than that in the gamma-irradiated mice (4 Gy). In gamma-irradiated mice, ceruloplasmin activity increased and serum copper concentration decreased immediately after irradiation, and both of them were constant during the 7th and 21st day post-irradiation. It was concluded that ferrous ions in irradiated mice were oxidized to ferric ions by ionizing radiation. Free radicals induced by gamma radiation and ceruloplasmin mutually participated in this oxidation process. The ferroxidase effect of ceruloplasmin was achieved by transfer of electrons from ferrous ions to cupric ions. (orig.)

Increased numbers of spleen colony forming units in B cell deficient CBA/N mice

International Nuclear Information System (INIS)

Wiktor-Jedrzejczak, W.; Krupienicz, A.; Scher, I.

1986-01-01

The formation of exogenous and endogenous spleen colonies was studied in immune-defective mice expressing the CBA/N X-linked xid gene. Bone marrow and spleen cells of immune deficient mice formed increased numbers of eight-day exogenous spleen colonies when transferred to either normal or B cell deficient lethally irradiated recipients. Moreover, defective mice showed increased formation of five-day endogenous spleen colonies (derived from transient endogenous colony forming units; T-CFU) and of ten-day endogenous spleen colonies (derived from CFU-S). Among the possible mechanisms responsible for the observed effects, the most probable appears the one in which decreased numbers of B cell precursors stimulate stem cell pools through a feedback mechanism. (orig.) [de

Acute skin reaction after fractionated irradiation

International Nuclear Information System (INIS)

Kozubek, S.

1983-01-01

Experimental data on acute mouse and pig skin reaction after fractionated γ or X irradiation have been analysed in terms of a new cell tissue kinetic model. The exponential-quadratic and generalized Huggett formulae have been used for cell lethality description. Fairly better results could be demonstrated with generalized Huggett formula. The speed of repopulation has been determined for fractionated regimes as well as for some irregular schedules. The repopulation is slower in the case of fractionated treatment. On considering the normal cell loss factor in the tissue, minimum cell cycle time has been calculated. Its value differs for various strains (Tsub(d)=28.8 hours for SAS/TO mice and Tsub(d) < or approximately 17 hours for WHT/Ht mice) and does not differ for plucked skin. The repopulation has been shown to follow exponential dependence after some latent period. Other factors influencing the effectiveness of radiation treatment (the length of the latent period or the changes of the survival curve during fractionated irradiation) have been considered, too

Effect of dietary poly unsaturated fatty acids on total brain lipid concentration and anxiety levels of electron beam irradiated mice

International Nuclear Information System (INIS)

Suchetha Kumari; Bekal, Mahesh

2013-01-01

The whole brain irradiation causes injury to the nervous system at various levels. Omega-3 poly unsaturated fatty acids are very much essential for the growth and development of nervous system. Dietary supplementation of these nutrients will promote the development of injured neuronal cells. Therefore this study was undertaken to establish the role of Omega-3 poly unsaturated fatty acids on total brain lipid concentration, lipid peroxidation and anxiety levels in the irradiated mice. The effect of Electron Beam Radiation (EBR) on total brain lipid concentration, lipid peroxidation and anxiety level were investigated in male Swiss albino mice. The study groups were subjected to a sub-lethal dose of EBR and also the flax seed extract and fish oil were given orally to the irradiated mice. Irradiated groups show significant elevation in anxiety levels when compared to control group, indicating the acute radiation effects on the central nervous system. But the oral supplementation of dietary PUFA source decrees the anxiety level in the irradiated group. The analysis of lipid peroxidation showed a significant level of changes when compared between control and radiation groups. Dietary PUFA supplementation showed a significant level of decrease in the lipid peroxidation in the irradiated groups. The observation of total lipids in brain shows decrease in concentration in the irradiated groups, the differences in the variables follow the similar patterns as of that the MDA levels. This study suggests that the dietary intake of PUFAs may help in prevention and recovery of the oxidative stress caused by radiation. (author)

Radiotoxicity of α-emitter 211At for testes and its LD50 in mice

International Nuclear Information System (INIS)

Lin Ning; Jin Jiannan; Xia Qingjie; Zhang Shuyuan

1998-01-01

The radiotoxicity of α-emitter 211 At for testes in NIH strain mice was investigated by a singular i.p. injection with 5.55 x 10 5 Bq of Na 211 At, and the histopathological change of testicular cells was observed. Testes mass decreased rapidly at 6∼30 days post-injection. Histopathological observation revealed that some cells of interstitial tissue are irradiated to death at 6 days, the seminiferous tubules become empty at 30 days post-injection, and there is no spermatogenesis any more at this time. Additionally, the lethal dose (LD 50 ) of 211 At in the mice was investigated also by i.p injection and a LD 50 /7 of 8.14 x 10 4 Bq/g was measured

Chromosome condensation may enhance X-ray-related cell lethality in a temperature-sensitive mutant (tsBN2) of baby hamster kidney cells (BHK21)

International Nuclear Information System (INIS)

Sasaki, H.; Nishimoto, T.

