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Sample records for body irradiated mice

  1. Change in the mineralization of the healing bone callus after whole-body irradiation in mice

    International Nuclear Information System (INIS)

    The delayed consolidation of diaphysial long-bone fractures in mice subjected to whole-body X-irradiation is expressed biochemically by a faulty mineralization of the repair callus. This deficiency is proportional to the irradiation intensity and is not corrected by previous administration of cycteamine

  2. Increased sensitivity of C. parvum treated mice to ionizing whole body irradiation

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    Basic, I.; Withers, R.H.; Kastelan, A.; Milas, L.

    1977-04-13

    We have investigated whether C. parvum (CP)-induced stimulation of hematopoiesis affects the survival of mice exposed to the whole body irradiation (WBI). C3Hf/Bu mice treated with CP exhibit an increased hematopoietic colony forming activity in their spleens and blood, but not in their bone marrow, as determined by the exogenous spleen colony assay. Also, CP-treated C3Hf/Bu as well as CBA mice show an increase in their endogenous colonies. This increased hematopoietic activity caused by CP treatment did not protect mice from the consequences of the WBI ranging from 650 to 950 rads. In fact, more mice died if they had been treated with CP. A decrease in the number of erythrocytes was more pronouned in mice treated with CP and irradiation than in those given irradiation alone.

  3. Effect of whole body gamma irradiation on delayed hypersensitivity to dinitrofluorobenzene in CBA mice

    International Nuclear Information System (INIS)

    Effect of whole body γ-irradiation of CBA mice on the subsequent development of delayed hypersensitivity (DH) response to 2,4 dinitrofluorobenzene (DNFB) was studied. Mice were irradiated with 60Co-γrays 24 hr prior to the first epicutaneous sensitization with DNFB. Mice irradiated at doses up to 1.08 Gy showed unaltered DH response. Increasing doses resulted in progressive suppression of DH response and the D50 was 3.86 Gy. Marked reduction in the number of lymph node cells was observed in irradiated, sensitized as well as unsensitized mice. This could be due to interphase death of precursor cells (antigen-sensitive cells), resulting in lower number of effector lymphocytes for DH(Tsub(DH)). Furthermore, the maximum DH response in irradiated, sensitized mice was obtained later on in comparison with the controls. The effector lymphocytes from irradiated sensitized mice were, however, functionally unimpaired. It was observed that the radiation-induced suppression of DH to DNFB in these mice could be partly due to the damage to antigen sensitive cells and also to the cells other than effector lymphocytes which participated in the inflammatory reaction. (author)

  4. Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

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    Van der Meeren, A.; Lebaron-Jacobs, L. [Inst. de Protection et de Surete Nucleaire, Dept. de Protection de la sante de l' Homme et de Dosimetrie, Section Autonome de Radiobiologie Appliquee a la Medecine, IPSN, Fontenay-aux-Roses (France)

    2001-02-01

    The effects of an 8 Gy {gamma} total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

  5. Immunologic changes after loco-regional radiotherapy and fractionated total body irradiation (TBI) in mice

    International Nuclear Information System (INIS)

    The immunologic effects of fractionated irradiation to both hind limbs and the tail of adult mice were investigated. A dose of 34 Gy given in 17 fractions of 2 Gy, 1 fraction per day, 5 days per week, was delivered with a 60Co source. A significant decrease of the total splenocyte count and of the PHA(phytohemagglutinin)-induced proliferation of T cells was found immediately after irradiation. Both parameters normalized within 30 days after irradiation. Immediately after irradiation, the MLC (mixed lymphocyte culture) was supranormal, dropped to 45% 1 week later, and normalized within 1 month after radiotherapy. The NK (natural killer) activity was significantly decreased only the first week after loco-regional irradiation, while the LAK (lymphokine activated killer) activity was not altered at all. The percentage of goat-anti-mouse+ cells (mainly B lymphocytes) was not changed immediately after loco-regional irradiation, but rose to supranormal values (175% of control level) 3 months after irradiation. A persistent decrease of the percentage and the absolute numbers of the Lyt2+ cells (= CD8+ cells, suppressor/cytotoxic phenotype) was observed up to 3 months after irradiation, while the percentage of L3T4+ cells (= CD4+ cells, helper phenotype) remained normal for the total follow-up. No differences in allogeneic skin graft survival could be demonstrated between irradiated and control animals. The observed immunological effects could not be explained by the scatter irradiation to the whole body as total body irradiation (TBI) administered in a dose and dose rate similar to the scatter dose did not result in persistent immunologic changes. No dose-rate effect could be demonstrated in a low dose fractionated total body irradiation schedule. A total body irradiation similar to the scatter dose in humans did not result in significant immunologic changes

  6. Sesamol attenuates cytogenetic damages in bone marrow cells of whole body gamma irradiated mice

    International Nuclear Information System (INIS)

    Whole body radiation exposure cause damages to all vital organs and bone marrow is the most sensitive. Pre-treatment with antioxidant as single prophylactic dose is expected to lower induction of damages in bone marrow. In the present study we have focused on sesamol, a dietary antioxidant mediated radioprotection in bone marrow cells of gamma irradiated mice and compared with melatonin. Male C57BL/6 mice were intraperitoneally administered with sesamol (10 and 20 mg/kg body) and after 30 minutes exposed to whole body gamma radiation using 60Co Teletherapy unit. Mice were injected with 0.2 ml of a metaphase arresting agent (0.05% colchicine) intra-peritoneally 3 hours prior to sacrifice (24 hrs. post-irradiation). Bone marrow cells were flushed out from femurs of each animal and processed for chromosomal aberration assay. Another set of experiment without colchicine injection was performed to access the DNA damage in bone marrow using alkaline comet assay. At least 100 metaphases per animal were scored under light microscope to record various aberrations and total chromosomal aberrations (TCA) was calculated. Similar measurements were performed with melatonin for comparing the efficacy of sesamol. Gamma irradiation has increased the chromatid type aberrations (break formation, fragment) and chromosomal type aberrations (ring formation, acentric) in bone marrow cells. The results have shown significant (p< 0.001) increase in TCA of irradiated mice than control. While pre-treatment of sesamol and melatonin 10 mg/kg significantly (p<0.05) reduced the TCA. The extend of protection has increased at 20 mg/kg significantly (p<0.001) as evident from the reduced TCA compared to irradiated group. Interestingly, sesamol and melatonin have shown similar extent of reduction of TCA. Thus sesamol has demonstrated strong ability to protect bone marrow at low dosage. These investigations on sesamol mediated protection in bone marrow are likely to benefit development of

  7. Antimutagenic and redox regulatory activities of curcumin in whole body γ - irradiated mice

    International Nuclear Information System (INIS)

    the aim of the current study is understanding the redox regulatory activity ( pro- and anti-oxidant properties) and mutagenic burden following whole body -irradiation with special reference to its control by curcumin in mice. the antimutagenic effects of curcumin; diferuloylmethane ( C21 H20 O6) were evaluated in vitro using chromosomal aberration assay in male mice,induced after-exposure to 3 Gy γ-rays that is a known mutagenic and carcinogenic agent, when curcumin was given at a dose of 400 mmol/kg body wt through gastric intubation for 5 following days either before-, after-or both before and after-exposure, the incidence of aberrant cells and aberration types (mostly chromatids, breaks and fragments) reduced with curcumin dosage as compared to irradiated group. the cellular biochemical changes were estimated using liver tissue damage marker enzymes: alkaline phosphatase (ALP) and γ -glutamyl transferase (GGT), pro-oxidant: xanthine oxidase (XO), lipid per oxidative indices: thiobarbituric acid reactive substances (TBARS) and hydroperoxide (HP. the non-enzymatic antioxidant : glutathione (GSH) and the enzymatic antioxidants: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). TBARS ,HP,XO and liver marker enzymes were increased significantly , whereas the levels of GSH and the enzymatic antioxidants were significantly depleted in -irradiated groups. curcumin-treatment either before-, after-or both before and after -irradiation has attenuated the liver toxic effects of radiation obvious by reducing the levels of tbars and HP and diminished the increases of the activity of XO and liver marker enzymes. it has also re sued the depletion of the non enzymatic -and the enzymatic-antioxidant status.conclusion:curcumin has anti-oxidant potential against -rays-induced chromosomal mutations and redox imbalance regulatory status

  8. Sesamol attenuates genotoxicity in bone marrow cells of whole-body γ-irradiated mice.

    Science.gov (United States)

    Kumar, Arun; Selvan, Tamizh G; Tripathi, Akanchha M; Choudhary, Sandeep; Khan, Shahanshah; Adhikari, Jawahar S; Chaudhury, Nabo K

    2015-09-01

    Ionising radiation causes free radical-mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30 min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only (P < 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice. PMID:25863274

  9. The relationship between the alkaline phosphatase network and the haematopoiesis in mice subjected to whole-body irradiation

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    Almohamad Khaled M.

    2014-08-01

    Full Text Available Purpose: To investigate the relationship between the alkaline phosphatase (ALP network of the marrow stroma and the haematopoietic regeneration after mice whole-body irradiation. Materials and methods: Three groups of mice were irradiated with a non-lethal ionising radiation dose: the fi rst one received an intraperitoneal injection of Levamisole, ALP inhibitor, 24 h before irradiation; the second one received an intraperitoneal injection of Lisinopril, haematopoiesis inhibitor, 24 h before irradiation; the third was left untreated, but irradiated. The fourth group, untreated and not irradiated, was the control. The total surface occupied by ALP positive processes, revealed by means of ALP cytochemistry in the marrow area, was evaluated semi-quantitively. Nucleated bone marrow cells were also counted. Results: ALP network began to increase 24 h after irradiation to reach a maximum after 72 h, when the bone marrow was almost become completely empty of the haematopoietic cells. This increase advances the haematopoietic recovery. This process was substantially delayed when the mice were injected with Levamisole 24 h before irradiation. On the contrary, ALP network increased strongly since the fi rst day after irradiation when the mice were injected with Lisinopril 24 h before irradiation. Conclusions: These data have indicated that the haematopoietic recovery and repopulation of the bone marrow were advanced by the ALP network recovery.

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

    International Nuclear Information System (INIS)

    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

  11. Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

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    Zois, Christos E. [Department of Radiotherapy - Oncology, Democritus University of Thrace, Alexandroupolis 68100 (Greece); Giatromanolaki, Alexandra [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece); Kainulainen, Heikki [Department of Biology of Physical Activity, University of Jyvaeskylae (Finland); Botaitis, Sotirios [Department of Experimental Surgery, Democritus University of Thrace, Alexandroupolis (Greece); Torvinen, Sira [Department of Biology of Physical Activity, University of Jyvaeskylae (Finland); Simopoulos, Constantinos [Department of Experimental Surgery, Democritus University of Thrace, Alexandroupolis (Greece); Kortsaris, Alexandros [Department of Biochemistry, Democritus University of Thrace, Alexandroupolis (Greece); Sivridis, Efthimios [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece); Koukourakis, Michael I., E-mail: targ@her.forthnet.gr [Department of Radiotherapy - Oncology, Democritus University of Thrace, Alexandroupolis 68100 (Greece)

    2011-01-07

    Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function

  12. Effect of whole body neutron irradiation on certain enzyme activities in different brain areas in mice

    International Nuclear Information System (INIS)

    Male swiss albino mice were exposed to whole-body irradiation by fast neutrons of 14 MeV average energy. Two single doses of 0.08 sievert and 0.16 sievert were used, corresponding to fluences of 1.27 X 108 and 2.54 X 108 n/cm2 respectively. Two enzymes were assessed in different layers of the cerebrum and cerebellum of mouse brain. Changes in the activities of acid phosphatase (ACP) and succinic dehydrogenase (SDH) were taken to measure alterations in lysosomal and mitochondrial functions respectively. The degrees of lysosomal affection in different layers of the cerebrum were not uniform, while changes in A activity were very prominent in certain layers (e.g. external pyramidal layer, polymorphous cells layer and white matter), they were practically absent in others (e.g. internal pyramidal layer). Stronger effect was noted in the tissue layers of the cerebellum. The activity of SDH decreased as result of fast neutron irradiation. The response was more apparent for this enzyme than for ACP. This indicates more liability for a decrease in energy metabolism with consequent effect on behavioural and physiological functions under central nervous system control. 4 figs., 4 tabs

  13. Effects of low dose total body irradiation (LDTBI) and recombinant human interleukin-2 in mice

    International Nuclear Information System (INIS)

    10-16-week-old female BALB/c mice received low dose total body irradiation (LDTBI) in one fraction immediately before the beginning of treatment with recombinant human interleukin-2 (rIL-2). LDTBI prevented in a dose-dependent manner the weight increase of the spleen, liver and lungs induced by fluid extravasation provoked by rIL-2 injections. It also limited the increase of the number of mononuclear cells in the spleen induced after in vivo treatment with rIL-2. Immunofluorescence analysis of spleen cells revealed that LDTBI decreased the relative sIgM+ cell number in spleen, while the relative numbers of Lyt-1+, Thy-1+ and L3T4+ cells were increased, indicating that a T and/or NK population, radioresistant to LDTBI, could still proliferate under rIL-2 stimulation in vivo. Such lymphocytes were capable of in vitro lysis of YAC cells in a 4-hour 51Cr release assay, as well as lymphokine-activated killer (LAK) cells obtained in mice treated with rIL-2 alone. Thus, LDTBI given prior to rIL-2, yet preserving the cytotoxic capacity of the LAK cells activated by rIL-2, could prevent the vascular leak syndrome toxicity induced by rIL-2 injection. (author). tabs., figs

  14. Suppression of delayed-type hypersensitivity to oxazolone in whole-body-irradiated mice and protection by WR-2721

    International Nuclear Information System (INIS)

    The effect of whole-body irradiation on cellular immunity, as measured in vivo by delayed-type hypersensitivity (DTH) to oxazolone, was determined in CD2F1 mice. DTH, determined by changes in ear swelling after challenge with oxazolone, was significantly depressed in irradiated mice (500-900 rad of 60Co) in a dose-dependent fashion when animals were irradiated after sensitization and before challenge with oxazolone. Administration of WR-2721 30 min before irradiation (2 days after sensitization) resulted in protection against suppression of DTH, which was dependent on drug and radiation dose. An effective dose of WR-2721 provided an approximate dose-modifying factor of 1.3. The data suggest that WR-2721 interacts with cells involved in that DTH response and that WR-2721 may be useful in protecting against radiation-induced decrements in cell-mediated immunity

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

    International Nuclear Information System (INIS)

    Single dose of SBL-1 administered at the rate 30 mg/kg body weight (b.w.) 30 min prior to whole body 60Co-gamma-irradiation at lethal dose (10 Gy), rendered >90% survival in comparison to zero survival in the non-SBL-1 treated 60Co-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; 60Co 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)

  16. Immunological network activation by low-dose rate irradiation. Analysis of cell populations and cell surface molecules in whole body irradiated mice

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    Ina, Yasuhiro; Sakai, Kazuo [Central Research Inst. of Electric Power Industry, Low Dose Radiation Research Center, Komae, Tokyo (Japan)

    2003-07-01

    The effects of low-dose rate whole body irradiation on biodefense and immunological systems were investigated using female C57BL/6 (B6) mice. These B6 mice were exposed continuously to {gamma}-rays from a {sup 137}Cs source in the long-term low-dose rate irradiation facility at CRIEPI for 0 - 12 weeks at a dose rate of 0.95 mGy/hr. In the bone marrow, thymus, spleen, lymph nodes, and peripheral blood of the irradiated mice, changes in cell populations and cell surface molecules were examined. The cell surface functional molecules (CD3, CD4, CD8, CD19, CD45R/B220, ICAM-1, Fas, NK-1.1, CXCR4, and CCR5), and activation molecules (THAM, CD28, CD40, CD44H, CD70, B7-1, B7-2, OX-40 antigen, CTLA-4, CD30 ligand, and CD40 ligand) were analyzed by flow cytometry. The percentage of CD4{sup +} T cells and cell surface CD8 molecule expressions on the CD8{sup +} T cells increased significantly to 120-130% after 3 weeks of the irradiation, compared to non-irradiated control mice. On the other hand, the percentage of CD45R/B220{sup +} CD40{sup +} B cells, which is one of the immunological markers of inflammation, infection, tumor, and autoimmune disease, decreased significantly to 80-90% between the 3rd to 5th week of irradiation. There was no significant difference in other cell population rates and cell surface molecule expression. Furthermore, abnormal T cells bearing mutated T cell receptors induced by high-dose rate irradiation were not observed throughout this study. These results suggest that low-dose rate irradiation activates the immunological status of the whole body. (author)

  17. Early micro-rheological consequences of single fraction total body low-dose photon irradiation in mice.

    Science.gov (United States)

    Szluha, Kornelia; Lazanyi, Kornelia; Furka, Andrea; Kiss, Ferenc; Szabo, Imre; Pintye, Eva; Miko, Iren; Nemeth, Norbert

    2014-01-01

    Despite of the studies on widespread biological effects of irradiation, surprisingly only little number of papers can be found dealing with its in vivo hemorheological impact. Furthermore, other studies suggested that low-dose irradiation might differ from high-dose in more than linear ways. On Balb/c Jackson female adult mice hematological and hemorheological impacts of total body irradiation were investigated 1 hour following 0.002, 0.005, 0.01, 0.02, 0.05 and 0.1 Gy dose irradiation. In case of 0.01 Gy further groups were analyzed 30 minutes, 2, 4, 6, 24 and 48 h after irradiation. According to the results, it seems that the dose-dependent changes of blood micro-rheological parameters are not linear. The irradiation dose of 0.01 Gy acted as a point of 'inflexion', because by this dose we found the most expressed changes in hematological parameters, as well as in red blood cell aggregation, deformability and osmoscan data. The time-dependent changes showed progressive decrease in pH, rise in lactate concentration, further decrease in erythrocyte aggregation index and deformability, with moderate shifting of the optimal osmolarity point and modulation in membrane stability. As conclusion, low-dose total body irradiation may cause micro-rheological changes, being non-linearly correlated with the irradiation dose.

  18. Erythropoiesis in mice exposed to continuous whole body irradiation of gamma-rays

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    Joshima, Hisamasa; Fukutsu, Kumiko; Matsushita, Satoru; Kashima, Masatoshi

    1988-09-01

    The erythropoietic effects of continuous ..gamma..-irradiation with a daily regime of 0.029, 0.083 and 0.374 Gy were studied in mice. Irradiation was performed with /sup 137/Cs ..gamma..-rays for 22 hr/day. The length of irradiation time varied from 3 to 112 days. Erythropoiesis was investigated on the basis of clearance of /sup 59/Fe from the circulation and of incorporation of /sup 59/Fe into circulating erythrocytes and erythropoietic tissue. A chemical method for the separation of heme and nonheme iron-containing fractions was employed to examine the uptake of /sup 59/Fe into both the heme and nonheme iron fractions. Daily exposure to 0.029 and 0.083 Gy caused no significant changes in erythropoiesis. Daily exposure to 0.374 Gy caused some significant changes in erythropoiesis. On day 7 of continuous irradiation, the amount of /sup 59/Fe incorporated into erythrocytes decreased, but the values returned to normal on day 14 and 28 of continuous irradiation, indicating recovery within erythropoietic tissues at earlier time. On day 56, depressed incorporation of /sup 59/Fe into erythrocytes with normal rate of disappearance of /sup 59/Fe from the circulation and increased heme level of /sup 59/Fe in the femoral marrow were observed. Results observed on day 56 may suggest the possibility of ineffective erythropoiesis during the continuous irradiation. On day 112, some mice showed almost the same changes in erythropoiesis as those mice exposed to acute X-rays radiation.

  19. Effect of whole-body irradiation of mice on the number of background plaque-forming cells

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    Anderson, R.E.; Lefkovits, I.; Soeederberg, A.

    1983-08-01

    Mice were exposed in whole-body fashion to several doses of radiation and killed at various times thereafter for a determination of the number of background plaque-forming cells (PFCs) as assayed on either sheep erythrocytes or bromelain-treated autologous mouse erythrocytes. Increased numbers of both types of PFC were found in the irradiated groups. These increases were dependent on radiation dose and time after exposure. They did not appear to be caused by a disruption of normal lymphocyte traffic or a switch in immunoglobulin isotype. An increased number of PFCs on bromelain-treated mouse RBCs but not on sheep RBCs were found in irradiated congenitally athymic nude mice. On the basis of this and related observations, background PFCs on bromelain-treated mouse RBCs and on sheep RBCs appear to fall under different forms of homeostatic control.

  20. Effect of whole-body irradiation of mice on the number of background plaque-forming cells.

    Science.gov (United States)

    Anderson, R E; Lefkovits, I; Söederberg, A

    1983-08-01

    Mice were exposed in whole-body fashion to several doses of radiation and killed at various times thereafter for a determination of the number of background plaque-forming cells (PFCs) as assayed on either sheep erythrocytes or bromelain-treated autologous mouse erythrocytes. Increased numbers of both types of PFC were found in the irradiated groups. These increases were dependent on radiation dose and time after exposure. They did not appear to be caused by a disruption of normal lymphocyte traffic or a switch in immunoglobulin isotype. An increased number of PFCs on bromelain-treated mouse RBCs but not on sheep RBCs were found in irradiated congenitally athymic nude mice. On the basis of this and related observations, background PFCs on bromelain-treated mouse RBCs and on sheep RBCs appear to fall under different forms of homeostatic control.

  1. Arabinoxylan rice bran (MGN-3/Biobran) provides protection against whole-body γ-irradiation in mice via restoration of hematopoietic tissues

    International Nuclear Information System (INIS)

    The aim of the current study is to examine the protective effect of MGN-3 on overall maintenance of hematopoietic tissue after γ-irradiation. MGN-3 is an arabinoxylan from rice bran that has been shown to be a powerful antioxidant and immune modulator. Swiss albino mice were treated with MGN-3 prior to irradiation and continued to receive MGN-3 for 1 or 4 weeks. Results were compared with mice that received radiation (5 Gy γ rays) only, MGN-3 (40 mg/kg) only and control mice (receiving neither radiation nor MGN-3). At 1 and 4 weeks post-irradiation, different hematological, histopathological and biochemical parameters were examined. Mice exposed to irradiation alone showed significant depression in their complete blood count (CBC) except for neutrophilia. Additionally, histopathological studies showed hypocellularity of their bone marrow, as well as a remarkable decrease in splenic weight/relative size and in number of megakaryocytes. In contrast, pre-treatment with MGN-3 resulted in protection against irradiation-induced damage to the CBC parameters associated with complete bone marrow cellularity, as well as protection of the aforementioned splenic changes. Furthermore, MGN-3 exerted antioxidative activity in whole-body irradiated mice, and provided protection from irradiation-induced loss of body and organ weight. In conclusion, MGN-3 has the potential to protect progenitor cells in the bone marrow, which suggests the possible use of MGN-3/Biobran as an adjuvant treatment to counteract the severe adverse side effects associated with radiation therapy

  2. Metabolic changes in serum steroids induced by total-body irradiation of female C57B/6 mice.

    Science.gov (United States)

    Moon, Ju-Yeon; Shin, Hee-June; Son, Hyun-Hwa; Lee, Jeongae; Jung, Uhee; Jo, Sung-Kee; Kim, Hyun Sik; Kwon, Kyung-Hoon; Park, Kyu Hwan; Chung, Bong Chul; Choi, Man Ho

    2014-05-01

    The short- and long-term effects of a single exposure to gamma radiation on steroid metabolism were investigated in mice. Gas chromatography-mass spectrometry was used to generate quantitative profiles of serum steroid levels in mice that had undergone total-body irradiation (TBI) at doses of 0Gy, 1Gy, and 4Gy. Following TBI, serum samples were collected at the pre-dose time point and 1, 3, 6, and 9 months after TBI. Serum levels of progestins, progesterone, 5β-DHP, 5α-DHP, and 20α-DHP showed a significant down-regulation following short-term exposure to 4Gy, with the exception of 20α-DHP, which was significantly decreased at each of the time points measured. The corticosteroids 5α-THDOC and 5α-DHB were significantly elevated at each of the time points measured after exposure to either 1 or 4Gy. Among the sterols, 24S-OH-cholestoerol showed a dose-related elevation after irradiation that reached significance in the high dose group at the 6- and 9-month time points.

  3. p38 MAPK Inhibitor Insufficiently Attenuates HSC Senescence Administered Long-Term after 6 Gy Total Body Irradiation in Mice

    Directory of Open Access Journals (Sweden)

    Lu Lu

    2016-06-01

    Full Text Available Senescent hematopoietic stem cells (HSCs accumulate with age and exposure to stress, such as total-body irradiation (TBI, which may cause long-term myelosuppression in the clinic. However, the methods available for long-term myelosuppression remain limited. Previous studies have demonstrated that sustained p38 mitogen-activated protein kinases (p38 MAPK activation in HSCs following exposure to TBI in mice and the administration of its inhibitor twenty-four hours after TBI may partially prevent long-term myelosuppression. However, long-term myelosuppression is latent and identified long after the administration of radiation. In this study, we investigated the effects of SB203580 (a small molecule inhibitor of p38 MAPK on long-term myelosuppression induced by TBI. Mice with hematopoietic injury were injected intraperitoneally with SB203580 every other day five times beginning 70 days after 6 Gy of 137Cs γ ray TBI. Our results at 80 days demonstrated that SB203580 did not significantly improve the TBI-induced long-term reduction of peripheral blood cell and bone marrow nucleated cell (BMNC counts, or defects in hematopoietic progenitor cells (HPCs and HSC clonogenic function. SB203580 reduced reactive oxygen species (ROS production and p-p38 expression; however, SB203580 had no effect on p16 expression in the HSCs of mice. In conclusion, these findings suggest that treatment with SB203580 70 days after TBI in mice inhibits the ROS-p38 oxidative stress pathway; however, it has no therapeutic effect on long-term myelosuppression induced by TBI.

  4. Studies on immunity to Schistosoma mansoni in vivo: whole-body irradiation has no effect on vaccine-induced resistance in mice

    Energy Technology Data Exchange (ETDEWEB)

    Vignali, D.A.A.; Bickle, Q.D.; Taylor, M.G.

    1988-02-01

    Actively immunized mice, whole-body irradiated with 650 or 525 rad., manifested comparable levels of resistance to Schistosoma mansoni compared with unirradiated, immunized mice in spite of a marked reduction in circulating leucocytes and platelets, and despite an abrogation of delayed-type hypersensitivity (DTH) (Type IV) reponse to schistosomular antigens. However, limited histopathological comparison of lung sections from irradiated and unirradiated mice 7 days post-challenge showed that cellular reactions ('foci') around parasites were similar in size and cellular composition except that in irradiated mice, eosinophils were poorly represented both in the foci and in lung tissue in general. Neither presumed immune complex-mediated (Type III, Arthus reaction) hypersensitivity nor serum anti-schistosomulum extract antibody levels were affected. The pattern of /sup 125/I-labelled schistosomular surface antigens immunoprecipitated with serum from irradiated and unirradiated mice was essentially similar. These results are consistent with antibody playing an important role in vaccine-induced immunity in mice but suggest that radiosensitive T cell function and radiosensitive cells, such as platelets and polymorphonuclear cells, including eosinophils, may not be essential.

  5. Distribution in pregnant mice of radioactivity after injection of 131I, and immunosuppressive effect by the whole body irradiation

    International Nuclear Information System (INIS)

    For the purpose of decreasing resistance to leprous bacilli, 100 μCi of 131I was injected subcutaneously to 2-3 week pregnant, dd-strain mice. Internal distribution of 131I was followed up by measuring radioactivity in each organ of parent mice (I-P) and fetal mice (I-F). 300 rad in all of 60Co was irradiated to 2-3 week pregnant mice (R-P) in two directions from the dorsal side of the abdomen. Immunosuppressive effect of the irradiation was evaluated in the parent mice and their offsprings (R-F) and compared with that in the 131I-treated mice using a skin graft method. It was shown that 131I of parent mice stayed in the uterus and was transmitted to their fetus through the placenta, and clarified that 131I which remained in parent mice was continually supplied to their infant mice through milk still after birth. These findings seem to explaine the result that I-F which had been affected continually by 131I had higher sensitivity to leprous bacilli than I-P. Immunosuppressive effect on a skin graft disclosed that the chief mechanisms of 131I are to decrease the function of the reticulo-endothelial system by iodine and to suppress cellular immunity by its radioactivity. The rejecting time for the mouse skin homograft in the untreated mouse was 8.8 days on the average, and the lymph node weight was 33 mg. The order of the duration in the graft survival was R-P>I-F>I-P>R-F> normal mice, while that of lymph node weights was completely inverse. Therefore, the immunosuppressive effect on I-P and I-F mice, when it is compared with normal mice, could be confirmed, and the I-F was said to be favorable further than to I-P when based on this immunity test by transplantation. (Ueda, J.)

  6. Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism

    Institute of Scientific and Technical Information of China (English)

    Qiao Shukai; Ren Hanyun; Shi Yongjin; Liu Wei

    2014-01-01

    Background Radiation-induced injury after accidental or therapeutic total body exposure to ionizing radiation has serious pathophysiological consequences,and currently no effective therapy exists.This study was designed to investigate whether transplantation of allogeneic murine compact bone derived-mesenchymal stem cells (CB-MSCs) could improve the survival of mice exposed to lethal dosage total body irradiation (TBI),and to explore the potential immunoprotective role of MSCs.Methods BALB/c mice were treated with 8 Gy TBI,and then some were administered CB-MSCs isolated from C57BL/6 mice.Survival rates and body weight were analyzed for 14 days post-irradiation.At three days post-irradiation,we evaluated IFN-Y and IL-4 concentrations; CD4+CD25+Foxp3+ regulatory T cell (Treg) percentage; CXCR3,CCR5,and CCR7 expressions on CD3+T cells; and splenocyte T-bet and GATA-3 mRNA levels.CB-MSC effects on bone marrow hemopoiesis were assessed via colony-forming unit granulocyte/macrophage (CFU-GM) assay.Results After lethal TBI,compared to non-transplanted mice,CB-MSC-transplanted mice exhibited significantly increased survival,body weight,and CFU-GM counts of bone marrow cells (P<0.05),as well as higher Treg percentages,reduced IFN-Y,CXCR3 and CCR5 down-regulation,and CCR7 up-regulation.CB-MSC transplantation suppressed Th1 immunity.Irradiated splenocytes directly suppressed CFU-GM formation from bone marrow cells,and CB-MSC co-culture reversed this inhibition.Conclusion Allogeneic CB-MSC transplantation attenuated radiation-induced hematopoietic toxicity,and provided immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition,expanding Tregs,regulating T cell chemokine receptor expressions,and skewing the Th1/Th2 balance toward anti-inflammatory Th2 polarization.

  7. SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

    International Nuclear Information System (INIS)

    Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3+ apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver of SIGN-R1 KO mice, followed by a significant increase of CD11b+ cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1+ macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver

  8. SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee [Department of Biomedical Science & Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Choi, Hyeong-Jwa [Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4, 75 Nowon gil Nowon-Gu, Seoul, 139-706 (Korea, Republic of); Na, Tae-Young [College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-741 (Korea, Republic of); Nemeno, Judee Grace E.; Lee, Jeong Ik [Regenerative Medicine Laboratory, Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul, 143-701 (Korea, Republic of); Yoon, Taek Joon [Department of Food and Nutrition, Yuhan College, Bucheon, Gyeonggi-do, 422-749 (Korea, Republic of); Choi, In-Soo [Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Lee, Minyoung [Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4, 75 Nowon gil Nowon-Gu, Seoul, 139-706 (Korea, Republic of); Lee, Jae-Seon [Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, 400-712 (Korea, Republic of); Kang, Young-Sun, E-mail: kangys1967@naver.com [Department of Biomedical Science & Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of)

    2015-08-07

    Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3{sup +} apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver of SIGN-R1 KO mice, followed by a significant increase of CD11b{sup +} cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1{sup +} macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver.

  9. Effect of Fluosol-DA 20% and oxygen on response of C57BL/6 mice to whole-body irradiation

    International Nuclear Information System (INIS)

    Normal tissue effects in mice due to combinations of a perfluorochemical emulsion, Fluosol-DA 20%, 100% oxygen, and whole-body irradiation were investigated. Eight-to-10-week-old C57BL/6 male mice were injected via the tail vein with 10 ml/kg of Fluosol-DA with and without subsequent exposure to oxygen for 60 minutes. Animals then received graded doses of whole-body radiation (4 MV photons) at a dose rate of 2.85 +/- .015 Gy/minute. Using linear regression analysis, the lethal doses of radiation to 50% and 10% of the animals within 30 days in the absence of Fluosol-DA and oxygen were 8.35 Gy (95% c.l.:7.77-8.93 Gy) and 6.73 Gy (95% cl.:6.21-7.25 Gy), respectively, and were unaffected by Fluosol-DA and/or oxygen pre-treatment. However, Fluosol-DA given alone or in combination with oxygen produced increased balding and decreased graying incidence in mice within 60 days, and resulted in depressed weight gain 15 to 60 days post-treatment. Normal tissue effects due to administration of Fluosol-DA and oxygen in combination with whole-body irradiation have been demonstrated but appear minimal compared to other anti-tumor modalities currently under investigation

  10. Chronic radiation injury with mice and dogs exposed to external whole-body irradiation at the Argonne National Laboratory

    International Nuclear Information System (INIS)

    This document describes studies on chronic radiation injury in experimental animals and the extrapolation of derived injury parameters to man. Most of the large studies have used mice given single, weekly, or continuous exposure to cobalt-60 gamma rays, or, more recently, single or weekly exposure to fission neutrons from the JANUS reactor. Primary measures of injury have been life shortening and the associated major pathological changes, particularly neoplastic diseases. Recent and ongoing studies compare the effects of extremely low neutron exposures with gamma irradiations delivered as a single dose or in 60 equal weekly increments. Total neutron doses range from 1 to 40 rads; gamma-ray doses range from 22.5 to 600 rads. Selected genetic studies are performed concurrently to provide a nearly complete matrix of somatic and genetic effects of these low exposures. Studies with the beagle have complemented those with mice and have shown a strong parallelism in the responses of the two species. Present exposures are at 0.3, 0.75, and 1.88 rads per day of continuous gamma irradiation to test a model for the prediction of life shortening in man which has evolved from Argonne's long-term studies. The dog offers the opportunity for longitudinal clinical evaluations that are not possible in the mouse, to develop a broader view of the neoplastic disease spectrum, and to study the mechanisms of radiation induction of leukemia. Diverse statistical approaches have been used to measure excess risk, dose-response functions, and rates of injury and repair. Actuarial statistical methods have been favored since they permit a more direct means of extrapolation to man. 50 refs., 4 figs

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

    Science.gov (United States)

    Wang, Bing; Tanaka, Kaoru; Ji, Bin; Ono, Maiko; Fang, Yaqun; Ninomiya, Yasuharu; Maruyama, Kouichi; Izumi-Nakajima, Nakako; Begum, Nasrin; Higuchi, Makoto; Fujimori, Akira; Uehara, Yoshihiko; Nakajima, Tetsuo; Suhara, Tetsuya; Ono, Tetsuya; Nenoi, Mitsuru

    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.

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

    International Nuclear Information System (INIS)

    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 11C-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)

  13. Age and sex dependence in tumorigenesis in mice by continuous low-dose-rate gamma-ray whole-body irradiation

    International Nuclear Information System (INIS)

    We investigated the dependency of sex and age in mice in the induction of neoplasms by gamma-rays from cesium-137 at a low dose rate of 0.375Gy/22h/day. Thymic lymphomas occurred significantly at the same incidence in both sexes, and more frequently when younger mice were exposed to radiation. Strain C57BL/6J mice were divided into 8 groups, which were whole-body irradiated with a total dose of 39Gy for 105 days each. The exposure was begun at 28 days of age (male:AM1, female:AF1), and then stepwise increasing the starting age by 105 days, i.e., from 133 days (AM2 and AF2), from 238 days (AM3 and AF3), and from 343 days (AM4 and AF4), respectively. Unirradiated mice served as control (UM and UF). The incidence of thymic lymphomas was about 60 % in AM1, AM2, AF1 and AF2, 40 % in AM3 and AF3 and 20 % in AF4 and AF4, demonstrating no sex dependency, but a distinct age dependency, for lymphomogenesis. It was proven that mice showed a tendency to become less susceptible to radiation induced thymic lymphoma with increasing age. Concomitantly, life-shortening also was caused, and the greater the degree of life-shortening was, the younger the mice were the start of exposure. Life-shortening was attributed to thymic lymphoma, and hemorrhage and infectious diseases due to the depletion of bone marrow cells. (author)

  14. Abrogation of bone marrow allograft resistance in mice by increased total body irradiation correlates with eradication of host clonable T cells and alloreactive cytotoxic precursors

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, E.; Lapidot, T.; Gozes, D.; Singer, T.S.; Reisner, Y.