1987-01-01

In the tsBN2 cell line, which has a temperature-sensitive defect in the regulatory mechanism for chromosome condensation, the lethal effect of X rays was enhanced by incubating the cells at a nonpermissive temperature (40 degrees C) following X irradiation. This enhancement was suppressed in the presence of cycloheximide, which inhibits induction of premature chromosome condensation. The findings obtained in the case of delayed incubation at 40 degrees C and in synchronized cells indicate that X-ray-related potentially lethal damage, which can be expressed by chromosome condensation, is produced in the cells at any stage of the cell cycle, but it is repairable for all cells except those at around the late G2-M phase, where chromosome condensation occurs at a permissive temperature (33.5 degrees C). These observations suggest that the high sensitivity of late G2-M cells to X rays is caused by the events associated with chromosome condensation

Late vascular effects in irradiated mice brain. In relation to experimental radionecrosis

Energy Technology Data Exchange (ETDEWEB)

Yoshii, Y; Maki, Y [Tsukuba Univ., Sakura, Ibaraki (Japan); Phillips, T L

1982-03-01

The whole brains of mice were irradiated with 250 kVp X-ray at 120 rad min/sup -1/ (1.6 mm Cu HVL, TSD 50 cm) and a histological study was done. The dose range of X-irradiation was from 1300 to 2500 rads. i.e., 1300, 1500, 1750, 2000, and 2500 rads. In the microscopic examination, the mice were killed at the regular postirradiation intervals of between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. A histological examination was performed by a morphometric estimation of vascular lesion in which the degree of the damage to the arterial system was scored through whole serial brain sections. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectatic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large artery were observed. Incidence of the fibrinoid necrosis increased dose dependently between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 - 87 weeks and can be used to quantify the vessel injury and a fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis.

Protective effect of WR-2823 in irradiated mice

International Nuclear Information System (INIS)

Milovanovicj, A.; Tanasijevicj, D.; Cvetkovicj, M.; Cjosicj, M.; Chizmicj, Z.

1987-01-01

A chemical compound named WR-2823 has been synthetised. The acute toxicity after IP application has been investigated and LD 50 estimated. The protective ability of the radioprotector has been investigated in mice with gamma rays of 60 Co, or at the origin of 252 Cf. High protective potency in mice, treated with lethal doses of gamma rays and neutrons have been estimated. (author) 8 refs.; 1 tab

Experimental prophylaxis and therapy of radiation damage by newly synthesized S-heteryl mercaptoalkyl N-aryl hydrazidimides

Energy Technology Data Exchange (ETDEWEB)

Pantev, T P

1975-01-01

The synthesis is described of representatives of a new class of potential antiradiation agents, the S-heteryl mercaptoalkyl N-aryl hydrazidimices (MHA), obtained by molecular combination of three basic groups of radioprotectors. Toxicity characteristics (LD/sub 100/, LD/sub 50/, and maximum tolerable doses) indicated the compounds tested to be no more toxic for mide and rats than most of the established radioprotective agents. Under acute X-irradiation conditions with minimum absolutely lethal doses, 6 out of the 14 compounds tested showed clear-cut protective properties in mice. These 6 compounds also raised by 20 to 50% the survival of lethally irradiated rats. The most effective preparation was Y-64 (S-2-benzimidazolyl mercaptopropio N-p-tolyl hydrazidimide). This compound is observed to protect hematopoietic tissue in mice (Dose Reduction Factor of 1.29) and rats (Dose Reduction Factor of 1.52) given X-ray doses in the range of 400 to 900 R. With acute gamma irradiation, Y-64, as well as cysteamine, ensured survival of a larger amount of hematopoietic stem cells in bone marrow (using exogenous spleen colony techniques) and a more rapid recovery rate of the stem cell pool. With fractionated X-rays (5 x 100 R daily), Y-64 failed to increase survival, showing, nevertheless, a favorable effect on hematopoietic indices. When administered postradiation, Y-64 failed to influence the course of acute radiation disease in lethally irradiated mice; but, reducing hematopoietic damage, it raised by 40% the survival of lethally irradiated rats. No effect was observed with Y-64 post treatment following either fractionated irradiation (15 x 100 R daily) given to rats or prolonged gamma irradiation (0.28 R/min) to mice. The studies shed light on the mechanism of action of MHA.

Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation

International Nuclear Information System (INIS)

MacVittie, T.J.; Monroy, R.L.; Patchen, M.L.; Souza, L.M.

1990-01-01

Recombinant human G-CSF (rhG-CSF) was studied for its ability to modulate haemopoiesis in normal dogs as well as to decrease therapeutically the severity and duration of neutropenia in sublethally and lethally irradiated dogs. Data indicate that in the lethally irradiated dog, effective cytokine therapy with rhG-CSF will increase survival through the induction of earlier recovery of neutrophils and platelets. (author)

The electrocorticograms of the aged mouse x-irradiated at juvenile or young adult

International Nuclear Information System (INIS)

Minamisawa, Takeru; Sasaki, Shunsaku.

1984-01-01

The electrocorticograms (ECoGs) of the (C57BL/6 x C3H)F 1 mice irradiated at juvenile or young adult were studied when they attained the age of 24-26 months. One group of mice was irradiated 35 days post partum (35-DPP) and another 105 days (105-DPP). All the animals were irradiated with 300 R of X-rays to whole body. The ECoGs were recorded from the freely moving animals with the permanently implanted electrodes fixed over the visual cortical surface. The resulted ECoGs were divided into 3 patterns: wakefulness (W), slow wave sleep (SWS), and paradoxical sleep (PS). Six parameters of the 3 patterns were compared among the 2 irradiated groups and the non-irradiated control group. The mean SWS- and PS-cycle times, and mean SWS length were significantly longer in the 35-DPP group than in the control group. Changes in the ECoGs were less profound in the 105-DPP group than those in the 35-DPP group: only a significant change due to irradiation at 105-DPP was a decrease in the ratio of the total PS time to the total sleep time (TST = total SWS time + total PS time). There was no difference in the body weight and brain weight among the 2 irradiated groups and the control group. (author)

Combined effect of x irradiation and cell-mediated immune reaction

International Nuclear Information System (INIS)

Song, C.W.; Guertin, D.P.