    1987-01-15

    Host-vs-graft activity presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, conditioned exactly like leukemia patients, it was shown that residual host clonable T cells, as well as alloreactive cytotoxic precursors, were present in peripheral blood and spleen after completion of cytoreduction. We have now extended this study in a mouse model for allogeneic bone marrow transplantation. C/sub 3/H/HeJ mice were treated by 9 Gy total body irradiation (TBI), and 24 hr later their spleen cells were cultured in the presence of T cell growth factor and phytohemagglutinin according to the limit dilution procedure. After 7 days of culture the average frequency of clonable cells was 2.5 X 10(-3) compared with 37 X 10(-3) in the spleens of normal mice. The T cell derivation of the growing cells was ascertained by complement-mediated cytotoxicity with anti-Thy-1 as well as with anti-Lyt-2 and anti-Ly-3T4. In parallel, we found that the initial engraftment rate of bone marrow allograft in mice given 9 Gy TBI was lower than that found in recipients of syngeneic marrow. The initial engraftment rate was measured by the number of colony-forming units in the spleen and by splenic uptake of /sup 125/IUdR. A slight increase in TBI from 9 Gy to 11 Gy markedly reduced the difference in the number of spleen colony-forming units or the IUdR uptake between recipients of allogeneic and syngeneic bone marrow. This increase in TBI also coincided with eradication of detectable clonable T cells. Moreover, in mice transplanted with T cell-depleted bone marrow after 9 Gy TBI, we also demonstrate that cytotoxicity against donor-type target cells is present in the spleen 10 to 14 days posttransplantation, whereas in mice treated by 11 Gy TBI such alloreactivity could not be detected.

  15. The Application of Flow Cytometry to Examine Damage Clearance in Stem Cells From Whole-Body Irradiated Mice

    Energy Technology Data Exchange (ETDEWEB)

    Marples, Brian; Kovalchuk, Olga; McGonagle, Michele; Martinez, Alvaro; Wilson, George, D.

    2010-02-26

    The bone marrow contains many types of cells. Approximately 1-2% of these cells are critical for life, these are the so-called ‘bone marrow stem cells’ which divide indefinitely to produce platelets, red blood cells and white blood cells. Death of the bone marrow stem cells results in a diminished ability of the organism to make new blood cell components and can be fatal without medical intervention, such as a bone marrow transplant. Bone marrow stem cells are considered to be particularly sensitive to radiation injury. Therefore, it is important to understand how these cells response to total body radiation exposure and how these cells can be protected from radiation damage. The aim of this project was to determine if these critical cells in the bone marrow are susceptible to short-term and long-term injury after a whole-body exposure to a sub-lethal low dose of ionizing radiation. The overall aims were to determine if the extent of injury produced by the sub-lethal radiation exposure would be cleared from the stem cells and therefore present no long- term genetic risk to the organism, or if the radiation injury persisted and had an adverse long-term consequences for the cell genome. This research question is of interest in order to define the risks to exposed persons after occupational, accidental or terrorism-related sub-lethal low-dose radiation exposures. The novel aspect of this project was the methodology used to obtain the bone marrow stem cell-like cells and examining the outcomes of sub-lethal low-dose radiation in a mammalian animal model. Four radiation treatments were used: single treatments of 0.01Gy, 0.1 Gy, 1 Gy and ten treatments of 0.1 Gy given over 10 days. Bone marrow stem cell-like cells were then harvested 6 hours, 24 hours and 24 days later. The levels of radiation-induced cell death, damage to DNA and permanent changes to cellular DNA were measured in the isolated stem cell-like cells after each radiation treatment and time point and

  16. Single administration of p2TA (AB103, a CD28 antagonist peptide, prevents inflammatory and thrombotic reactions and protects against gastrointestinal injury in total-body irradiated mice.

    Directory of Open Access Journals (Sweden)

    Salida Mirzoeva

    Full Text Available The goal of this study was to elucidate the action of the CD28 mimetic peptide p2TA (AB103 that attenuates an excessive inflammatory response in mitigating radiation-induced inflammatory injuries. BALB/c and A/J mice were divided into four groups: Control (C, Peptide (P; 5 mg/kg of p2TA peptide, Radiation (R; total body irradiation with 8 Gy γ-rays, and Radiation + Peptide (RP; irradiation followed by p2TA peptide 24 h later. Gastrointestinal tissue damage was evaluated by analysis of jejunum histopathology and immunohistochemistry for cell proliferation (Cyclin D1 and inflammation (COX-2 markers, as well as the presence of macrophages (F4/80. Pro-inflammatory cytokines IL-6 and KC as well as fibrinogen were quantified in plasma samples obtained from the same mice. Our results demonstrated that administration of p2TA peptide significantly reduced the irradiation-induced increase of IL-6 and fibrinogen in plasma 7 days after exposure. Seven days after total body irradiation with 8 Gy of gamma rays numbers of intestinal crypt cells were reduced and villi were shorter in irradiated animals compared to the controls. The p2TA peptide delivery 24 h after irradiation led to improved morphology of villi and crypts, increased Cyclin D1 expression, decreased COX-2 staining and decreased numbers of macrophages in small intestine of irradiated mice. Our study suggests that attenuation of CD28 signaling is a promising therapeutic approach for mitigation of radiation-induced tissue injury.

  17. Spontaneous pulmonary metastasis of human cancer cells in X-irradiated and nonirradiated nude mice

    International Nuclear Information System (INIS)

    The effect of whole body X-irradiation on the spontaneous pulmonary metastasis of human cancer cells transplanted into adult nude mice was investigated. Human cancer cells were inoculated into footpads of adult nude mice following 3 Gy whole body X-irradiation. The incidence of pulmonary metastasis was increased in the irradiated mice. Cytotoxicity of splenocytes, particularly adherent cells, was lower in the irradiated mice than in the nonirradiated mice. Histological examinations revealed decreased mononuclear cell infiltration around the primary tumor and pulmonary metastatic foci in the irradiated mice. The suppressive effect of cytotoxicity of the splenocytes by whole body X-irradiation may thus relate to ensuing metastasis both in the phase of release and intravasation from the primary tumor and in the phase of lodgement and proliferation in the target organ. (author)

  18. Effects of total body irradiation on b16f10 melanoma-bearing mice%全身放射线照射对 B16 F10黑色素瘤小鼠的影响

    Institute of Scientific and Technical Information of China (English)

    王冰; 屈朋欢; 王艳华; 崔乃鹏; 蔡建辉; 陈保平

    2015-01-01

    目的:观察全身放射线照射( TBI)对B16F10黑色素瘤小鼠移植肿瘤生长及小鼠存活的影响。方法建立C57BL/6小鼠B16F10黑色素瘤移植肿瘤模型,采用不同剂量分别对小鼠进行TBI,观察小鼠移植肿瘤的生长和小鼠的存活情况;检测放疗后小鼠外周血白细胞水平。结果不同剂量TBI对各组小鼠肿瘤面积及存活率无影响(P均>0.05)。给予7 Gy TBI 10 d后,B16F10荷瘤小鼠外周血白细胞水平下降(P<0.05)。结论 TBI不影响B16 F10黑色素瘤小鼠移植肿瘤生长及荷瘤小鼠的生存;7 Gy TBI可改变荷瘤小鼠外周血白细胞水平,有利于肿瘤免疫治疗。%Objective To investigate effects of total body irradiation (TBI) on tumor growth and B16F10 melanoma-bearing mice survival.Methods C57BL/6 mice bearing B16-melanoma tumors were irradiated with 0, 5, or 7 Gy total body irradiation ( TBI) , or 7 Gy TBI pus bone marrow transplantation .Tumor areas were measured every 3 days to assess the influences of irradiation treatment on tumor regression .B16-melanoma bearing mice were irradiated with 7 Gy TBI and peripheral blood were harvested at days 1, 3, 5, 7, 9, 11 and 13 after irradiation to test WBC levels .Results TBI with variant dosage on the B 16-melanoma-bearing mice did not influence tumor regression compared with control group ( all P>0.05).WBC levels significantly decreased in the B16F10 melanoma-bearing mice on 10 d after 7 Gy TBI(P<0.05). Conclusion TBI dose do not influence tumor growth and survival of B 16F10 melanoma-bearing mice.Seven Gy TBI can alter WBC levels of peripheral bloods in B 16F10 melanoma-bearing mice, which helps to tumor immunotherapy .

  19. Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice

    NARCIS (Netherlands)

    Noach, EJK; Ausema, A; Dillingh, JH; Dontje, B; Weersing, E; Akkerman, [No Value; Vellenga, E; Haan, GC

    2002-01-01

    Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell en

  20. Immunity to Trichinella spiralis in irradiated mice

    International Nuclear Information System (INIS)

    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)

  1. 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)

    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.)

  2. Protective effects of a preparation(hemoHIM) of herb mixture on self-renewal tissues and immune system in whole body irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae-Ran; Oh, Heon; Jo, Sung-Kee [Korea Atomic Energy Research Institute, Daejon (Korea, Republic of); Kim, Sung-Ho [Chonnam National Univ., Kwangju (Korea, Republic of); Yee, Sung-Tae [Sunchon National Univ., Sunchon (Korea, Republic of)

    2002-07-01

    A preparation (HemoHIM) of herb mixture was designed to protect the gastrointestine and hematopoietic organs and to promote recovery of the immune system against radiation damage. The mixture of 3 edible medicinal herbs (Angelica gagantis Radix, etc.) was decocted with hot water and the extract was fractionated with ethanol. The preparation HemoHIM was made up with addition of ethanol- insoluble fraction yielded from one half of the total water extract to the other half of the total water extract. In vitro, lymphocytes were protected by HemoHIM, its polysaccharide and ethanol fractions against radiation. The proliferation of lymphocytes and bone marrow cells by HemoHIM was due to its polysaccharide fraction. In mice administered with the preparation (HemoHIM) before gamma- irradiation, the jejunal crypt survival was increased and the apoptosis of crypt cells was decreased. HemoHIM administration increased the survival of bone marrow stem cells and promoted the repopulation of blood cells following irradiation. In the analysis of the repopulated lymphocyte subsets, B cells were firstly regenerated and then T cells were recovered in mice administrated with HemoHIM. The antibody production against T-dependent antigen DNP-KLH was augmented by HemoHIM in irradiated mice. These results indicated that HemoHIM, a preparation of the herb mixture, protected the stem cells of self-renewal tissues and hematopoietic organs and promoted recovery of the immune system against radiation damage. Since the preparation of herb mixture is a relatively nontoxic natural product, it might be a useful modifier for prevention and control of radiation damages.

  3. Dosimetry of total body irradiation

    International Nuclear Information System (INIS)

    In the treatment of disseminated malignancies an improvement in the curability and reduction of complication rates require high precision total body irradiation (TBI) and correct reporting of relevant treatment parameters. Optimal TBI dosimetry is the basis. Radiooncological and radiobiological requirements as well as the special physical situation have to be considered. To review the efforts of medical physicists, highlights from TBI workshops and publications are summarized. Additionally, dosimetric data from 34 European radiooncological centres contributing to the recent ESTRO inquiry on TBI are analysed. The topics are: absorbed dose and dose monitor calibration, determination of absolute and relative doses, dose ratios, attenuation data and heterogeneity corrections; TBI dose calculation methods regarding patient position, beam incidence, body shape and thickness, lung size and density; methods of TBI treatment planning including calculated dose modification and of TBI quality assurance. In conclusion, the following recommendations can be given: TBI dosimetry shall be performed under TBI conditions, close to the real treatment situation. The absorbed dose to water must be determined. The dose monitor should be calibrated against dose measurements at the centre of a water equivalent phantom of TBI equivalent size and typical thickness. Photon fluence profiles have to be measured with small phantoms. Influences on the local dose must be investigated systematically. A reproducible AP/PA TBI technique should be used. The TBI dose shall be specified to mid-abdomen and reported in units of gray. The single and total dose and the dose rate to the lungs, the number of fractions and the treatment time schedule must be stated. In vivo dosimetry is required if non-reliable TBI techniques are used. An international TBI dosimetry intercomparison could assist these efforts to improve the treatment of acute leukaemia. (author). 89 refs, 3 figs, 13 tabs

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

    International Nuclear Information System (INIS)

    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 60Co whole-body irradiation increased the survival rate of mice in the lethal dose range. (L.M.J.)

  5. Differential susceptibility of C57BL/6NCr and B6.Cg-Ptprca mice to commensal bacteria after whole body irradiation in translational bone marrow transplant studies

    Directory of Open Access Journals (Sweden)

    Toubai Tomomi

    2008-02-01

    Full Text Available Abstract Background The mouse is an important and widely utilized animal model for bone marrow transplant (BMT translational studies. Here, we document the course of an unexpected increase in mortality of congenic mice that underwent BMT. Methods Thirty five BMTs were analyzed for survival differences utilizing the Log Rank test. Affected animals were evaluated by physical examination, necropsy, histopathology, serology for antibodies to infectious disease, and bacterial cultures. Results Severe bacteremia was identified as the main cause of death. Gastrointestinal (GI damage was observed in histopathology. The bacteremia was most likely caused by the translocation of bacteria from the GI tract and immunosuppression caused by the myeloablative irradiation. Variability in groups of animals affected was caused by increased levels of gamma and X-ray radiation and the differing sensitivity of the two nearly genetically identical mouse strains used in the studies. Conclusion Our retrospective analysis of thirty five murine BMTs performed in three different laboratories, identified C57BL/6NCr (Ly5.1 as being more radiation sensitive than B6.Cg-Ptprca/NCr (Ly5.2. This is the first report documenting a measurable difference in radiation sensitivity and its effects between an inbred strain of mice and its congenic counterpart eventually succumbing to sepsis after BMT.

  6. Ginsan activated the antioxidant defense systems in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jie Young; Son, Soo Jung; Ahn, Ji Yeon; Shim, Ji Young; Han, Young Soo; Jung, In Sung; Yun, Yeon Sook [KIRMS Daegu (Korea, Republic of)

    2003-07-01

    Ginsan, a polysaccharide extracted from Panax ginseng, has hematopoietic activity and is also known as a good biological-response modifier. In this investigation, we studied the effects of ginsan on the {gamma}-radiation induced alterations of some antioxidant systems in spleen of Balb/c mice. There are many data that irradiation induces Reactive Oxygen Species (ROS), which plays an important causative role in radiation damage of cell. The level of ROS in cells is regulated by enzymatic and nonenzymatic antioxidant systems. The most powerful ones among them are superoxide dismutases (SODs) catalyzing the dismutation of superoxide anion radical o{sub 2} to H{sub 2}O{sub 2}, catalase deactivating h-2O{sub 2} and reduced glutathion (GSH) detoxifying H{sub 2}O{sub 2} and other ROS> At the 5{sub th} day after sublethal whole body irradiation, splenocytes of irradiated mice expressed only marginally increased levels of Mn-SOD, however, Cu/Zn-SOD, catalase, thioredoxine reductase (TR) and thioredoxine (TRX) mRNA (135% increase compared to control), however, the combination of irradiation with ginsan increased the SODs and GPX production more effectively. In addition to the above results, we obtained the similar data of protein expression. The enzyme activities of SOD, catalase, and GPX of ginsan-treated and irradiated mice were significantly enhanced by 140, 115, 126% respectively, compared with those of irradiated mice. Based on these results, we propose that the induction of antioxidant enzymes of ginsan is at least in part due to its capacity to protect against radiation.

  7. Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice.

    Science.gov (United States)

    Uckun, Fatih M; Myers, Dorothea E; Cheng, Jianjun; Qazi, Sanjive

    2015-06-01

    This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 ("C61-LNP"). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12 × BCR-ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone.

  8. Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice

    Directory of Open Access Journals (Sweden)

    Fatih M. Uckun

    2015-06-01

    Full Text Available This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP formulation of the SYK-P-site inhibitor C61 (“C61-LNP”. C61-LNP plus low dose total body irradiation (TBI was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12×BCR–ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone.

  9. Low Dose Total Body Irradiation Combined With Recombinant CD19-Ligand × Soluble TRAIL Fusion Protein is Highly Effective Against Radiation-resistant B-precursor Acute Lymphoblastic Leukemia in Mice

    Directory of Open Access Journals (Sweden)

    Fatih M. Uckun

    2015-04-01

    Full Text Available In high-risk remission B-precursor acute lymphoblastic leukemia (BPL patients, relapse rates have remained high post-hematopoietic stem cell transplantation (HSCT even after the use of very intensive total body irradiation (TBI-based conditioning regimens, especially in patients with a high “minimal residual disease” (MRD burden. New agents capable of killing radiation-resistant BPL cells and selectively augmenting their radiation sensitivity are therefore urgently needed. We report preclinical proof-of-principle that the potency of radiation therapy against BPL can be augmented by combining radiation with recombinant human CD19-Ligand × soluble TRAIL (“CD19L–sTRAIL” fusion protein. CD19L–sTRAIL consistently killed radiation-resistant primary leukemia cells from BPL patients as well as BPL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. Low dose total body irradiation (TBI combined with CD19L–sTRAIL was highly effective against (1 xenografted CD19+ radiochemotherapy-resistant human BPL in NOD/SCID (NS mice challenged with an otherwise invariably fatal dose of xenograft cells derived from relapsed BPL patients as well as (2 radiation-resistant advanced stage CD19+ murine BPL with lymphomatous features in CD22ΔE12xBCR-ABL double transgenic mice. We hypothesize that the incorporation of CD19L–sTRAIL into the pre-transplant TBI regimens of patients with very high-risk BPL will improve their survival outcome after HSCT.

  10. Implantation of total body irradiation in radiotherapy

    International Nuclear Information System (INIS)

    Before implementing a treatment technique, the characteristics of the beam under irradiation conditions must be well acknowledged and studied. Each one of the parameters used to calculate the dose has to be measured and validated before its utilization in clinical practice. This is particularly necessary when dealing with special techniques. In this work, all necessary parameters and measurements are described for the total body irradiation implementation in facilities designed for conventional treatments that make use of unconventional geometries to generate desired enlarged field sizes. Furthermore, this work presents commissioning data of this modality at Hospital das Clinicas of Sao Paulo using comparison of three detectors types for measurements of entrance dose during total body irradiation treatment. (author)

  11. Humanized Chronic Graft-versus-Host Disease in NOD-SCID il2rγ-/- (NSG Mice with G-CSF-Mobilized Peripheral Blood Mononuclear Cells following Cyclophosphamide and Total Body Irradiation.

    Directory of Open Access Journals (Sweden)

    Hisaki Fujii

    Full Text Available Chronic graft-versus-host disease (cGvHD is the major source of late phase morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Humanized acute GvHD (aGvHD in vivo models using NOD-SCID il2rγ-/- (NSG mice are well described and are important tools for investigating pathogenicity of human cells in vivo. However, there have been only few reported humanized cGvHD mouse models. We evaluated if prolonged inflammation driven by low dose G-CSF-mobilized human PBMCs (G-hPBMCs would lead to cGvHD following cyclophosphamide (CTX administration and total body irradiation (TBI in NSG mice. Engraftment was assessed in peripheral blood (PB and in specific target organs by either flow cytometry or immunohistochemistry (IHC. Tissue samples were harvested 56 days post transplantation and were evaluated by a pathologist. Some mice were kept for up to 84 days to evaluate the degree of fibrosis. Mice that received CTX at 20mg/kg did not show aGvHD with stable expansion of human CD45+ CD3+ T-cells in PB (mean; 5.8 to 23.2%. The pathology and fibrosis scores in the lung and the liver were significantly increased with aggregation of T-cells and hCD68+ macrophages. There was a correlation between liver pathology score and the percentage of hCD68+ cells, suggesting the role of macrophage in fibrogenesis in NSG mice. In order to study long-term survival, 6/9 mice who survived more than 56 days showed increased fibrosis in the lung and liver at the endpoint, which suggests the infiltrating hCD68+ macrophages may be pathogenic. It was shown that the combination of CTX and TBI with a low number of G-hPBMCs (1x106 leads to chronic lung and liver inflammation driven by a high infiltration of human macrophage and mature human T cells from the graft, resulting in fibrosis of lung and liver in NSG mice. In conclusion this model may serve as an important pre-clinical model to further current understanding of the roles of human macrophages in cGvHD.

  12. Humanized Chronic Graft-versus-Host Disease in NOD-SCID il2rγ-/- (NSG) Mice with G-CSF-Mobilized Peripheral Blood Mononuclear Cells following Cyclophosphamide and Total Body Irradiation.

    Science.gov (United States)

    Fujii, Hisaki; Luo, Zhi-Juan; Kim, Hye Jin; Newbigging, Susan; Gassas, Adam; Keating, Armand; Egeler, R Maarten

    2015-01-01

    Chronic graft-versus-host disease (cGvHD) is the major source of late phase morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Humanized acute GvHD (aGvHD) in vivo models using NOD-SCID il2rγ-/- (NSG) mice are well described and are important tools for investigating pathogenicity of human cells in vivo. However, there have been only few reported humanized cGvHD mouse models. We evaluated if prolonged inflammation driven by low dose G-CSF-mobilized human PBMCs (G-hPBMCs) would lead to cGvHD following cyclophosphamide (CTX) administration and total body irradiation (TBI) in NSG mice. Engraftment was assessed in peripheral blood (PB) and in specific target organs by either flow cytometry or immunohistochemistry (IHC). Tissue samples were harvested 56 days post transplantation and were evaluated by a pathologist. Some mice were kept for up to 84 days to evaluate the degree of fibrosis. Mice that received CTX at 20mg/kg did not show aGvHD with stable expansion of human CD45+ CD3+ T-cells in PB (mean; 5.8 to 23.2%). The pathology and fibrosis scores in the lung and the liver were significantly increased with aggregation of T-cells and hCD68+ macrophages. There was a correlation between liver pathology score and the percentage of hCD68+ cells, suggesting the role of macrophage in fibrogenesis in NSG mice. In order to study long-term survival, 6/9 mice who survived more than 56 days showed increased fibrosis in the lung and liver at the endpoint, which suggests the infiltrating hCD68+ macrophages may be pathogenic. It was shown that the combination of CTX and TBI with a low number of G-hPBMCs (1x106) leads to chronic lung and liver inflammation driven by a high infiltration of human macrophage and mature human T cells from the graft, resulting in fibrosis of lung and liver in NSG mice. In conclusion this model may serve as an important pre-clinical model to further current understanding of the roles of human macrophages in cGvHD.

  13. Radioprotective effects of Cordyceps sinensis extracts on {gamma}-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Beong Gyu [Wongwang Health Science College, Iri (Korea, Republic of); Kim, On Joong; Kim, Jae Young [Dongguk University, Seoul (Korea, Republic of)

    1999-06-01

    Effect of single intraperitoneal administration of Cordyceps sinensis (Cs) extract at 24 hour before whole-body {gamma} - irradiation on the survival ratio, body weight, organ weight changes and serum metabolites in the irradiated mice were investigated. The single pre-administration of Cs extract increased the 40-day survival ration of irradiated mice from 66.7 percent to 83.4 percent. The administration of Cs extract completely prevented weight reductions of spleen and thymus produced by {gamma} - irradiation (P < 0.05, P < 0.01). Similar but somewhat less radioprotective effect was also found in the testis of the Cs treated mice. The administration of Cs inhibited the serum hyperglycemia produced by irradiation on the day 7th(P < 0.01). However, it did not influence the serum cholesterol and protein levels on the days examined. The present study is the first report regarding Cs which was tested and found to be radioprotective. (Author)

  14. 低剂量辐射对荷S180肉瘤小鼠肿瘤的抑制作用及信号传导影响%The effect of low-dose total body irradiation on tumor-inhibition and signal transduction in tumor tissues of mice bearing S180 sarcoma

    Institute of Scientific and Technical Information of China (English)

    Hongsheng Yu; Weihua Sun; Ning Liu

    2011-01-01

    Objective: By studying the influence of low-dose total body irradiation to proliferating cell nuclear antigens (PCNA), epidermal growth factor receptor (EGFR), erythropoietin (EPO) and vascular endothelial growth factor receptor (VEGFR) of tumor tissues in mice bearing S180 sarcoma, to further explore the mechanism of low doses radiation. Methods: S180 sarcoma cells were implanted subcutaneously into 58 male Kunming mice. Randomly these mice were divided into sham-irradiation (S) group and low-dose radiation (LDR) group. 12 days after implantation, the mice in LDR group were once delivered 75 mGy total-body 60Co γ-ray irradiation, while the mice in S group were left without irradiation. Then the mice in LDR group were executed at 6 h (LDR-6h group), 12 h (LDR-12 h group), 24 h (LDR-24 h group), 48 h (LDR-48 h group) and 72 h (LDR-72h group) after irradiation. Tumor tissues were weighed and histological observed. Immunohistochemical stain-ing was used to detect the expression of PCNA, VEGF, EPO and VEGFR of tumor tissues. Results: Though there was no significant difference between LDR group and S group in tumor weight, after irradiation the expression of PCNA and EPO of tumor tissues in LDR group decreased with time. LDR-24h, LDR-48h and LDR-72h groups were all statistically significantly different from S group. The expression of EGFR and VEGFR also decreased, and LDR-24h group was the lowest (P < 0.05). Conclusion: Seventy-two h after low-dose total body irradiation, there was no significant change in tumor size of mice bear-ing S180 sarcoma. Low-dose total body radiation decreased the expression of PCNA inhibiting tumor growth; reduced the expression of EGFR in tumor tissue impacting the signal transduction of tumor cells. The study also indicated that low-dose total body irradiation, within a certain period of time, can decrease the expression of hypoxia factor EPO and VEGFR, which may improve the situation of tumor hypoxia and radiosensitivity of tumor itself.

  15. Tissue air ratio in total body irradiation

    International Nuclear Information System (INIS)

    On the basis of dose readings in 102 patients treated with total body irradiation (TBI), a 'tissue air ratio (TAR) curve' has been produced. It could be useful to precalculate treatment time in TBI, for dose prescription to a specific point, provided the same source (60Co) and treatment setting (lateral irradiation; 3 m source-axis distance; reference point at thighs bifurcation, neat the perineum) is used. The TAR curve produced, and the formula relating tissue depth to TAR value, are presented, and compared to preexisting data for 'magna fields' treatments. This curve is exponential, and in semilog representation becomes straight, as every classic TAR curve; it is lower than others, reflecting non full-scatter situation in patient irradiation. (orig.)

  16. Ocular sensitization of mice by live (but not irradiated) Chlamydia trachomatis serovar A

    International Nuclear Information System (INIS)

    Ocular exposure of mice to live elementary bodies of Chlamydia trachomatis serovar A results in immunological sensitization of the mice. This reactivity is manifested by the development of early (5 h) and delayed-type (24 h) dermal reactivity and serovar-specific antibody formation against either live or irradiated (100 kilorads) elementary bodies. Parallel ocular exposure of mice to irradiated elementary bodies does not result in this sensitization. The early and late dermal immune responses induced by ocular exposure to live organisms can be transferred to unexposed mice by serum and lymphoid cell transfers, respectively. It appears that successful murine ocular sensitization by human C. trachomatis serovar A elementary bodies is an ability manifested by live organisms and not by inactivated but antigenic organisms

  17. Radioprotection of vitamin D on mice injured by irradiation

    International Nuclear Information System (INIS)

    To investigate the radioprotective effect of vitamin D against irradiation injury, the mice exposed to 60Co γ-rays at 6 Gy was treated with preparation of vitamin D(Alfacalcidol Soft Capsules). Cell cycle and apoptosis was analyzed by flow cytometry (FCM) following staining of cells with propidium iodide (PI). Peripheral blood cell counts were analyzed by autoanalyzer. It has been found that vitamin D significantly increases white blood cell (WBC) counts, decreases bone marrow PEC micronucleus rate. FCM analysis shows that compared with damaged group, G2 and S phases of bone marrow cells in vitamin D protection group increases significantly at 24 h after whole body irradiation, whereas G1 phase cells decrease at the same times. So vitamin D might be a new radioprotection agent and it should be deserved further study. (authors)

  18. Treatment of wound sepsis in irradiated mice

    International Nuclear Information System (INIS)

    The local and systemic effect of penicillin therapy, supplemented by immunoglobulins, and pentoxifylline on wounds infected by Staphylococcus aureus was evaluated in mice irradiated with 6.5 Gy 60Co γ-rays. Treatment with 62.5 mg/kg penicillin-G was administered for 10 days. Numbers of bacteria were significantly reduced from 7.3 (± 0.3) to 5.3 (± 0.4) log10 CFU/mg ± muscle in treated animals. Administration of immunoglobulin G i.v. or pentoxifylline i.p. alone, or in addition to penicillin-G, did not further reduce the number of bacteria. Increase in the dose of penicillin to 250 mg/kg decreased the number of bacteria more than 62.5 mg/kg. Bacteria were recovered from spleens and/or livers of all 13 untreated mice, and only in six of the 13 penicillin-treated mice (P<0.05). Penicillin therapy reduced the systemic spread of S. aureus. (author)

  19. Treatment of wound sepsis in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Elliott, T.B. (Armed Forces Radiobiology Research Inst., Bethesda, MD (USA))

    1989-07-01

    The local and systemic effect of penicillin therapy, supplemented by immunoglobulins, and pentoxifylline on wounds infected by Staphylococcus aureus was evaluated in mice irradiated with 6.5 Gy {sup 60}Co {gamma}-rays. Treatment with 62.5 mg/kg penicillin-G was administered for 10 days. Numbers of bacteria were significantly reduced from 7.3 (+- 0.3) to 5.3 (+- 0.4) log{sub 10} CFU/mg +- muscle in treated animals. Administration of immunoglobulin G i.v. or pentoxifylline i.p. alone, or in addition to penicillin-G, did not further reduce the number of bacteria. Increase in the dose of penicillin to 250 mg/kg decreased the number of bacteria more than 62.5 mg/kg. Bacteria were recovered from spleens and/or livers of all 13 untreated mice, and only in six of the 13 penicillin-treated mice (P<0.05). Penicillin therapy reduced the systemic spread of S. aureus. (author).

  20. Effects of 5-fluorouracil on survival and hematopoiesis in irradiated mice

    International Nuclear Information System (INIS)

    The effects of whole-body irradiation on survival and hematopoiesis were studied in mice treated with 5-fluorouracil (5-FU). Animals (ddy-SLC male mice, 8 - 10 weeks old) were injected with 5-FU (i.p.) as a single dose (150 mg/kg) at various times before or after irradiation with X-rays. In mice pretreated with 5-FU at different intervals before X-irradiation (1.9 Gy), the radiosensitivity of the CFU-S population changed day by day after the treatment. The maximal survival for femoral CFU-S was obtained in mice treated with 5-FU at 5 days before irradiation. The post-irradiation recovery for femoral and splenetic CFU-S in mice pretreated with 5-FU at 3 days before X-irradiation (1.9 Gy) was faster than in mice given irradiation alone. The pattern of change for thrombocyte counts in the circulating blood after X-irradiation (1.9 Gy) was greatly modified by the pretreatment with 5-FU at 5 days before irradiation, being effective in lessening the radiation-induced depression. For survival experiments, treatment of mice with 5-FU at 5 days before X-irradiation with graded doses (4.8 to 7.6 Gy) was the most effective in reducing for radiation lethality. The dose reduction factor was obtained as 1.24. However, treatment with 5-FU at 1 day and 2 hours before, and at times after irradiation increased the radiation lethality compared to the untreated controls. Such phenomena on the decrease or the increase of radiation lethality of 5-FU exhibited a similar pattern to the radiation-dose relation on endogenous and exogenous CFU-S. (author)

  1. Effect of Fractionated Doses of Cerastes Cerastes Crude Venom on Tissues of Irradiated Mice

    International Nuclear Information System (INIS)

    This Work aims to study the effect of fractionated doses of Cerastes cerastes (C. cerastes) crude venom (CCV) on physiological alterations in different tissues of 5.5 Gy γ-irradiated mice. Male mice were grouped into: Control group. CCV group; mice received via inter peritoneum (i.p.) ⅓LD50 CCV in fractionated doses over a period of 2 weeks. Irradiated group; mice whole body exposed to 5.5 Gy γ-rays. Irradiated+ CCV; mice received via i.p ⅓LD50 CCV in fractionated doses over a period of 2 weeks starting 1 h post irradiation. Exposure to 5.5 Gy γ-rays elevated advanced oxidation protein products (AOPP) and malondialdehyde (MDA) levels and decreased glutathione (GSH) content of liver, spleen and kidney. Moreover, γ-irradiation significantly decreased calcium (Ca) and elevated zinc (Zn), and cupper (Cu) in liver, spleen and kidney tissues compared to the control, whereas, iron (Fe) was significantly elevated in liver and spleen and decreased in kidney. In addition, serum urea and creatinine and their ratio were significantly increased. Irradiated mice treated with fractionated CCV showed significant amelioration of oxidative stress and element alterations in the different tissues. It could be concluded that the fractionated doses of CCV (⅓LD50) might have favourable potential against irradiation induced-biochemical injuries.

  2. Effects of total body irradiation on functions of small intestinal intraepithelial lymphocytes

    International Nuclear Information System (INIS)

    Objective: To explore the characteristics of intestinal mucosal immunity after gamma irradiation. Methods: The number, proliferation activity, cytotoxic activity of small intestinal intraepithelial lymphocytes (IELs), and the TNF-α and TGF-β concentrations in supernatant of cultured IELs were studied using IELs freshly isolated from whole small intestine of Kunming strain mice after 3,8 and 12 Gy total body 60Co γ-irradiation. Results: (1) The number of IELs in small intestinal mucosa of all irradiated mice significantly decreased at 8 h, reaching the lowest level at 48-72 h post-irradiation, then began to rise, but it still did not return to its normal level on day 15. (2) The proliferation activity and cytotoxic activity of IELs isolated from irradiated mice were reduced sharply. They followed the same pattern of decreasing at 8h, reaching the lowest level at 48-72 h post-irradiation, then began to rise, but it did not return to their normal levels on day 15. (3) The TNF-α and TGF-β concentrations in supernatant of cultured IELs isolated from irradiated mice were elevated at 8h, reaching their peak at 48-72 h. Conclusion: The decrease in number and important functions of IELs is one of the factors damaging the intestinal mucosal immunity barrier after total body irradiation

  3. Protective effect of intermittent fasting on the mortality of gamma-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Kozubik, A.; Pospisil, M.

    1982-12-01

    The effect of 1 to 6 weeks' adaptation to intermittent fasting (alternating periods of 24 h fasting and subsequent 24 h feeding) on the manifestations of radioresistance of mice subjected to whole-body gamma-irradiation was studied. A favourable effect of this feeding regimen on the survival of irradiated animals was observed. The optimal redioprotective effect was achieved in mice adapted to intermittent fasting for 2 to 3 weeks and irradiated after 24 h of food intake. Furthermore, it was shown that the radioresistance of the adapted organism depends on the momentary state of food intake. After renewal of the normal ad libitum feeding the adaptively induced radioresistance decreases.

  4. Protective effect of intermittent fasting on the mortality of gamma-irradiated mice

    International Nuclear Information System (INIS)

    The effect of 1 to 6 weeks' adaptation to intermittent fasting (alternating periods of 24 h fasting and subsequent 24 h feeding) on the manifestations of radioresistance of mice subjected to whole-body gamma-irradiation was studied. A favourable effect of this feeding regimen on the survival of irradiated animals was observed. The optimal redioprotective effect was achieved in mice adapted to intermittent fasting for 2 to 3 weeks and irradiated after 24 h of food intake. Furthermore, it was shown that the radioresistance of the adapted organism depends on the momentary state of food intake. After renewal of the normal ad libitum feeding the adaptively induced radioresistance decreases. (orig.)