1978-01-01

The combined effect of radiation and cell-mediated immune reaction on tumor cells was investigated in vitro. Mastocytoma P815-X2 cells of DBA mice either were irradiated first and subjected to immune lysis by immune splenic lymphocytes of C57Bl mice, or the tumor cells were subjected to immune reaction first and then irradiated. Cell survival was quantitated by colony formation in soft agar medium. It was observed that cellular immune damage to tumor cells did not influence the response of tumor cells to subsequent radiation. Irradiation of tumor cells first, followed by subjection of the cells to cellular immune reaction, slightly enhanced the death of the tumor cells. It appears that this enhanced death might have resulted from a relative increase in the ratio of the number of cytotoxic immune cells to the number of target tumor cells in the incubation mixture as a consequence of the decrease in the number of viable tumor cells by radiation

Residual haematopoietic damage in adult and 8 day-old mice exposed to 7 Gy of x-rays

International Nuclear Information System (INIS)

Grande, T.; Bueren, J.A.; Gaitan, S.; Tejero, C.

1993-01-01

The authors' experiments have focused on the analysis of residual haematopoietic damage in 8-day-old and 12-week-old mice X-irradiated with a single dose of 7 Gy. In the case of adult mice, analysis of femoral and splenic CFU-S, CFU-GM and BFU-E showed a persistent depletion of these haematopoietic progenitor cells after irradiation. In contrast, in 1-week-old irradiated mice, a progressive recovery of the femoral haematopoietic progenitors was observed, achieving essentially normal values 1 year after irradiation. The spleens of these mice, however, contained significantly less haematopoietic progenitors than the control group, mainly as a consequence of the size reduction of this organ. In the peripheral blood, normal cellularity values were observed in most cases, although in the adult group a decline in numbers or circulating cells was noted after the first year following irradiation. (author)

Formation and Expansion of Leukemia-Specific Chromosome Aberrations in Hematopoietic Cells of X-ray Irradiated Mice

International Nuclear Information System (INIS)

Ban, N.; Kai, M.; Kusama, T.

2004-01-01

C3H/He mice develop acute myeloid leukemia (AML) after whole-body irradiation, and typical chromosome 2 deletions are found in the leukemia cells. To investigate a process of the formation and the expansion of the AML-specific deletions, we have examined its frequency in primitive hematopoietic cells that could be the target of the leukemogenesis. Male C3H/He mice were exposed to 3Gy x-rays and sacrificed after certain periods of time. Bone marrow cells were collected from the femora and a single-cell suspension from each animal was divided into two parts. One part of the cell suspension was cultured in methylcellulose medium and metaphase spreads were prepared from each growing colony. The other part was sorted to obtain Lin+ and Lin Scal cells and those cells were scored with FISH for the AML-specific deletions. Karyotyping of the cultured cells detected signs of the delayed chromosomal instability, but an aberration involving chromosome 2 has not been found so far. FISH to the sorted cells, however, revealed the ANL-specific deletions could be produced in the primitive hematopoietic cells as an early event of radiation exposure. (Author) 16 refs

Derangement of cellular plasma membranes due to non-lethal radiation doses

International Nuclear Information System (INIS)

Koeteles, G.J.; Kubasova, T.; Somosy, Z.; Horvath, L.

1983-01-01

Earlier observations in the laboratory on fibroblasts and various blood cells of animal and human origins pointed to alteration of concanavalin A binding sites of plasma membranes as well as to concomitant morphological changes and scanning electron microscopic appearance of cell surfaces following sub-lethal doses of X-, fission neutron and beta irradiations. The effects appeared early and existed temporarily; their intensities and the restitution of membrane function depended on radiation doses, types and conditions of cells. In the present paper further aspects of structural and functional derangements of plasma membranes are introduced which were provoked by X- and tritium beta irradiation in the dose range up to 2.5 Gy and in the concentration range from 3.7 kBq/mL, respectively. The state of membrane structure was followed by bindings of various ligands of different receptor requirements, concanavalin A, cationized ferritin and polio virus. In the case of X-irradiation the binding conditions suggest the shift of overall negative surface charges to less negative ones. It was also found that radiation-induced phenomena appear on the cell surface unevenly. Long- and short-term treatments of cells with 3 H-thymidine and 3 H-water also perturb the plasma membrane; beta irradiation affects it directly. Membrane structure and function are suggested to offer good biological models to study correlation of energy deposition and biological effects, both restricted to domains of nanometre range. The data give evidence for radiation-induced membrane alterations in the sub-lethal or non-lethal ranges which might have consequences in the development of stochastic and non-stochastic effects. (author)

Mutagenic effects of irradiated glucose in Drosophila melanogaster

International Nuclear Information System (INIS)

Varma, M.B.; Rao, K.P.; Nandan, S.D.; Rao, M.S.

1982-01-01

The mutagenic effects of irradiated glucose were studied using the sex-linked recessive lethal test in Drosophila melanogaster. Oregon K males of D. melanogaster reared on a medium containing 20 or 40% glucose irradiated with a dose of 0.02, 0.10, 0.20, 2 or 5 Mrad #betta#-rays were scored for the induction of sex-linked recessive lethals. The results showed no significant increase in the frequency of X-lethals in Drosophila at any of the dose levels. (author)

Induction of interferon by levamisole in mice. [X radiation

Energy Technology Data Exchange (ETDEWEB)

Matsubara, S.; Suzuki, F.; Ishida, N.

1979-03-01

Viral inhibitor(s) with the properties of interferon (IF) was found in the sera of DDI mice injected intraperitoneally with 5 to 10 mg/kg of levamisole. A significant level of IF activity appeared by 20 hr and reached a peak by 24 hr after the injection. The induction was abrogated when the mice were pretreated with either whole-body x irradiation of more than 500 R or 2.5 mg of hydrocortisone acetate but was not affected by macrophage-specific depressors such as carrageenan and trypan blue. Also, no induction was detected in thymus-defective nude mice. These results suggest that thymus-derived lymphocytes in the mouse may be required for IF induction by levamisole.