  5. Influence of prolonged dietary consumption of zeolites on a survival rate and intestine response in mice different age after irradiation

    International Nuclear Information System (INIS)

    Effect of long-term dietary consumption of zeolites on the structural-functional status of adherent mucous layers of digestive tract in mice of different age is studied as well as zeolites effect on the survival and mean life span in irradiation mice. Mice were exposed to whole-body acute irradiation at 4 Gy dose. RUM-17 X-ray apparatus was used for exposure. It is shown that the zeolites increase the survival and mean life span in mice following irradiation. Shivirtuin caused more expressed effect than that of pegasin

  6. Transplantation of Hymenolepis diminuta into naive, immune and irradiated mice

    International Nuclear Information System (INIS)

    Almost 100% of 7- to 10-day-old Hymenolepis diminuta became established when surgically transplanted from donor mice into the duodenum of naive recipient mice. Transplanted tapeworms survived 8 to 12 days, by which time they had survived much longer in total than they would have done in the donor. Mice previously immunized by a primary infection rejected transplants within 4 days. Sub-lethal irradiation (550 rad) delayed rejection by immune mice but such mice still rejected worms much more quickly than did naive mice. Surgery was shown to delay by 2 to 3 days the rejection of worms by naive mice, and the importance of circumventing surgery by administering the worms per os is emphasized. Prospects for reconstituting irradiated immune mice are considered vis-a-vis work with nematodes, and the differences which, on present knowledge, appear to exist between nematode and cestode rejection are briefly discussed. (author)

  7. 60Coγ射线半身照射对非照射区域骨髓造血组织基质细胞衍生因子1表达的影响%Influences of 60Coγray irradiation on expression stromal cell derived factor-1 in bone marrow hematopoietic tissue of non-irradiation area in left-half-body ionizing irradiated mice

    Institute of Scientific and Technical Information of China (English)

    高作文; 杨龙; 陈乐如; 娄金书; 张国强; 李开信; 程天民

    2013-01-01

    Objective To invesligale the mouse bone marrow hemalopoielic functions in non-irradiation area after irradiated by way of left-half- body. Methods The 6-8-week male Kunming strain mice were randomly divided into normal control( NC) , total-body-irradiated( TBI) , left-half-body-irradiated( LHBI) , and total-body-shield-irradia-ted( TBSI) groups. Left-half-body-irradiated group was treated with two pieces of 5 cm x 8 cm x 16 cm overlapped lead bricks shielding right-side body and irradiated with 8. 0 Gy60Coγ-ray. The leukocyte in peripheral blood and the number of bone marrow hematopoietic cells( BMHCs) were studied, the concentration of SOD, MDA in mouse serum were measured, and the expression SDF-1 in bone marrow hematopoietic tissues were observed by the Western blotting method and laser scanning confocal microscope combined with immunohistochemistry. Results In the left-half-body irradiated condition, the leucocyte in peripheral blood and the BMHCs were diminished, the concentration of MDA was increased and the SOD was decreased in the mouse serum remarkably ( compared with NC, P <0. 01) ; In non-irradiation area, the SDF-1-positive cells and the expression SDF-1 in bone marrow hematopoietic tissues were reduced significantly. Conclusion Our study suggested that the local irradiation resulted in the decrease of SDF-1-positive cells and the decline expression SDF-1 in bone marrow hematopoietic tissues in non-irradiation area, and the increase of reactive oxygen or free radicals might play an important role in the abnormal expression of SDF-1 in BMHT and the injury of hematopoietic microenvironment.%目的 探讨局部电离辐射对小鼠非照射区域骨髓造血组织基质细胞衍生因子-1(SDF-1)表达的影响.方法 将6~8周龄雄性昆明小鼠随机分为健康对照组、全身照射组、全身屏蔽照射组以及左半身照射组4组,用铅屏蔽建立半身照射模型,以8.0 Gy 60Co γ射线照射,观察小鼠外周血白细胞和骨髓有核

  8. Diagnosis of partial body radiation exposure in mice using peripheral blood gene expression profiles.

    Directory of Open Access Journals (Sweden)

    Sarah K Meadows

    Full Text Available In the event of a terrorist-mediated attack in the United States using radiological or improvised nuclear weapons, it is expected that hundreds of thousands of people could be exposed to life-threatening levels of ionizing radiation. We have recently shown that genome-wide expression analysis of the peripheral blood (PB can generate gene expression profiles that can predict radiation exposure and distinguish the dose level of exposure following total body irradiation (TBI. However, in the event a radiation-mass casualty scenario, many victims will have heterogeneous exposure due to partial shielding and it is unknown whether PB gene expression profiles would be useful in predicting the status of partially irradiated individuals. Here, we identified gene expression profiles in the PB that were characteristic of anterior hemibody-, posterior hemibody- and single limb-irradiation at 0.5 Gy, 2 Gy and 10 Gy in C57Bl6 mice. These PB signatures predicted the radiation status of partially irradiated mice with a high level of accuracy (range 79-100% compared to non-irradiated mice. Interestingly, PB signatures of partial body irradiation were poorly predictive of radiation status by site of injury (range 16-43%, suggesting that the PB molecular response to partial body irradiation was anatomic site specific. Importantly, PB gene signatures generated from TBI-treated mice failed completely to predict the radiation status of partially irradiated animals or non-irradiated controls. These data demonstrate that partial body irradiation, even to a single limb, generates a characteristic PB signature of radiation injury and thus may necessitate the use of multiple signatures, both partial body and total body, to accurately assess the status of an individual exposed to radiation.

  9. Establishment of a mouse model of 70% lethal dose by total-body irradiation.

    Science.gov (United States)

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun; Choi, Yang-Kyu

    2016-06-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model.

  10. Establishment of a mouse model of 70% lethal dose by total-body irradiation.

    Science.gov (United States)

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun; Choi, Yang-Kyu

    2016-06-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model. PMID:27382380

  11. The effects of 3Gy total body irradiation on mouse intestinal intraepithelial lymphocytes' number and functions

    International Nuclear Information System (INIS)

    To explore the characteristics of intestinal mucosal immunity after radiation injury, IEL number, proliferation activity, cytotoxic activity as well as the TNF-α and TGF-β concentrations of supernatant of cultured IEL were studied using IEL freshly isolated from whole small intestine of Kunming strain mice received 3Gy total body 60Co γ-ray irradiation. The proliferation activity, cytotoxic activity as well as the number of IEL in small intestinal mucosa were significantly decreased at 8h post-irradiation, reaching lowest level at 72h. The TNF-α and TGF-β concentrations of supernatant of cultured IEL isolated from irradiated mice were elevated at 8h, reaching peak at 72h. The decrease in number and functions of IEL may play an important role in the damage intestinal mucosal immunity barrier after total body irradiation

  12. Evaluation of the radioprotective effects of propolis and flavonoids in gamma-irradiated mice. The alkaline comet assay study

    International Nuclear Information System (INIS)

    The radioprotective effects of water-soluble derivate of propolis (WSDP) collected in Croatia, and single flavonoids, caffeic acid, chrysin and naringin in the whole-body irradiated CBA mice were investigated. Irradiation was performed using a γ-ray source (60Co), and absorbed doses were 4 and 9 Gy. The efficiency of test components was evaluated when given intraperitoneally (i.p.) at dose of 100 mg kg-1 for 3 consecutive days before and/or after irradiation. Moreover, possible genotoxic effects of all test components were assessed on non-irradiated animals. The higher efficiency of test components was observed when given preventively. The results suggest that propolis and related flavonoids given to mice before irradiation protected mice from lethal effects of whole-body irradiation and diminish primary DNA damage in their white blood cells as detected by the alkaline comet assay. (author)

  13. Effects of Propolis on Peripheral White Cells, Antioxidative Activity and Tumor Growth in Irradiated mice

    Institute of Scientific and Technical Information of China (English)

    Takashi Nakamura; Yuka Itokawa; Kwang-Ho Cho; Jung-Sook Choi; Ikukatsu Suzuki; Toshihoro Miura; Torao Ishida; Yeunhwa Gu

    2006-01-01

    The effect of continuous water-soluble propolis administration on radioactivity-induced reduction of hemocytes, and the antioxidant and antitumor effects were investigated. Following a 1-week adjustment period, water-soluble propolis was administered intraperitoneally to male ICR mice at a dose of 100mg/kg every other day for 2 weeks. Following administration, 2 Gy whole-body irradiation was performed and the counts of leukocytes, lymphocytes, and granulocytes and monocytes in the peripheral blood were determined 1, 3, 7, 15 and 30 days after irradiation. In the second experiment, water-soluble propolis was similarly administered to the mice for 2 weeks after a 1-week adjustment period, and 2 Gy whole-body irradiation was performed. The antioxidant effects in hemocytes were then investigated using 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), a radical generator. In the third experiment, 1×l06 Sarcoma-180 cells were inoculated into the right thigh of mice, which were divided into four groups: control, water-soluble propolis-treated, 6 Gy irradiated and water-soluble propolis-treated + 6 Gy irradiated groups, and changes in tumor size were measured for 20 days. Results show that administration of water-soluble propolis inhibits the reduction of hemocytes caused by whole-body irradiation, enhances antioxidant effects against radioactivity, and inhibits tumor growth.

  14. Effect of recombinant human granulocyte colony-stimulating factor on granulocytopenia in mice induced by irradiation

    International Nuclear Information System (INIS)

    We report the effect of human granulocyte colony-stimulating factor (hG-CSF) on the recovery from granulocytopenia induced by irradiation. Female 9-week old C3H/He mice were used. The irradiation schedule was as follows: Group 1 and 2 received whole-body irradiation of 1 Gy and 5 Gy, respectively, on day 0; Group 3 and 4 received whole-body irradiation of 0.5 and 1.0 Gy, respectively, for 5 consecutive days; Group 5 received upper hemibody irradiation of 3 Gy for 5 consecutive days. Daily subcutaneous injections of G-CSF (3 x 10(5) Unit/mouse) or 0.3 ml of saline to each group were started from the day after the first irradiation and continued for 18 days. Mice were sampled randomly from each group, and the total number of leukocytes, erythrocytes of peripheral blood, nucleated cells in femur, and spleen weight were counted and measured, respectively, on day 0, 3, 5, 7, 9, 12, and 18. The leukocyte counts decreased with an increase in radiation doses. In Group 1 and 2 mice, G-CSF enhanced the leukocyte count more than saline. In Group 3 mice, the recovery of leukocytopenia was facilitated by G-CSF, but in Group 4 mice, G-CSF had no effect on the leukocyte count decrease or on leukocytopenia recovery. In Group 5 mice, G-CSF greatly affected leukocytopenia recovery. Increase in spleen weight paralleled the peripheral leukocyte count. Daily administration of recombinant hG-CSF accelerated the granulocytopenia recovery which was induced by irradiation, and it may be a useful therapeutic agent for treating myelosuppressive cases

  15. Thrombopoietin protects mice from mortality and myelosuppression following high-dose irradiation: importance of time scheduling

    Energy Technology Data Exchange (ETDEWEB)

    Mouthon, M.-A.; Van der Meeren, A.; Vandamme, M.; Squiban, C.; Gaugler, M.-H. [Inst. de Protection det de Surete Nucleaire, IPSN, Fontenay-aux-Roses CEDEX (France)

    2002-07-01

    Thrombopoietin is the major regulator of platelet production and a stimulator of multilineage hematopoietic recovery following irradiation. The efficacy of three different schedules of thrombopoietin administration was tested on blood cell counts, hematopoietic bone marrow progenitors, and 30-day animal survival in C57BL6/J mice receiving a total body irradiation, with doses ranging from 7 to 10 Gy. A single dose of murine thrombopoietin was injected 2 h before, 2 h after, or 24 h after irradiation. Thrombopoietin promoted multilineage hematopoietic recovery in comparison to placebo up to 9 Gy at the level of both blood cells and bone marrow progenitors, whatever the schedule of administration. The injection of thrombopoietin 2 h before or 2 h after irradiation equally led to the best results concerning hematopoietic recovery. On the other hand, thrombopoietin administration promoted 30-day survival up to 9 Gy with the highest efficacy obtained when thrombopoietin was injected either 2 h before or 2 h after irradiation. However, when its injection was delayed at 24 h, thrombopoietin had almost no effect on survival of 9 Gy irradiated mice. Altogether, our results show that the time schedule for thrombopoietin injection is of critical importance and when thrombopoietin is administered before or shortly after irradiation, it efficiently promotes mice survival to supra-lethal irradiation (up to 9 Gy) in relation with hematopoietic recovery. (author)

  16. Radiation-induced apoptosis in SCID mice spleen after low dose irradiation

    Science.gov (United States)

    Takahashi, A.; Kondo, N.; Inaba, H.; Uotani, K.; Kiyohara, Y.; Ohnishi, K.; Ohnishi, T.

    To assess the radioadaptive response of the whole body system in mice, we examined the temporal effect of low dose priming as an indicator of challenging irradiation-induced apoptosis through a p53 tumor suppressor protein- mediated signal transduction pathway. The p53 protein also plays an important role both in cell cycle control and DNA repair through cellular signal transduction. Using severe combined immunodeficiency mice defective in DNA-dependent protein kinase catalytic subunit, we examined the role of DNA-dependent protein kinase activity in radioadaptation induced by low dose irradiation. Specific pathogen free 5-week-old female severe combined immunodeficiency mice and the parental mice (CB-17 Icr +/ + were irradiated with X-ray at 3.0 C3y at 1, 2, 3 or 4 weeks after the conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after the challenging irradiation. The p53-dependent apoptosis related Bax proteins on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method The apoptosis incidence in the sections was measured by hematoxylin-eosin staining. The frequency of Bax- and apoptosis-positive cells increased up to 12 h after the challenging irradiation in the spleen of both mice. However, these cells were not observed after a low dose irradiation at 0.15-0.60 Gy When pre-irradiation at 0.45 Gy 2 weeks before the challenging irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by challenging irradiation were depressed in the spleens of CB-17 Icr +/ + mice, but not in severe combined immunodeficiency mice. These data suggest that DNA-dependent protein kinase might play a major role in radioadaptation induced by pre-irradiation with a low dose in mice spleen. We expect that the present findings will provide useful information in the health care of space crews.

  17. Total body irradiation with a sweeping beam

    Energy Technology Data Exchange (ETDEWEB)

    Pla, M.; Chenery, S.G.; Podgorsak, E.B.

    1983-01-01

    A technique for total body irradiation, in which the patient lies in the prone or supine position in the beam of a conventional column mounted 4 MV linear accelerator, is described. A sufficiently large radiation field is obtained by rotating the beam in a vertical plane about the source (i.e., sweeping beam) at a source-to-skin distance of 190 cm on the vertical axis. The variation of the midplane dose is less than +lt. slash-5% in parallel-opposed beams, when attenuators are placed over the region containing the lungs and bolus is employed around the head and legs. The percentage depth dose for the sweeping beam is identical to that of a stationary beam for the same collimator setting and source-to-skin distance. A method for monitoring the dose to the patient by means of a thimble ionization chamber located on the vertical beam axis is outlined. The average dose rates used are between 5 and 10 cGy/min. The design and placement of lung attenuators is simple. The treatment technique with the sweeping beam requires minimal modification of a treatment unit and can be applied on any unit which has a head swivel option.

  18. Total body irradiation in bone marrow transplantation

    International Nuclear Information System (INIS)

    Total body irradiation was used in 22 patients as part of their conditioning regimen for bone marrow transplantation. Nine patients with acute leukemia received 1000 cGy TBI in addition with chemotherapy. None of them survived and the main cause of death was interstitial pneumonitis (50%). 4 patients received 1000 cGy with a lung shielding of 500 cGy. Two patients with acute leukemia died of leukemia and sepsis, two patients had aplastic anemia, one is surviving, the other died of severe GVHD and infectious complications. Nine patients with severe aplastic anemia strongly immunized by previous blood transfusions received 800 cGy TBI with a lung shielding of 400 cGy. No rejection was observed and 7 patients (63%) are currently alive. One patient died of interstitial pneumonitis probably related to CMV infection, one of subacute necrotizing hepatitis, two of severe acute GVHD. It is concluded from this study that TBI remains the best immunosuppressive conditioning regimen even in strongly immunized patients. It may be a contributing factor of the incidence and severity of interstitial pneumonitis. A reduction of the dose of the lung to 400-500 cGy seems to decrease the severity of this complication

  19. Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1α

    International Nuclear Information System (INIS)

    Recombinant human interleukin-1α (rhIL-1α) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1α in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1α administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1α-induced increase in ACTH levels at the doses used. In fact, the rhIL-1α-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus. 36 refs., 3 figs

  20. Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Perlstein, R.S.; Mehta, N.R.; Neta, R.; Whitnall, M.H. [Armed Forces Radiobiology Research Institute, Bethesda, MD (United States); Mougey, E.H. [Walter Reed Army Institute of Research, Washington, DC (United States)

    1995-03-01

    Recombinant human interleukin-1{alpha} (rhIL-1{alpha}) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1{alpha} in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1{alpha} administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1{alpha}-induced increase in ACTH levels at the doses used. In fact, the rhIL-1{alpha}-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus. 36 refs., 3 figs.

  1. Total body irradiation: current indications; L`irradiation corporelle totale: les indications actuelles

    Energy Technology Data Exchange (ETDEWEB)

    Giraud, P.; Danhier, S.; Dubray, B.; Cosset, J.M. [Institut Curie, 75 - Paris (France)

    1998-05-01

    The choice of dose and fractionation for total body irradiation is made difficult by the large number of considerations to be taken into account. The outcome of bone marrow transplantation after total body irradiation can be understood in terms of tumor cell killing, engraftment, and normal tissue damage, each of these endpoints being influenced by irradiation-, disease-, transplant-, and patient- related factors. Interpretation of clinical data is further hampered by the overwhelming influence of logistic constraints, the small numbers of randomized studies, and the concomitant variations in total dose and fraction size or dose rate. So far, three cautious conclusions can be drawn in order to tentatively adapt the total body irradiation schedule to clinically-relevant situations. Firstly, the organs at risk for normal tissue damage (lung, liver, lens, kidney) are protected by delivering small doses per fraction at low dose rate. This suggests that, when toxicity is at stake (e.g. in children), fractionated irradiation should be preferred, provided that inter-fraction intervals are long enough. Secondly, fractionated irradiation should be avoided in case of T-cell depleted transplant, given the high risk of graft rejection in this setting. An alternative would be to increase total (or fractional) dose of fractionated total body irradiation, but this approach is likely to induce more normal tissue toxicity. Thirdly, clinical data have shown higher relapse rates in chronic myeloid leukemia after fractionated or low dose rate total body irradiation, suggesting that fractionated irradiation should not be recommended, unless total (or fractional) dose is increased. Total body irradiation-containing regimens, primarily cyclophosphamide / total body irradiation, are either equivalent to or better than the chemotherapy-only regimens, primarily busulfan / cyclophosphamide. Busulfan / cyclophosphamide certainly represents a reasonable alternative, especially in patients who

  2. Intraesophageal manganese superoxide dismutase-plasmid liposomes ameliorates novel total-body and thoracic radiation sensitivity of NOS1-/- mice.

    Science.gov (United States)

    Rajagopalan, Malolan S; Stone, Brandon; Rwigema, Jean-Claude; Salimi, Umar; Epperly, Michael W; Goff, Julie; Franicola, Darcy; Dixon, Tracy; Cao, Shaonan; Zhang, Xichen; Buchholz, Bettina M; Bauer, Anthony J; Choi, Serah; Bakkenist, Christopher; Wang, Hong; Greenberger, Joel S

    2010-09-01

    The effect of deletion of the nitric oxide synthase 1 gene (NOS1(-/-)) on radiosensitivity was determined. In vitro, long-term cultures of bone marrow stromal cells derived from NOS1(-/-) were more radioresistant than cells from C57BL/6NHsd (wild-type), NOS2(-/-) or NOS3(-/-) mice. Mice from each strain received 20 Gy thoracic irradiation or 9.5 Gy total-body irradiation (TBI), and NOS1(-/-) mice were more sensitive to both. To determine the etiology of radiosensitivity, studies of histopathology, lower esophageal contractility, gastrointestinal transit, blood counts, electrolytes and inflammatory markers were performed; no significant differences between irradiated NOS1(-/-) and control mice were found. Video camera surveillance revealed the cause of death in NOS1(-/-) mice to be grand mal seizures; control mice died with fatigue and listlessness associated with low blood counts after TBI. NOS1(-/-) mice were not sensitive to brain-only irradiation. MnSOD-PL therapy delivered to the esophagus of wild-type and NOS1(-/-) mice resulted in equivalent biochemical levels in both; however, in NOS1(-/-) mice, MnSOD-PL significantly increased survival after both thoracic and total-body irradiation. The mechanism of radiosensitivity of NOS1(-/-) mice and its reversal by MnSOD-PL may be related to the developmental esophageal enteric neuronal innervation abnormalities described in these mice. PMID:20726721

  3. Total body irradiation for bone marrow transplantation

    International Nuclear Information System (INIS)

    Purpose/Objective: The primary goal of this course is to develop an understanding of the rationale for the use of total body irradiation (TBI) as a component of cytoreduction for bone marrow transplantation, the techniques used, and the results of changing important parameters, such as dose, dose rate, and fractionation. Materials and Methods: Basic radiobiological principles relevant to TBI are reviewed; in particular, emphasis is placed on cell and animal studies which suggest means of optimizing TBI delivery to achieve maximum tumor cell kill and immunosuppression along with minimal normal tissue damage. Techniques utilized at various centers are described, with some discussion of achieving homogeneity, as well as inhomogeneity when desired with partial shielding or 'boosting'. A review of clinical studies, both randomized and non-randomized, is done; these are then interpreted in terms of potential optimization of the TBI parameters. Finally, comparison of TBI-containing regimens with chemotherapy-only regimens is done. Results: Radiobiological studies suggest a potential advantage for fractionated TBI over single dose TBI. Clinical studies support this view: highly fractionated regimens have allowed higher total doses to be used to increase malignant cell kill and immunosuppression without increasing toxicity. Randomized studies of TBI combined with VP-16 or cyclophosphamide versus busulfan combined with cyclophosphamide have either shown an advantage with TBI (in acute myelocytic leukemia in first remission) or no difference (in chronic myelogenous leukemia, chronic phase). Conclusion: TBI has been an effective component of cytoreductive regimens for marrow transplantation in patients with malignant disease, especially leukemias, which constitute 73% of all marrow transplants worldwide. Evidence supports fractionated TBI, to doses ≥ 13 Gy, when compared with single dose TBI. Randomized studies support the continued use of TBI in AML, and suggest that

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

    International Nuclear Information System (INIS)

    Experimental testicular dysfunction was produced by X-ray irradiation to the testes in mice. Mecobalamin (CH3-B12) 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 CH3-B12 (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 CH3-B12 improved the experimental testicular dysfunction in mice induced by the irradiation. These results suggest that CH3-B12 might accelerate testicular function. (author)

  5. Changes in hemopoiesis of dying and surviving mice after fractionated irradiation and repeated bone marrow transplantation

    International Nuclear Information System (INIS)

    Mice received doses of 3 Gy of 60Co-gamma rays total body irradiation at four-day intervals up to a total dose of 24 Gy. After each dose per fraction half of the animals were injected with 106 bone marrow cells. At four- and nine-day intervals evaluations were made of the blood count, bone marrow and spleen cellularities, and spleen mass. In animals subjected only to irradiation the damage of hemopoietic organs was becoming deeper until the end of observation; the majority of these mice died by nine days after the irradiation with the last dose per fraction (by 37 days of the experiment). The authors consider anemia as the main cause of their death. All of the mice that were given bone marrow injections survived; nine days after the last dose of irradiation the mean cellularities of their bone marrows and spleens were 76.8% and 112.3% of the unirradiated controls respectively. In general, regeneration of erythropoiesis was quite successful, the number of thrombocytes was positively influenced, and the number of leukocytes nearly unchanged in bone marrow recipients when compared with the only irradiated mice. We observed two periods of maximum and one of minimum bone marrow and spleen regeneration, which were not synchronized. These results deny an unrepairable damage to the hemopoietic microenvironment in conditions of our experiment. This paper follows up with our preceding work describing results of an experiment which ended on day 24. (orig.)

  6. Comparative studies in the cellular immunostimulation by whole body irradiation

    International Nuclear Information System (INIS)

    The effect of the cellular immune response by total body irradiation was investigated. The transplant survival (skin grafts) was determined as immune parameter. Donors were colony bred Wistar rats and recipients were colony bred Sprague Dawley rats. The investigations were carried out with irradiated rats and with rats irradiated after thymectomy and/or adrenalectomy as well as with animals without irradiation. A single total-body irradiation (1 and 2 Gy) was administered. The skin graft survival in irradiated rats was significant shorter (radiogenic immunostimulation) than in unirradiated rats; there were no significant differences between the operated (thymectomy and/or adrenalectomy) and not operated animals. Including precedent examinations this radiogenic immunostimulation is caused by relativly selective inactivation of T-suppressor cells. (orig.)

  7. Development of a new method of whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Kazushi (Wakayama Medical Coll. (Japan))

    1989-08-01

    A new method of whole body irradiation was developed using a linear accelerator linked to microprocessor. By this modified arc technique, a total body photon irradiation and a total skin electron irradiation were practical for narrow room. Approximative calculations were deviced for dose distribution. Dosimetric results were consistent with those previosly calculated. Local doses in lungs, neck and other areas were easily adjustable with arrangements of pre-set dose rate. In total skin electron irradation, six predeterminated postures and 'make up' irradiation were necessary to dose homogeneity over 'shady area' such as axillae. Clinically, a large arteriovenous malformation in an arm decreased with normalization of plethysmogram after treatment, and remarkable reductions of mycosis fungoides tumor were observed. This new method of total skin electron irradiation and total body photon therapy will clinically expand with the progress of bone marrow transplantation. (author).

  8. Analysis of blood gas values in mice following pulmonary irradiation

    International Nuclear Information System (INIS)

    The arterial pH and partial pressures of oxygen (P/sub a/O2) and carbon dioxide (P/sub a/CO2) of mice were investigated at times from 1 to 16 weeks after a single radiation dose of 1100 rad to the thorax. The mice breathed air during the irradiation and either air, 7% O2:93% N2, or 100% O2 during the blood gas determinations. P/sub a/O2 values of mice breathing 7% O2:93% N2 or 100% O2 were reduced 4 to 6 weeks after the irradiation. Also, all P/sub a/O2 values were reduced and all hemoglobin (Hb) levels were elevated 16 weeks after irradiation. The majority of the animals died between 16 and 26 weeks after irradiation, but decreased P/sub a/O2 and increased Hb levels also were observed 27 weeks after the treatment in a few of the surviving mice. These findings indicate that the arterial blood gases may change following pulmonary irradiation and may provide an endpoint for the study of radiation-induced pulmonary damage

  9. Trauma enhanced mortality in irradiated mice

    International Nuclear Information System (INIS)

    Burn (B) or wound (W) trauma after exposure to radiation (R) may complicate 1) the elucidation of injury induction mechanisms and, 2) development of effective treatments for tissue damage and infections. Mouse models of sublethal B and W trauma with R, termed ''combined injury'' (CI), were used to evaluate dose and quality of R with type of injury, as well as responses to and therapy for bacterial challenges. B6D2F/J female mice were bilaterally exposed to doses of 60Co R (5-12 Gy), 0.4 Gy/min. Two hr after exposure, mice were anesthetized with methoxyfluorane and subjected to either 30% dorsal skin B or W. After R, W, B, RW, or RB, mice were given 0.5 ml 0.9% NaCl i.p. The LD50/30 radiation doses were: R = 9.63, RB = 8.2, and RW = 7.61 Gy. Slopes of CI survival curves were the same, but different (rho < .01) from that for R mice, and survival times of CI mice were 25-75% lower than for R mice. W, 48 hr before or 0.1, 24 or 48 hr after sublethal 7 Gy resulted in synergistic increases in mortality of 40, 25, 60 and 80%, respectively. In all CI, R, W, and B mice, intestinal bacteria were cultured from blood, spleen and liver. Challenge with opportunistic pathogens that routinely results in 5% mortality in normal mice, yielded increased mortality (95, 60, 26, 15, and 15% respectively) in RW, RB, R, W, and B animals. These CI models are used to evaluate immuno-modulators of non-specific resistance to bacterial infections

  10. Oral ofloxacin therapy of Pseudomonas aeruginosa sepsis in mice after irradiation

    International Nuclear Information System (INIS)

    Death subsequent to whole-body irradiation is associated with gram-negative bacterial sepsis. The effect of oral therapy with the new quinolone ofloxacin for orally acquired Pseudomonas aeruginosa infection was tested in B6D2F1 mice exposed to 7.0 Gy of bilateral radiation from 60Co. A dose of 10(7) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Only 4 of 20 untreated mice (20%) survived for at least 30 days compared with 19 of 20 mice (95%) treated with ofloxacin (P less than 0.005). P. aeruginosa was isolated from the livers of 21 to 28 untreated mice (75%), compared with only 2 of 30 treated mice (P less than 0.005). Ofloxacin reduced colonization of the ileum by P. aeruginosa; 24 of 28 untreated mice (86%) harbored the organisms, compared with only 5 of 30 (17%) with ofloxacin (P less than 0.005). This experiment was replicated twice, and similar results were obtained. These data illustrate the efficacy of the quinolone ofloxacin for oral therapy of orally acquired P. aeruginosa infection in irradiated hosts

  11. Oral ofloxacin therapy of Pseudomonas aeruginosa sepsis in mice after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Ledney, G.D. (Research Institute, Bethesda, MD (USA))

    1990-07-01

    Death subsequent to whole-body irradiation is associated with gram-negative bacterial sepsis. The effect of oral therapy with the new quinolone ofloxacin for orally acquired Pseudomonas aeruginosa infection was tested in B6D2F1 mice exposed to 7.0 Gy of bilateral radiation from 60Co. A dose of 10(7) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Only 4 of 20 untreated mice (20%) survived for at least 30 days compared with 19 of 20 mice (95%) treated with ofloxacin (P less than 0.005). P. aeruginosa was isolated from the livers of 21 to 28 untreated mice (75%), compared with only 2 of 30 treated mice (P less than 0.005). Ofloxacin reduced colonization of the ileum by P. aeruginosa; 24 of 28 untreated mice (86%) harbored the organisms, compared with only 5 of 30 (17%) with ofloxacin (P less than 0.005). This experiment was replicated twice, and similar results were obtained. These data illustrate the efficacy of the quinolone ofloxacin for oral therapy of orally acquired P. aeruginosa infection in irradiated hosts.

  12. Inhibitory effect of low dose irradiation on tumor metastases in tumor bearing in mice

    Institute of Scientific and Technical Information of China (English)

    魏道严; 金敖兴; 等

    1996-01-01

    By using the models of tumor blood-borne metastasis and spontaneous one,the antitumor metastasis effect of 75mGy X-ray whole body irradiation on tumor bearing mice is investigated.The results demonstrate that irradiation could significantly inhigit B16 Melanoma blood borne pulmonary metastases(P<0.05) and Lewis lung carcinoma(LLC) spontaneous pulmonary metastases(P<0.01),The immunofunction test of B16 melanoma beraing mice shows that the NK(P<0.05) and LAK(P<0.001) cytotoxicities,and responsibility of splenocytes to IL-2(P<0.005) for the irradiated group are increased greatly comperaed with those of control group.These results suggest that the enhancement of immunofunctions is induced by low dose radiation to raise antitumor metastasis effects.

  13. Kinetics of Hesperetin for Liver Fortification in gamma-Irradiated Mice

    International Nuclear Information System (INIS)

    Hesperetin (3',5,7-trihydroxy-4'-methoxyflavonone), the aglycone of the flavanone glycosides hesperidin, exerts pharmacological properties such as antioxidation, anti-inflammation, blood lipid and cholesterol lowering is effectively used as a supplemental agent in the treatment protocols of complementary settings. Four groups were prepared: Control group: received 0.5 ml normal saline for 7 days. Hesperetin group: Mice received 7 doses of hesperetin injections (100 mg/ kg body wt/ day). Irradiated group: Mice submitted to total body irradiation with 4 Gy gamma-rays. Protected group (Hesperetin plus irradiation): Mice received hesperetin for 7 days and then submitted to 4 Gy of gamma-rays. The mice were sacrificed at 24 h, 1 week and 2 weeks after the end of the experimental treatments. Irradiated mice exhibited significant hyperglycaemia and augmented hepatic glycogen after the first day and 1 week but significant hypoglycemia and reducing hepatic glycogen after 2 weeks. Also, they exhibited significant increased serum total cholesterol (TC) and triacylglycerols (TG) and decreased hepatic TC and TG after 1 and 2 weeks. This treatment also resulted in a significant dropped in hepatic glucokinase (GK), glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) activities after 1 and 2 weeks. Hesperetin injections modulated the serum glucose and hepatic glycogen, adjusted TC and TG in both serum and liver and ameliorated the lessening in hepatic GK, G6P and PEPCK. The attending results demonstrated that hesperetn treatment modulated the biochemical symptoms of radiation disorders in mice. In conclusion, administration of hesperetin may have a useful role in modulating oxidative stress induced by exposure to gamma-radiation by improving the natural antioxidant mechanism and fortification liver functions

  14. Radioprotective Effect Of Green Tea Extract On GAMMA Irradiated Mice

    International Nuclear Information System (INIS)

    This study aimed to evaluate the possible radioprotective role of green tea extract (GTE) in mice exposed to gamma radiation. Eighty male mice were divided into four groups; group (A) was considered the control, group (B) received 1.5% GTE for 14 days, group (C) exposed to 4 Gy gamma radiation and group (D) received GTE and exposed to 4 Gy gamma radiation. Blood and liver tissue were collected from these groups 24 hours, 3 days and 5 days post-irradiation to measure the levels of hepatic malondialdehyde (MDA) and superoxide dismutase (SOD), serum aminotransferases (ALT and AST), Hb concentration, RBCs, WBCs and platelets counts, in addition to ultra-structure examination of the liver. The results revealed that GTE supplementation prior to irradiation significantly decreased hepatic MDA, increased hepatic antioxidant enzyme (SOD) and decreased serum ALT and AST compared to irradiated mice. Also, supplementation of mice with GTE led to regeneration and protection of hepatocytes and the levels of the hematological parameters were significantly increased in the GTE pre-treated group as compared to irradiated animals. It could be conclude that the GTE may be a good agent to attenuate radiation-induced damage to the liver and hematopoietic system.

  15. The influence of Listeria monocytogenes cells on the primary immunologic response in irradiated mice

    International Nuclear Information System (INIS)

    The influence of killed Listeria monocytogenes cells on the primary immunologic response in mice irradiated with 300 or 500 R was studied. The immunologic response of the mice to sheep red blood cells used as antigen was assessed at the cellular level (by counting PFC) and humoral level. Injection of killed Listeria monocytogenes cells before irradiation of the mice diminished the immunosuppressive effect of roentgen radiation. Injection of the cells after irradiation accelerated regeneration of immunologic reactivity in the irradiated mice. (author)

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

    International Nuclear Information System (INIS)

    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

  17. Enhanced responses to tumor immunization following total body irradiation are time-dependent.

    Directory of Open Access Journals (Sweden)

    Adi Diab

    Full Text Available The development of successful cancer vaccines is contingent on the ability to induce effective and persistent anti-tumor immunity against self-antigens that do not typically elicit immune responses. In this study, we examine the effects of a non-myeloablative dose of total body irradiation on the ability of tumor-naïve mice to respond to DNA vaccines against melanoma. We demonstrate that irradiation followed by lymphocyte infusion results in a dramatic increase in responsiveness to tumor vaccination, with augmentation of T cell responses to tumor antigens and tumor eradication. In irradiated mice, infused CD8(+ T cells expand in an environment that is relatively depleted in regulatory T cells, and this correlates with improved CD8(+ T cell functionality. We also observe an increase in the frequency of dendritic cells displaying an activated phenotype within lymphoid organs in the first 24 hours after irradiation. Intriguingly, both the relative decrease in regulatory T cells and increase in activated dendritic cells correspond with a brief window of augmented responsiveness to immunization. After this 24 hour window, the numbers of dendritic cells decline, as does the ability of mice to respond to immunizations. When immunizations are initiated within the period of augmented dendritic cell activation, mice develop anti-tumor responses that show increased durability as well as magnitude, and this approach leads to improved survival in experiments with mice bearing established tumors as well as in a spontaneous melanoma model. We conclude that irradiation can produce potent immune adjuvant effects independent of its ability to induce tumor ablation, and that the timing of immunization and lymphocyte infusion in the irradiated host are crucial for generating optimal anti-tumor immunity. Clinical strategies using these approaches must therefore optimize such parameters, as the correct timing of infusion and vaccination may mean the difference

  18. Enhancement of committed hematopoietic stem cell colony formation by nandrolone decanoate after sublethal whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Gallicchio, V.S.; Chen, M.G.; Watts, T.D.

    1984-11-01

    The ability of an anabolic steroid, nandrolone decanoate, to increase committed topoietic stem cell (CFU-gm, CFU-e, and BFU-e) colony formation after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation and on the next two days, each mouse was injected intraperitoneally with nandrolone decanoate (1.25 mg) in propylene glycol. Irradiated control mice received only propylene glycol. Compared to controls, drug-treated mice showed marked peripheral blood leukocytosis and more stable packed red cell volume. Drug-treated mice also demonstrated increased erythropoiesis, as CFU-e/BFU-e concentrations from both marrow (9% to 581%) and spleen (15% to 797%) were elevated. Granulopoiesis was increased similarly, as CFU-gm concentrations from marrow (38% to 685%) and spleen (9% to 373%) were elevated. These results demonstrate that nandrolone decanoate enhances hematopoietic stem cell recovery after sublethal whole body irradiation. This suggests that following hematopoietic suppression, nandrolone decanoate may stimulate the recovery of hematopoiesis at the stem cell level and in peripheral blood.

  19. The Effects of Nerve Growth Factor on Skin Healing and Blood Recovery in Irradiated Mice

    Institute of Scientific and Technical Information of China (English)

    史春梦; 程天民; 屈纪富

    2002-01-01

    @@ It is known that radiation could cause bone marrow aplasia and delay wound healing.To promote cellular proliferation and blood recovery are 2 major goals in the treatment of radiation injury.We have observed that the expression of nerve growth factor (NGF) gene decreased greatly in the wound tissue of irradiated animals by immunohistochemistry and in situ hybridization methods.This study was designed to elucidate the effects of NGF on the skin wound healing and blood recovery in mice after total body irradiation.

  20. Genetic Effects of Neutron Irradiation in Mice

    International Nuclear Information System (INIS)

    The limited amount of information already published on this subject, mainly relating to the induction of dominant lethal mutations by fast neutrons at high intensity, is reviewed. Our work is mainly concerned with the genetic effects of fast neutrons at low intensity, using the reactor GLEEP. At a dose-rate of 0.01 rad/min., these fast fission neutrons are about six times as effective as acute X-irradiation for the induction of dominant lethal mutations in spermatozoa. This value, and the linear dose-mutation relationship, are similar to previous findings with neutron irradiation at high intensity. We are also comparing the rate of induction of specific locus mutations in mouse spermatogonia by about 215 rad of fast neutrons (with slight gamma contamination) and 650 rad of Co60 gamma-rays, administered nearly continuously over twelve weeks. Results to date suggest that these neutrons are about 50 times as effective as gamma-rays for the induction of specific locus mutations; they would also appear to be about six times as effective as acute X-irradiation. It is concluded that the type of dose-rate dependence associated with specific locus mutations induced by low LET radiations is most unlikely to occur with high LET ones; in fact it may be reversed. (author)

  1. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model

    Science.gov (United States)

    Gulani, Jatinder; King, Gregory; Hieber, Kevin; Chappell, Mark; Ossetrova, Natalia

    2016-01-01

    Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6–14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2–4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies. PMID:27579862

  2. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

    Science.gov (United States)

    Koch, Amory; Gulani, Jatinder; King, Gregory; Hieber, Kevin; Chappell, Mark; Ossetrova, Natalia

    2016-01-01

    Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6-14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2-4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies.