Effect of tocopherol-monoglucoside (TMG), a water-soluble glycosylated derivate of vitamin E, on hematopoietic recovery in irradiated mice.

Science.gov (United States)

Cherdyntseva, Nadezda; Shishkina, Anna; Butorin, Ivan; Murase, Hironobu; Gervas, Polina; Kagiya, Tsutomu V

2005-03-01

A preparation of alpha-tocopherol monoglucoside (TMG) administered i.p. at a dose of 600 mg/kg immediately after whole body gamma irradiation was examined for its radioprotective efficacy towards bone marrow and peripheral blood nucleated cells. When mice received X-rays at a dose of 5,6 Gy, a marked decrease in bone marrow karyocytes and a reduction of peripheral leukocytes within the early post-irradiated period were observed. However these changes were attenuated in TMG-treated mice. Significant protection of blood lymphocytes was found for the TMG group of mice. The return to normal value of the reduced blood leukocyte count starting from the 8th day was more rapid in TMG-treated mice than in untreated irradiated mice. TMG administration was found to enhance hematopoietic recovery, as measured by the exceeded nucleated bone marrow cell count due to elevated amount of both lymphoid and granulocytic elements in the TMG-group, in comparison with that of both control irradiated and non-irradiated animals. These findings indicate that the radioprotective effect of TMG is apparently realized through its influence on hematopoietic system.

Regulation of immune responses in SJL and F1 hybrid mice by gamma-irradiated syngeneic lymphoma cells

International Nuclear Information System (INIS)

Katz, I.R.; Nagase, F.; Bell, M.K.; Ponzio, N.M.; Thorbecke, G.J.

1984-01-01

Syngeneic mixed lymphocyte-stimulating la+ lymphomas of SJL mice [reticulum cell sarcoma(s) (RCS)] were found to modulate immune responses in vivo. Simultaneous injection of 2 X 10(7) gamma-irradiated or glutaraldehyde-fixed RCS cells with the antigen sheep red blood cells (SRBC) or 2,4,6-trinitrophenol (TNP)-Ficoll markedly suppressed the subsequent plaque-forming cell response in the spleen. The suppression of the anti-SRBC response was prevented by pretreatment of the mice with cyclophosphamide, whereas the suppression of the anti-TNP-Ficoll response was not affected. RCS injection induced high interferon serum titers within 24 hours after injection, which were not prevented by pretreatment with cyclophosphamide. Injection of gamma-irradiated RCS cells (gamma-RCS) or RCS cell extract 2 days prior to antigen enhanced the anti-SRBC but markedly suppressed the anti- TNP-Ficoll response. Injection of RCS both on day -2 and day 0 enhanced the anti-SRBC response. SJL mice 8-9 months of age showed much less or no suppression when gamma-RCS cells were injected on day 0. Certain F1 hybrids of SJL also showed the gamma-RCS-induced suppression of the anti-SRBC response. Suppression was seen in SJL X BALB.B but not in SJL X BALB/c mice and in SJL X A.TH but not in SJL X A.TL mice, suggesting an I-region effect. F1 hybrids of SJL by B10 background mice showed no significant suppression. Enhancement of the anti-SRBC response by prior injection of gamma-RCS was seen in all F1 hybrid mice examined

Effects of sub-lethal dose of γ-irradiation on lysosomal enzymes in tissue of pigeon

International Nuclear Information System (INIS)

Shah, V.C.; Gadhia, P.K.

1979-01-01

Effects of total body γ-irradiation with sub-lethal dose (300 rad) on three lysosomal enzymes namely acid phosphatase, ribonuclease-II and deoxyribonuclease-II have been studied in pigeons. Liver, kidney and spleen were the tissues studied at different intervals like 1-h, 24-h, 48-h, and 72-h of irradiation. The specific activities ('crude' fraction) of acid phosphatase and ribonuclease-II increased significantly in spleen and liver at 48-h of irradiation. The activity of deoxyribonuclease-II in liver and spleen was increased only at 72-h post-irradiation. On the other hand, the total activities of three lysosomal enzymes did not show remarkable change throughout 72-h of irradiation. (author)

Human cathepsin L rescues the neurodegeneration and lethality incathepsin B/L double deficient mice

Energy Technology Data Exchange (ETDEWEB)

Sevenich, Lisa; Pennacchio, Len A.; Peters, Christoph; Reinheckel, Thomas

2006-01-09

Cathepsin B (CTSB) and cathepsin L (CTSL) are two widelyexpressed cysteine proteases thought to predominantly reside withinlysosomes. Functional analysis of CTSL in humans is complicated by theexistence of two CTSL-like homologues (CTSL and CTSL2), in contrast tomice which contain only one CTSL enzyme. Thus transgenic expression ofhuman CTSL in CTSL deficient mice provides an opportunity to study the invivo functions of this human protease without interference by its highlyrelated homologue. While mice with single gene deficiencies for murineCTSB or CTSL survive without apparent neuromuscular impairment, murineCTSB/CTSL double deficient mice display degeneration of cerebellarPurkinje cells and neurons of the cerebral cortex, resulting in severehypotrophy, motility defects, and lethality during their third to fourthweek of life. Here we show that expression of human CTSL through agenomic transgene results in widespread expression of human CTSL in themouse which is capable of rescuing the lethality found in CTSB/CTSLdouble-deficient animals. Human CTSL is expressed in the brain of thesecompound mutants predominantly in neurons of the cerebral cortex and inPurkinje cells of the cerebellum, where it appears to prevent neuronalcell death.

Leukemic transformation of donor spleen cells following their transplantation into supralethally irradiated mice with pre-existing viral leukemia. [X Radiation

Energy Technology Data Exchange (ETDEWEB)

Kuhnert, P M; OKunewick, J P; Erhard, P

1974-01-01

Fialkow et al. previously reported leukemia induction in donor-type cells after treating patients for acute lymphoblastic leukemia with total-body irradiation and hematopoietic cell transplantation. Utilizing a murine model and paralleling their treatment protocol, we have documented that induction of leukemia can occur in normal donor cells transplanted into Rauscher viral leukemic mice at 0, 1 and 2 days after irradiation. The induction of leukemia in the grafted cells was verified by: the occurrence of splenomegaly; and secondary spleen cell transplants, whereby the secondary donors were transplanted mice still alive at 30 days and the secondary recipients were normal unirradiated mice. The spleen weights of the grafted leukemic mice were found to be significantly greater than those of the controls and all secondary recipients that received spleen cells from the primary grafted leukemic mice also died of leukemia. Verification that the regenerating hematopoietic tissue was from donor (males) and not host source (females) was accomplished by spleen chromosome preparations taken from randomly selected mice at 14 and at 30 days after cell transplantation. In these preparations, the Y chromosome was clearly distinguishable on the basis of size, shape, and differential staining. The data indicate that induction of leukemia after whole-body irradiation and hematopoietic cell transplantation can occur in immunologically matched donor cells when a viral agent is present and that the incidence of this induction is not affected by a time delay between irradiation and transplant.

Induction of external abnormalities in offspring of male mice irradiated with 252Cf neutron

International Nuclear Information System (INIS)

Kurishita, Akihiro; Ono, Tetsuya; Mori, Yuriko; Okada, Shigefumi; Sawada, Syozo

1992-01-01

To assess the genetic effects of fission neutron, the induction of external malformations was studied in F 1 fetuses after F 0 male mice were irradiated. Male mice of the ICR:MCH strain were irradiated with 252 Cf neutron at doses of 0.238, 0.475, 0.95 and 1.9 Gy. They were mated with non-irradiated female mice at 71-120 days after irradiation. Pregnant females were autopsied on day 18 of gestation and their fetuses were examined for deaths and external abnormalities. No increases of pre- and post-implantation losses were noted at any dose. External abnormalities were observed at rates of 1.40% in the 0.238 Gy, 2.23% in the 0.475 Gy, 3.36% in the 0.95 and 3.26% in the 1.9 Gy groups; the rate in the control group was 1.65%. The dose-response curve was linear up to 0.95 Gy, and then flattened out; the induction rate of external abnormalities was 2.7x10 -4 /gamete/cGy based on the linear regression. These results indicated that fission neutron effectively induces external abnormalities in F 1 fetuses after spermatogonial irradiation. (author). 29 refs.; 1 fig.; 2 tabs

Effects of genistein following fractionated lung irradiation in mice

International Nuclear Information System (INIS)

Para, Andrea E.; Bezjak, Andrea; Yeung, Ivan W.T.; Van Dyk, Jake; Hill, Richard P.

2009-01-01

Background and purpose: This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response. Material and methods: C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet (∼10 mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of small lung nodules (KHT fibrosarcoma). Results: Genistein caused about a 50% reduction in the MN damage observed during the fractionated radiation treatment and this damage continued to decrease at later times to background levels by 16 weeks. In mice not receiving Genistein MN levels remained well above background out to 28 weeks after irradiation. Genistein reduced macrophage accumulation by 22% and reduced collagen deposition by 28%. There was minimal protection against increases in breathing rate or severe morbidity during pneumonitis. No tumor protection by genistein treatment was observed. Conclusions: Genistein at the dose levels used in this study partially reduced the extent of fibrosis developing in mouse lung caused by irradiation but gave minimal protection against pneumonitis. There was no evidence that genistein caused protection of small tumors growing in the lung.

Clostridium sordellii lethal toxin kills mice by inducing a major increase in lung vascular permeability.

Science.gov (United States)

Geny, Blandine; Khun, Huot; Fitting, Catherine; Zarantonelli, Leticia; Mazuet, Christelle; Cayet, Nadège; Szatanik, Marek; Prevost, Marie-Christine; Cavaillon, Jean-Marc; Huerre, Michel; Popoff, Michel R

2007-03-01

When intraperitoneally injected into Swiss mice, Clostridium sordellii lethal toxin reproduces the fatal toxic shock syndrome observed in humans and animals after natural infection. This animal model was used to study the mechanism of lethal toxin-induced death. Histopathological and biochemical analyses identified lung and heart as preferential organs targeted by lethal toxin. Massive extravasation of blood fluid in the thoracic cage, resulting from an increase in lung vascular permeability, generated profound modifications such as animal dehydration, increase in hematocrit, hypoxia, and finally, cardiorespiratory failure. Vascular permeability increase induced by lethal toxin resulted from modifications of lung endothelial cells as evidenced by electron microscopy. Immunohistochemical analysis demonstrated that VE-cadherin, a protein participating in intercellular adherens junctions, was redistributed from membrane to cytosol in lung endothelial cells. No major sign of lethal toxin-induced inflammation was observed that could participate in the toxic shock syndrome. The main effect of the lethal toxin is the glucosylation-dependent inactivation of small GTPases, in particular Rac, which is involved in actin polymerization occurring in vivo in lungs leading to E-cadherin junction destabilization. We conclude that the cells most susceptible to lethal toxin are lung vascular endothelial cells, the adherens junctions of which were altered after intoxication.