  3. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

    Science.gov (United States)

    Koch, Amory; Gulani, Jatinder; King, Gregory; Hieber, Kevin; Chappell, Mark; Ossetrova, Natalia

    2016-01-01

    Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6-14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2-4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies. PMID:27579862

  4. Anti-tumor immunological mechanisms of low dose whole-body irradiation in the protocol of tumor generadiotherapy

    International Nuclear Information System (INIS)

    Objective: To investigate the immunologic enhancement of low dose whole-body irradiation in mice bearing Lewis lung carcinoma (LLC) under recombinant plasmid pEgr-IL18-B7.1 gene-radiotherapy. Methods: LLC cells were implanted subcutaneously in the right-hind leg of C57BL/6J mice. The pEgr-IL18- B7.1 recombinant plasmids mediated by polyethylenimine were injected locally into tumors of the mice with gene- radiotherapy, and then the tumors received different therapeutic regimens containing local irradiation with 2 Gy and whole-body irradiation with 0.075 Gy, respectively. Cytotoxic activity of CTL and NK were detected with isotope labeling of 3H-TdR. The secretion activities of TNF-α and IFN-γ were detected with ELISA. The anti-tumor immunological effects of low dose whole-body irradiation in protocol of gene-radiotherapy on the tumor-bearing mice were observed. Results: Compared with conventional repeated high dose local irradiation, single high dose local irradiation in combination with repeated low dose whole-body irradiation could enhance the cytotoxic activity of CTL and NK, and increase the secretion of TNF-α and IFN-γ under pEgr-IL18-B7.1 gene-radiotherapy. Conclusions: Low dose whole-body irradiation superimposed upon a local high dose could significantly enhance the anti-tumor effect in the protocol of gene-radiotherapy through promoting the cytotoxic activity of CTL and NK, and up-regulating the expression of TNF-α and IFN-γ. (authors)

  5. Pulsed Irradiation Studies in Mice, Rats and Dogs

    International Nuclear Information System (INIS)

    Radiation lethality as a function of radiation dose rate has been extensively explored over the range of less than one rad to a few hundreds of rad/min, but comparatively little is known of the biological consequences at exposure intensities of the order of 105-106 rad/min. In the present experiments radiations produced by a TRIGA reactor have been used to study the comparative acute-mortality responses (LD50/30) of mice and dogs irradiated either at moderate dose rates (40 or 100 rad/min for mice and 23 rad/min for dogs) or by a single high dose-rate radiation pulse (∼ 106 rad/min for mice and ∼2.0 X 105 rad/min for dogs). In the mouse experiments, the LD50/30 of animals exposed at the moderate dose rates of 40 rad of n/min or 100 rad for gamma-radiation/min was not significantly different from the LD50/30 of animals exposed to the same radiation given as a pulsed exposure. Likewise, in acute mortality studies conducted with unilaterally neutron-irradiated dogs, no significant differences in LDso/sowere found between groups irradiated at 23 rad/min or exposed to pulsed dose rates in excess of 1.5 x 105 rad/min. Other studies have been conducted to determine if recovery from radiation injury in mice, as estimated by the split-dose irradiation technique, is influenced by the rate at which the initial sublethal injury is produced. Recovery has been compared at 5 and 14 days post-irradiation in groups of animals exposed at either 40 or 9 x 104 rad/min and no dose-rate dependency of recovery has been detected. (author)

  6. Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicorynomycolate (S-TDCM). (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-12-31

    Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. The authors 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. However, this treatment did not increase survival of the irradiated/wounded mice.

  7. Effects of 8 Gy whole body irradiation on number and functions of small intestinal intraepithelial lymphocytes (IELs)

    International Nuclear Information System (INIS)

    Objective: To explore the characteristics of intestinal mucosal immunity after radiation injury. Methods: Number, proliferation activity, cytotoxicity of IEL as well as the TNF-α and TGF-β concentrations in supernatant of cultured IELs were studied using freshly isolated IELs from whole small intestine of Kunming strain mice whole-body irradiated with 8 Gy 60Co rays. Results: The proliferation activity, cytotoxicity as well as the number of IELs in small intestinal mucosa were significantly decreased from 8h and reached the lowest level at 72 h post-irradiation. The TNF-α and TGF-β concentrations in supernatant of cultured IELs isolated from irradiated mice elevated at 8h and reached the peak values at 72h. Conclusion: The decrease in number and important factions of IELs might be one of the reasons which damage the intestinal mucosal immunity barrier after whole body irradiation

  8. Acute and delayed toxicities of total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Deeg, H.J.

    1983-12-01

    Total body irradiation is being used with increasing frequency for the treatment of lymphopoietic malignancies and in preparation for marrow transplantation. Acute toxicities include reversible gastroeneritis, mucositis, myelosuppression alopecia. As the success of treatment improves and more patients become long-term survivors, manifestations of delayed and chronic toxicity become evident. These include impairment of growth and development, gonadal failure and sterility, cataract formation and possibly secondary malignancies. The contribution of total body irradiation to the development of pneumonitis and pulmonary fibrosis is still poorly understood. Some of these changes are reversible or correctable, whereas others are permanent. Nevertheless, until equally effective but less toxic regimens become available, total body irradiation appears to be the treatment of choice to prepare patients with leukemia for marrow transplantation.

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

    International Nuclear Information System (INIS)

    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

  10. 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.

  11. Effects of DMSO and Vit E on lipid peroxidation of irradiated mice

    International Nuclear Information System (INIS)

    DMSO and Vit E are scavengers of free radicals, they can suppress or stop reactions of peroxidation. In the study, the fluorescence spectrophotometry was used to determine MDA levels in serum of irradiated mice. The results indicated that both DMSO and Vit E could reduce MDA levels, their suitable doses were 10 mg/g body weight and 0.25 mg/g body weight respectively. The effect of DMSO was better than that of Vit E. The best effect took place when they were used combinatorially

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

  13. 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.

  14. Long-Term Quantitative Biodistribution and Side Effects of Human Mesenchymal Stem Cells (hMSCs Engraftment in NOD/SCID Mice following Irradiation

    Directory of Open Access Journals (Sweden)

    Sabine François

    2014-01-01

    Full Text Available There is little information on the fate of infused mesenchymal stem cells (MSCs and long-term side effects after irradiation exposure. We addressed these questions using human MSCs (hMSCs intravenously infused to nonobese diabetic/severe combined immunodeficient (NOD/SCID mice submitted to total body irradiation (TBI or local irradiation (abdominal or leg irradiation. The animals were sacrificed 3 to 120 days after irradiation and the quantitative and spatial distribution of hMSCs were studied by polymerase chain reaction (PCR. Following their infusion into nonirradiated animals, hMSCs homed to various tissues. Engraftment depended on the dose of irradiation and the area exposed. Total body irradiation induced an increased hMSC engraftment level compared to nonirradiated mice, while local irradiations increased hMSC engraftment locally in the area of irradiation. Long-term engraftment of systemically administered hMSCs in NOD/SCID mice increased significantly in response to tissue injuries produced by local or total body irradiation until 2 weeks then slowly decreased depending on organs and the configuration of irradiation. In all cases, no tissue abnormality or abnormal hMSCs proliferation was observed at 120 days after irradiation. This work supports the safe and efficient use of MSCs by injection as an alternative approach in the short- and long-term treatment of severe complications after radiotherapy for patients refractory to conventional treatments.

  15. Marrow Stromal Cell Infusion Rescues Hematopoiesis in Lethally Irradiated Mice despite Rapid Clearance after Infusion

    Directory of Open Access Journals (Sweden)

    Xiaodong Yang

    2012-01-01

    Full Text Available Marrow stromal cells (MSCs, also termed mesenchymal stem cells have been proposed as a promising cellular therapy for tissue injury including radiation-induced marrow failure, but evidence for a direct effect is lacking. To assess the effects of MSCs on survival after lethal irradiation, we infused syngeneic MSCs (either as immortalized MSCs clones or primary MSCs intravenously into wild-type C57/Bl6 mice within 24 hours of lethal total body irradiation (TBI. Mice receiving either of the MSC preparations had significantly improved survival when compared to controls. In vivo imaging, immune histochemistry, and RT-PCR employed to detect MSCs indicated that the infused MSCs were predominantly localized to the lungs and rapidly cleared following infusion. Our results suggest that a single infusion of MSCs can improve survival after otherwise lethal TBI but the effect is not due to a direct interaction with, or contribution to, the damaged marrow by MSCs.

  16. Differential effect of melatonin on {gamma}-irradiated ovarian follicles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.K.; Lee, C.J. [Korea Atomic Energy Research Inst., Taejon (Korea, Republic of)

    2000-05-01

    The present study was performed to obtain evidence of the radioprotective function of melatonin on the ovarian follicles in {gamma}-irradiated immature mice. Three weeks old immature mice were i.p. injected with 10 {mu}g and 100 {mu}g of melatonin dissolved in 100 {mu}l of alcoholic saline. Two hours after the treatments, they were whole-body irradiated with a dose of LD{sub 80(30)} (8.3 Gy). The ovaries were dissected out of the animals at -2, 2, 8, and 14 h after the onset of irradiation and prepared for the histological observation using glutaraldehyde fixation. In terms of morphometry, it was observed that the number of primordial follicles of the irradiation group or the melatonin-treated group was less than that of the control. However, the number of primary, preantral, and early antral follicles was not different from that of the control group. In the group pretreated with 100 {mu}g of melatonin before irradiation, the percentage of normal primordial follicles was significantly higher than that of the irradiation group at any time after irradiation. The high concentration of melatonin also reduced radiation-induced degeneration of the primary follicles at 14 h after irradiation. The pretreatment of 10 {mu}g of melatonin had little of no effect on radiation-induced degeneration of the primordial follicles and of the primary follicles. However it gave a protective effect on the radiation-induced degeneration in the preantral and early antral follicles. From the above results, it is concluded that the exogenous melatonin has different functions depending on the follicular stages, and that the radioprotective effect of exogenous melatonin on follicular degeneration is related to its concentration. (author)

  17. Subcutaneous administration of rhIGF-I post irradiation exposure enhances hematopoietic recovery and survival in BALB/c mice

    International Nuclear Information System (INIS)

    It is unclear how to effectively mitigate against irradiation injury. In this study, we studied the capacity of recombinant human insulin-like growth factor-I (rhIGF-I) on hematologic recovery in irradiated BALB/c mice and its possible mechanism. BALB/c mice were injected with rhIGF-I subcutaneously at a dose of 100 μg/kg twice daily for 7 days after total body irradiation. Compared with a saline control group, treatment with rhIGF-I significantly improved the survival of mice after lethal irradiation (7.5 Gy). It was found that treatment with rhIGF-I not only could increase the frequency of Sca-1+ cells in bone marrow harvested at Day 14 after irradiation, but also it could decrease the apoptosis of mononuclear cells induced by irradiation as measured by flow cytometry, suggesting that rhIGF-I may mediate its effects primarily through promoting hematopoietic stem cell/progenitor survival and protecting mononuclear cells from apoptosis after irradiation exposure. Moreover, we have found that rhIGF-I might facilitate thrombopoiesis in an indirect way. Our data demonstrated that rhIGF-I could promote overall hematopoietic recovery after ionizing radiation and reduce the mortality when administered immediately post lethal irradiation exposure. (author)

  18. Effect of pulmonary irradiation from inhaled 90Y on immunity to Listeria monocytogenes in mice

    International Nuclear Information System (INIS)

    The immunological response of mice subjected to irradiation from particles deposited in the lungs and challenged with Listeria monocytogenes was investigated. Mice, exposed by inhalation to 90Y (a beta-emitting radionuclide) in relatively insoluble fused aluminosilicate particles, were immunized with L. monocytogenes either before or after exposure. Two additional groups of mice were either immunized or irradiated only. A group of control mice received no irradiation or immunization. The beta radiation dose absorbed by the lungs of each mouse at time of challenge averaged 10,000 rads. Fourteen days after immunization, all mice were challenged with 2 LD50 doses of L. monocytogenes via the respiratory route. Survival of all immunized mice either with or without exposure to 90Y varied from 90 to 100% as compared to 10 to 20% for the mice irradiated only and for control mice through 14 days after challenge. Pulmonary clearance of inhaled L. monocytogenes during the first 4 hr after challenge was suppressed in the mice irradiated only but not in those immunized only, or in the immunized and irradiated groups, and control mice. There appeared to be a suppression of proliferation of L. monocytogenes in lungs and spleen in the immunized groups 72 hr after challenge, whereas the lungs and spleens of the mice irradiated only and the control mice had extensive bacterial invasion. It was concluded that the 10,000 rads of beta radiation absorbed by the lungs did not suppress the immune mechanisms of the immunized mice

  19. Effects of methylandrostenediol and a lymphostimulatory thymic factor (leucotrofin) on the reactivity of adrenal cortex of X-irradiated A2G mice

    Energy Technology Data Exchange (ETDEWEB)

    Abraham, A.D.; Rusu, V.M.; Borsa, M.; Uray, Z.; Banu, C. (Biological Research Centre, Cluj (Romania))

    1982-03-01

    Administration of methylandrostenediol alone or with Leucotrofin to whole-body irradiated A2G mice was associated with the diminuation of some enzymatic reactions in the zona fasciculata of the adrenals after 30 days on irradiation in comparison with the irradiated controls. The incorporation rate of (2-/sup 14/C)acetate into free cholesterol and glucocorticoid, de novo synthesized in the adrenals of the protected mice, was decreased compared to the untreated animals. These data showed that late irradiation damage - caused by enhanced synthesis and secretion of catabolic corticosteroids - could be prevented by administration of anabolic steroids and lymphostimulatory thymic factors, which protect the lymphoid system from lymphotoxic agents.

  20. Effects of Ganoderma lucidum on cellular immunocompetence in gamma-irradiated mice

    International Nuclear Information System (INIS)

    We have investigated the effects on mice treated with Ganoderma lucidum (Gl) when the whole body was exposed to 400 rad gamma-irradiation. The mice were divided into five groups. Group A was the normal control; group B, the experimental control, was treated with GI; group C was the radiation control (RT); group D was treated with RT and Gl; group E was treated with Gl, RT and Gl. The results revealed that the relative spleen weight had increased significantly in groups B and E on day 7 and increased in all experimental groups on day, 28 after irradiation. The leukocyte counts decreased obviously in groups C, D and E on day 7, and recovered in groups D and E was faster than that in group C on day 28. The blastogenic response of splenocytes to LPS, Con A and PHA in groups administered GI were higher than that in group C on days 7and 28. Therefore, Gl seemed to assist the recovery of cellular immunocompetence in gamma-irradiated mice. (author)

  1. Transcriptome profiling of mice testes following low dose irradiation

    DEFF Research Database (Denmark)

    Belling, Kirstine C.; Tanaka, Masami; Dalgaard, Marlene Danner;

    2013-01-01

    cell types of the adult testis. We observed large expression changes in the somatic cell profile, which mainly could be attributed to changes in cellularity, but hyperplasia of Leydig cells may also play a role. We speculate that the possible hyperplasia may be caused by lower testosterone production......ABSTRACT: BACKGROUND: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types...... in the adult testis. METHODS: Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were...

  2. Analysis of changes in the intestine microflora of irradiated mice

    International Nuclear Information System (INIS)

    It has been shown on γ-irradiated CBA mice (900, 600 and 300 R) that the integral manifestation of the postirradiation dysbacteriosis in the intestine can be determined by means of the informational index h that takes account of all the alterations occurring in certain representatives of intestinal microflora. Differential analysis of radiation dysbacteriosis indicated that it results from a decreased lactobacilli number, and increased content of Enterococcus, proteus, E. coli, and yeast in the small intestine, and of E. coli, Clostridium, proteus and Enterococcus in the large intestine

  3. Mitigating effects of hUCB-MSCs on the hematopoietic syndrome resulting from total body irradiation.

    Science.gov (United States)

    Shim, Sehwan; Lee, Seung Bum; Lee, Jong-geol; Jang, Won-Suk; Lee, Sun-Joo; Park, Sunhoo; Lee, Seung-Sook

    2013-04-01

    This study evaluated the clinical and pathologic effects of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the recovery from total body irradiation by comparing it with the effects of granulocyte-colony stimulating factor (G-CSF), an efficacious drug in the treatment of acute bone marrow radiation syndrome. BALB/c mice were treated with G-CSF or hUCB-MSCs after they were irradiated with 7 Gy cobalt-60 γ-rays. Circulating blood counts, histopathologic changes in the bone marrow, and plasma level of Flt-3L and transforming growth factor (TGF-β1) were monitored in the postirradiation period. Hematologic analysis revealed that the peripheral leukocyte counts were markedly increased in the hUCB-MSCs-treated group, whereas G-CSF-treated mice did not recover significantly. Moreover, differential counts showed that hUCB-MSC treatment has regenerative effects on white blood cells, lymphocytes, and monocytes compared with the irradiated group. Treatment with hUCB-MSCs or G-CSF significantly increased immunoreactivity of Ki-67 until 3 weeks after total body irradiation. However, at 3 weeks, the number of Ki-67 immunoreactive cells significantly increased in the hUCB-MSCs-treated group compared with the G-CSF-treated group. Furthermore, hUCB-MSC treatment significantly modulated plasma levels of the hematopoietic cytokines Flt-3L and TGF-β1, whereas G-CSF treatment failed to decrease the plasma Flt-3L levels at 2 weeks after irradiation. Based on the differences in circulating blood cell reconstitution and cell density of bone marrow, the authors suggest that MSC treatment is superior to G-CSF treatment for hematopoietic reconstitution following sublethal dose radiation exposure.

  4. The restorative effect of mouse intestinal RNA on the small intestine of mice of the same strain after γ ray irradiation

    International Nuclear Information System (INIS)

    Mouse intestinal RNA was injected into the mice of the same strain within 1-3 h after different doses of abdominal or whole body 60Co γ irradiation, so as to explore the initial effective time of mouse intestinal RNA and the affection of radiation condition on its restorative effect, by measuring the survival of mouse intestinal crypt. The results showed (1) A decrease in the survival of mouse intestinal crypt began 6h after the irradiation, and the lowest survival rate appeared on the fourth day. (2) The survival of mouse intestinal crypt of the abdominal irradiated mice increased 21.4% at 6h after intestinal RNA injection as compared with that of the irradiated control group. (3) The dose modifying factor (DMF) of normal mouse intestinal RNA in the promotion of the recovery of the duodenum, jejunum and ileum of mice after whole body irradiation 1.17, 1.12 and 1.10 respectively. The above results suggest that mouse intestinal RNA can raise not only the survival of jejunum crypt of the mice of the same strain after abdominal irradiation but also the survival of crypt of the duodenum, jejunum and ileum of the mouse after whole body irradiation, which may be observed 6h after the irradiation

  5. Lipid metabolism and body composition in Gclm(-/-) mice

    Energy Technology Data Exchange (ETDEWEB)

    Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

  6. Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection

  7. Stability in Effects of gamma-Irradiated Chinese Medicinal Prescriptions on Protection of Mice from Radiation

    International Nuclear Information System (INIS)

    The radioprotective effects of irradiated medicinal plants on biological system were studied to apply the irradiation technology for hygienic purpose that is usually performed by chemical preservatives. We previously reported that the three Chinese medicinal prescriptions, Si-Wu-Tang, Bu-Zhong-Yi-Qi-Tang and San-Ling-Bai-Shu-San, showed radioprotective effects in mice. In these experiments, to investigate the difference in radioprotective effects between irradiated (10 kGy) and non-irradiated medicinal plants, mice were administered with the irradiated or non-irradiated prescriptions and then the mice were exposed to gamma-rays with low and high dosage. Non-exposed mice were also prepared as a control. The effects of prescriptions on the jejunal crypt survival, endogenous spleen colony formation, and apoptosis of jejunal crypt cells in mice were investigated after exposure. All of the prescriptions showed the protective effects of the jejunal crypt (p0.05) and the adminstration of the prescriptions increased the formation of endogenous spleen colony (p0.05) and reduced the frequency of radiation-induced apoptosis (p0.05). No significant difference in effects between irradiated and non-irradiated prescreption on the parameters was found in mice administered with each prescription before exposure to gamma-rays. In non-exposed mice, there were no different findings in the parameters between irradiated and non-irradiated prescription

  8. The effects of G-CSF combined with SB203580 on the immune system of mice received 4 Gy total body irradiation%G-CSF联合SB203580对4Gy照射小鼠免疫系统的作用

    Institute of Scientific and Technical Information of China (English)

    李德冠; 路璐; 吴红英; 张俊伶; 孟爱民

    2014-01-01

    Objective To observe the effects of G-CSF combined with SB203580(SB) on the immune system of mice received 4 Gy total body irradiation (TBI).Methods Thirty male C57BL/6 mice were randomly divided into control group,irradiated group,combined group.The mice in irradiated and combined group received 4 Gy TBI.In combined group,G-CSF (1 μg/each) was intraperitoneally (ip) injected twice one day for 5 days,SB (15 mg/kg) was ip injected every other day after 4 Gy TBI for 5 times.After 4 Gy TBI 10 days,the peripheral bloods were counted,the CD4,CD8,B220 cells in WBC and CD4,CD8 in thymocytes were analyzed by flowcytometry.The reactive oxygen species levels (ROS) of bone marrow cells were detected by microplate reader.Results Compared to the control group,the proportion of CD8,B220 and WBC in the irradiated mice significantly decreased,CD4+CD8+ thymocytes and ROS levels of bone marrow cells increased significantly.Compared to irradiation group,red blood,platelet,CD4 and CD8 cells in peripheral blood,CD4+CD8+ thymocytes decreased in the combined group.Conclusion G-CSF combined with SB has protective effects on the radiation-induced injury in immune system.%目的 研究G-CSF联合p38抑制剂SB203580 (SB)对免疫细胞辐射损伤的作用.方法 C57BL/6雄性小鼠按体质量随机分为对照组、照射组和给药组.照射组和给药组给予4 Gy全身照射.给药组小鼠给予腹腔注射G-CSF和SB,G-CSF于4Gy照射后2h和6h给药(1μg/只),每天2次,连续给药5d,SB于照射后24h给药(15 mg/kg),隔日给药,共给药5次.照射后10d测外周血计数,进行白细胞CD4、CD8、B220检测、胸腺细胞CD4、CD8检测和骨髓细胞活性氧检测.结果 照射组外周血计数和CD8、B220比例下降,而胸腺细胞中CD4+CD8+细胞比例及骨髓细胞活性氧水平显著增加.与照射组相比,联合给药组外周血红细胞数、血小板、CD4、CD8细胞比例升高,胸腺细胞中CD4+CD8+细胞比例下降.结论 G-CSF联合SB对4 Gy照射

  9. Accelerated recovery of hematopoiesis following sub-lethal whole body irradiation with recombinant murine interleukin-1 (IL-1)

    International Nuclear Information System (INIS)

    This communication reports the results of studies designed to investigate the ability of recombinant murine interleukin-1 (rIL-1) to enhance the recovery of hematopoiesis following administration of sub-lethal whole body irradiation (2 Gy). Mice were administered rIL-1 (100 and 500 units) i.p. Twenty-four hours later these mice were administered 2 Gy radiation. Irradiated control mice were given only phosphate buffered saline (PBS). Animals were then serially sacrificed (on days 1, 2, 4, 7, 9, and 12 following irradiation) and their peripheral blood was analyzed for indices (packed red cell volume, WBC, platelets, and differential). Femoral bone marrow was harvested and assayed for their stem cell content--erythroid (CFU-E, BFU-E), granulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-MEG). Irradiated mice pretreated with rIL-1 demonstrated accelerated hematopoietic recovery as measured by higher WBC, platelets and femoral stem cell content than PBS-treated irradiated controls. These results indicate IL-1 may be an effective radioprotective agent against the hematotoxicity induced by ionizing radiation

  10. 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.

  11. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    Science.gov (United States)

    Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

  12. Life shortening and carcinogenesis in mice irradiated at the perinatal period with gamma rays

    International Nuclear Information System (INIS)

    This study elucidates the life-span radiation effects in mice irradiated at the perinatal period in comparison to mice irradiated at the young adult period. B6C3F1 female mice were irradiated at 17 days of prenatal age, at 0 days of postnatal age, or as young adults at 15 weeks of age with 190, 380, or 570 rads of 137Cs gamma rays. Mice irradiated at the late fetal period showed dose-dependent life shortening of somewhat lesser magnitude than that seen after neonatal or young adult irradiation. Mice exposed at the late fetal period were highly susceptible to induction of pituitary tumors for which the latent period was the longest of all induced neoplasms. Incidence of lung tumors in mice irradiated at the late fetal period with 190 and 380 rads was higher than in controls. Malignant lymphomas of the lymphocytic type developed in excess, after a short latent period, in mice irradiated fetally with the highest dose; susceptibility of prenatally exposed mice was lower than that of early postnatally exposed mice. Liver tumors developed more frequently in mice irradiated in utero than in controls; susceptibility to induction of this type of neoplasm was highest at the neonatal period. In general, carcinogenic response of mice exposed at the late fetal period resembled that of neonatally exposed mice but was quite different from that of young adult mice. Mice exposed as young adults have no, or low, susceptibility to induction of pituitary, lung, and liver tumors; and a higher susceptibility to induction of myeloid leukemias and Harderian gland tumors. 19 refs., 4 figs., 3 tabs

  13. Total body irradiation and allogeneic bone-marrow transplantation

    International Nuclear Information System (INIS)

    The aim of the present study is to present the first case in the Bulgarian oncological practice of total-body irradiation (TBI) followed by allogeneic transplantation of hemopoietic peripheral steam cells from a haploidentical family donor to a patient with acute lymphoblastic leukemia. The patient was a 10-year old boy with a verified non-Hodgkin lymphoma - IV clinical stage (leukemia-lymphoma syndrome) with initial mediastinal and bone-marrow engagement. After the disease recurrence the patient was hospitalized in the Transplantation Department of the Specialized Pediatric Hospital for Active Treatment of Oncological Diseases for realizing allogeneic transplantation. The application of the conditioning regime includes Melphalan, Fludarabine, ATG and TBI with 5x2 Gy. The patient was discharged on the 30th day in a good general condition with compensated haematological parameters and stable function of the transplant, and with instructions for the control check-ups and examinations each 14 days till the day + 100. The TBI method applied by the team was simple for realization and did not require special equipment. The patient received irradiation by a vertical radiation beam in a small procedure room in a comfortable spinal and prone position, which allowed the realization of sufficiently homogeneous dose in the body and effective lung protection. The irradiation time was acceptable, compared with the time for the application of horizontal radiation beams at large distances. (authors)

  14. Effect of Green Tea Extract on T cell Mediated Hypersensitivity Reaction in BALB/c Mice Exposed to Gamma Irradiation

    International Nuclear Information System (INIS)

    Gamma radiation is widely used in the treatment of malignant neoplasms. However, it deprives the host immune function which may retard tumor rejection by the immune response. The main purpose of the present study is to test the ability of green tea dry extract to restore the T cell hypersensitivity reaction in gamma irradiated BALB/c mice. It aims also to elucidate the possible mechanism of action of ionizing radiation and green tea dry extract in the immune function. Four groups of BALB/c mice, each of ten, have been used in each experiment. The first group served as a control, the second group received green tea dry extract and the third group was exposed to 2 Gy gamma irradiation, while the fourth group received green tea dry extract before and after gamma irradiation. The following parameters were determined, the contact sensitivity reaction by the mouse ear swelling response, local dendritic cell migration, local lymph node weight, lymphocyte proliferation, spleen and thymus weight with their lymphocyte count. The effect of gamma irradiation and green tea dry extract on the elicitation phase of contact sensitivity was also determined. Data from the present study showed that gamma irradiation caused a significant decrease of the mouse ear swelling response and retarded dendritic cell migration. They also showed a significant decline in the lymphocytes proliferation in lymph node draining the contact sensitizer application. Total body exposure to 2 Gy gamma irradiation induced marked decline of thymus weight and thymocyte count, while it reduced spleen weight and spleenocyte count to a lesser extent. Exposure to gamma irradiation enhanced the elicitation phase of contact sensitivity. Administration of green tea dry extract partially preserved the contact sensitivity response to oxazolone in gamma irradiated BALB/c mice. It markedly minimized the enhancement of the elicitation phase of ear swelling. In conclusion, the present study heralds a beneficial role of

  15. Systematic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis

    International Nuclear Information System (INIS)

    Chronic irradiation of mice with ultraviolet (uv) light produces a systemic alteration of an immunologic nature. This alteration is detectable in mice long before primary skin cancers induced by uv light begin to appear. The alteration results in the failure of uv-irradiated mice to reject highly antigenic, transplanted uv-induced tumors that are rejected by unirradiated syngeneic recipients. The immunologic aspect of this systemic alteration was demonstrated by transferring lymphoid cells from uv-irradiated mice to lethally x-irradiated recipients. These recipients were unable to resist a later challenge with a syngeneic uv-induced tumor, whereas those given lymphoid cells from normal donors were resistant to tumor growth. Parabiosis of normal mice with uv-irradiated mice, followed by tumor challenge of both parabionts with a uv-induced tumor, resulted in the growth of the challenge tumors in both uv-irradiated and unirradiated mice. Splenic lymphocytes from tumor-implanted uv-treated mice were not cytotoxic in vitro against uv-induced tumors, whereas under identical conditions cells from tumor-implanted, unirradiated mice were highly cytotoxic. Our findings suggest that repeated uv irradiation can circumvent an immunologic mechanism that might otherwise destroy nascent uv-induced primary tumors that are strongly antigenic

  16. Total Body Irradiation with Step Translation and Dynamic Field Matching

    Directory of Open Access Journals (Sweden)

    Ho-Hsing Chen

    2013-01-01

    Full Text Available The purpose of this study is to develop a total body irradiation technique that does not require additional devices or sophisticated processes to overcome the space limitation of a small treatment room. The technique aims to deliver a uniform dose to the entire body while keeping the lung dose within the tolerance level. The technique treats the patient lying on the floor anteriorly and posteriorly. For each AP/PA treatment, two complementary fields with dynamic field edges are matched over an overlapped region defined by the marks on the body surface. A compensator, a spoiler, and lung shielding blocks were used during the treatment. Moreover, electron beams were used to further boost the chest wall around the lungs. The technique was validated in a RANDO phantom using GAFCHROMIC films. Dose ratios at different body sites along the midline ranged from 0.945 to 1.076. The dose variation in the AP direction ranged from 96.0% to 104.6%. The dose distribution in the overlapped region ranged from 98.5% to 102.8%. Lateral dose profiles at abdomen and head revealed 109.8% and 111.7% high doses, respectively, at the body edges. The results confirmed that the technique is capable of delivering a uniform dose distribution to the midline of the body in a small treatment room while keeping the lung dose within the tolerance level.

  17. Fractionated irradiation combined with carbogen breathing and nicotinamide of two human glioblastomas grafted in nude mice

    OpenAIRE

    Sun, Lin-Quan; Buchegger, Franz; Coucke, Philippe; MIRIMANOFF

    2001-01-01

    This study addressed the potential radiosensitizing effect of nicotinamide and/or carbogen on human glioblastoma xenografts in nude mice. U-87MG and LN-Z308 tumors were irradiated with either 20 fractions over 12 days or 5 fractions over 5 days in air-breathing mice, mice injected with nicotinamide, mice breathing carbogen, or mice receiving nicotinamide plus carbogen. The responses to treatment were assessed using local control and moist desquamation. In U-87MG tumors, the enhancement ratios...

  18. Effect of low dose whole-body X-irradiation on the efficacy of pEgr-IL18-B7.1 gene-radiotherapy

    International Nuclear Information System (INIS)

    Objective: To observe the therapeutic effect of whole-body irradiation with low dose X-rays in mice bearing Lewis lung carcinoma under recombinant plasmid pEgr-IL18-B7.1 gene-radiotherapy. Methods: The pEgr-IL18-B7.1 recombinant plasmids mediated by polyethylenimine were injected locally into tumors of the mice with gene-radiotherapy, and then the tumors received different therapeutic regimens containing local X-irradiation with 2 Gy and whole-body X-irradiation with 0.075 Gy, respectively. The anti-tumor effects of low dose X-rays in optimizing the protocol of pEgr-IL18-B7.1 gene-radiotherapy on the tumor-bearing mice were observed. Results: As compared with repeated high dose local X-irradiation alone, single high dose local X-irradiation in combination with repeated low dose of whole-body X-irradiation showed more significant inhibition of tumor growth under pEgr-IL18-B7.1 gene-radiotherapy. Conclusions: Low dose whole-body X-irradiation superimposed upon a local high dose could significantly enhance the anti-tumor effect in the protocol of pEgr-IL18-B7.1 gene-radiotherapy. (authors)

  19. Some genetic profiles in liver of Ehrlich ascites tumor-bearing mice under the stress of irradiation

    Directory of Open Access Journals (Sweden)

    Amal I. Hassan

    2014-04-01

    Full Text Available Radiation therapy aims to kill cancer cells with a minimum of normal tissue exposure. In an attempt to define the molecular and biochemical changes associated with exposure to radiotherapy, the objective of the present study is to explore the effect of gamma (γ irradiation on nuclear factor, erythroid 2 (NFE2, P53, stromelysin-1 (matrix metalloproteinase-3 (MMP3, BCL-2 and BAX genes expression in Ehrlich ascites carcinoma (EAC bearing mice. Various biochemical parameters such as liver function, H2O2, B% and T% lymphocytes, total antioxidants and MDA were investigated to evaluate their usefulness as possible during cancer treatment with radiotherapy. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 0.5 Gy. Sixty-four female mice, weighing 20–25 g were used in this study and divided into three main groups. The first group served as control group, while the second were injected intraperitoneally with EAC then was subdivided into two groups, II A and II B. The latter one (group II B, the animals were exposed to a single dose of 0.5 Gy whole body γ irradiation. The third main group, were irradiated with a single dose of 0.5 Gy whole body γ irradiation. Blood and liver tissue samples were collected at 4, 24 and 96 h post-irradiation. The gene expression levels in the livers of animals from each exposure group were compared individually with that of pooled sham-irradiated animals. MMP3 and NFE2 were overexpressed in liver samples of EAC group post 4, 24 and 96 h of γ irradiation (IIB. On the other hand, P53 and BCL-2 genes were downregulated by using RT-PCR analysis post 4, 24 and 96 h of γ irradiation (IIB. As well as, liver function and MDA were increased significantly in the γ - irradiation group (3rd group when compared to control mice (1st group. Gamma irradiation 3rd group revealed increase in the level of T% and B% lymphocytes. According to the obtained results, both γ rays and time period alter

  20. The Role of DNA Methylation Changes in Radiation-Induced Bystander Effects in cranial irradiated Mice

    Science.gov (United States)

    Zhang, Meng; Sun, Yeqing; Xue, Bei; Wang, Xinwen; Wang, Jiawen

    2016-07-01

    Heavy-ion radiation could lead to bystander effect in neighboring non-hit cells by signals released from directly-irradiated cells. The exact mechanisms of radiation-induced bystander effect in distant organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in bystander effect. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were cranial exposed to 40, 200, 2000mGy dose of carbon heavy-ion radiation, while the rest of the animal body was shielded. The γH2AX foci as the DNA damage biomarker in directly irradiation organ ear and the distant organ liver were detected on 0, 1, 2, 6, 12 and 24h after radiation, respectively. Methylation-sensitive amplifcation polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that cranial irradiated mice could induce the γH2AX foci and genomic DNA methylation changes significantly in both the directly irradiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate were highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation in ear. The global DNA methylation changes tended to occur in the CG sites. We also found that the numbers of γH2AX foci and the genomic methylation changes of heavy-ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo. Keywords: Heavy-ion radiation; Bystander effect; DNA methylation; γH2

  1. Effect of irradiation on the viability of Toxoplasma gondii cysts in tissues of mice and pigs

    Energy Technology Data Exchange (ETDEWEB)

    Dubey, J.P.; Brake, R.J.; Murrell, K.D.; Fayer, R.

    1986-03-01

    Muscles from tongue, heart, and limbs of 14 pigs inoculated orally with Toxoplasma gondii oocysts were irradiated with 10, 20, 25, and 30 krad of gamma (cesium-137 and cobalt-60) irradiation. Viability of T gondii cysts was assayed by feeding porcine muscles to T gondii-free cats and/or by inoculation of sediment from acid-pepsin digested porcine muscle into mice. Cats fed 500-g samples of muscles irradiated with up to 20 krad shed T gondii oocysts. Cats fed muscles irradiated with 25 or 30 krad did not shed oocysts. Mice were inoculated with 8 isolates of T gondii, and tissue cysts in their brains irradiated with up to 40 krad were infective to mice; however, there was a 10,000-fold reduction in the viability of organisms in tissue cysts irradiated with 40 krad, compared with that in nonirradiated cysts. At 50 krad of gamma irradiation, there were no detectable infective organisms in infected mouse brains.