Intermittent feeding as a factor enhancing hemopoietic stem cell proliferation and spleen colony formation in irradiated mice

International Nuclear Information System (INIS)

Kozubik, A.; Pospisil, M.

1985-01-01

The influence of metabolic stimulation induced by a 3 weeks' adaption of the animals to intermittent food intake on hemopoietic stem cells was investigated in mice. The methods used included transplantation of bone marrow to lethally irradiated recipients, assay of CFUs number, seeding efficiency, and incorporation of 125 iodode oxyuridine into the DNA of spleen cells. A stimulatory effect of the metabolically influenced hemopoietic environment on the proliferative activity in stem cell compartments and on the recovery of hemopoietic organs was demonstrated. These stimulatory effects were most marked when the bone marrow of metabolically influenced donors was transplanted to similarly influenced recipients. (orig.)

Cytogenetic analysis of X-ray induced chromosome aberrations in spontaneous leukaemic AKR mice

International Nuclear Information System (INIS)

Szollar, J.

1975-01-01

The increased frequency of numerical and structural chromosomal aberrations in spontaneously leukaemic AKR mice, compared with the values of healthy control CBA/H-T 6 T 6 mice, induced by X-irradiation, might be connected with the predisposition to malignant growth, probably indirectly helping the virus activation, or acting together with the immune deficiency, by creating a weaker system that is more sensitive to carcinogenic agents

Factors influencing circadian rhythms in acetaminophen lethality.

Science.gov (United States)

Schnell, R C; Bozigian, H P; Davies, M H; Merrick, B A; Park, K S; McMillan, D A

1984-01-01

Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

Preventive effect of ganoderma lucidum (Reishi) on the suppression of hematopoietic system by X-ray irradiation

International Nuclear Information System (INIS)

Itoh, Hiroko; Nakata, Fukuyoshi; Sasaki, Hiroyuki; Ito, Hitoshi

2013-01-01

Reishi has been used for a roborant or the elixir of life from ancient times. In the present study, the preventive effects of Reishi on hematopoietic suppression from X-ray irradiation in mice were investigated. 5.0 Gy-irradiated mice induced the decrease of red blood cell, platelet, white blood cell, granulocytes, the index of spleen and thymus, and the number of spleen cells. Oral administration of Reishi tended to decrease these damage on hematopoiesis, and reticuloendothelial system. Reishi enhanced the degree of spleen cells-mediated sheep red blood cells (SRBC) hemolysis (quantitative hemolysis of SRBC). Reishi augmented the level of erythroid burst-forming cell (BFU-E), and accelerated the recovery of the number of BFU-E in X-irradiated mice, although Reishi did not influence red blood cell counts and colony-forming unit-erythropoetin dependent (CFU-E) number. A significant elevation in the CFU-GM (granulocytes-macrophages) level was observed. Histological examinations revealed that Reishi accerelated the hematopoietic recovery and decrease on damage of spleen and thymus. (author)

Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice.

Science.gov (United States)

Brütsch, Simone Hanna; Wang, Chi Chiu; Li, Lu; Stender, Hannelore; Neziroglu, Nilgün; Richter, Constanze; Kuhn, Hartmut; Borchert, Astrid

2015-02-01

Glutathione peroxidases (Gpx) and lipoxygenases (Alox) are functional counterplayers in the metabolism of hydroperoxy lipids that regulate cellular redox homeostasis. Gpx4 is a moonlighting protein that has been implicated not only as an enzyme in anti-oxidative defense, gene expression regulation, and programmed cell death, but also as a structural protein in spermatogenesis. Homozygous Gpx4 knock-out mice are not viable, but molecular reasons for intrauterine lethality are not completely understood. This study was aimed at investigating whether the lack of catalytic activity or the impaired function as structural protein is the dominant reason for embryonic lethality. We further explored whether the pro-oxidative enzyme mouse 12/15 lipoxygenase (Alox15) plays a major role in embryonic lethality of Gpx4-deficient mice. To achieve these goals, we first created knock-in mice, which express a catalytically inactive Gpx4 mutant (Sec46Ala). As homozygous Gpx4-knock-out mice Sec46Ala-Gpx4(+/+) knock-in animals are not viable but undergo intrauterine resorption between embryonic day 6 and 7 (E6-7). In contrast, heterozygous knock-in mice (Sec46Ala-Gpx4(-/+)) are viable, fertile and do not show major phenotypic alterations. Interestingly, homozygous Alox15 deficiency did not rescue the U46A-Gpx4(+/+) mice from embryonic lethality. In fact, when heterozygous U46A-Gpx4(-/+) mice were stepwise crossed into an Alox15-deficent background, no viable U46A-Gpx4(+/+)+Alox15(-/-) individuals were obtained. However, we were able to identify U46A-Gpx4(+/+)+Alox15(-/-) embryos in the state of resorption around E7. These data suggest that the lack of catalytic activity is the major reason for the embryonic lethality of Gpx4(-/-) mice and that systemic inactivation of the Alox15 gene does not rescue homozygous knock-in mice expressing catalytically silent Gpx4.

Cell kinetics of Ehrlich ascites carcinoma transplanted in mice with different degrees of tumor resistance

International Nuclear Information System (INIS)

Brandt, K.L.B.