  2. Effect of irradiation on the viability of Toxoplasma gondii cysts in tissues of mice and pigs

    International Nuclear Information System (INIS)

    Muscles from tongue, heart, and limbs of 14 pigs inoculated orally with Toxoplasma gondii oocysts were irradiated with 10, 20, 25, and 30 krad of gamma (cesium-137 and cobalt-60) irradiation. Viability of T gondii cysts was assayed by feeding porcine muscles to T gondii-free cats and/or by inoculation of sediment from acid-pepsin digested porcine muscle into mice. Cats fed 500-g samples of muscles irradiated with up to 20 krad shed T gondii oocysts. Cats fed muscles irradiated with 25 or 30 krad did not shed oocysts. Mice were inoculated with 8 isolates of T gondii, and tissue cysts in their brains irradiated with up to 40 krad were infective to mice; however, there was a 10,000-fold reduction in the viability of organisms in tissue cysts irradiated with 40 krad, compared with that in nonirradiated cysts. At 50 krad of gamma irradiation, there were no detectable infective organisms in infected mouse brains

  3. Total body irradiation in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Fundagul Andic

    2014-06-01

    Full Text Available Total body irradiation is used in conjunction with chemotherapy as a conditioning regimen in the treatment of many disease such as leukemia, myelodysplastic syndrome, aplastic anemia, multiple myeloma and lymphoma prior to the hematopoetic stem cell transplantation. The main purposes of the hematopoetic stem cell transplantation are eradication of the recipient bone marrow and any residual cancer cells, creation of space in the receipient bone marrow for donor hematopoetic stem cells, and immunosuppression to prevent rejection of donor stem cells in the case of an allotransplant. [Archives Medical Review Journal 2014; 23(3.000: 398-410

  4. Electron microscopic studies on the central nervous system of mice irradiated antenatally with low levels of reactor radiation, 1

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Yuichiro; Ogawa, Yoshihiro; Yamada, Shinichi; Honda, Yoshihide; Hoshino, Hiroshi; Lian, Shi-Long; Hashimoto, Shozo

    1984-09-01

    To study electron microscopic changes of the central nervous system during development and growth of mice exposed to low levels of reactor radiation using a low power reactor, UTR-KINKI operating at 1 Watt, ICR-mice were irradiated at fetal stage of 14 days after conception with about 20, 40 and 90 cGy, respectively. At the irradiation, 9 pregnant mice in a group were put into a cylindrical plastic cage and were fed only water for irradiation periods of 6-24 hours. The irradiated mice were sacrificed in 1, 3, 6 and 12 months after birth and the brain tissues were treated with an usual method for electron microscopy. No obvious changes were observed on the nerve cells, neuroglia cells and nerve fibers. However, some changes such as electron dense bodies, vacuole formation were observed on the capillaries and their adjacent tissues with increasing in radiation doses as well as with time elapsed. The scanning electron microscopic changes on the capillary walls were also demonstrated in the exposed groups. (author).

  5. Computer-based anthropometrical system for total body irradiation.

    Science.gov (United States)

    Sánchez-Nieto, B; Sánchez-Doblado, F; Terrón, J A; Arráns, R; Errazquin, L

    1997-05-01

    For total body irradiation (TBI) dose calculation requirements, anatomical information about the whole body is needed. Despite the fact that video image grabbing techniques are used by some treatment planning systems for standard radiotherapy, there are no such systems designed to generate anatomical parameters for TBI planning. The paper describes an anthropometrical computerised system based on video image grabbing which was purpose-built to provide anatomical data for a PC-based TBI planning system. Using software, the system controls the acquisition and digitalisation of the images (external images of the patient in treatment position) and the measurement procedure itself (on the external images or the digital CT information). An ASCII file, readable by the TBI planning system, is generated to store the required parameters of the dose calculation points, i.e. depth, backscatter tissue thickness, thickness of inhomogeneity, off-axis distance (OAD) and source to skin distance (SSD). PMID:9246868

  6. Response of adrenal gland to whole body 60Co irradiation

    International Nuclear Information System (INIS)

    Whole body of the adult albino rates was exposed to 60Co radiation in a single dose of 600 R. Following irradiation the adrenal serotonin level was found higher till the end of 8th week except a fall on 14th day, whereas the blood 5HT level remained lower than the normal except a slight rise at the end of 1st week and dropped down at 14 days followed by a further rise. The blood catecholamine level was found increased at the end of 14th day followed by a fall at 4th and 8th weeks, but the levels were moving round the normal value. The histological studies of adrenal gland showed degranulation and hypertrophy of adrenal cortex and medullary cells at various intervals of post-irradiation. On the whole it is observed that maximum changes in the level of biogenic amines take place within 14 days after irradiation, and maximum rate of mortality also coincide with this period. Thus bringing out the fact that adrenal bioamines play an important role in the vital activities of the animals. (author)

  7. Whole body irradiation by high energy electron for mycosis fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Koga, Kenji; Nishikawa, Kiyoshi; Wakuta, Yuhji; Asada, Keiko; Murai, Nobuko; Watanabe, Katsushi; Takada, Takuo

    1985-02-01

    Five patients with mycosis fungoides were treated with whole body irradiation by high energy electron. They were irradiated by a linear accelerator (ML-15MIII, Mitsubishi Company) with the electron of 8 MeV, using the acrylics decelerator at the window to reduce the electron energy. Source skin distance was 150 cm and three beams with a separation of 60 cm were used. The dose distribution at the skin surface was within homogeneity of +-7.5%. The 2 patients have been alive without evidence of disease for 2 years, and 1 year and half after the treatment, respectively. Three patients were dead; two of the dead were associated with pancytopenia, one irradiated 6 times for 2 years and 4 months and the other 3 times for 2 years. The remaining one patient developed the brain metastasis without skin lesions 6 months later. Our results suggest that mycosis fungoides is curable in infiltrative stage, but not in tumorous stage. Some discussion on the problem of this treatment technique and haematological changes caused by the contaminated X-ray as well as high energy electron were made, reviewing the pertinent literatures on the device to reduce the contaminated X-ray. (author).

  8. Plasmodium berghei berghei: irradiated sporozoites of the ANKA strain as immunizing antigens in mice. [X radiation

    Energy Technology Data Exchange (ETDEWEB)

    Beaudoin, R.L.; Strome, C.P.A.; Tubergen, T.A.; Mitchell, F.

    1976-06-01

    Mice were protected against challenge with infective sporozoites following immunization with x-ray irradiated sporozoites. The immunity lasted at least 8 weeks. Mice immune against sporozoite challenge remained fully susceptible to challenge with erythrocytic stages. Immunization of mice with extracts of mosquito thorax failed to protect them, indicating that mosquito antigens were not directly responsible for the immunity observed in the basic experiments.

  9. Life span, testis damage and immune cell populations of spleen in C57BL mice with neutron irradiation by lying flat pose

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Ki Jung; kim, Myung Sup; Kyung, Yoo Bo [KAERI, Taejon (Korea)

    2003-10-01

    This study deals with the biological effects of black mouse (C57BL) irradiated with neutron irradiation by using Boron Neutron Capture Therapy facility in HANARO reactor. These include mortality, body wt., hair color, testis volume, sperm count and immune cell populations in mouse spleen after 80 days later by thermal neutron irradiation. Six week old C57BL male mice were irradiated with neutron irradiation for 1 hr or 2 hrs (flux : 1.036739E +09). These irradiat ion doses estimated 15Gy and 30Gy, respectively. Survival days and hair color in mice was checked. On day 80 after irradiation, testis were taken for volume and sperm count. Also spleen was taken for FACS and spleen cells were isolatd and discarded RBC by treating with lysising solution. These cells were placed on ice and immunofluorescence staining was performed. Phycoerythrin (PE )-anti-CD3e, fluorescein isothiocyanate (FITC)-anti-CD4, and FITC-anti-CD8 were added, then the immunostaining cells were incubated on ice for 40 min. The resulting cells were washed with a PBS buffer 3 times and analyzed using a Flow cytometer. All experimental animals survived over 90 days but in case of 30 Gy neutron irradiation, black mice hair were changed white color on the center of the back. Neutron irradiation of black mice show similar in damage of spleen immune cells by subpopulation of T helper and T cytotoxic cells compared to the control non - irradiated group. These results show that treatment of neutron irradiation without boron compounds for 2 hrs in mice can survive over 90 days with hair color change from black to white. Damaged spleen cells recover after long time by irradiation but testis volume and no. of sperm are not recover compared to the normal group in response to neutron irradiation.

  10. A Longitudinal Evaluation of Partial Lung Irradiation in Mice by Using a Dedicated Image-Guided Small Animal Irradiator

    International Nuclear Information System (INIS)

    Purpose: In lung cancer radiation therapy, the dose constraints are determined mostly by healthy lung toxicity. Preclinical microirradiators are a new tool to evaluate treatment strategies closer to clinical irradiation devices. In this study, we quantified local changes in lung density symptomatic of radiation-induced lung fibrosis (RILF) after partial lung irradiation in mice by using a precision image-guided small animal irradiator integrated with micro-computed tomography (CT) imaging. Methods and Materials: C57BL/6 adult male mice (n=76) were divided into 6 groups: a control group (0 Gy) and groups irradiated with a single fraction of 4, 8, 12, 16, or 20 Gy using 5-mm circular parallel-opposed fields targeting the upper right lung. A Monte Carlo model of the small animal irradiator was used for dose calculations. Following irradiation, all mice were imaged at regular intervals over 39 weeks (10 time points total). Nonrigid deformation was used to register the initial micro-CT scan to all subsequent scans. Results: Significant differences could be observed between the 3 highest (>10 Gy) and 3 lowest irradiation (<10 Gy) dose levels. A mean difference of 120 ± 10 HU between the 0- and 20-Gy groups was observed at week 39. RILF was found to be spatially limited to the irradiated portion of the lung. Conclusions: The data suggest that the severity of RILF in partial lung irradiation compared to large field irradiation in mice for the same dose is reduced, and therefore higher doses can be tolerated

  11. A Longitudinal Evaluation of Partial Lung Irradiation in Mice by Using a Dedicated Image-Guided Small Animal Irradiator

    Energy Technology Data Exchange (ETDEWEB)

    Granton, Patrick V.; Dubois, Ludwig; Elmpt, Wouter van; Hoof, Stefan J. van; Lieuwes, Natasja G. [Department of Radiation Oncology (MAASTRO), GROW–School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Department of Radiation Oncology (MAASTRO), GROW–School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Radiation Oncology, University Hospitals Leuven/KU Leuven (Belgium); Verhaegen, Frank, E-mail: frank.verhaegen@maastro.nl [Department of Radiation Oncology (MAASTRO), GROW–School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Medical Physics Unit, Department of Oncology, McGill University, Montréal, Québec (Canada)

    2014-11-01

    Purpose: In lung cancer radiation therapy, the dose constraints are determined mostly by healthy lung toxicity. Preclinical microirradiators are a new tool to evaluate treatment strategies closer to clinical irradiation devices. In this study, we quantified local changes in lung density symptomatic of radiation-induced lung fibrosis (RILF) after partial lung irradiation in mice by using a precision image-guided small animal irradiator integrated with micro-computed tomography (CT) imaging. Methods and Materials: C57BL/6 adult male mice (n=76) were divided into 6 groups: a control group (0 Gy) and groups irradiated with a single fraction of 4, 8, 12, 16, or 20 Gy using 5-mm circular parallel-opposed fields targeting the upper right lung. A Monte Carlo model of the small animal irradiator was used for dose calculations. Following irradiation, all mice were imaged at regular intervals over 39 weeks (10 time points total). Nonrigid deformation was used to register the initial micro-CT scan to all subsequent scans. Results: Significant differences could be observed between the 3 highest (>10 Gy) and 3 lowest irradiation (<10 Gy) dose levels. A mean difference of 120 ± 10 HU between the 0- and 20-Gy groups was observed at week 39. RILF was found to be spatially limited to the irradiated portion of the lung. Conclusions: The data suggest that the severity of RILF in partial lung irradiation compared to large field irradiation in mice for the same dose is reduced, and therefore higher doses can be tolerated.

  12. Total body irradiation in France in the past twenty years

    International Nuclear Information System (INIS)

    A review of the activity and techniques of total body irradiation (TBI) in France in the last 20 years is presented. In order to have on overall view of the activity and techniques of total body irradiation in France, the group of cancer centre radiation oncologists sent a questionnaire to all the cancer centres or public hospitals radiotherapy departments dealing with this treatment. Thirty-six questionnaires were sent and thirty-one departments answered. Three departments do not offer this treatment. Five departments did not answer. Results, therefore, concern the activity of the 28 departments that agreed to give detailed and clear answers. A total of 10 630 TBIs have been documented, 850 to 900 TBI have been done each year since 1995. Single fraction TBIs are used in only five centres and are being progressively abandoned. For Multiple-fraction TBIs, the techniques described here are the ones used in 1999, at the time the questionnaires were sent. A majority (98%) of the teams used linear accelerators. The collected data are synthesised in tables. Nowadays, single fraction TBIs are only indicated in exceptional cases, Most of the TBIs are fractionated in six twice-daily fractions with pulmonary shielding to limit the dose between 6 and 11 Gy depending on departments' protocols and pathologies. (author)

  13. Biological basis of total body irradiation; Bases biologiques de l`irradiation corporelle totale

    Energy Technology Data Exchange (ETDEWEB)

    Dubray, B.; Helfre, S.; Dendale, R.; Cosset, J.M. [Institut Curie, 75 - Paris (France). Dept. d`Oncologie-Radiotherapie; Giraud, P. [Hopital Tenon, 75 - Paris (France). Service de Radiotherapie

    1999-03-01

    A comprehensive understanding of the radiobiological bases of total body irradiation (TBI) is made difficult by the large number of normal and malignant tissues that must be taken into account. In addition, tissue responses to irradiation are also sensitive to associated treatments, type of graft and a number of patient characteristics. Experimental studies have yielded a large body of data, the clinical relevance of which still requires definite validation through randomized trials. Fractionated TBI schemes are able to reduce late normal tissue toxicity, but the ultimate consequences of the fractional dose reduction do not appear to be equivocal. Thus, leukemia and lymphoma cells are probably more radio-biologically heterogeneous than previously thought, with several cell lines displaying relatively high radioresistance and repair capability patterns. The most primitive host-type hematopoietic stem cells are likely to be at least partly protected by TBI fractionation and may hamper late engraftment. Similarly, but with possibly conflicting consequences on the probability of engraftment, the persistence of a functional marrow stroma may also be fractionation-sensitive, while higher rejection rates have been reported after T-depletion grafts and fractionated TBI. in clinical practice (as for performance of relevant clinical trials), the influence of these results are rather limited by the heavy logistic constraints created by a sophisticated and time-consuming procedure. Lastly, clinicians are now facing an increasing incidence of second cancers, at least partly induced by irradiation, which jeopardize the long-term prospects of otherwise cured patients. (authors)

  14. Investigation of wholesomeness of feeding low-irradiated diet to mice. Part of a coordinated programme on the wholesomeness of the process of food irradiation

    International Nuclear Information System (INIS)

    Studies are carried out on the wholesomeness of irradiated food with special reference to gamma irradiation (0.75 kGy) maize, (1 kGy) walnuts and (2 kGy) prune-plums. These include physico-chemical changes in the food constituents as well as toxicity and mutagenic effects on animals after long-term feeding test. The results indicate an increase of the carbonyl compounds after irradiation in all studied foodstuffs, but there is not significant difference in the number of the new-formed carbonyl compounds when compared with controls. Biomedical investigation are carried out to define any toxicity, consideration being given to both direct effects in adult or growing organisms and to effect in their progeny. Effects of gamma irradiated diet, including maize, walnuts and prune-plums, exposed to the above mentioned doses fed to three consecutive generations of mice have been studied. A 35% addition of irradiated feed to standard diet is shown to produce no deleterious effects as judged by mean litter size, body weight at weaning, adult body weight and organ weight, haematological measures and some enzyme activities

  15. Early Energetic Particle Irradiation of the HED Parent Body Regolith

    Science.gov (United States)

    Bogard, D. D.; Garrison, D. H.; Rao, M. N.

    1996-01-01

    Previous studies have shown that many individual grains within the dark phase of the Kapoeta howardite were irradiated with energetic particles while residing on the surface of the early HED regolith. Particle tracks in these grains vary in density by more than an order of magnitude and undoubtedly were formed by energetic heavy (Fe) ions associated with early solar flares. Early Irradiation of HED Regolith: Concentrations of excess Ne alone are not sufficient to decide between competing galactic and solar irradiation models. However, from recent studies of depth samples of oriented lunar rocks, we have shown that the cosmogenic 21-Ne/22-Ne ratio produced in feldspar differs substantially between Galactic Cosmic Radiation (GCR) and solar protons, and that this difference is exactly that predicted from cross-section data. Using Ne literature data and new isotopic data we obtained on acid-etched, separated feldspar from both the light and dark phases of Kapoeta, we derive 21-Ne/22-Ne = 0.80 for the recent GCR irradiation and 21-Ne/22-Ne = 0.68 for the early regolith irradiation. This derived ratio indicates that the early Ne production in the regolith occurred by both galactic and solar protons. If we adopt a likely one-component regolith model in which all grains were exposed to galactic protons but individual grains had variable exposure to solar protons, we estimate that this early GCR irradiation lasted for about 3-6 m.y. More complex two-component regolith models involving separate solar and galactic irradiation would permit this GCR age to be longer. Higher-energy solar protons would permit the GCR to be longer. Higher-energy solar protons would permit the GCR age to be shorter. Further, cosmogenic 126(Xe) in Kapoeta dark is no more than a factor of about 2 higher than that observed in Kapoeta light. Because 126(Xe) can only be formed by galactic protons and not solar protons, these data support a short GCR irradiation for the HED regolith. This would also be

  16. Influence of diethylmaleate on the survival of irradiated mice and on serum protein levels

    International Nuclear Information System (INIS)

    Glutathione (GSH) is the major of the living plants or animal cell low molecular weight thiol compound which serves as a main endogenous cellular radioprotector. In order to improve radiotherapy, a possible approach should be to try to administrate hypoxic cell radiosensitizers altogether with glutathione intracellular depletors, for example, a binding GSH agent like diethylmaleate (DEM), in an attempt to overcome the neurotoxic side effects while maintaining their radiosensitizing properties. This study was performed to investigate whether the administration of DEM alone could modify the radioresistance of mice as measure by the 30-day-survival after irradiation and to establish whether this modification can be reflected in the murine serum protein profiles. Millimolar concentrations of DEM were dissolved alternatively in commercial peanut oil or absolute ethanol (final concentration 0.27%) and administered to male or female albino mice ip 1 h prior to 9 Gy sup(60) Cowhole-body irradiation with an average dose rate of 5.2 Gy/min. (author)

  17. Protective effects of egg-milk with MT on mice damaged by irradiation

    International Nuclear Information System (INIS)

    Objective: To explore the protective effects of egg-milk with metallothionein (MT) on mice damaged by irradiation. Methods: After the mice were irradiated with 2.5 Gy (12.5 mGy·min-1) X-rays, they were fed with egg-milk with MT for 14 days. The level of WBC in peripheral blood, lymphocyte proliferation rate, DNA content in marrow cells, malondiadehyde (MDA) levels and the activities of antioxidant enzymes (SOD, CAT and GSH-Px) in liver and kidney were measured. Results: After the irradiated mice were fed with egg-milk with MT, especially in the egg-milk with MT of mild and high doses plus irradiation groups, the WBC number, lymphocyte proliferation rate and DNA content of marrow cells in the mice were significantly higher than those in the irradiation group (PC 0.01), at the same time, the percentage of thymocyte G0/G1 phase of these mice were significantly lower than that of the irradiation group (P2/M phase were significantly higher than those in the irradiation group (P<0.01 or P<0.05). Compared with the normal control, MDA levels in liver and kidney of the irradiation group increased significantly (P<0.01 or P<0.05), and the antioxidant enzyme activities of SOD, CAT and GSH-Px decreased significantly (P<0.01 or P<0.05). While in the egg-milk with MT plus irradiation groups, the MDA contents were significantly lower than those in the irradiation group (P<0.01) and the activities of SOD, CAT and GSH-Px were significantly higher than those in the irradiation group (P<0.01 or P<0.05). Conclusion; The egg-milk with MT has protective effects on mice injuried by irradiation. (authors)

  18. Changes with age in swimming performance of X-irradiated mice

    International Nuclear Information System (INIS)

    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 (ST50) 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 (TRS50) 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 ST50 and TRS50 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)

  19. Partial body irradiation of small laboratory animals with an industrial X-ray tube

    Energy Technology Data Exchange (ETDEWEB)

    Frenzel, Thorsten; Kruell, Andreas [Universitaetsklinikum Hamburg-Eppendorf, Hamburg (Germany). Bereich Strahlentherapie; Grohmann, Carsten; Schumacher, Udo [Universitaetsklinikum Hamburg-Eppendorf, Hamburg (Germany). Inst. fuer Anatomie und Experimentelle Morphologie

    2014-07-01

    Dedicated precise small laboratory animal irradiation sources are needed for basic cancer research and to meet this need expensive high precision radiation devices have been developed. To avoid such expenses a cost efficient way is presented to construct a device for partial body irradiation of small laboratory animals by adding specific components to an industrial X-ray tube. A custom made radiation field tube was added to an industrial 200 kV X-ray tube. A light field display as well as a monitor ionization chamber were implemented. The field size can rapidly be changed by individual inserts of MCP96 that are used for secondary collimation of the beam. Depth dose curves and cross sectional profiles were determined with the use of a custom made water phantom. More components like positioning lasers, a custom made treatment couch, and a commercial isoflurane anesthesia unit were added to complete the system. With the accessories described secondary small field sizes down to 10 by 10 mm{sup 2} (secondary collimator size) could be achieved. The dosimetry of the beam was constructed like those for conventional stereotactical clinical linear accelerators. The water phantom created showed an accuracy of 1 mm and was well suited for all measurements. With the anesthesia unit attached to the custom made treatment couch the system is ideal for the radiation treatment of small laboratory animals like mice. It was feasible to shrink the field size of an industrial X-ray tube from whole animal irradiation to precise partial body irradiation of small laboratory animals. Even smaller secondary collimator sizes than 10 by 10 mm{sup 2} are feasible with adequate secondary collimator inserts. Our custom made water phantom was well suited for the basic dosimetry of the X-ray tube.

  20. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

    Directory of Open Access Journals (Sweden)

    Jianhui Chang

    Full Text Available One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE particles, such as oxygen (16O, carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE. Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n irradiation and examined the effects on peripheral blood (PB cells, and bone marrow (BM hematopoietic stem cells (HSCs and hematopoietic progenitor cells (HPCs at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS, enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the

  1. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

    Science.gov (United States)

    Chang, Jianhui; Luo, Yi; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  2. Total body irradiation in non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Between October 1972 and August 1977, low-dose fractionated total body irradiation (TBI), 150 to 300 rad,, was selected for 48 patients with previously untreated non-Hodgkin's lumphoma staged II, III, and IV. In 63% of the patients the disease had a nodular pattern; there were no patients with diffuse histiocytic lymphoma. All but 2 patients responded to TBI. The 4-year acutarial survival was 71% for the nodular group and 57% for the diffuse group. There were no acute symptoms during the course of treatment and no mortality associated with the treatment. Seventeen per cent of the patients developed transient platelet counts less than 30,000/mm3. Four required hospitilization for correction of thrombocytopenia and/or infection. The majority of patients who failed more than 3 months after initial complete remission were placed back in remission with either chemotherapy, TBI, or local irradiation. Patients with persistent disease after TBI showed a less favorable response with chemotherapy. A selected group of 15 patients in relapse after chemotherapy or localized radiotherapy were treated with TBI. Eleven responded to treatment, while 4 showed no useful response. The median survival for this group was slightly over 2 years. Twenty percent developed transient platelet counts less than 30,000/mm3

  3. Development of a translating bed for total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Connors, S.; Scrimger, J.; Logus, W.; Johnson, L.; Schartner, E. (Cross Cancer Institute, Edmonton (Canada))

    1988-12-01

    Total body irradiation is used to prepare a patient for bone marrow transplantation. Traditional techniques often sacrifice dose uniformity for patient comfort and ease of treatment. A method has been developed using a translational bed under a cobalt 60 photon beam. The bed and controller were designed and built on site. A bolused patient lying in the bed is moved at constant speed through the beam. Using this technique, dose homogeneity is optimized by the use of bolus, extended source-skin distance, adequate field size and use of anterior/posterior fields. The dose rate represents a compromise between a value high enough to keep treatment times tolerable by the patient and one that is sufficiently low to avoid treatment complications. The value of 50 cGy/min which was used meets these requirements. Extensive phantom measurements have shown that the dose homogeneity can be obtained to within an acceptable limit of +/- 5%.

  4. In vivo dosimetry with silicon diodes in total body irradiation

    International Nuclear Information System (INIS)

    The aim of this work is the characterization and application of silicon diode detectors for in vivo dosimetry in total body irradiation (TBI) treatments. It was evaluated the diode response with temperature, dose rate, gantry angulations and field size. A maximum response variation of 2.2% was obtained for temperature dependence. The response variation for dose rate and angular was within 1.2%. For field size dependence, the detector response increased with field until reach a saturation region, where no more primary radiation beam contributes for dose. The calibration was performed in a TBI setup. Different lateral thicknesses from one patient were simulated and then the calibration factors were determined by means of maximum depth dose readings. Subsequent to calibration, in vivo dosimetry measurements were performed. The response difference between diode readings and the prescribed dose for all treatments was below 4%. This difference is in agreement as recommended by the International Commission on Radiation Units and Measurements (ICRU), which is ±5%. The present work to test the applicability of a silicon diode dosimetry system for performing in vivo dose measurements in TBI techniques presented good results. These measurements demonstrated the value of diode dosimetry as a treatment verification method and its applicability as a part of a quality assurance program in TBI treatments. - Highlights: ► Characterization of a silicon diode dosimetry system. ► Application of the diodes for in vivo dosimetry in total body irradiation treatments. ► Implementation of in vivo dosimetry as a part of a quality assurance program in radiotherapy

  5. Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

    1980-07-01

    The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable.

  6. Treatment of irradiated mice with high-dose ascorbic acid reduced lethality.

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    Tomohito Sato

    Full Text Available Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg up to 24 h (1, 6, 12, or 24 h after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure.

  7. Radioprotective effects of Aloe vera leaf extract on skin of Swiss mice after gamma irradiation

    International Nuclear Information System (INIS)

    Full text: Biological effects of radiation are detrimental to life. Skin being a cell-renewal system is one of the best organ for studying radiation induced effects and their modulation by antioxidants. An attempt has been made to evaluate radioprotective efficacy of Aloe vera leaf extract on skin in Swiss mice (1g/kg body wt/day). The mice selected from inbreed colony were divided into two groups. The first group was given Aloe vera extract orally for 15th consecutive days and served as experimental group while the other group received DDW (vol. equal to Aloe extract) to serve as control group. On the 15th day, after 30 min of above treatment animals of both the groups were exposed to 2 Gy gamma irradiation and autopsied on 6h 1, 3, 7, 14 and 21 days. DNA as well as total protein decreases in control group as compared to the normal value. Surprisingly, in experimental group, DNA and protein increases in comparison to the control group. Thus, Aloe vera were found to have positive influence against radiation induced alterations on skin of Swiss albino mice

  8. Effect of roentgen, cyclotron neutron, or mixed neutron-photon fractionated irradiation of mice

    International Nuclear Information System (INIS)

    Mice were whole-body-irradiated with 5 fractions of roentgen rays in 5 days, 5 fractions of cycotron neutrons in 5 days, or with mixed neutron-photon fractionated radiation, in the sequence n-n-x-x-x or n-x-x-x-n. The LD50 sub(/) 4 day values were determined. Roentgen rays and neutrons interact in the additive manner in the mixed fractionation schemes: effective dose per fraction is as predicted from the roentgen ray-only and neutron-only experiments. This essentially agrees with HENDRY et coll. (1976). However, no trend was found towards a less-than-additive effect which was observed by those authors and has also been suggested in skin response to mixed schemes (NELSON et coll 1975). (author)

  9. Protective role of coriandrum sativum oily extracts on ehrlich tumour bearing mice subjected to gamma irradiation

    International Nuclear Information System (INIS)

    This study was planned to evaluate the potency of coriandrum, sativum oily extract [in a dose of 1 mg/kg body weight; for six successive doses] as a chemopreventive agent against solid ehrlich tumour transplanted to the thigh of the left leg of mice subjected or not to gamma irradiation. The protective role of coriander oil was assessed through studying the level of serum phosphorus, calcium, prostaglandins, and anti-thyroid antibodies levels. Meanwhile, the content of cholesterol and triacylglycerols both in hepatic and tumor tissues were also measured. The levels of serum calcium ions revealed significant decline in the tested groups as compared with the control ones. Measurements of serum PGE2 and anti-thyroid antibodies levels exhibited significant fluctuated changes as compared with the control levels. Serum phosphorus levels induced only non-significant changes. The contents of cholesterol both in hepatic and tumor tissues induced significant decline in the tested proups as compared with the control ones

  10. Use of WR-2721 with total body irradiation in treatment of mouse lymphoma

    International Nuclear Information System (INIS)

    Efficacy of total body irradiation (TBI) in treatment of non-Hodgkin's lymphoma is limited by bone marrow radiosensitivity. WR-2721 has been shown to be an effective chemical protector of the hemotopoietic system. In this study, a spontaneous T-cell lymphoma implanted in BALB/c mice was used to determine the effect of WR-2721 on TBI of lymphoma. Mice were randomly assigned to 5 radiation dose groups (0-200 rad TBI) when the tumors reached the desired size. The experimental group received the half-maximum tolerated dose (365 mg/kg) of WR-2721/IP 30 min. before 150 rad TBI. Using tumor regrowth delay as an endpoint, WR-2721 was seen not to lessen the delay as would a tumor protector but rather to slightly increase the delay to 216 +- 9 hrs as compared with an expected value of 188 +- 20 hrs based on controls. In a subsequent experiment to determine the effect of WR-2721 alone, the experimental mice received 3 IP injections of WR-2721 (400 mg/kg/day) while the control group received saline. The geometric mean tumor regrowth delay times were 47 +- 3 hrs for the control group compared to 112 +- 10 hrs for the WR-2721 group ( p <.001). The authors conclude that WR-2721 does not give net radiation protection of this lymphoma at the doses studied and has an apparent cytotoxic effect on lymphoma that has not been previously reported

  11. Effect of photon irradiation on blood--brain barrier permeability to methotrexate in mice

    International Nuclear Information System (INIS)

    Methotrexate was administered by intraperitoneal injection (100 mg/kg) to unirradiated mice, and to mice receiving varying doses of cranial irradiation. The animals were sacrificed 24 hours after injection, and methotrexate assays were performed on brain tissue. No methotrexate was detected in the brains of the unirradiated animals. Detectable levels of methotrexate were present after 2000 rad cranial irradiation, but not after 500 rad, 1000 rad, or 1500 rad. The implications of these findings are discussed

  12. The effects of DP and AMP on immune functions in irradiated mice

    International Nuclear Information System (INIS)

    The effects of DP and AMP on the immune function in X-ray irradiated mice with different doses were studied in this dissertation. Mice (BALB/C) were irradiated with different doses (0, 1, 2, 4 Gy) of X-rays. The spontaneous proliferation of thymocytes and ConA-induced proliferation reaction of splenocytes in mice pretreated with DP( 2 mg) and AMP (5 mg) were detected. The results were as follows: the spontaneous proliferation of the thymocytes and the ConA-induced proliferation reaction of splenocytes in mice injected with DP and AMP decreased markedly, but increased significantly in mice treated with DP and AMP prior to irradiation by 1Gy and 2Gy X-rays

  13. THE EFFECT OF DONOR LYMPHOCYTES-T AND TOTAL-BODY IRRADIATION ON HEMATOPOIETIC ENGRAFTMENT AND PULMONARY TOXICITY FOLLOWING EXPERIMENTAL ALLOGENEIC BONE-MARROW TRANSPLANTATION

    NARCIS (Netherlands)

    DOWN, JD; MAUCH, P; WARHOL, M; NEBEN, S; FERRARA, JLM

    1992-01-01

    To study the effects of donor T lymphocytes on engraftment and graft-versus-host disease in relation to recipient total-body irradiation, we have returned small numbers of T cells to T-cell-depleted bone marrow transplanted across a minor histocompatibility barrier in mice (B10.BR --> CBA). T-cell-d

  14. Acute whole-body irradiation, even at moderate dose, induces alterations in blood-brain-barrier permeability

    International Nuclear Information System (INIS)

    Full text: A radiation-induced blood-brain barrier (BBB) breakdown has been evoked, but clearly demonstrated only at high doses of ionizing radiations. By using two protocols, we have searched an impairment in BBB integrity induced by moderate doses. First, the effects of irradiation on the permeability of striatal BBB to [3H]AIBA and [14C]sucrose were investigated in rats by using brain microdialysis. 32 rats, irradiated at 4.5Gy were serially experimented from 0 to 24 hours, from 24 to 48 hours and at later delays after exposure. 32 sham-irradiated rats served as controls. Second, the entry of pyridostigmine (PYR would not be expected to cross the BBB) into the brain was investigated in mice subjected to (neutron-g) exposure at 0.7Gy or 4Gy. For each dose 120 animals were irradiated and 120 sham-irradiated mice were included. At different delays after exposure, 10 mice were injected with 0.9% NaCl (control) or PYR bromide (0.1 mg/kg). Mice were killed 10min after injection and striatum, cortex and hippocampus were quickly dissected. Penetration of the drug into the brain was examined by measurement of AChE activity. Concerning microdialysis protocol, no late modification of the permeability of BBB was observed. But, in the course of the initial syndrome, we observed a transient increase of the permeability to the two markers, between the third and the 17th hour after exposure. A secondary transient 'opening' of the BBB to [14C] sucrose was noticed about 28 hours following irradiation with no modification of the permeability to [3H]AIBA. Concerning the BBB permeability to PYR, by comparing irradiated-PYR mice to sham-PYR mice, a decrease of AChE activity in the three cerebral areas was noted 48 hours after exposure at 4 Gy ; at 0.7 Gy this decrease is noted in the striatum only. In conclusion, our experiments by using two animal models, two types of radiations, and different tracers show modifications of the BBB permeability after moderate doses whole-body

  15. Purple grape juice as a protector against acute X-irradiation induced alterations on mobility, anxiety, and feeding behaviour in mice

    Directory of Open Access Journals (Sweden)

    Félix A. A. Soares

    2014-04-01

    Full Text Available The aim of this work was to test the hypothesis that a moderate intake of organic purple grape juice shows a positive radiomodifier effect over early behavioural damage following acute X-irradiation in mice. Anxiety-, locomotion-, and feeding-related responses to 6 Gy total body X-irradiation (TBI were studied via open field, Rotarod, and feeding/drinking recording. Thirty-two male mice weighing 25-30 g were grouped according grape juice (J or water (W ad libitum drinking and either non-irradiated (N or irradiated (R. 24 h post-TBI the access frequency to the center and corners of the open field was decreased, and the total stay in the corners increased, in RW vs. NW mice. Anxiety-related parameters decreased in RJ vs. RW mice. Rotarod latency times increased 72 h post-TBI in RJ vs RW mice. No overall changes in food and drink intake were observed along the experimental period. On the irradiation day, bout number was increased and bout duration was decreased in RW mice. The changes were reversed by purple grape juice intake. Grape juice intake before and after TBI can overcome several radiation-induced changes in behaviour within 24-72 hours after sub-lethal X-irradiation. This beneficial effect on short-term anxiety and mobility-related activities could probably be included in the list of flavonoid bio-effects. The present findings could be relevant in designing preventive interventions aimed to enhance body defense mechanisms against short-term irradiation damage.

  16. Foxp3(+)-Treg cells enhanced by repeated low-dose gamma-irradiation attenuate ovalbumin-induced allergic asthma in mice.

    Science.gov (United States)

    Park, Bum Soo; Hong, Gwan Ui; Ro, Jai Youl

    2013-05-01

    Gamma radiation is used for several therapeutic indications such as cancers and autoimmune diseases. Low-dose whole-body γ irradiation has been shown to activate immune responses in several ways, however, the effect and mechanism of irradiation on allergic asthma remains poorly understood. This study investigated whether or not irradiation exacerbates allergic asthma responses and its potential mechanism. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. The mice received whole-body irradiation once daily for 3 consecutive days with a dose of 0.667 Gy using (137)Cs γ rays 24 h before every OVA challenge. Repeated low-dose irradiation reduced OVA-specific IgE levels, the number of inflammatory cells including mast cells, goblet cell hyperplasia, collagen deposition, airway hyperresponsiveness, expression of inflammatory cytokines, CCL2/CCR2, as well as nuclear factor kappa B (NF-κB) and activator protein-1 activities. All of these factors were increased in BAL cells and lung tissue of OVA-challenged mice. Irradiation increased the number of Treg cells, expression of interleukin (IL)-10, IL-2 and IL-35 in BAL cells and lung tissue. Irradiation also increased Treg cell-expressed Foxp3 and IL-10 by NF-κB and RUNX1 in OVA-challenged mice. Furthermore, while Treg cell-expressing OX40 and IL-10 were enhanced in lung tissue or act-bone marrow-derived mast cells (BMMCs) with Treg cells, but BMMCs-expressing OX40L and TGF-β were decreased. The data suggest that irradiation enhances Foxp3(+)- and IL-10-producing Treg cells, which reduce OVA-induced allergic airway inflammation and tissue remodeling through the down-regulation of migration by the CCL2/CCR2 axis and activation of mast cells via OX40/OX40L in lung tissue of OVA-challenged mice. PMID:23560633

  17. Modeling a radiotherapy clinical procedure: total body irradiation.

    Science.gov (United States)

    Esteban, Ernesto P; García, Camille; De La Rosa, Verónica

    2010-09-01

    Leukemia, non-Hodgkin's lymphoma, and neuroblastoma patients prior to bone marrow transplants may be subject to a clinical radiotherapy procedure called total body irradiation (TBI). To mimic a TBI procedure, we modified the Jones model of bone marrow radiation cell kinetics by adding mutant and cancerous cell compartments. The modified Jones model is mathematically described by a set of n + 4 differential equations, where n is the number of mutations before a normal cell becomes a cancerous cell. Assuming a standard TBI radiotherapy treatment with a total dose of 1320 cGy fractionated over four days, two cases were considered. In the first, repopulation and sub-lethal repair in the different cell populations were not taken into account (model I). In this case, the proposed modified Jones model could be solved in a closed form. In the second, repopulation and sub-lethal repair were considered, and thus, we found that the modified Jones model could only be solved numerically (model II). After a numerical and graphical analysis, we concluded that the expected results of TBI treatment can be mimicked using model I. Model II can also be used, provided the cancer repopulation factor is less than the normal cell repopulation factor. However, model I has fewer free parameters compared to model II. In either case, our results are in agreement that the standard dose fractionated over four days, with two irradiations each day, provides the needed conditioning treatment prior to bone marrow transplant. Partial support for this research was supplied by the NIH-RISE program, the LSAMP-Puerto Rico program, and the University of Puerto Rico-Humacao.

  18. Patterns of patient specific dosimetry in total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Akino, Yuichi [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States); Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871 (Japan); McMullen, Kevin P.; Das, Indra J. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States)

    2013-04-15

    Purpose: Total body irradiation (TBI) has been used for bone marrow transplant for hematologic and immune deficiency conditions. The goal of TBI is to deliver a homogeneous dose to the entire body, with a generally accepted range of dose uniformity being within {+-}10% of the prescribed dose. The moving table technique for TBI could make dose uniform in whole body by adjusting couch speed. However, it is difficult to accurately estimate the actual dose by calculation and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors present patterns of patient-specific IVD in 161 TBI patients treated at our institution. Methods: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial Products, Inc., Fishers, IN) were used for TBI treatment. During treatment, OneDose{sup TM} (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect Transistor detectors were placed at patient body surface; both entrance and exit side of the beam at patient head, neck, mediastinum, umbilicus, and knee to estimate midplane dose. When large differences (>10%) between the prescribed and measured dose were observed, dose delivery was corrected for subsequent fractions by the adjustment of couch speed and/or bolus placement. Under IRB exempt status, the authors retrospectively analyzed the treatment records of 161 patients who received TBI treatment between 2006 and 2011. Results: Across the entire cohort, the median {+-} SD (range) percent variance between calculated and measured dose for head, neck, mediastinum, umbilicus, and knee was -2.3 {+-} 10.2% (-66.2 to +35.3), 1.1 {+-} 11.5% (-62.2 to +40.3), -1.9 {+-} 9.5% (-66.4 to +46.6), -1.1 {+-} 7.2% (-35.2 to +42.9), and 3.4 {+-} 12.2% (-47.9 to +108.5), respectively. More than half of treatments were within {+-}10% of the prescribed dose for all anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was within {+-}10

  19. Pegylated G-CSF Inhibits Blood Cell Depletion, Increases Platelets, Blocks Splenomegaly, and Improves Survival after Whole-Body Ionizing Irradiation but Not after Irradiation Combined with Burn

    Directory of Open Access Journals (Sweden)

    Juliann G. Kiang

    2014-01-01

    Full Text Available Exposure to ionizing radiation alone (radiation injury, RI or combined with traumatic tissue injury (radiation combined injury, CI is a crucial life-threatening factor in nuclear and radiological accidents. As demonstrated in animal models, CI results in greater mortality than RI. In our laboratory, we found that B6D2F1/J female mice exposed to 60Co-γ-photon radiation followed by 15% total-body-surface-area skin burns experienced an increment of 18% higher mortality over a 30-day observation period compared to irradiation alone; that was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At the 30th day after injury, neutrophils, lymphocytes, and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were similar to basal levels. Comparing CI and RI mice, only RI induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It was observed that only the RI mice treated with pegylated G-CSF after RI resulted in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment sustained RBC balance, hemoglobin levels, and hematocrits and inhibited splenomegaly after RI. The results suggest that pegylated G-CSF effectively sustained animal survival by mitigating radiation-induced cytopenia, thrombopenia, erythropenia, and anemia.

  20. Gene Expression Changes in Mouse Intestinal Tissue Following Whole-Body Proton or Gamma-Irradiation

    Science.gov (United States)

    Purgason, Ashley; Zhang, Ye; Mangala, Lingegowda; Nie, Ying; Gridley, Daila; Hamilton, Stanley R.; Seidel, Derek V.; Wu, Honglu

    2014-01-01

    Crew members face potential consequences following exposure to the space radiation environment including acute radiation syndrome and cancer. The space radiation environment is ample with protons, and numerous studies have been devoted to the understanding of the health consequences of proton exposures. In this project, C57BL/6 mice underwent whole-body exposure to 250 MeV of protons at doses of 0, 0.1, 0.5, 2 and 6 Gy and the gastrointestinal (GI) tract of each animal was dissected four hours post-irradiation. Standard H&E staining methods to screen for morphologic changes in the tissue showed an increase in apoptotic lesions for even the lowest dose of 0.1 Gy, and the percentage of apoptotic cells increased with increasing dose. Results of gene expression changes showed consistent up- or down- regulation, up to 10 fold, of a number of genes across exposure doses that may play a role in proton-induced oxidative stress including Gpx2. A separate study in C57BL/6 mice using the same four hour time point but whole-body gamma-irradiation showed damage to the small intestine with lesions appearing at the smallest dose of 0.05 Gy and increasing with increasing absorbed dose. Expressions of genes associated with oxidative stress processes were analyzed at four hours and twenty-four hours after exposure to gamma rays. We saw a much greater number of genes with significant up- or down-regulation twenty-four hours post-exposure as compared to the four hour time point. At both four hours and twenty-four hours post-exposure, Duox1 and Mpo underwent up-regulation for the highest dose of 6 Gy. Both protons and gamma rays lead to significant variation in gene expressions and these changes may provide insight into the mechanism of injury seen in the GI tract following radiation exposure. We have also completed experiments using a BALB/c mouse model undergoing whole-body exposure to protons. Doses of 0, 0.1, 1 and 2 Gy were used and results will be compared to the work mentioned

  1. Optimization of total body irradiation: the match between (maximal) leukemic cell kill and (minimal) late effects

    NARCIS (Netherlands)

    Harteveld, M.L. van

    2007-01-01

    Optimization of total body irradiation: the match between (maximal) leukemic cell kill and (minimal) late effects: In this thesis, cataract formation and renal dysfunction as late effects of high-dose total body irradiation (TBI) as part of the conditioning before hematological stem cell transplanta

  2. Total body irradiation: present and future; Irradiation corporelle totale: present et avenir

    Energy Technology Data Exchange (ETDEWEB)

    Zilli, T.; Miralbell, R.; Ozsahin, M. [Hopitaux Universitaires de Geneve, Service de Radio-Oncologie (Switzerland); Ozsahin, M. [Centre Hospitalier Universitaire Vaudois, Service de Radio-Oncologie, Lausanne (Switzerland)

    2009-09-15

    Total body irradiation (T.B.I.) has an established role as preparative regimen for bone-marrow transplantation in the treatment of hematological malignancies. Many randomized trials demonstrated that the clinical outcomes obtained from the association of T.B.I. and cyclophosphamide are equivalent, or, sometimes, better than those based on chemotherapeutic agents. Despite the therapeutic progress of the last years, and the consequent improvement in the overall survival, this preparative regimen remains always associated with a relatively high rate of acute and late toxicity. In this article, we review the actual indications of T.B.I. in clinical practice, and analyze the technological progress in this domain. We focus on the hypothesis that a selective irradiation of the hematopoietic or lymphoid organs is actually possible with intensity-modulated radiotherapy. Technical limits and preliminary results in terms of acute and late toxicities of intensity-modulated T.B.I. are analyzed. With these new technologies, treatment-related toxicity is not anymore a major limiting factor in the preparative regimens for bone-marrow transplantation, allowing for a larger spectrum of T.B.I. indications, a possible extension to patients older than 50 years, or a dose escalation. Preliminary results warrant, however, further evaluation in clinical trials to better assess the impact of this new approach on disease control and the long-term toxicity. (authors)

  3. Dominant lethal mutations research in mice fed with irradiated black beams

    International Nuclear Information System (INIS)

    To evaluate the potential mutagenic effects of irradiated black beans (Phaseolus vulgaris) with conservation purpose, in germ cells of mice, dominant lethal assay were employed. Three groups of albino swiss male mice (S W-55) were fed with a normal ration, or unirradiated or irradiated (0,2; 0,5; 1; 5; 10; 15 e 20 KGy) test diets for eight weeks. After the feeding period the males were mated with groups of untreated females mice for four consecutive weeks. Numbers of pregnancy rates females were observed. The females were autopsied at mid-term pregnancy for evaluation of dominant lethal mutations. (author)

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

    International Nuclear Information System (INIS)

    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)

  5. Effects of osteoblasts on recovery of hematopoiesis and angiogenesis in acute irradiation injured mice

    International Nuclear Information System (INIS)

    Objective: To explore the effects of osteoblasts on the recovery of hematopoiesis and angiogenesis in acute irradiation injury mice. Methods: The femurs of 18 male BALB/c mice were used to prepare the bone marrow osteoblasts, and the rest mice were divided into 3 groups as normal group, saline group and osteoblast group. The mice in normal group received no treatment, and the other two groups were received 6.0 Gy 60Co γ-ray irradiation. After irradiation each mouse of osteoblast group was administered with 2 × 106 osteoblasts through tail vein injection, and equal volume saline was given to each mouse of saline group by the same way. The following factors were measured at 7, 14, 21 d after irradiation, they were the counts of peripheral blood cells and bone marrow mononuclear cells (BMMNC), the percentage of CD34 + cells in BMMNC, the histology changes and micro vascular density (MVD) of bone marrow tissue. Results: The counts of peripheral blood cells, BMMNC and hematopoietic tissue area in osteoblast group were higher than those in saline group.The percentage of CD34 + cells in BMMNC and the MVD of bone marrow in osteoblast group were also higher than those in saline group at 7, 14, 21 d after irradiation (t=2.46-64.51, P<0.05). Conclusions: Osteoblasts could significantly promote the recovery of hematopoiesis and angiogenesis in mice after acute irradiation injury. (authors)

  6. Protective effect of egg-milk with MT on mice injured by X-irradiation

    International Nuclear Information System (INIS)

    Objective: To explore the protective effect of egg-milk with metallothionein (MT) on the mice injured by X-irradiation. Methods: After fed intragastrically with egg-milk plus MT for 14 d, mice were irradiated with 2.5 Gy X-rays. Twenty-four hours after the mice were irradiated, the number of WBC in peripheral blood, lymphocyte proliferation rate, DNA content of marrow cells, thymocyte cycle progression, malondialdehyde (MDA) level and the activities of SOD, CAT, GSH-Px in liver, serum and kidney were measured. Results: In irradiated mice fed with egg-milk plus MT, the WBC number, lymphocyte proliferation rate, DNA content of marrow cells, the activities of SOD, CAT and GSH-Px in liver, kidney and serum were all significantly higher than those in the irradiation alone group. Besides in the former group the MDA level decreased significantly, the G1 phase arrest in thymocytes was weakened and DNA synthesis was promoted. Conclusion: The egg-milk with MT has protective effect on the mice injured by X-irradiation. (authors)

  7. 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.

  8. Protective effect of gingerol on leucocyte and bone marrow DNA of 60Co γ-rays irradiated mice

    International Nuclear Information System (INIS)

    In this article, the effect of gingerol on peripheral leucocyte and bone marrow DNA of 60Co γ-rays irradiated mice was developed., Twenty-four healthy healthy female Kunming mice were randomly divided into 4 groups: control, gingerol, irradiation and gingerol + irradiation group. Gingerol group and gingerol + irradiation group were given gingerol intragastrically once a day for five days. Irradiation group and gingerol + irradiation group were suffered from 5 Gy 60Co γ-rays irradiation at the rate of 1.2 Gy/min on the 6th day. Blood samples, spleens, livers and thigh bones were collected to be measured after 48 h. The results showed that, compared with irradiation group, gingerol + irradiation group had significantly higher spleen index (p60Co γ-rays irradiated mice. (authors)

  9. Systemic LPS Translocation Activates Cross-Presenting Dendritic Cells but Is Dispensable for the Breakdown of CD8+ T Cell Peripheral Tolerance in Irradiated Mice.

    Directory of Open Access Journals (Sweden)

    Gabriel Espinosa-Carrasco

    Full Text Available Lymphodepletion is currently used to enhance the efficacy of cytotoxic T lymphocyte adoptive transfer immunotherapy against cancer. This beneficial effect of conditioning regimens is due, at least in part, to promoting the breakdown of peripheral CD8+ T cell tolerance. Lymphodepletion by total body irradiation induces systemic translocation of commensal bacteria LPS from the gastrointestinal tract. Since LPS is a potent activator of the innate immune system, including antigen presenting dendritic cells, we hypothesized that LPS translocation could be required for the breakdown of peripheral tolerance observed in irradiated mice. To address this issue, we have treated irradiated mice with antibiotics in order to prevent LPS translocation and utilized them in T cell adoptive transfer experiments. Surprisingly, we found that despite of completely blocking LPS translocation into the bloodstream, antibiotic treatment did not prevent the breakdown of peripheral tolerance. Although irradiation induced the activation of cross-presenting CD8+ dendritic cells in the lymphoid tissue, LPS could not solely account for this effect. Activation of dendritic cells by mechanisms other than LPS translocation is sufficient to promote the differentiation of potentially autoreactive CD8+ T cells into effectors in irradiated mice. Our data indicate that LPS translocation is dispensable for the breakdown of CD8+ T cell tolerance in irradiated mice.

  10. In vivo dosimetry with silicon diodes in total body irradiation

    Science.gov (United States)

    Oliveira, F. F.; Amaral, L. L.; Costa, A. M.; Netto, T. G.

    2014-02-01

    The aim of this work is the characterization and application of silicon diode detectors for in vivo dosimetry in total body irradiation (TBI) treatments. It was evaluated the diode response with temperature, dose rate, gantry angulations and field size. A maximum response variation of 2.2% was obtained for temperature dependence. The response variation for dose rate and angular was within 1.2%. For field size dependence, the detector response increased with field until reach a saturation region, where no more primary radiation beam contributes for dose. The calibration was performed in a TBI setup. Different lateral thicknesses from one patient were simulated and then the calibration factors were determined by means of maximum depth dose readings. Subsequent to calibration, in vivo dosimetry measurements were performed. The response difference between diode readings and the prescribed dose for all treatments was below 4%. This difference is in agreement as recommended by the International Commission on Radiation Units and Measurements (ICRU), which is ±5%. The present work to test the applicability of a silicon diode dosimetry system for performing in vivo dose measurements in TBI techniques presented good results. These measurements demonstrated the value of diode dosimetry as a treatment verification method and its applicability as a part of a quality assurance program in TBI treatments.

  11. Bone markers after total body irradiation in childhood.

    Science.gov (United States)

    Couto-Silva, A-C; Trivin, C; Espérou, H; Michon, J; Baruchel, A; Souberbielle, J-C; Brauner, R

    2010-03-01

    Total body irradiation (TBI) can cause short stature because of decreased growth hormone (GH) and skeletal abnormalities. To evaluate the plasma concentrations of markers of bone formation (osteocalcin and procollagen type 1 amino-terminal propeptide, P1NP) and resorption (carboxy-terminal telopeptide, CTX), in patients (n=65) who had been given TBI at 6.6+/-0.4 years were evaluated at 9.8+/-0.4 years. Patients given single 10 Gy or fractionated 12 Gy TBI had similar characteristics, except that plasma insulin-like growth factor (IGF-1) was lower in those given a single 10 Gy. Seven had lower osteocalcin and two had higher CTX than controls. Bone markers (as zs) were positively correlated (osteocalcin with P1NP, rho=0.42, P=0.0007; osteocalcin with CTX, rho=0.3, Pirradiated when young (P=0.0002) or given single TBI lost more height between TBI and adult height. Most TBI patients had normal bone formation and resorption markers. Thus, impaired bone turnover is probably not the cause of their short stature and poor response to GH.

  12. Recombinant human interleukin-6 protects mice from lethal irradiation and has effects on platelets

    International Nuclear Information System (INIS)

    Objective: To study the effects of rhIL-6 on platelets and its possible utilization in irradiation-induced myelosuppression. Methods: The rhIL-6 (5μg/day x 7 days) was injected into lethally irradiated C57BL/6 mice before or after irradiation. Results: The survival was significantly prolonged by rhIL-6 administration either before or after irradiation when compared with HBSS group (P<0.01). The mean survival period prolonged from 9.3 days to 12.7 days (rhIL-6 administration after irradiation) or to 11.5 days (rhIL-6 administration before irradiation). rhIL-6 enhanced the contents of RBC, HGB, HCT and PLT. Conclusion: The research indicates that rhIL-6 may improve platelets and be a possibly potential candidate for the treatment of irradiation-induced myelosuppression in clinic

  13. Recovery of hematopoietic colony-forming cells in irradiated mice pretreated with interleukin 1 (IL-1)

    International Nuclear Information System (INIS)

    Data in this report determined the effect of a single injection of recombinant interleukin 1 alpha (rIL-1) prior to irradiation of B6D2F1 mice on the recovery of colony-forming cells (CFC) at early and late times after sublethal and lethal doses of radiation. Injection of rIL-1 promoted an earlier recovery of mature cells in the blood and CFC in the bone marrow and spleen. For example, 8 days after 6.5 Gy irradiation, the number of CFU-E (colony-forming units-erythroid), BFU-E (burst-forming units-erythroid), and GM-CFC (granulocyte-macrophage colony-forming cells) per femur was approximately 1.5-fold higher in rIL-1-injected mice than in saline-injected mice. Also, 5, 9, and 12 days after irradiation, the number of both day 8 and day 12 CFU-S (colony-forming units-spleen) was almost twofold greater in bone marrow from rIL-1-injected mice. The earlier recovery of CFU-S in rIL-1-injected mice was not associated with an increase in the number of CFU-S that survived immediately after irradiation. Also, 7 months after irradiation, the number of CFU-S per femur of both saline- and rIL-1-injected mice was still less than 50% of normal values. Data in this report demonstrate that a single injection of rIL-1 prior to irradiation accelerates early hematopoietic recovery in irradiated mice, but does not prevent expression of radiation-induced frontend damage or long-term damage to hematopoietic tissues

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

    International Nuclear Information System (INIS)

    To evaluate late biological effects of chronic low dose-rate radiation, the life-span and pathological changes were evaluated in mice which had been continuously irradiated with gamma-rays for 400 days. Two hundred (100 male and 100 female) specific-pathogen-free (SPF) B6C3F1 mice at six weeks of age were purchased every month. After a 2-week quarantine, they were divided into 4 groups (1 unirradiated control and 3 irradiated). Irradiation was performed using 137Cs gamma-rays at dose-rates of 20 mGy/day, 1 mGy/day and 0.05 mGy/day with accumulated doses equivalent to 8000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. Results of the monthly microbiological examinations confirmed that the mice were maintained under SPF-conditions throughout the experimental period. A total of 4000 mice have been admitted into the experiment since it started in February 1996, all of which have received their predetermined doses and have been transferred to the animal room. Data on the 20 mGy/day group of both sexes suggested a shortened life span. The most common lethal neoplasms in pooled data of unirradiated 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. (author)

  15. Protective Effect of HemoHIM on Epidermal Melanocytes in Ultraviolet-B irradiated Mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae June [Korea Institute of Radiological and Medical Science, Seoul (Korea, Republic of); Kim, Jong Choon; Moon, Chang Jong; Kim, Sung Ho [Chonnam National University, Gwangju (Korea, Republic of); Jung, U Hee; Park, Hae Ran; Jo, Sung Kee [Jeongeup Campus of Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Jang, Jong Sik; Kim, Tae Hwan [Kyungpook National University, Daegu (Korea, Republic of)

    2011-06-15

    We induced the activation of melanocytes in the epidermis of C57BL/6 mice by ultraviolet-B (UV-B) irradiation, and observed the effect of an herbal preparation (HemoHIM, HH) on the formation, and decrease of UV-B-induced epidermal melanocytes. C57BL/6 mice were irradiated by UV-B 80 mJ:cm{sup -2} (0.5 mW:sec{sup -1}) daily for 7 days, and HH was intraperitoneally, orally or topically applied pre- or post-irradiation. For the estimation of change of epidermal melanocytes, light microscopic observation with dihydroxyphenylalanine (DOPA) stain was performed. Split epidermal sheets prepared from the ear of untreated mice exhibited 13∼15 melanocytes:mm{sup -2}, and one week after UV irradiation, the applied areas showed an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal, oral or topical treatment with HH before each irradiation interrupted UV-B-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to the number found in UV-B-irradiated, untreated control skin. The number and size of DOPA-positive epidermal melanocytes were also significantly decreased in intraperitoneally injected or topically applicated group after irradiation with HH at 3rd and 6th weeks after irradiation. The present study suggests the HH as inhibitor of UV-B-induced pigmentation, and depigmenting agent.

  16. Radioprotective effects of kojic acid against mortality induced by gamma irradiation in mice

    International Nuclear Information System (INIS)

    To evaluate the protective effects of kojic acid on mortality induced by gamma irradiation in mice. The efficacy was compared with amifostine as a reference radioprotector. This experimental study was conducted in the Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari and Babolsar Radiotherapy Hospital, Babolsar, Iran, between October 2006 and January 2008. Kojic acid was administrated subcutaneously as single doses of 142, 175, 232, and 350 mg/kg, one hour prior to a lethal dose of gamma irradiation (8 Gy). Amifostine was injected subcutaneously at a dose of 200 mg/kg at a similar irradiation dose. The mortality was recorded 30 days after irradiation. The antioxidant activity of the kojic acid was assessed using the 1, 1-diphenyl-2-picrylhydrazyl free stable radical (DPPH) method. One hundred and twenty NMRI mice were divided into 6 groups with 20 mice in each group. At 30 days after treatment, the percentage of survival in each group was: control, 5%; 142 mg/kg, 5%; 175 mg/kg, 0%; 232 mg/kg, 30%; 350 mg/kg, 40%; and amifostine, 40% one hour treatment prior gamma irradiation. The survival rate was statistically increased in animals treated with kojic acid (350 mg/kg), one hour prior irradiation, as compared with the irradiated control group. Kojic acid exhibited concentration-dependent scavenging activity on DPPH possessing strong antioxidant activity. Kojic acid with antioxidant activity reduced the mortality induced by gamma irradiation. (author)

  17. Immune response of mice and sheep to bluetongue virus inactivated by gamma irradiation

    International Nuclear Information System (INIS)

    Gamma irradiation is being tested as a means of inactivating bluetongue virus (BTV) for use in vaccines. Exposure of BTV 17 to various levels of irradiation revealed that a dose of approximately 0.6 megarad was required to reduce the virus titer by one log10, or 90%. To test the immunogenicity of irradiated BTV, mouse brain passaged virus and concentrated cell culture passaged virus were inactivated by 6 megarads of gamma irradiation, and vaccines were prepared by emulsifying the virus preparations in equal volumes of a modified incomplete Freund's adjuvant. These vaccines stimulated the production of neutralizing antibodies in mice and sheep, a cell mediated immune response in mice, and a protective immune response in sheep. The results suggest that gamma irradiation would be an effective means of inactivating BTV for the preparation of vaccines

  18. Virtual bolus for total body irradiation treated with helical tomotherapy.

    Science.gov (United States)

    Moliner, Gilles; Izar, Françoise; Ferrand, Régis; Bardies, Manuel; Ken, Soléakhéna; Simon, Luc

    2015-11-08

    Intensity-modulated radiation therapy (IMRT) for total body irradiation (TBI) is practiced in several centers using the TomoTherapy System. In this context the planning target volume (PTV) is the entire body including the skin. A safety margin in the air surrounding the body should be added to take into account setup errors. But using inverse planning, over-fluence peak could be generated in the skin region to insure dose homogeneity. This work proposes to study the performance of the use of a virtual bolus (VB). A VB is a material placed on the skin surface during planning, but absent for the real treatment. The optimal VB that compensates large setup errors without introducing a high-dose increase or hot spots for small setup errors was determined. For two cylindrical phantoms, 20VBs with different densities, thicknesses or designs were tested. Dose coverage of the PTV (V95%) in the presence of simulated setup errors was computed to assess the VB performance. A measure of the dose increase in the phantom center due to the absence of the VB during treatment was also achieved. Finally, the fluence peak at the phantom edge was measured in complete buildup conditions using a large phantom and a detector matrix. Using these VBs, simulated setup errors were compensated to a minimum value of 2.6 and 2.1 cm for small and large phantom, respectively (and only 1.2 and 1.7 cm with no VB). An optimal double-layer VB was found with a density of 0.4 kg.m(-3) and a total thickness of 8mm; an inner layer of 5 mm was declared as the target for the treatment planning system and an additional layer of 3 mm was added to avoid the over-fluence peak. Using this VB, setup errors were compensated up to 2.9 cm. The dose increase was measured to be only +1.5% at the phantom center and over-fluence peak was strongly decreased.

  19. Bone marrow-derived cells rescue salivary gland function in mice with head and neck irradiation.

    Science.gov (United States)

    Sumita, Yoshinori; Liu, Younan; Khalili, Saeed; Maria, Ola M; Xia, Dengsheng; Key, Sharon; Cotrim, Ana P; Mezey, Eva; Tran, Simon D

    2011-01-01

    Treatment for most patients with head and neck cancers includes ionizing radiation. A consequence of this treatment is irreversible damage to salivary glands (SGs), which is accompanied by a loss of fluid-secreting acinar-cells and a considerable decrease of saliva output. While there are currently no adequate conventional treatments for this condition, cell-based therapies are receiving increasing attention to regenerate SGs. In this study, we investigated whether bone marrow-derived cells (BMDCs) can differentiate into salivary epithelial cells and restore SG function in head and neck irradiated mice. BMDCs from male mice were transplanted into the tail-vein of 18Gy-irradiated female mice. Salivary output was increased in mice that received BMDCs transplantation at week 8 and 24 post-irradiation. At 24 weeks after irradiation (IR), harvested SGs (submandibular and parotid glands) of BMDC-treated mice had greater weights than those of non-treated mice. Histological analysis shows that SGs of treated mice demonstrated an increased level of tissue regenerative activity such as blood vessel formation and cell proliferation, while apoptotic activity was increased in non-transplanted mice. The expression of stem cell markers (Sca-1 or c-kit) was detected in BMDC-treated SGs. Finally, we detected an increased ratio of acinar-cell area and approximately 9% of Y-chromosome-positive (donor-derived) salivary epithelial cells in BMDC-treated mice. We propose here that cell therapy using BMDCs can rescue the functional damage of irradiated SGs by direct differentiation of donor BMDCs into salivary epithelial cells.

  20. Long-Term Effects of 56Fe Irradiation on Spatial Memory of Mice: Role of Sex and Apolipoprotein E Isoform

    International Nuclear Information System (INIS)

    Purpose: To assess whether the effects of cranial 56Fe irradiation on the spatial memory of mice in the water maze are sex and apolipoprotein E (apoE) isoform dependent and whether radiation-induced changes in spatial memory are associated with changes in the dendritic marker microtubule-associated protein 2 (MAP-2) and the presynaptic marker synaptophysin. Methods and Materials: Two-month-old male and female mice expressing human apoE3 or apoE4 received either a 3-Gy dose of cranial 56Fe irradiation (600 MeV/amu) or sham irradiation. Mice were tested in a water maze task 13 months later to assess effects of irradiation on spatial memory retention. After behavioral testing, the brain tissues of these mice were analyzed for synaptophysin and MAP-2 immunoreactivity. Results: After irradiation, spatial memory retention of apoE3 female, but not male, mice was impaired. A general genotype deficit in spatial memory was observed in sham-irradiated apoE4 mice. Strikingly, irradiation prevented this genotype deficit in apoE4 male mice. A similar but nonsignificant trend was observed in apoE4 female mice. Although there was no change in MAP-2 immunoreactivity after irradiation, synaptophysin immunoreactivity was increased in irradiated female mice, independent of genotype. Conclusions: The effects of 56Fe irradiation on the spatial memory retention of mice are critically influenced by sex, and the direction of these effects is influenced by apoE isoform. Although in female mice synaptophysin immunoreactivity provides a sensitive marker for effects of irradiation, it cannot explain the apoE genotype-dependent effects of irradiation on the spatial memory retention of the mice.

  1. Recovery and radio-resistance in mice after external irradiation; Restauration et radio-resistance chez la souris apres irradiation externe

    Energy Technology Data Exchange (ETDEWEB)

    Le Guillou, S. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1965-07-01

    The author presents a literature study concerning recovery from external irradiation and an analysis of experimental data (which appear to suggest the idea of a radio-resistance in animals), as well as the hypotheses put forward for explaining this phenomenon. The author then describes an experiment carried out on mice whose LD 50/30 days increased from 1005 to 1380 rads and for which it was shown that an increase occurs in the number of certain anti-bodies circulating after a low dose of {gamma} irradiation. (author) [French] L'auteur presente une etude bibliographique de la restauration apres irradiation externe et une analyse des donnees experimentales qui paraissent suggerer la notion de radioresistance chez les animaux ainsi que les hypotheses cherchant a expliquer ce phenomene. Il relate ensuite une experience realisee sur des souris dont la DL 50/30 jours est passee de 1005 a 1380 rads et dans laquelle est montree l'augmentation de certains anticorps circulant apres une faible dose d'irradiation gamma. (auteur)

  2. Effects of low dose irradiation on the main immune parameters and on the antitumor immune surveillance in mice

    International Nuclear Information System (INIS)

    Complete text of publication follows. Objectives: We investigated the effect of low dose ionizing radiation on the quantitative and qualitative changes of major immune parameters in healthy mice and studied how low doses influence the anti-tumor immune surveillance. Methods: Mice were irradiated with different doses of gamma-radiation (0.01, 0.05, 0.1 and 2 Gy) and 24 h later a moderately immunogenic mouse glioma 261 tumor was transplanted subcutaneously into the mice and tumor growth followed. To study radiation effects on various lymphocyte subsets, mice were irradiated (0.01, 0.05, 0.1, 0.5, 1, 2 and 4 Gy), one, three or seven days later the animals were killed and lymphocytes isolated from spleen. The ratio of various lymphocyte subsets were determined by flow cytometry. The proliferative response of lymphocytes to non-specific stimuli (Concanavalin A) was also investigated. Results: Pre-irradiation of mice before tumor transplantation seriously prohibited tumor growth. Three days after whole body irradiation, non-specific stimuli-induced lymphocyte proliferation was inhibited in a dose dependent manner; even radiation doses as low as 0.01 Gy suppressed lymphocyte proliferation. The anti-proliferative effect persisted at least for a week. Flow cytometry data show that low dose irradiation affects the main compartments of T-cell immunity, but ample differences exist in the radiosensitivity of various cellular compartments, with the Cd4+CD8+ compartment being the most radiosensitive and the CD4+CD25+ compartment being the most radioresistant. Interestingly, these lymphocyte subsets presented hypersensitivity to radiation at low doses (10, 50 and 100 mGy). The low dose hypersensitivity was most prevalent for NK cells, where 100 mGy and 1 Gy radiation doses killed nearly the same number of NK cells (about 50% survival). The time course of these alterations was followed, and the most ample changes could be seen at day 3 after irradiation. Conclusion: The experiments

  3. Protective effects of cimetidine on micronucleated polychromatic erythrocytes in mice irradiated with 0.7Gy

    Directory of Open Access Journals (Sweden)

    Jun-ling ZHANG

    2016-01-01

    Full Text Available Objective  To study the radioprotective effect of cimetidine on single low-dose irradiated mice with radiosensitive detection indexes. Methods  Forty-eight healthy male C57BL/6 mice were randomly divided into normal control group, model control group, positive group (200mg/kg WR2721 and cimetidine groups (7.5mg/kg, 15mg/kg and 30mg/kg. The mice were given intraperitoneal injection of cimetidine 2h before irradiation in cimetidine groups and WR2721 before irradiation once a day for two days in positive group. All the mice except those in normal control group were irradiated with 0.7Gy 60Co γ-ray at 5.83mGy/min rate. Peripheral blood cells, superoxide dismutase (SOD activity and malondialdehyde (MDA content both in serum and liver, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMPEs were determined 24h after irradiation. Results  Compared with normal control group, the peripheral white blood cells (WBCs of irradiated mice decreased significantly (P<0.01, and fMPEs increased significantly (P<0.01 after irradiation. Except for 15mg/kg cimetidine group, the bone marrow DNA content was decreased significantly after irradiation (P<0.01, P<0.05. The SOD activity and MDA content in irradiated mice showed no significant difference compared with that of normal mice. Compared with model control group, peripheral WBCs and bone marrow DNA content showed no significant changes in treatment groups. The f MPE of 7.5mg/kg cimetidine group was 0.027‰, which was decreased significantly compared with that of model control group (P<0.01, and the dose reduction factor (DRF of 7.5mg/kg cimetidine group was 3.338. Conclusion  Cimetidine has good protective effect on micronucleated polychromatic erythrocytes (MPEs in mice irradiated by 0.7Gy in single low-dose. DOI: 10.11855/j.issn.0577-7402.2015.12.03

  4. Effect of soft x-ray irradiation on immunological functions in mice

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Minoru; Shibata, Hiroshi; Nasu, Tetsuyuki (Yamaguchi Univ. (Japan))

    1992-08-01

    Effect of soft x-ray irradiation on immunological functions in mice was investigated. Soft x-ray irradiation with 100R or more induced a significant reduction in the number of plaque-forming cells (PFC). The reduction in the number of PFC depended on the irradiation doses. Irradiation with 600R or more showed a significant reduction in the delayed reaction of footpad swelling. However, soft x-ray irradiation with doses ranging from 100R to 1000R did not exert significant influence on the K values of carbon clearance test. Irradiation with 100R or more of soft x-ray showed a remarkable reduction of response to concanavalin A (ConA) or lipopolysaccharide (LPS) in spleen cells, and the response to ConA was lower than that to LPS. These results suggest that in the soft x-ray-irradiated mice, antibody-producing ability, delayed type hypersensitivity reaction and mitogenic activity are sensitive to soft x-ray irradiation and furthermore, T cell is more sensitive than B cell, but phagocytic activity of reticuloendothelial system (RES) is resistant to soft x-ray irradiation. (author).

  5. 16Oxygen irradiation enhances cued fear memory in B6D2F1 mice

    Science.gov (United States)

    Raber, Jacob; Marzulla, Tessa; Kronenberg, Amy; Turker, Mitchell S.

    2015-11-01

    The space radiation environment includes energetic charged particles that may impact cognitive performance. We assessed the effects of 16O ion irradiation on cognitive performance of C57BL/6J × DBA/2J F1 (B6D2F1) mice at OHSU (Portland, OR) one month following irradiation at Brookhaven National Laboratory (BNL, Upton, NY). Hippocampus-dependent contextual fear memory and hippocampus-independent cued fear memory of B6D2F1 mice were tested. 16O ion exposure enhanced cued fear memory. This effect showed a bell-shaped dose response curve. Cued fear memory was significantly stronger in mice irradiated with 16O ions at a dose of 0.4 or 0.8 Gy than in sham-irradiated mice or following irradiation at 1.6 Gy. In contrast to cued fear memory, contextual fear memory was not affected following 16O ion irradiation at the doses used in this study. These data indicate that the amygdala might be particularly susceptible to effects of 16O ion exposure.