1974-01-01

Cell proliferation kinetics of Ehrlich ascites carcinoma grown in two strains of mice with different degrees of resistance to this tumor were examined. In the first portion of the study, growth of Ehrlich ascites carcinoma in nonresistant Swiss (Iowa) and slightly resistant CF1 mice was examined by measuring animal weight gain and host survival time after intraperitoneal injection of tumor cells. Since it appeared that CF1 mice were inherently more resistant than Swiss mice to the Ehrlich carcinoma, the second part of this investigation involved attempts to immunize CF1 mice against the tumor. Subcutaneous injections of Ehrlich cells previously exposed in vitro to 5000 R of 250 kVp x rays were utilized. One immunizing inoculation of lethally irradiated tumor cells afforded protection against an intraperitoneal challenge of 40 thousand Ehrlich cells. By varying the number and timing of immunizing inoculations it was possible to induce different degrees of tumor resistance in these mice. The most effective immunizing procedure utilized multiple inoculations of lethally irradiated tumor cells (LITC), followed by challenges with viable tumor cells (less than 1 million) which were rejected. These mice could then resist challenge inocula of 4 million viable tumor cells. In a few animals the immunizing procedures were ineffective; these animals, when challenged, developed even larger tumors than control mice. Tumor cell proliferation kinetics in these animals as well as in mice that were rejecting the tumor were examined in the third phase of the project. A shortening of the cell cycle was observed in almost all LITC-treated mice, whether tumor growth was eventually inhibited or stimulated. Decreased duration of the DNA-synthesis phase (S) of the tumor cell cycle was also a consistent finding. The role of the immune response in stimulating mitosis as well as in killing foreign cells was discussed. (U.S.)

Protection effect of ginkgo albumin extract on γ-ray irradiated mice

International Nuclear Information System (INIS)

Deng Qianchun; Duan Huike; Wang Lan; Xie Bijun; Chen Chunyan

2005-01-01

Water soluble ginkgo albumin extract (GAE), which was extracted for the first time from seeds of Ginkgo bilbo L in our laboratory has good antioxidant and anti-aging activity. In this paper, protective effect of GAE on γ-rays irradiated mice was studied. The results showed that the mice irradiated to 8.5 Gy were zero, whereas survival rate of the high dosage GAE group was 20 percent. Blood picture of the 8.5 Gy irradiated mice suffered damages of different degrees, while blood picture index of the GAE group decreased slower and recovered faster significantly than the irradiation control group. GAE and Vitamin C could significantly enhance serum SOD activity in serum and increase DNA content in bone marrow cells, and also promote recovery of damaged immunology function of the irradiated mice. These suggest that GAE may protect mice from the radiation damages by enhancement of antioxidant activity, hemopoiesis function and immunologic function of mice. (authors)

Cyclophosphamide/x-ray: combined mode preparation for transplantation therapy

International Nuclear Information System (INIS)

Meredith, R.; Okunewick, J.; Shadduck, R.; Raikow, R.; Brozovich, B.; Seeman, P.

1979-01-01

Use of total body irradiation (TBI) and/or chemotherapy as a preparation for marrow transplantation in the treatment of leukemia has been only moderately successful in the clinic. Although cyclophosphamide (CY) has shown promise as a marrow ablative agent, leukemia relapses are often found, and optimal therapeutic protocols have not been established. Our transplantation therapy studies of murine leukemia with parental recipients and hybrid donors provide an excellent model for research aimed at improved survival of human transplant patients. Utilizing a murine leukemia induced by a virus, various doses of CY in combination with sub-lethal irradiation were compared to determine the optimal pretreatment for transplantation therapy. Both normal and leukemic mice were engrafted with virus resistant, histocompatible marrow following these preparations, then monitored for survival and long term effects. Leukemic mice were also evaluated for pluripotent as well as myeloid committed stem cells as a measure of the effectiveness of the treatment in elimination of leukemic cells. Leukemic groups were also compared for the percentage and time of leukemia relapse. All CY/X-ray combinations were more effective in elimination of stem cell populations than supralethal TBI alone. However, the best survival was obtained with lethal TBI alone or low dose CY in combination with 550 R

Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

International Nuclear Information System (INIS)

Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

1988-01-01

The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage. (author)

Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

Energy Technology Data Exchange (ETDEWEB)

Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

1988-09-01

The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage.

OH radicals from the indirect actions of X-rays induce cell lethality and mediate the majority of the oxygen enhancement effect.

Science.gov (United States)

Hirayama, Ryoichi; Ito, Atsushi; Noguchi, Miho; Matsumoto, Yoshitaka; Uzawa, Akiko; Kobashi, Gen; Okayasu, Ryuichi; Furusawa, Yoshiya

2013-11-01

We examined OH radical-mediated indirect actions from X irradiation on cell killing in wild-type Chinese hamster ovary cell lines (CHO and AA8) under oxic and hypoxic conditions, and compared the contribution of direct and indirect actions under both conditions. The contribution of indirect action on cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide, which suppresses indirect action by quenching OH radicals without affecting the direct action of X rays on cell killing. The contributions of indirect action on cell killing of CHO cells were 76% and 50% under oxic and hypoxic conditions, respectively, and those for AA8 cells were 85% and 47%, respectively. Therefore, the indirect action on cell killing was enhanced by oxygen during X irradiation in both cell lines tested. Oxygen enhancement ratios (OERs) at the 10% survival level (D10 or LD90) for CHO and AA8 cells were 2.68 ± 0.15 and 2.76 ± 0.08, respectively. OERs were evaluated separately for indirect and direct actions, which gave the values of 3.75 and 2.01 for CHO, and 4.11 and 1.32 for AA8 cells, respectively. Thus the generally accepted OER value of ∼3 is best understood as the average of the OER values for both indirect and direct actions. These results imply that both indirect and direct actions on cell killing require oxygen for the majority of lethal DNA damage, however, oxygen plays a larger role in indirect than for direct effects. Conversely, the lethal damage induced by the direct action of X rays are less affected by oxygen concentration.

Effect of tocopherol-monoglucoside (TMG), a water-soluble glycosylated derivate of vitamin E, on hematopoietic recovery in irradiated mice

International Nuclear Information System (INIS)

Cherdyntseva, N.; Shishkina, A.; Butorin, I.; Gervas, P.