  6. OK-432 reduces mortality and bacterial translocation in irradiated and granulocyte-colony stimulating factor (G-CSF)-treated mice

    Energy Technology Data Exchange (ETDEWEB)

    Nose, Masako; Uzawa, Akiko; Ogyu, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan); Suzuki, Gen

    2001-06-01

    Acute radiation induces bacterial translocation from the gut, followed by systemic infection and sepsis. In order to reduce the mortality after acute whole body irradiation, it is essential to control bacterial translocation. In this study, we established a bacterial translocation assay as a sensitive method to detect minor mucosal injury by radiation. By utilizing this assay, we evaluated the adverse effects, if any, of hematopoietic reagents on the mucosal integrity in the respiratory and gastro-intestinal tracts. Bacterial translocation to the liver and spleen occurred after whole-body irradiation if the dose exceeded 6 Gy. The administration of G-CSF unexpectedly increased the bacterial translocation in 8 Gy-irradiated mice. The pharmaceutical preparation of low-virulent Streptococcus pyogenes, OK-432, significantly reduced the endotoxin levels in peripheral blood without any reduction of bacterial translocation. A combined treatment with G-CSF and OK-432 decreased bacterial translocation and prevented death. This result indicates that the early administration of G-CSF has an adverse effect on bacterial translocation, and that a combined treatment of G-CSF and OK-432 attenuates the adverse effect of G-CSF and improves the survival rate after acute irradiation. (author)

  7. Evaluation of the role of laser bio stimulation on skin and liver of gamma-irradiated mice

    International Nuclear Information System (INIS)

    Low level laser therapy (LLLT) is used in different medical fields due to its therapeutic effects on reparative processes, pain relief and bio stimulation (Castro-e-silva et al., 2003). The present study aimed at evaluating the therapeutic efficacy of He-Ne laser in stimulating the reparative processes after whole body irradiation of mice using a sublethal dose (5 Gy) of gamma rays. Two vital organs were studied, a radio-sensitive one (the skin) as well as a relatively radio-resistant one (the liver) . During the course of the present work, some biochemical parameters as well as histopathological changes in the skin and liver tissues induced by whole body gamma ionizing radiation were studied. Female mice (240) were used and divided into 6 groups and laser therapy was carried out using a computerized scanner emitting He-Ne(C W) with a wavelength of 632.8 nm and the fluence was 5 j/cm2. Experimental investigation have been carried out along two main lines: Biochemical investigations for the assessment of serum transferases and histopathological assessment of liver and skin biopsy.On the basis of the current results it could be concluded that mice exposed to whole body gamma irradiation either by the US of the shot or the fractionated sublethal dose suffered an aggravated histopathological changes in the skin and liver tissues which were associated with certain biochemical disturbances of the liver function testes. These undesirable alterations were ameliorated by the early treatment of mice by He -Ne laser immediately post exposure before being irreversibly damaged

  8. Delayed renal dysfunction after total body irradiation in pediatric malignancies.

    Science.gov (United States)

    Watanabe Nemoto, Miho; Isobe, Koichi; Togasaki, Gentaro; Kanazawa, Aki; Kurokawa, Marie; Saito, Makoto; Harada, Rintaro; Kobayashi, Hiroyuki; Ito, Hisao; Uno, Takashi

    2014-09-01

    The purpose of this study was to retrospectively evaluate the incidence of delayed renal dysfunction after total body irradiation (TBI) in long-term survivors of TBI/hematopoietic stem cell transplantation (HSCT). Between 1989 and 2006, 24 pediatric patients underwent TBI as part of the conditioning regimen for HSCT at Chiba University Hospital. Nine patients who survived for more than 5 years were enrolled in this study. No patient had any evidence of renal dysfunction prior to the transplant according to their baseline creatinine levels. The median age at the time of diagnosis was 6 years old (range: 1-17 years old). The follow-up period ranged from 79-170 months (median: 140 months). Renal dysfunction was assessed using the estimated glomerular filtration rate (eGFR). The TBI dose ranged from 8-12 Gy delivered in 3-6 fractions over 2-3 d. The patients were treated with linear accelerators in the supine position, and the radiation was delivered to isocentric right-left and left-right fields via the extended distance technique. The kidneys and the liver were not shielded except in one patient with a left adrenal neuroblastoma. No patient required hemodialysis. The eGFR of four patients (44.4%) progressively decreased. The remaining patients did not demonstrate any eGFR deterioration. Only one patient developed hypertension. By evaluating the changes in eGFR, renal dysfunction among long-term survivors of TBI/HSCT could be detected. Our results suggested that the TBI schedule of 12 Gy in 6 fractions over three consecutive days affects renal function.

  9. Neuro-immune response and sleep studies after whole body irradiation with high-LET particles

    International Nuclear Information System (INIS)

    In order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: 12C, 16O and 20Ne (95 MeV/u, at 42-76 mGy). Animals were also exposed to 42 mGy of 60Co radiation for comparison with HZE. The neuro-immune response, evaluated by interleukin-I (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by 16O or 60Co. In contrast, neither 12C (56.7 mGy) nor 20Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of 12C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of 16O and 76 mGy of 20Ne: only the 20Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to 12C and 16O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight. (authors)

  10. Neuroimmune response and sleep studies after whole body irradiation with high-LET particles

    Science.gov (United States)

    Marquette, C.; Mathieu, J.; Bertho, J.-M.; Galonnier, M.; Wysoki, J.; Maubert, C.; Balanzat, E.; Gerbin, R.; Aigueperse, J.; Clarençon, D.

    2009-10-01

    In order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: 12C, 16O and 20Ne (95 MeV/u, at 42-76 mGy). Animals were also exposed to 42 mGy of 60Co radiation for comparison with HZE. The neuroimmune response, evaluated by interleukin-1 (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by 16O or 60Co. In contrast, neither 12C (56.7 mGy) nor 20Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of 12C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of 16O and 76 mGy of 20Ne: only the 20Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to 12C and 16O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight.

  11. Neuro-immune response and sleep studies after whole body irradiation with high-LET particles

    Energy Technology Data Exchange (ETDEWEB)

    Marquette, C.; Bertho, J.M.; Wysoki, J.; Maubert, C.; Gerbin, R.; Aigueperse, J. [IRSN, F-92260 Fontenay Aux Roses, (France); Mathieu, J.; Galonnier, M.; Clarencon, D. [CRSSA, Dept Radiobiol and Radiopathol, F-38700 La Tronche, (France); Balanzat, E. [CEA, DSM, CIRIL, Ganil, Caen, (France)

    2009-07-01

    In order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: {sup 12}C, {sup 16}O and {sup 20}Ne (95 MeV/u, at 42-76 mGy). Animals were also exposed to 42 mGy of {sup 60}Co radiation for comparison with HZE. The neuro-immune response, evaluated by interleukin-I (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by {sup 16}O or {sup 60}Co. In contrast, neither {sup 12}C (56.7 mGy) nor {sup 20}Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of {sup 12}C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of {sup 16}O and 76 mGy of {sup 20}Ne: only the {sup 20}Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to {sup 12}C and {sup 16}O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight. (authors)

  12. Characterization of spontaneous bone marrow recovery after sublethal total body irradiation: importance of the osteoblastic/adipocytic balance.

    Directory of Open Access Journals (Sweden)

    Géraldine Poncin

    Full Text Available Many studies have already examined the hematopoietic recovery after irradiation but paid with very little attention to the bone marrow microenvironment. Nonetheless previous studies in a murine model of reversible radio-induced bone marrow aplasia have shown a significant increase in alkaline phosphatase activity (ALP prior to hematopoietic regeneration. This increase in ALP activity was not due to cell proliferation but could be attributed to modifications of the properties of mesenchymal stem cells (MSC. We thus undertook a study to assess the kinetics of the evolution of MSC correlated to their hematopoietic supportive capacities in mice treated with sub lethal total body irradiation. In our study, colony-forming units-fibroblasts (CFU-Fs assay showed a significant MSC rate increase in irradiated bone marrows. CFU-Fs colonies still possessed differentiation capacities of MSC but colonies from mice sacrificed 3 days after irradiation displayed high rates of ALP activity and a transient increase in osteoblastic markers expression while pparγ and neuropilin-1 decreased. Hematopoietic supportive capacities of CFU-Fs were also modified: as compared to controls, irradiated CFU-Fs significantly increased the proliferation rate of hematopoietic precursors and accelerated the differentiation toward the granulocytic lineage. Our data provide the first evidence of the key role exerted by the balance between osteoblasts and adipocytes in spontaneous bone marrow regeneration. First, (preosteoblast differentiation from MSC stimulated hematopoietic precursor's proliferation and granulopoietic regeneration. Then, in a second time (preosteoblasts progressively disappeared in favour of adipocytic cells which down regulated the proliferation and granulocytic differentiation and then contributed to a return to pre-irradiation conditions.

  13. Influence of whole-body irradiation on calcium and phosphate homeostasis in the rat

    International Nuclear Information System (INIS)

    Previous irradiation studies have revealed marked alterations in calcium metabolism. Moreover, the maintenance of calcium homeostasis with parathyroid hormone or calcium salts has been reported to reduce radiation lethality. Therefore, the present study was designed to evaluate the influence of irradiation on calcium homeostasis in the rat. Nine hundred rad of whole-body irradiation produced a significant depression of both plasma calcium and phosphate at 4 days postirradiation. This effect of irradiation was observed to be dose-dependent over a range of 600 to 1200 rad, and possibly related to irradiation-induced anorexia. The physiological significance of these observations is discussed

  14. Differential effects of whole-body {gamma}-irradiation on antinociception induced by morphine and {beta}-endorphin administered intracerebroventricularly in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.K. [Korea Atomic Energy Research Inst., Taejon (Korea, Republic of); Chung, K.M.; Park, T.W.

    2000-05-01

    Two separate lines of evidence suggested the present study. First, intracerebroventricularly (i.c.v.) administered morphine (a {mu}-opioid receptor agonist) and {beta}-endorphin (an {epsilon}-opioid receptor agonist) produce antinociception by activating different descending pain inhibitory systems. Second, {gamma}-irradiation attenuates the acute antinociceptive action of i.c.v. injected morphine, but not DPLPE (a {delta}-opioid receptor agonist), in mice. These findings prompted us to investigate the effect of {gamma}-irradiation on the antinociception produced by i.c.v. injected morphine and {beta}-endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a {sup 60}Co {gamma}-source and the antinociceptive effects were tested 5, 30, 60,90 and 180 min after irradiation using the 1% acetic acid-induced writhing test (10 ml/kg). The antinociceptive effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for antinociception produced by i.c.v. administration of morphine (50 and 100 ng/mouse) or {beta}-endorphin (31 ng/mouse). Irradiation significantly potentiated the antinociception produced by {beta}-endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results demonstrate a differential sensitivity of {mu}- and {epsilon}-opioid receptors to {gamma}-irradiation, in addition, support the hypothesis that morphine and {beta}-endorphin administered supraspinally produce antinociception by different neuronal mechanisms. (author)

  15. HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses in fractionated γ-irradiated mice by modulating the IL-12p70-STAT4 signaling pathway.

    Science.gov (United States)

    Park, Hae-Ran; Jo, Sung-Kee; Choi, Nam-Hee; Jung, Uhee

    2012-05-01

    Whole body irradiated mice appear to experience a down-regulation of the helper T (Th)1-like immune response, and maintain a persistent immunological imbalance. In the current study, we evaluated the effect of HemoHIM (an herbal product made from Angelica Radix, Cnidium officinale , and Paeonia japonica cultivated in Korea) to ameliorate the immunological imbalance induce in fractionated γ-irradiated mice. The mice were exposed to γ rays twice a week (0.5 Gy fractions) for a total dose of 5 Gy, and HemoHIM was administrated orally from 1 week before the first irradiation to 1 week before the final analysis. All experiments were performed 4 and 6 months after their first exposure. HemoHIM ameliorated the Th1- and Th2-related immune responses normally occur in irradiated mice with or without dinitrophenylated keyhole limpet hemocyanin immunization. HemoHIM also restored the natural killer cell activities without changing the percentage of natural killer cells in irradiated mice. Furthermore, the administration of HemoHIM prevented the reduction in levels of interleukin-12p70 in irradiated mice. Finally, we found that HemoHIM enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 4 that was reduced in irradiated mice. Our findings suggest that HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses by modulating the IL-12p70/pSTAT4 signaling pathway. PMID:22439601

  16. HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses in fractionated γ-irradiated mice by modulating the IL-12p70-STAT4 signaling pathway.

    Science.gov (United States)

    Park, Hae-Ran; Jo, Sung-Kee; Choi, Nam-Hee; Jung, Uhee

    2012-05-01

    Whole body irradiated mice appear to experience a down-regulation of the helper T (Th)1-like immune response, and maintain a persistent immunological imbalance. In the current study, we evaluated the effect of HemoHIM (an herbal product made from Angelica Radix, Cnidium officinale , and Paeonia japonica cultivated in Korea) to ameliorate the immunological imbalance induce in fractionated γ-irradiated mice. The mice were exposed to γ rays twice a week (0.5 Gy fractions) for a total dose of 5 Gy, and HemoHIM was administrated orally from 1 week before the first irradiation to 1 week before the final analysis. All experiments were performed 4 and 6 months after their first exposure. HemoHIM ameliorated the Th1- and Th2-related immune responses normally occur in irradiated mice with or without dinitrophenylated keyhole limpet hemocyanin immunization. HemoHIM also restored the natural killer cell activities without changing the percentage of natural killer cells in irradiated mice. Furthermore, the administration of HemoHIM prevented the reduction in levels of interleukin-12p70 in irradiated mice. Finally, we found that HemoHIM enhanced the phosphorylation of signal transducer and activator of transcription (STAT) 4 that was reduced in irradiated mice. Our findings suggest that HemoHIM ameliorates the persistent down-regulation of Th1-like immune responses by modulating the IL-12p70/pSTAT4 signaling pathway.

  17. Therapeutic effect of recombinant human interleukin-11 and curcumin on jejunal damage in mice after neutron irradiation

    International Nuclear Information System (INIS)

    Objective: To explore the therapeutic effect of recombinant human interleukin (rhIL-11) and curcumin on jejunal damage in mice after neutron irradiation. Methods: 140 male BALB/c mice were randomly divided into 4 groups: 20 mice in healthy control group, 60 mice in mere irradiation group, 30 mice in IL-11 treatment group and 30 mice in curcumin treatment group. The mere irradiation group mice were wholly exposed to 3 Gy neutron irradiation. The treatment groups mice were imtraperitoneally injected with rhIL-11 at the dosage of 500 μg·kg-1·d-1 and ourcumin of 200 mg·kg-1·/-1 through enterocoelia once a day for a d after irradiation. The mortality of the mice were observed. The mice in the control and mere irradiation groups were killed 6 h, 1, 3, and 6 d post-irradiation, respectively, and the mice of the 2 treatment groups were killed 3 and 6 d post-irradiation, respectively and the samples of jujunum were colleted. HE staining, argyrophilic of nucleolar organizer staining, Feulgen staining, and image analysis were used to observe the pathology and levels of argyrophilic proteins and DNA. Results: The mice in the mere irradiation group all died at 5 d post-irradiation, while 2 mice in the IL-11 treatment group and 3 in the curcumin group survived. Large area necrosis and exfoliation were found in the intestinal epithelial mucosa of the mere irradiated group mice since 6 h to 3 d after irradiation. Crypt cell regeneration was seen occasionally found 3 days later and much more 5 days later. Crypt cell regeneration was obviously found in the intestinal epithelial mucosa and lots of new villi were observed 5 d after irradiation in both treatment groups, however, the amounts of crypt cells and new villi of the curcumin treatment group were less than those of the IL-11 treatment group. The contents of AgNOR and DNA in the intestinal epithelial cells 5 days after irradiation of the 2 treatment groups were all significantly higher than those of the mere irradiation

  18. Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on recovery from neutropenia induced by fractionated irradiation in mice

    International Nuclear Information System (INIS)

    The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 μg/body/day from day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also reveals an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation. (author)

  19. Cardiac injury after 10 gy total body irradiation: indirect role of effects on abdominal organs.

    Science.gov (United States)

    Lenarczyk, Marek; Lam, Vy; Jensen, Eric; Fish, Brian L; Su, Jidong; Koprowski, Stacy; Komorowski, Richard A; Harmann, Leanne; Migrino, Raymond Q; Li, X Allen; Hopewell, John W; Moulder, John E; Baker, John E

    2013-09-01

    The objective of this study was to determine whether radiation-induced injury to the heart after 10 Gy total body irradiation (TBI) is direct or indirect. Young male WAG/RijCmcr rats received a 10 Gy single dose using TBI, upper hemi-body (UHB) irradiation, lower hemi-body (LHB) irradiation, TBI with the kidneys shielded or LHB irradiation with the intestines shielded. Age-matched, sham-irradiated rats served as controls. The lipid profile, kidney injury, heart and liver morphology and cardiac function were determined up to 120 days after irradiation. LHB, but not UHB irradiation, increased the risk factors for cardiac disease as well as the occurrence of cardiac and kidney injury in a way that was quantitatively and qualitatively similar to that observed after TBI. Shielding of the kidneys prevented the increases in risk factors for cardiac disease. Shielding of the intestines did not prevent the increases in risk factors for cardiac disease. There was no histological evidence of liver injury 120 days after irradiation. Injury to the heart from irradiation appears to be indirect, supporting the notion that injury to abdominal organs, principally the kidneys, is responsible for the increased risk factors for and the occurrence of cardiac disease after TBI and LHB irradiation.

  20. An explanation for the ability of cytotoxic drug pretreatment to reduce bone marrow related lethality of total body irradiation (TBI)

    International Nuclear Information System (INIS)

    Mice given 9 to 10 Gy total body irradiation (TBI) die a hematological death 10 to 14 days after exposure. This lethality can be avoided by pretreatment with a cytotoxic drug two days before irradiation. The best example of this is seen when 200 mg/Kg cytosine arabinoside (ara-C) is given two days before TIB. Improved survival results from an earlier onset in the recovery of marrow stem cells (CFU-s) in animals given ara-C before irradiation as compared to controls. In animals given radiation alone there is a lag phase in the recovery of CFU-s; drug pretreatment before irradiation abolishes this delay. We postulate that the cells that repopulate the CFU-s compartment after irradiation are a sub-population of the DFU-s with higher self-renewal capability, lower proliferative activity and higher radiosensitivity (D0 = .8 Gy) than the overall population D0 = 1.1 Gy). Further, we suggest that drug pretreatment alters the radiosensitivity of the first population, increasing it temporarily to that of the overall population. This may come about by ara-C triggering these CFU-s into a relatively radioresistant phase of the cell cycle. In the Lewis lung tumor ara-C pretreatment does not affect the response to radiation, even at times when the drug promotes the early recovery of the CFU-s. It would therefore seem that a potentially useful gain in the therapeutic index may result from these findings

  1. Effect of infection by irradiated Trichinella Spirals larvae on mice and assessment the role of Al bendazole in treating them

    International Nuclear Information System (INIS)

    The present study was carried out to investigate the effect of infection with irradiated Trichinella Spiralis larvae on mice and to asses the role of albendazole in treating them. This study included parasitological and histopathological studies on mice infected with irradiated Trichinella Spiralis larvae in comparison with mice infected with non-irradiated Trichinella Spiralis only or with mice treated after infection by albendazole. The obtained data revealed that, in mice infected with irradiated Trichinella Spiralis larvae (50 Krad or 80 Krad), the number and length of worms in the small intestine, as well as, the number of encysted larvae in muscles of mice, especially diaphragm and tongue, were significantly decreased. Also, using al bendazole 24 hours after infection with irradiated larvae lead to high significant decrease in all the previously mentioned parameters

  2. Design for shielding kit for local irradiation in mice and test of its shielding effect

    International Nuclear Information System (INIS)

    In order to fulfill the immediate requirement for experimental studies on biological effect of low dose radiation. A shielding kit for local irradiation in mice is designed. Its advantages are: (1) several mice can be irradiated at the same time; (2) the radiation condition is identical; (3) it is easy to control and perform; (4) during irradiation, the animals don't need any special treatments such as anaesthesia. It was proved by TLD test, that absorbed dose in areas of spleen and head in mice after shielding has decreased to 0.85% and 0.5% of the original dose in the center of radiation field respectively. The results suggest that the kit was able to satisfy the needs of the experimental studies on radiation biology

  3. Protective effects of acanthopanax senticosus saponins on mice with irradiation damage induced by X-rays

    International Nuclear Information System (INIS)

    Objective: To evaluate the protective effects of acanthopanax senticosus saponins (ASS) on mice with irradiation damage induced by X-rays. Methods: The mice were randomly divided into normal control group, irradiation control group and three experimental groups. Peripheral blood WBC and PLT were detected and accounted. The transformation test of lymphocytes was done and the spleen index (SI), thymus index (TI); the activities of superaxide dismulase (SOD) and GSH-Px in serum were determined. Results: Compared with the control group, Tl and the activities of SOD and GSH-Px in serum in three experimental groups were increased significantly (P<0.05). Conclusion: ASS have protective effects on mice with irradiation damage induced by X-rays. (authors)

  4. Enhanced antibody affinity in sublethally irradiated mice and bone marrow chimeras

    International Nuclear Information System (INIS)

    Sublethally irradiated mice primed with dinitrophenyl (Dnp)-keyhole limpet hemocyanin immediately after irradiation or 30 days later and subsequently boosted with a second injection of antigen displayed a secondary response to Dnp characterized by antibody affinity greater than that in unirradiated controls. Also, in radiation chimeras primed with Dnp-keyhole limpet hemocyanin 120 days after syngeneic or allogeneic bone marrow transplantation the antibodies against Dnp produced after boosting were of higher affinity than the antibodies raised in normal mice. These findings are tentatively attributed to lack of suppressor thymus-derived lymphocytes (T cells) in sublethally irradiated mice and bone marrow chimeras, in which the enhanced ability to produce antibodies of high affinity may compensate for quantitative defects of the immune system

  5. Hematological Effects of Total or Partial Irradiation of the Human Body

    International Nuclear Information System (INIS)

    Many studies have been devoted to hematological effects of total body irradiation in various animal species, but there are few human data. In addition, the origin of these documents limited value. It is indeed, sometimes accidentally irradiated subjects, including irradiation was not uniform and that the dosimetry performed a posteriori, is random, sometimes irradiated patients or for the treatment of cancer or to suppress immunological reactions so that a transplant of tissue or an organ transplant, and one may wonder if the reactions such subjects are similar to those of normal subjects. Documents valid for partial irradiation of a human body by a single session even fewer and almost all relate to accidental irradiation

  6. Evaluation of reduced allergenicity of irradiated peanut extract using splenocytes from peanut-sensitized mice

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sejo; Jang, Da-In [Department of Pediatrics, Ajou University School of Medicine, Suwon 442-749 (Korea, Republic of); Lee, Ju-Woon; Kim, Jae-Hun; Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Lee, Soo-Young [Department of Pediatrics, Ajou University School of Medicine, Suwon 442-749 (Korea, Republic of)], E-mail: jsjs87@ajou.ac.kr

    2009-07-15

    Peanut (PN) allergy is one of the most serious forms of IgE-mediated food hypersensitivity. Gamma irradiation has been widely used for the preservation of food. The results of our previous studies showed that the IgE-binding capacity to several antigens were profoundly reduced after gamma irradiation. In this study, we evaluated the changes of allergenecity and cytokine production profiles after exposure of irradiated PN extract in a PN-allergy mouse model. Mice were sensitized to PN extract by intragastric administration on days 0, 1, 2, and 7, and then challenged on day 21. Four weeks later, we evaluated the cytokine production patterns and proliferation responses of splenocytes that were stimulated with intact PN extract, compared to 10 and 50 kGy irradiated PN extract. When the cells were stimulated with 10 kGy of irradiated PN extract, a higher level of production of IFN-{gamma} and IL-10 cytokines was observed. However, stimulation with 50 kGy of irradiated PN extract resulted in a higher level of production of only IFN-{gamma} cytokines. In addition, the Th1/Th2 ratio increased in response to treatment with gamma-irradiated PNs. The results of this study show that the allergenicity of PN extracts could be reduced by gamma irradiation which caused downregulation of Th2 lymphocyte activity in the PN-sensitized mice.

  7. Lung damages in mice and rats with thoracic irradiation

    International Nuclear Information System (INIS)

    Irradiation of the lung can produce serious tissue disruption and result in significant, potentially fatal pulmonary dysfunction. The sterilization of tumours in the lung is often limited by the clinical tolerance of the normal lung tissues. Many experiments have been carried out so far in order to elucidate the lung damages with thoracic irradiation. Earlier lung damages are an increase of alveolar surfactant, an induced proliferation of type II pneumocytes and dysfunctions in capillary endothelial cells. The increased amounts of alveolar surfactant were measurable by 24 hours beyond 10 Gy. Labelling indices of type II pneumocytes with tritiated thymidine have a peak at about 4 weeks after irradiation. Pulmonary angiotensin converting enzyme activity, plasminogen activator activity, and prostacyclin and thromboxane production served as indices of lung endothelial function. There were dose-dependent decrease in angiotensin converting enzyme and plasminogen activator activity and increases in prostacyclin and thromoboxane production at two months after irradiation. Radiation pneumonitis as a late effect appears at approximately 20 weeks after irradiation. An increase of breathing rates was observed at the time of pneumonitis. Animals which survived pneumonitis may suffer from lung fibrosis beyond one year after irradiation. RBEs of fast neutrons and negative pions were reported to be between 1 and 6 depending upon indices of effects and upon exposure patterns. (author)

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

    International Nuclear Information System (INIS)

    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)

  9. Radioprotective effects in mice by a single dose of subcutaneous administration of cobaltous chloride post γ-rays irradiation with a sublethal dose

    International Nuclear Information System (INIS)

    Radioprotective effects were investigated in mice which received subcutaneously a single dose of each inorganic metal: Co, Cu, Rb, Sr, Mo and W 24 hours post irradiation of 60Co γ-rays with a sublethal dose. The effects were observed in mice injected with Co at an optimum dosage of 20 mg/kg·body weight. Then to elucidate mechanisms of the effects, mice were injected with Co containing the radioactive tracer (60Co) following the radiation exposure, measured elimination of the radioactivity for 7 days, then sacrificed and divided to some tissues and organs. The radioactivity in whole body during this period resulted in a markedly higher retention than that for mice injected with [60Co] alone, as well as liver in the organs. These higher retentions appeared to be related to the radioprotective effects. (author)

  10. Characteristics of a Teflon rod antenna for millimeter and submillimeter wave irradiation on living bodies

    OpenAIRE

    TATSUKAWA, Toshiaki; Doi, Akitaka; TERANAKA, Masato; Takashima, Hitoshi; Goda, Fuminori; Idehara, Toshitaka; Ogawa, Isamu; KANEMAKI, Tomohiro; NISHIZAWA, Seiji; NAMBA, Tunetoyo

    2003-01-01

    The development of a millimeter and submillimeter wave catheter for irradiation on living bodies using a Teflon rod dielectric antenna is described. The power sources of electromagnetic wave are an Impatt oscillator (90 GHz, 0.3 W) and gyrotron (302 GHz, 30 W). Irradiation tests using various Teflon rod dielectric antennas were performed on beef livers. Irradiation results were considered by microwave theory and ray optics.

  11. The peripheral chimerism of bone marrow-derived stem cells after transplantation: regeneration of gastrointestinal tissues in lethally irradiated mice.

    Science.gov (United States)

    Filip, Stanislav; Mokrý, Jaroslav; Vávrová, Jiřina; Sinkorová, Zuzana; Mičuda, Stanislav; Sponer, Pavel; Filipová, Alžběta; Hrebíková, Hana; Dayanithi, Govindan

    2014-05-01

    Bone marrow-derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. In our study, we examined a model using whole-body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP(+)) transplanted cells into non-haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP(+) lin(-) Sca-1(+) cells into non-haematopoietic tissues. The transplantation of BM cells or GFP(+) lin(-) Sca-1(+) cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract (GIT) following whole-body irradiation. Our results demonstrate that whole-body irradiation does not significantly alter the integrity of tissues such as those in the small intestine and liver. Whole-body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP(+) lin(-) Sca-1(+) cells are not transient in the GIT. Thus, these transplanted cells could be used for the long-term treatment of various pathologies or as a one-time treatment option if myeloablation-induced chimerism alone is not sufficient to induce the entry of transplanted cells into non-haematopoietic tissues.

  12. Total body irradiation as a form of preparation for bone marrow transplantation

    International Nuclear Information System (INIS)

    The history of total body irradiation and bone marrow transplantation is surprisingly old. Following the success of Thomas et al. in the 1970s, bone marrow transplantation appeared to be the sole curative treatment modality for high-risk leukemia. A supralethal dose of total body irradiation was widely accepted as a form of preparation for bone marrow transplantation. In this paper, I described the present status of bone marrow transplantation for leukemia patients in Japan based on the IVth national survey. Since interstitial pneumonitis was one of the most life threatening complications after bone marrow transplantation, I mentioned the dose, dose-rate and fraction of total body irradiation in more detail. In addition, I dealt with some problems of the total body irradiation, such as dose prescription, compensating contour as well as inhomogeneity, and shielding for the highrisk organs. (author) 82 refs

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

    International Nuclear Information System (INIS)

    To evaluate late biological effects of chronic low dose-rate radiation, the life-span and pathological changes were evaluated in mice that were continuously irradiated with gamma-rays for 400 days. Two hundred (100 male and 100 female) specific-pathogen-free (SPF) B6C3F1 mice at six weeks of age were purchased every month. After a 2-week quarantine, they were divided into 4 groups (1 unirradiated control and 3 irradiated). Irradiation was performed using 137Cs gamma-rays at dose-rates of 20 mGy (22 h-day)-1, 1 mGy (22 h-day)-1 and 0.05 mGy (22 h-day)''-1 with accumulated doses equivalent to 8,000 mGy, 400 mGy and 20 mGy, respectively. All mice were kept until they died a natural death. Results of the monthly microbiological examinations confirmed that the mice were maintained under SPF-conditions throughout the experimental period. A total of 4,000 mice have been admitted into the experiment since it started in February 1996, all of which have received their predetermined doses and have been transferred to the animal room. Data on the 20 mGy (22 h-day)-1 group of both sexes suggested a shortened life span. The most common lethal neoplasms in pooled data of unirradiated control male mice and irradiated male mice in order of frequency were neoplasms of the lymphohematopoietic system, liver, lung, and soft tissue. In female mice, neoplasms of the lymphohematopoietic system, soft tissue, endocrine system, and liver were most common. (author)

  14. Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice.

    Directory of Open Access Journals (Sweden)

    Junye Zhang

    Full Text Available One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO to restore the secretory function of radiation-damaged salivary glands in mice.DFO (50 mg/kg/d was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy of submandibular glands. The total 55 mice were randomly divided into: (1 Normal group: mice received no treatment (n = 5; (2 Irradiation group (IR: mice only received irradiation (n = 5; (3 Pre-DFO group (D+IR (n = 10; (4 Pre+Post DFO group (D+IR+D (n = 10; (5 Post-DFO group (IR+D (n = 10; (6 For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5; sham2: Pre+Post sterilized water group (n = 5; sham3: Post-sterilized water group (n = 5. The salivary flow rate (SFR was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.

  15. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    International Nuclear Information System (INIS)

    High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic) brain tumors. Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy). In the sham group, 9/10 animals (90%) showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18%) died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy

  16. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    Directory of Open Access Journals (Sweden)

    Haveman Jaap

    2007-09-01

    Full Text Available Abstract Background High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic brain tumors. Methods Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy. Results In the sham group, 9/10 animals (90% showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18% died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. Conclusion The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.

  17. Light Irradiation And Response Of The Living Body - Effect Of Pain Relief And Promotion Of Wound Healing -

    Science.gov (United States)

    Taguchi, Yoshio; Kurokawa, Yoshimochi; Ohara, Itaru; Ueki, Hamaichi; Inaba, Humio

    1989-09-01

    The first report of laser irradiation for wound healing was done by Mester, E., et al. in 1968. From their reports, we can get many knowledges and suggestions as for laser irradiation. At that time he used ruby laser (694.3 nm wave length) for surgical wounds and burns on the back skin of mice. The condition of irradiation was studied with energy density between 0.5-10 J/cm2 twice a week. As a result, they noticed 1 J/cm2 irradiation was effective for those wounds. After a few experimental reports, they published their clinical studies in 1975. Clinically, they used He-Ne laser (632.8 nm wave length) irradiation. Human leg ulcers due to peripheral circulatory disturbance were treated with energy density of 4 J/cm2 twice a week. And they got good results, obtaining complete healing in two-thirds of the cases. We became strongly stimulated by those reports. We have been studying the effect of light on experimental and clinical wound healing as well as on various kinds of biological phenomena since 1980. Particularly, its effect according to the difference of light has been studied. In October 1982, the first clinical case was tried by Argon laser (514.5 nm wave length) irradiation for therapeutic purpose. A man had a chronic ulcer of the left first toe due to Buerger's disease for 5 months. Surprizingly, on the 14th day after 6 treatments of the light irradiation, his ulcer completely healed. During these treatments, the patient noticed that the pain completely disappeared after 2 treatments. Fifty Argon laser treatments were carried out on clinical cases after these experiences, we reached to a conclusion that light irradiation stimulated something in the injured tissues and lead to good clinical results. Several studies concerning mechanism for these effects i.e. peripheral circulation, histology of granulation, cell proliferation, chemistry and other studies were carried out. From these investigations, peripheral circulation was improved when in those who were

  18. Physical exercise tolerance in patients with chronic lymphoproliferative diseases after whole-body therapeutic gamma irradiation

    International Nuclear Information System (INIS)

    It is stated that physical workability remains practically at the initial level after a course of fractionated whole-body therapeutic gamma irradiation at the integral doze of 1 Gy obtained during two weeks and at the integral dose of 2 Gy obtained during 4 weeks. Tendency to decrease of systolic arterial pressure (AP) is noted under fractionated whole-body therapeutic gamma irradiation at the integral dose of 1 Gy that should be necessarily taken into account under irradiation of patients with reduced AP and patients receiving hypotensive preparations for accompanying arterial hypertension

  19. Effects of IL-6 on proliferation and apoptosis of tumor cells multi-irradiated for tumor-bearing mice

    International Nuclear Information System (INIS)

    A study was carried out on effects of IL-6 on the proliferation and apoptosis of tumor cells and the expression of apoptosis relevant genes (p53, bcl-2) in tumor cells for three kinds of fractional total-body-irradiated tumor-bearing mice. The apoptotic index, proliferative index, S phase fraction of S180 sarcoma, H22 hepatocarcinoma and Lewis lung cancer cells were measured by flowcytometry (FCM) after total-body-irradiation and irradiation plus IL-6. The protein expression level of p53, bcl-2 in three kinds of tumors was also determined by the immunohisto-chemical method (UltraSensitive S-P). The results showed that the S phase fraction and proliferation index in Lewis lung cancer cells were lower in the irradiated plus IL-6 group than in the control, while apoptotic index was higher (P180 sarcoma cells were opposite (P22 hepatocarcinoma. These results revealed that IL-6 promoted the apoptosis of irradiated Lewis lung cancer cells (P180 sarcoma (P22 hepatocarcinoma (P>0.05). In Lewis lung cancer the expression level of p53 was lower in the IL-6 group and higher in S180 sarcoma (P22 hepatocarcinoma as compared with the control (P>0.05). It is considered that tumor cell's proportion in the cellular cycle is changed by IL-6 and the effects of IL-6 on the expression of p53, bcl-2 in different three kinds of tumors are different. IL-6 has radio-sensitive effects on some tumors and opposite effects on other tumors, it may be related to the expression of p53 and bcl-2 in tumor cells. (authors)

  20. Mutagenicity Evaluation of Irradiated Indian Mackerel in Swiss Mice. Dominant Lethal Assay and Micronucleus Test

    International Nuclear Information System (INIS)

    To evaluate the potential mutagenic effects of irradiated (150 krad) Indian mackerel (Rastrelliger kanagurta) in somatic and germ cells of mice, a micronucleus test and dominant lethal assay were employed. Four to five-weeks-old Swiss male mice were randomly assigned to four groups. Two groups were fed irradiated or unirradiated mackerel at 35% level dry weight for 16 weeks. Twenty males from each group were used for dominant lethal assay. The males in the positive control group were given 200 mg/kg of ethyl methane sulphonate (EMS) intraperitoneally about 24 hours before pairing with the females. The number of dead implantations (deciduomas and dead embryos) showed no significant difference among the groups fed on stock rations or irradiated or unirradiated mackerel diets at any stage of the test period. There was also no increase in the pre-implantation or total lethality. As expected, EMS-treated mice showed a highly significant increase in the dead implantation rates and a reduction of the live implantations during the postmeiotic phase of spermatogenesis. For micronucleus tests mackerel diets and stock rations were continued for a period of 21 weeks. The positive control group mice were given 80 mg/kg hycanthone methane sulphonate, intraperitoneally twice, 30 and 6 h before killing. Animals fed on irradiated or unirradiated mackerel diets or stock rations showed no significant differences either in the frequency of micronuclei or the ratio of polychromatic to normochromatic cells. (author)

  1. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Jianzhong Li

    2015-08-01

    Full Text Available Hong Shan Capsule (HSC, a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI. Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage.

  2. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats.

    Science.gov (United States)

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-08-12

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage.