2005-01-01

A preparation of alpha-tocopherol monoglucoside (TMG) administered intraperitoneal (i.p.) at a dose of 600 mg/kg immediately after whole body gamma irradiation was examined for its radioprotective efficacy towards bone marrow and peripheral blood nucleated cells. When mice received X-rays at a dose of 5, 6 Gy, a marked decrease in bone marrow karyocytes and a reduction of peripheral leukocytes within the early post-irradiated period were observed. However these changes were attenuated in TMG-treated mice. Significant protection of blood lymphocytes was found for the TMG group of mice. The return to normal value of the reduced blood leukocyte count starting from the 8th day was more rapid in TMG-treated mice than in untreated irradiated mice. TMG administration was found to enhance hematopoietic recovery, as measured by the exceeded nucleated bone marrow cell count due to elevated amount of both lymphoid and granulocytic elements in the TMG-group, in comparison with that of both control irradiated and non-irradiated animals. These findings indicate that the radioprotective effect of TMG is apparently realized through its influence on hematopoietic system. (author)

Effects of treating Drosophila females with TEM on their mortality, and the yield of mutation recovered from x-irradiated sperm

International Nuclear Information System (INIS)

Mollet, P.; Swiss Federal Inst. of Technology, Zuerich

1977-01-01

Ring-X-bearing Drosophila males were irradiated with 0, 1000, 2000 or 3000 R of X-rays and mated to females that had been injected with saline or 10 -4 M TEM. The mortality and the fertility of the treated females were recorded. The rate of dominant lethals, of entire sex chromosome loss and partial loss of the Y chromosome, the sex ratio, and the rate of mosaics were determined on the progeny. TEM slightly increased the rate of mortality of the females. But it did not influence the yield of mutations recovered from the irradiated spermatozoa

Therapeutic effect of para aminobenzoic acid (PABA) on the rat cornea administered in different ways after x-irradiation

International Nuclear Information System (INIS)

Panova, I.G.; Mel'nikova, I.I.; Stroeva, O.G.

1997-01-01

Comparative analysis of cytological state of nuclear apparatus in the mice cornea basal layer is carried out by two various method of introducing the para-aminobenzoic acid (PABA) after x-ray irradiation: 1) subcutaneous injections and 2) application of the solution on the cornea. The fact that PABA produced medicinal effect on the cornea of the irradiated mice by subcutaneous injections, shows that this action proceeds on the whole-body level

Role of marrow architecture and stromal cells in the recovery process of aplastic marrow of lethally irradiated rats parabiosed with healthy litter mates

International Nuclear Information System (INIS)

Hayashi, K.; Kagawa, K.; Awai, M.; Irino, S.

1986-01-01

Bone marrow aplasia was induced in rats by whole body lethal irradiation (1,000 rads by x-ray), and rats died of irradiation injury within 7 days. Correlative studies at light (LM), transmission (TEM) and scanning electron microscopy (SEM) demonstrated swelling of endothelial and reticular cells and hemorrhage due to detachment of sinus endothelial cells on days 1 and 2. With time, structural recovery occurred without hemopoietic recovery. Reticular cells developed small intracytoplasmic lipid droplets on days 3 and 4. This resulted in fatty aplastic marrow within 7 days. On the other hand, in the marrow of irradiated rats parabiosed with healthy mates by aortic anastomosis, hemopoiesis was initiated by adhesion of nucleated blood cells to fine cytoplasmic pseudopods of fat-stored cells on days 1 and 2 after parabiosis. On days 3 to 5, reticular cells with large lipid droplets and fine pseudopods increased, then hemopoietic foci became clear and extensive. On day 8 after parabiosis, the aplastic bone marrow recovered completely both its structure and hemopoietic activity. Thus, hemopoietic recovery in lethally irradiated marrow begins with recovery of vascular endothelial cells, re-establishment of sinusoidal structure, and morphological and functional recoveries of reticular cells from fat-storage cells by releasing intracytoplasmic lipid droplets. Marrow stromal cells, namely reticular, fat-storage and fibroblastoid cells, share a common cellular origin, and regain their structure and function when fat-storage cells and fibroid cells are placed in contact with hemopoietic precursor cells

The early effects in the brain after irradiation with carbon ions using mice

International Nuclear Information System (INIS)

Takai, Nobuhiko; Nakamura, Saori; Ohba, Yoshihito; Uzawa, Akiko; Furusawa, Yoshiya; Koike, Sachiko; Matsumoto, Yoshitaka; Hirayama, Ryoichi

2011-01-01

This study investigated both early and late effects in the brain after irradiation with carbon ions using mice. The irradiation dose was set at level known to produce vascular change followed by necrosis, which appeared the late period after irradiation with 30 Gy. The whole of brain was irradiated, excluding eyes and brain stem. The mice irradiated with single dose of 30 Gy showed deficit in short-term working memory assessed at 36 hr after irradiation, whereas mice receiving carbon irradiation showed no deficit in long-term reference memory. At 16 weeks after irradiation, the irradiated mice showed marked learning impairment compared with age-matched controls and the irradiated mice showed substantial impairment of working memory. Histopathological observation revealed no abnormal finding in the irradiated brain at 36 hr after irradiation, although irradiated mice showed marked neuronal degeneration at the hippocampus within CA1 to CA3 layers at 16 weeks after irradiation. In the irradiated group, neuronal cells in the hippocampal CA1-3 areas were reduced by 30-49%. These results suggest that although irradiation-induced hippocampal degeneration is associated with learning disability, cognitive deficits may also be detected on the early stage, not associated with hippocampal degeneration. (author)