  3. Chronic UVB-irradiation actuates perpetuated dermal matrix remodeling in female mice: Protective role of estrogen

    Science.gov (United States)

    Röck, Katharina; Joosse, Simon Andreas; Müller, Julia; Heinisch, Nina; Fuchs, Nicola; Meusch, Michael; Zipper, Petra; Reifenberger, Julia; Pantel, Klaus; Fischer, Jens Walter

    2016-01-01

    Chronic UVB-exposure and declined estradiol production after menopause represent important factors leading to extrinsic and intrinsic aging, respectively. Remodeling of the extracellular matrix (ECM) plays a crucial role in both responses. Whether the dermal ECM is able to recover after cessation of UVB-irradiation in dependence of estradiol is not known, however of relevance when regarding possible treatment options. Therefore, the endogenous sex hormone production was depleted by ovariectomy in female mice. Half of the mice received estradiol substitution. Mice were UVB-irradiated for 20 weeks and afterwards kept for 10 weeks without irradiation. The collagen-, hyaluronan- and proteoglycan- (versican, biglycan, lumican) matrix, collagen cleavage products and functional skin parameters were analyzed. The intrinsic aging process was characterized by increased collagen fragmentation and accumulation of biglycan. Chronic UVB-irradiation additionally augmented the lumican, versican and hyaluronan content of the dermis. In the absence of further UVB-irradiation the degradation of collagen and accumulation of biglycan in the extrinsically aged group was perpetuated in an excessive matter. Whereas estradiol increased the proteoglycan content, it reversed the effects of the perpetuated extrinsic response on collagen degradation. Suspension of the intrinsic pathway might therefore be sufficient to antagonize UVB-evoked long-term damage to the dermal ECM. PMID:27460287

  4. Relationship between chromosomal aberration of bone marrow cells and dosage of irradiation after 46Sc internal pollution and external low dose X-irradiation in mice

    International Nuclear Information System (INIS)

    The relationship between chromosomal aberration of bone marrow cells and dosage in mice 24 h after 46Sc internal pollution combined with external low dose whole body X-irradiation was quantiatively studied. The results showed that the relationship between chromosomal aberration and dosage was expressed in a linear regression equation. The chromosomal aberration rate was lower in the combined exposure than that of the sum of internal and external exposures, but higher than that of either the internal or external exposure singly. The relationship between chromosomal aberration and time was expressed in the following three phase exponential function: Y(t) = 2.9078 exp0.27668t + 2.9371 exp-0.0778t + 2.3786-0.01788t. By means of fit test, there was no significant difference between the determined and the theoretical values. The 90% theoretical values got from all the equations distributed over the determined values

  5. Evaluation of the radioprotective effect of the leaf extract of Syzygium cumini (Jamun) in mice exposed to a lethal dose of gamma-irradiation.

    Science.gov (United States)

    Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath

    2003-06-01

    The effects of various concentrations (5, 10, 20, 30, 40, 50, 60, and 80 mg/kg body weight (b.wt.) of the leaf extracts of Syzygium cumini Linn. and Eugenia cumini (SCE, black plum, Jamun, family Myrtaceae) on the radiation-induced sickness and mortality in mice exposed to 10 Gy gamma-irradiation were studied. The treatment of mice with different doses of SCE, consecutively for five days before irradation, delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the nondrug-treated irradiated controls. All doses of SCE provied protection against the gastrointestinal death increasing the survival by 66.66% after treatment with 20, 30, and 40 mg/kg SCE versus a 12% survival in the irradiated control group (oil + irradiation). Similarly, SCE provided protection against the radiation-induced bone marrow death in mice treated with 10-60 mg/kg b.wt. of SCE. However, the best protection was obtained for 30 mg/kg b.wt. SCE, where the number of, survivors after 30 days post-irradiation was highest (41.66%) when compared with the other doses of SCE. PMID:12866620

  6. Effect of antibiotics and bifidobacterial preparations on the intestinal microflora in mice irradiated with gamma quanta

    International Nuclear Information System (INIS)

    Mice weighing 19-20 g have been exposed to the dose of 700 R and devided into 3 groups. During the first five days animals of the first group received antibiotics perorally - 40 units phenoxypenicillin, 30 units oxytetracycline, 40 units streptomicine. On the 6th, 10th and 15th days after irradiation the bifidobacterium preparation (75-41 strain) has been introduced perorally in the amount of 5x108 cells. Animals of the second group have received antibiotics alone in the same period as mice of the first group but the sterile physiological solution has been introduced instead of bifidobacteria. The sterile physiological solution has been perorally introduced to animals of the third group instead of antibiotics and bifidobacteria. The complex treatment has lead to the increase of survival percentage as compared with animals which have not been treated. The normalization of the intestines microbic landscape is observed in irradiated mice, subjected to treatment with antibiotics and bifidobacteria. It is expressed in a considerable reduction in the amount of clostridium, enterococci, intestinal bacilli and proteus as compared with the amount of these microbes in the intestines of non-treated mice. At the same time, a certain increase of lactobacilli amount to the level characteristic of lactobacilli in the intestinal tract of non-treated animals is observed in the intestines of irradiated and treated mice

  7. Effect of genistein on cell cycle of bone marrow hematopoietic cells in normal and irradiated mice

    International Nuclear Information System (INIS)

    Objective: To study the effects of genistein on cell cycle, proliferation and expression of bcl-2 gene in bone marrow hematopoietic cells (BMHCs) of normal and irradiated mice in order to explore mechanisms for protection of genistein from radiation-induced hematopoietic system injury. Methods: Adult male BALB/c mice were orally administered with genistein (160 mg/kg b.w.) 24 h before irradiation. Cell cycles in BMHCs of the normal and irradiated mice were measured by flow cytometry. The protein and mRNA expressions of bcl-2 gene in BMHCs were analyzed by Western blot and RT-PCR, respectively. Results: a) Transitory and significant changes occurred in the cell cycle of BMHCs in the normal mice after administration of genistein: first, the proliferation suppression of BMHCs was observed and most cells were arrested in G0/G1 phase on day 1; second, progression of cells from G0/G1 phase into S phase was observed, accumulation of cells in S phase on day 2, and back to the normal level on day 4. b) Genistein, administration 24 h before irradiation, decreased the percentage of BMHCs in G0/G1 phase and increased cell proliferation. Moreover, genistein up-regulated the protein and mRNA expressions of bcl-2 in BMHCs in the irradiated mice. Conclusions: It was shown that changing with cell cycle, strengthening of radioresistant, suppressing of radiation-induced apoptosis, and enhancing of proliferation and differentiation of BMHCs maybe the underlying mechanisms for genistein protection of hematopoietic system against radiation damage. (authors)

  8. Physical aspects of total body irradiation as practised at Tuebingen

    International Nuclear Information System (INIS)

    From the outset it has been our overriding aim: administer the medically prescribed dose as correctly as possible to the patient. Both method and dosages we have taken over from the so-called Seattle technique. Only in the single fraction-irradiation (E) the dose rate of the linac (Philips SL 75/20 or SL 75/10) was reduced to 0.07 Gy/min. The report describes how the TBI was realized. (orig./HP)

  9. Type 2 Diabetes is a Delayed Late Effect of Whole-Body Irradiation in Nonhuman Primates

    Science.gov (United States)

    Kavanagh, Kylie; Dendinger, Michael D.; Davis, Ashley T.; Register, Thomas C.; DeBo, Ryne; Dugan, Greg; Cline, J. Mark

    2015-01-01

    One newly recognized consequence of radiation exposure may be the delayed development of diabetes and metabolic disease. We document the development of type 2 diabetes in a unique nonhuman primate cohort of monkeys that were whole-body irradiated with high doses (6.5–8.4 Gy) 5–9 years earlier. We report here a higher prevalence of type 2 diabetes in irradiated monkeys compared to age-matched nonirradiated monkeys. These irradiated diabetic primates demonstrate insulin resistance and hypertriglyceridemia, however, they lack the typical obese presentation of primate midlife diabetogenesis. Surprisingly, body composition analyses by computed tomography indicated that prior irradiation led to a specific loss of visceral fat mass. Prior irradiation led to reductions in insulin signaling effectiveness in skeletal muscle and higher monocyte chemoattractant protein 1 levels, indicative of increased inflammation. However, there was an absence of large defects in pancreatic function with radiation exposure, which has been documented previously in animal and human studies. Monkeys that remained healthy and did not become diabetic in the years after irradiation were significantly leaner and smaller, and were generally smaller and younger at the time of exposure. Irradiation also resulted in smaller stature in both diabetic and nondiabetic monkeys, compared to nonirradiated age-matched controls. Our study demonstrates that diabetogenesis postirradiation is not a consequence of disrupted adipose accumulation (generalized or in ectopic depots), nor generalized pancreatic failure, but suggests that peripheral tissues such as the musculature are impaired in their response to insulin exposure. Ongoing inflammation in these animals appears to be a consequence of radiation exposure and can interfere with insulin signaling. The reasons that some animals remain protected from diabetes as a late effect of irradiation are not clear, but may be related to body size. The translational

  10. Early weaning impairs body composition in male mice

    Directory of Open Access Journals (Sweden)

    Maria Carolina Borges

    2009-12-01

    Full Text Available This study aimed to evaluate the effect of early weaning on body composition and on parameters related to nutritional status in mice. The experimental group consisted of male Swiss Webster mice that were weaned early (at postnatal day fourteen and fed an appropriate diet for growing rodents until postnatal day twenty-one (EW group. The control group consisted of male mice breastfed until postnatal day twenty-one (CON group. All animals were sacrificed on the twenty-first day of life. The EW group showed a decrease in liver and muscle protein content and concentration, brain protein concentration, brain DNA content and concentration, as well as liver and muscle protein/RNA ratio (pO presente estudo objetivou avaliar o efeito do desmame precoce sobre a composição corporal e sobre parâmetros indicativos do estado nutricional de camundongos. O grupo experimental consistiu de camundongos Swiss Webster, machos, desmamados precocemente (14º dia de vida e alimentados com ração apropriada para roedores em crescimento até o 21º dia pós-natal (grupo DESM. O grupo controle consistiu de camundongos amamentados até o 21º dia pós-natal (grupo CON. Todos os animais foram sacrificados no 21º dia de vida. O grupo DESM apresentou redução da concentração e conteúdo hepático e muscular de proteínas, da concentração cerebral de proteínas, da concentração e conteúdo cerebral de DNA e da razão proteína/RNA hepática e muscular (p<0,05. Quanto à composição corporal, o grupo DESM apresentou maior conteúdo de umidade, maior percentual de umidade e lipídios e menor conteúdo e percentual de cinzas e proteína na carcaça (p<0,05. Os resultados indicam que o desmame precoce acarreta em prejuízo à composição corporal e a parâmetros indicativos do estado nutricional, o que pode estar relacionado ao retardo do processo de maturação química. Os dados do presente estudo podem contribuir para o entendimento da influência da alimenta

  11. Attenuated lung fibrosis in interleukin 6 knock-out mice after C-ion irradiation to lung

    International Nuclear Information System (INIS)

    There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice. The mice underwent thoracic irradiation with 10 Gy of C-ion beam or sham-irradiation and were examined by histology. Immunoreactivity for IL-6 was induced at the site of bronchiolar epithelium, in pneumocytes and in monocytes by C-ion irradiation. At 24 weeks after irradiation, the infiltration of macrophages, detected by positive immunohistological staining with Mac3 antibody, was observed in alveolar spaces both in WT and IL-6 KO mice. The thickening of bronchiolar and alveolar walls exhibited in WT mice, but not KO mice, and fibrotic changes detected by Masson-Trichrome staining, were observed only in the lungs of WT mice, while it was attenuated in IL-6 KO mice. These results indicated that IL-6 might not be essential for activating macrophages in the late phase, but plays an important role for fibrotic changes of the alveolar wall after irradiation. (author)

  12. Type 2 Diabetes is a Delayed Late Effect of Whole-Body Irradiation in Nonhuman Primates

    OpenAIRE

    Kavanagh, Kylie; Dendinger, Michael D.; Davis, Ashley T.; Register, Thomas C.; DeBo, Ryne; Dugan, Greg; Cline, J. Mark

    2015-01-01

    One newly recognized consequence of radiation exposure may be the delayed development of diabetes and metabolic disease. We document the development of type 2 diabetes in a unique nonhuman primate cohort of monkeys that were whole-body irradiated with high doses (6.5–8.4 Gy) 5–9 years earlier. We report here a higher prevalence of type 2 diabetes in irradiated monkeys compared to age-matched nonirradiated monkeys. These irradiated diabetic primates demonstrate insulin resistance and hypertrig...

  13. Behavior of peripheral reticulocytes following whole-body irradiation and stimulation of the bone marrow

    International Nuclear Information System (INIS)

    The relative reticulocyte content and the average Fe uptake of peripheral reticulocytes were investigated in rats after blood loss and whole-body irradiation as well as after a combined treatment for a time of 15 days. The acute loss of blood caused a rapid increase of cellular uptake within 24 hours, whereas after irradiation a considerable diminution could be observed. In addition to a direct stimulation or inhibition of bone marrow activity a direct influence of blood loss and irradiation on reticulocytes is discussed. (author)

  14. Rb and p53 gene deletions in lung adenocarcinomas from irradiated and control mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Woloschak, G.E. [Argonne National Lab., IL (United States). Center for Mechanistic Biology and Biotechnology

    1997-08-01

    This study was conducted on mouse lung adenocarcinoma tissues that were formalin-treated and paraffin-embedded 25 years ago to investigate the large gene deletions of mRb and p53 in B6CF{sub 1} male mice. A total of 80 lung tissue samples from irradiated mice and 40 lung samples from nonirradiated controls were randomly selected and examined in the mRb portion of this study. The results showed a significant (P < 0.05) higher percentage of mRb deletions in lung adenocarcinomas from mice exposed to 60 once-weekly {gamma}-ray doses than those from mice receiving 24 once-weekly {gamma}-ray doses at low doses and low dose rates; however, the percentage was not significantly different (P > 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose {gamma} irradiation at a similar total dose. mRb fragments 3 (71%) and 5 (67%), the parts of the gene that encoded the pocket binding region of Rb protein to adenovirus E1A and SV40 T-antigen, were the most frequently deleted fragments. p53 gene deletion analysis was carried out on normal lungs and lung adenocarcinomas that were initially found to bear mRb deletions. Exons 1,4,5,6, and 9 were chosen to be analyzed.

  15. cloning of mouse genes related to repairing of intestinal epithelium of the γ irradiated mice by treatment with the intestinal RNA of mice of the same strain

    International Nuclear Information System (INIS)

    To clone the new genes involved in the repair of radiation-damaged intestinal crypts of mice which were treated with the intestinal RNA of the mice of the same strain. As a test group, 45 mice which had been irradiated by γ rays were injected with intestinal RNA of mice of the same strain in 2h after irradiation and the specimens of the small intestine of these animals were collected at 6, 12 24h, 4d and 8d after irradiation respectively. The other 45 mice, as a control group, were treated with irradiation and physiological saline, and the specimens were collected as those in the test group. The genes which expressed more highly in the test group than in the control were cloned into T vectors after subtractive hybridization and LD-PCR and then sequenced. The sequences obtained were aligned through Gene Bank for the new gene search. 90 clones were found associate with the repairing of radiation-damaged mouse intestinal crypts, which was confirmed by RNA dot blot assays. Among the 90 clones, 18 were accepted by Gene Bank as new genes with the acceptance numbers AF240164-AF240181. Obtained ninety clones may be correlated closely with repairing of intestinal epithelium of the γ-irradiated mice by treatment with the intestinal RNA of mice of the same strain

  16. Four cases of protracted whole body irradiation (Algerian accident 1978)

    International Nuclear Information System (INIS)

    A 25 Ci iridium-192 source accidentally lost was introduced in a room where among others four young female patients (14 - 20 years old) one of them pregnant were irradiated during 4/5 weeks, 6/8 hours daily, cumulating skin doses in the range of 2500r and mean medullary doses in the range of 1250r. They developed a very protracted infections and haemorragic syndrome during which they were treated successfully by haematologic compensatory therapy with enormous quantities of packed isolated blood cells (R.B.C., W.B.C., platelets) and massive antibiotic, antimycotic and hydro-electrolytic therapy. The dosimetric (physical and biological) problems are discussed and the clinical and biological data are given in detail

  17. Interleukin 1 protects against the lethal effects of irradiation of mice but has no effect on tumors in the same animals

    International Nuclear Information System (INIS)

    Interleukin 1(IL-1) is a radioprotector of bone marrow and is cytotoxic to some tumor cells. This investigation examines these two properties in the same host animals and gives evidence of radioprotection against localized x-irradiation of the head and neck region. By LD50 analyses, recombinant human IL-1 (100 ng/mouse, approximately 3 μg/kg) was found to be radioprotective against whole-body irradiation for both C3H/Km and C57BL/Ka mice. The combined potency ratio for the two strains was 1.07 (95% confidence limit: 1.02-1.12). It was also radioprotective against the injury leading to acute lethality resulting from localized head and neck irradiation of C3H/Km mice; 100 ng of IL-1/mouse produced a potency ratio of 1.05 (95 confidence limit: 1.03-1.07). However, two tumors that originated in C3H/Km mice, RIF-1 and SCCVII, showed neither in vitro nor in vivo response to IL-1. Also, there was no IL-1-induced reduction in in vivo growth of the RL12NP lymphoma in C57BL/Ka mice

  18. Effect of the lipid fraction of Listeria monocytogenes cells on the immune response of irradiated mice. Pt. 2. Effect of lipids administered after irradiation

    International Nuclear Information System (INIS)

    Lipids from Listeria monocytegenes were tested for their effect on the process of recovery of the immune reactivity in mice irradiated with 250 and 500 R. The recovery was evaluated by determining cellular and humoral immune response to sheep erythrocytes given as antigen 15 and 30 days after irradiation. The administration of lipids was shown to accelerate the recovery of the immune mechanisms impaired by irradiation. The effect was greatly dependent upon the lipid dose and time of its administration. The effect was highest when the lipid was given 10 days after irradiation, the optimal dose being 0.25 mg. (author)

  19. Lethality and teratogenesis in F{sub 1} offspring mice following paternal fission neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shoji, Shuneki [Hiroshima Univ., Research Institute for Radiation Biology and Medicine, Hiroshima (Japan)

    2003-07-01

    Studies were conducted to determine whether following genetic damage at germ cell stages induced by paternal exposure to {sup 252}Cf fission neutron could lead to teratogenesis in the offspring. Seven-week-old C3H male mice were irradiated with graded doses of {sup 252}Cf fission neutrons and then were mated with nine-week-old C57BL females two weeks after the exposure. Three weeks later, it was found that testis and epididymal weight losses as well as the proportions of caudal epididymal sperm abnormalities in irradiated males were significantly greater than those in non-irradiated groups. Pregnant dams were sacrificed on day 18 of gestation and their fetuses were examined for the number of resorptions, intrauterine deaths and teratogenesis in F{sub 1} surviving offspring. Embryo lethality among the F{sub 1} offspring was found to be significantly higher in the irradiated group than in the non-irradiated group (p < 0.01), while the incidence of congenital malformations among the F{sub 1} offspring significantly increased in the irradiated groups. These results suggest that the paternal radiation exposure may have caused genetic transmission of DNA damage and genetic instability, which is in line with findings that show increases in incidence of teratogenesis in B{sub 6}C{sub 3}F{sub 1}. (author)

  20. The lymphocytotoxic effect of sera of irradiated and Trichinella spiralis infected mice

    International Nuclear Information System (INIS)

    The lymphocytotoxic effect of sera in mice relatively slowly (C3H/W) or strongly (BDF1) responding to T. spiralis infection was found to be higher in the latter than in the former. The effect was also induced by irradiation. The suppressive action of ionizing radiation on the immunological system of the host, expressed by enhanced intensity of invasion has been confirmed. 6 refs. (author)

  1. Assessment of apoptosis occurring in spleen cells from nitrogen mustard-treated or gamma-irradiated mice.

    Science.gov (United States)

    Hugel, B; Weltin, D; Holl, V; Marchal, J; Dufour, P; Freyssinet, J M; Bischoff, P L

    1998-01-01

    The short-term consequences on spleen cells of the intraperitoneal administration of nitrogen mustard (HN-2) to mice or of a whole-body gamma irradiation have been evaluated. Experiments were designed to assess the induction of apoptosis in spleen cells following exposure to these agents. The occurrence of this type of cell death was analysed by several methods, in particular the quantification in the blood of phosphotidylserine-bearing microparticles shed by apoptotic cells. In response to HN-2 or radiations, spleens undergo a rapid involution of their weight and cellularity. Ex vivo apoptosis occurs within 24 hours in cultured lymphocytes in a dose-dependent manner after both treatments. As compared with untreated controls, circulating microparticles increased 3-fold after the injection of 5 mg/kg of HN-2. PMID:9858897

  2. Effects of dsRNA on proliferative reaction and UDS of splenocytes in X-irradiated mice

    International Nuclear Information System (INIS)

    The effects of different concentrations of dsRNA on proliferative reaction of splenocytes induced by ConA and LPS and on UDS of splenocytes in 1.5 Gy X-irradiated mice are reported. The results show that the proliferative reaction of splenocytes induced by ConA and LPS in experimental groups increased significantly compared with that in positive group, and show that UDS in experimental groups was also much enhanced compared with that in positive group when concentration of dsRNA was higher than 6.25 mg/kg body weight. It is suggested that dsRNA increases proliferative reaction of splenocytes induced by ConA and LPA and inhibits decrease of UDS induced by X-rays

  3. Effects of low-level prenatal γ-ray irradiation on postnatal growth and behavior in mice

    International Nuclear Information System (INIS)

    Pregnant adult C57BL/6J mice were randomly allotted to six experimental groups. Doses of 0, 0.106, 0.156, 0.312, 0.518 or 0.656 Gy from 60Co γ-rays were delivered respectively on the 12.5th day of gestation by single radiation except for group 1 (used as control). Pups were observed for the growth (body weight, BW), the age of acquisition of three reflexes (surface righting, SR, negative geotaxis, NG and grasp reflex, GR), the appearance of three physiologic markers (eye opening, EO, pinna detachment, PD and incisor eruption, IE) and the sensuous functions (visual placing, VP and mother-taxis, MT). And by using these parameters 0.156 to 0.312 Gy irradiation may represent a threshold range for exposure on the 12.5th day of gestation to a single γ-radiation

  4. Image-guided microbeam irradiation to brain tumour bearing mice using a carbon nanotube x-ray source array

    International Nuclear Information System (INIS)

    Microbeam radiation therapy (MRT) is a promising experimental and preclinical radiotherapy method for cancer treatment. Synchrotron based MRT experiments have shown that spatially fractionated microbeam radiation has the unique capability of preferentially eradicating tumour cells while sparing normal tissue in brain tumour bearing animal models. We recently demonstrated the feasibility of generating orthovoltage microbeam radiation with an adjustable microbeam width using a carbon nanotube based x-ray source array. Here we report the preliminary results from our efforts in developing an image guidance procedure for the targeted delivery of the narrow microbeams to the small tumour region in the mouse brain. Magnetic resonance imaging was used for tumour identification, and on-board x-ray radiography was used for imaging of landmarks without contrast agents. The two images were aligned using 2D rigid body image registration to determine the relative position of the tumour with respect to a landmark. The targeting accuracy and consistency were evaluated by first irradiating a group of mice inoculated with U87 human glioma brain tumours using the present protocol and then determining the locations of the microbeam radiation tracks using γ-H2AX immunofluorescence staining. The histology results showed that among 14 mice irradiated, 11 received the prescribed number of microbeams on the targeted tumour, with an average localization accuracy of 454 µm measured directly from the histology (537 µm if measured from the registered histological images). Two mice received one of the three prescribed microbeams on the tumour site. One mouse was excluded from the analysis due to tissue staining errors. (paper)

  5. Quinine controls body weight gain without affecting food intake in male C57BL6 mice

    Directory of Open Access Journals (Sweden)

    Cettour-Rose Philippe

    2013-02-01

    Full Text Available Abstract Background Quinine is a natural molecule commonly used as a flavouring agent in tonic water. Diet supplementation with quinine leads to decreased body weight and food intake in rats. Quinine is an in vitro inhibitor of Trpm5, a cation channel expressed in taste bud cells, the gastrointestinal tract and pancreas. The objective of this work is to determine the effect of diet supplementation with quinine on body weight and body composition in male mice, to investigate its mechanism of action, and whether the effect is mediated through Trpm5. Results Compared with mice consuming AIN, a regular balanced diet, mice consuming AIN diet supplemented with 0.1% quinine gained less weight (2.89 ± 0.30 g vs 5.39 ± 0.50 g and less fat mass (2.22 ± 0.26 g vs 4.33 ± 0.43 g after 13 weeks of diet, and had lower blood glucose and plasma triglycerides. There was no difference in food intake between the mice consuming quinine supplemented diet and those consuming control diet. Trpm5 knockout mice gained less fat mass than wild-type mice. There was a trend for a diet-genotype interaction for body weight and body weight gain, with the effect of quinine less pronounced in the Trpm5 KO than in the WT background. Faecal weight, energy and lipid contents were higher in quinine fed mice compared to regular AIN fed mice and in Trpm5 KO mice compared to wild type mice. Conclusion Quinine contributes to weight control in male C57BL6 mice without affecting food intake. A partial contribution of Trpm5 to quinine dependent body weight control is suggested.

  6. Development of a metabolomic radiation signature in urine from patients undergoing total body irradiation.

    Science.gov (United States)

    Laiakis, Evagelia C; Mak, Tytus D; Anizan, Sebastien; Amundson, Sally A; Barker, Christopher A; Wolden, Suzanne L; Brenner, David J; Fornace, Albert J

    2014-04-01

    The emergence of the threat of radiological terrorism and other radiological incidents has led to the need for development of fast, accurate and noninvasive methods for detection of radiation exposure. The purpose of this study was to extend radiation metabolomic biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation at Memorial Sloan-Kettering Cancer Center prior to hematopoietic stem cell transplantation at 4-6 h postirradiation (a single dose of 1.25 Gy) and 24 h (three fractions of 1.25 Gy each). Global metabolomic profiling was obtained through analysis with ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (TOFMS). Prior to further analyses, each sample was normalized to its respective creatinine level. Statistical analysis was conducted by the nonparametric Kolmogorov-Smirnov test and the Fisher's exact test and markers were validated against pure standards. Seven markers showed distinct differences between pre- and post-exposure samples. Of those, trimethyl-l-lysine and the carnitine conjugates acetylcarnitine, decanoylcarnitine and octanoylcarnitine play an important role in the transportation of fatty acids across mitochondria for subsequent fatty acid β-oxidation. The remaining metabolites, hypoxanthine, xanthine and uric acid are the final products of the purine catabolism pathway, and high levels of excretion have been associated with increased oxidative stress and radiation induced DNA damage. Further analysis revealed sex differences in the patterns of excretion of the markers, demonstrating that generation of a sex-specific metabolomic signature will be informative and can provide a quick and reliable assessment of individuals in a radiological scenario. This is the first radiation metabolomics study in human urine laying the foundation for the use of metabolomics in biodosimetry and providing confidence in biomarker

  7. The influence of X-irradiation on immune phenomena in the course of experimental trichinellosis in mice

    International Nuclear Information System (INIS)

    The effects of irradiation with 600 R on mast cells, rosette-forming cells in the immunoadherence test and lymphocytes responsible for delayed hypersensitivity in mice infected with trichinellae were studied. Comparison of the results with the concurrent histopathologic picture and numbers of parasites in the intestines and muscles permitted more precise determination of the influence of X-irradiation on the course of trichinellosis in mice. (author)

  8. Lymphomyeloproliferative responses and survival from microbial antigens in mice after WR-2721 and irradiation

    International Nuclear Information System (INIS)

    The long-term effects of WR-2721 on lymphomyelopoietic proliferation in normal and irradiated animals and their resistance to microbial challenge was investigated in groups of B6CBF1 male mice given: (1) saline, (2) 500 mg/kg WR-2721 i.p., (3) 6 Gy /sup 60/Co radiation, (4) 500 mg/kg WR-2721 i.p. 15' before 10 Gy, and (5) 10 Gy /sup 60/Co radiation. Mice were assayed for (1) CFU-s, (2) GM-CFC, (3) T-cell response to PHA, and (4) B-cell response to LPS. Survival after i.p. injection with either 10/sup 8/-10/sup 9/ S. typhimurium or 10/sup 8/-10/sup 9/ S. aureus or S. typhosa endotoxin was determined. Testing was done 10, 20, 30, 40, 60, and 80 days after treatment. Animals treated with WR-2721 had significant perturbations in the hematopoietic parameters which were dependent on the assay used and the time tested. Proliferative responses of mice given WR-2721 and 10 Gy were equal to or greater than those for mice given 6 Gy alone at all times. S. typhimurium challenge resulted in 100% mortality in all groups. Injection with S. aureus 10 days after treatment killed all mice given either 6 Gy or WR-2721 prior to 10 Gy: all saline and WR-2721 treated mice survived. At all other times mortality responses were equal in all treatment groups infected with S. aureus. Mice given WR-2721 alone were resistant to S. typhosa endotoxin-induced lethality (65% vs 35% survival in controls). The survival rate for mice given endotoxin after WR-2721 and 10 Gy and for mice after 6 Gy was 85%

  9. Patient dose analysis in total body irradiation through in vivo dosimetry

    OpenAIRE

    Ganapathy, K.; Kurup, P. G. G.; Murali, V.; M. Muthukumaran; Bhuvaneshwari, N.; Velmurugan, J.

    2012-01-01

    Total body irradiation (TBI) is a special radiotherapy technique, administered prior to bone marrow transplantation. Due to the complex nature of the treatment setup, in vivo dosimetry for TBI is mandatory to ensure proper delivery of the intended radiation dose throughout the body. Lithium fluoride (LiF) TLD-100 chips are used for the TBI in vivo dosimetry. Results obtained from the in vivo dosimetry of 20 patients are analyzed. Results obtained from forehead, abdomen, pelvis, and mediastinu...

  10. Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to Total Body Irradiation.

    Science.gov (United States)

    Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

    2015-11-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

  11. Study of the influence of homologous serum globulin preparations on the intestinal automicroflora in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Pinegin, B.V.; Klemparskaya, N.N.; Mal' tsev, V.N.; Korshunov, G.A.; Shal' nova, G.A.; Kuz' mina, T.D.

    1984-09-01

    In spite of considerable experience of practical use of serum globulin preparations, their effect on automicroflora wasn't studied. The favorable effect of therapeutic injection of homologous serum globulin preparations on automicroflora of small and large intestine of mices was established for the model of acute radiation sickness caused by /sup 60/Co irradiation with 700 R dose. The effect of injecting two types of globulin preparations was studied: ones prepared of blood of intact and hemostimulated mices (to increase the content of normal antitissue antibodies in the serum). Besides the general globulin fraction isolated by ammonium sulfate precipitation a study was made on the effect of purified IgG and IgM preparations. Threefold subcutaneous or intraperitoneal globulin in ection of 1 ..mu..g dose in a mice prevented after 2, 24, 48 h after irradiation the development of bacteriosis, typical for radiation injury - decreased accumulation of putrefactive bacteria and reduced the suppression of lactobacilli content. Globulin preparations and fractions of hemostimulated mice serum, enriched by normal antitissue antibodies are the most effective ones.

  12. Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

    Energy Technology Data Exchange (ETDEWEB)

    Song, Chang W., E-mail: songx001@umn.edu [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yoon-Jin [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Park, Inhwan [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Koonce, Nathan A. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hui, Susanta [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Kim, Mi-Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Dusenbery, Kathryn E. [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Sperduto, Paul W. [Minneapolis Radiation Oncology and Gamma Knife Center, University of Minnesota, Minneapolis, Minnesota (United States); Cho, L. Chinsoo [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States)

    2015-09-01

    Purpose: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). Methods and Materials: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo–in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. Results: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. Conclusions: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS.

  13. Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). Methods and Materials: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo–in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. Results: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. Conclusions: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS

  14. SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

    International Nuclear Information System (INIS)

    Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers

  15. SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

    Energy Technology Data Exchange (ETDEWEB)

    Cvetkovic, D; Zhang, P; Wang, B; Chen, L; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2014-06-01

    Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers.

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

    International Nuclear Information System (INIS)

    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

  17. Changes in serum amylase and its isoenzymes after whole body irradiation

    International Nuclear Information System (INIS)

    A study was carried out to assess the effect of total body irradiation on pancreatic and parotid isoenzymes of amylase in patients about to undergo bone-marrow transplantation who had received high-dose cyclophosphamide. Twelve patients were studied, enzyme activity being measured before and at various times after total body irradiation. Serum total amylase activity rose rapidly within 12 hours of irradiation to a maximum at 36 hours, returning to normal by six days; most of the increase was derived from salivary damage, with a much smaller pancreatic component. These results confirm that radiation produces acute changes in amylase activity, which may be of use in assessing radiation-induced damage. (author)

  18. FORMATION BY IRRADIATION OF AN EXPANDED, CELLULAR, POLYMERIC BODY

    Science.gov (United States)

    Charlesby, A.; Ross, M.

    1958-12-01

    The treatment of polymeric esters of methacrylic acid having a softening polnt above 40 icient laborato C to form an expanded cellular mass with a smooth skin is discussed. The disclosed method comprises the steps of subjecting the body at a temperature below the softenpoint to a dose of at least 5 x lO/sup 6/ roentgen of gamma radiation from cobalt-60 source until its average molecular weight is reduced to a value within the range of 3 x lO/sup 5/ to 10/sup 4/, and heating at a temperature within the range of 0 to lO icient laborato C above its softening point to effect expansion.

  19. Mitigating the Effects of Xuebijing Injection on Hematopoietic Cell Injury Induced by Total Body Irradiation with γ rays by Decreasing Reactive Oxygen Species Levels

    Directory of Open Access Journals (Sweden)

    Deguan Li

    2014-06-01

    Full Text Available Hematopoietic injury is the most common side effect of radiotherapy. However, the methods available for the mitigating of radiation injury remain limited. Xuebijing injection (XBJ is a traditional Chinese medicine used to treat sepsis in the clinic. In this study, we investigated the effects of XBJ on the survival rate in mice with hematopoietic injury induced by γ ray ionizing radiation (IR. Mice were intraperitoneally injected with XBJ daily for seven days after total body irradiation (TBI. Our results showed that XBJ (0.4 mL/kg significantly increased 30-day survival rates in mice exposed to 7.5 Gy TBI. This effect may be attributable to improved preservation of white blood cells (WBCs and hematopoietic cells, given that bone marrow (BM cells from XBJ-treated mice produced more granulocyte-macrophage colony forming units (CFU-GM than that in the 2 Gy/TBI group. XBJ also decreased the levels of reactive oxygen species (ROS by increasing glutathione (GSH and superoxide dismutase (SOD levels in serum and attenuated the increased BM cell apoptosis caused by 2 Gy/TBI. In conclusion, these findings suggest that XBJ enhances the survival rate of irradiated mice and attenuates the effects of radiation on hematopoietic injury by decreasing ROS production in BM cells, indicating that XBJ may be a promising therapeutic candidate for reducing hematopoietic radiation injury.

  20. Efficiency of Immunization of Mice with Irradiated Antigen Against Schistosoma mansoni Infection in Comparison with Praziquantel

    Directory of Open Access Journals (Sweden)

    Mona A. El-Gawish, Manar N. Hafez, Fatma A. Eid* Maha G. Soliman*

    2006-12-01

    Full Text Available Introduction: The present study is an attempt to evaluate the protective effect of schistosomula antigen and the current antischistosomal drug praziquantel (PZQ as a reference drug on mice infected with S. mansoni. Material and Methods: Mice were vaccinated by irradiated or non-irradiated schistosomula antigen, both at a dose of 100 ug protein/mice once weekly for 3 weeks, before infection with alive cercariae and compared with the treatment with i.m. injection of praziquantel at a dose of 40 mg/kg b.wt. 4 times once weekly for 4 weeks after infection. The degree of resistance or protection induced by immunization and chemotherapy was assessed 45 days post­infection and evaluated by physiological, parasitological, immunological as well as histological parameters. Results: The results indicated that immunization with -irradiated antigen at 20 Krad or the treatment with PZQ resulted in significant reduction in ova count in liver and intestine tissues more than those vaccinated with non-irradiated antigen compared with infected group. Immunized group with irradiated antigen and the group treated with PZQ showed a significant decrease in liver enzymes activity (ALT, AST and -GT, while in immunized group with non-irradiated antigen, there was a significant increase in AST and -GT as compared to infected group. The level of alkaline phosphatase enzyme was significantly increased in all investigated groups compared to infected one. Treatment with PZQ or immunization with irradiated or non-irradiated schistosomula antigen induced amelioration in serum IL-10 and TNF-. Scanning electron microscope demonstrated normal mature worms in infected group after 45 days from infection. In contrast, many changes were detected in the rest groups as alterations in the tegument, implosion of tubercles which appeared pealed and sloughed off and most of the spines were detached and separated. Histological examination of liver sections of infected mice revealed lobular

  1. Bone Marrow Transplantation, 20 years of experience with total body irradiation in the 'Hermanos Ameijeiras' hospital

    International Nuclear Information System (INIS)

    Using Total Body Irradiation (ICT) for bone marrow transplants is indicated in several hematological malignancies such as Acute and Chronic Myeloid Leukemia, Acute Lymphocytic Leukemia, Lymphoma and Myelodysplastic Syndrome. The odds of survival with this procedure than those obtained with standard treatments in this type of condition, ensuring a better life expectancy for these patients. (Author)

  2. A SIMPLIFIED IN VIVO DOSLMETRY FOR TOTAL BODY IRRADIATION PRIOR TO BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    肖泽久

    1994-01-01

    For TBI (total body irradiation) prior to BMT (bone marrow transplantation) and in order to guarantee exact treatment, it is necessary to perfect is vivo dosimetry to detect any deviation of the treatment and to verify the dose dis-tribution. A simplified and convenient transmission type in vivo dosimetry and problems are introduced and discussed.

  3. Whole-body irradiation technique: physical aspects; Tecnica de irradiacion corporal total: aspectos fisicos

    Energy Technology Data Exchange (ETDEWEB)

    Venencia, D.; Bustos, S.; Zunino, S. [Instituto Privado de Radioterapia. Obispo Oro 425. Cordoba 5000 (Argentina)

    1998-12-31

    The objective of this work has been to implement a Total body irradiation technique that fulfill the following conditions: simplicity, repeatability, fast and comfortable positioning for the patient, homogeneity of the dose between 10-15 %, short times of treatments and In vivo dosimetric verifications. (Author)

  4. Schistosoma mansoni: quantitative aspects of the fertility and survival of worms obtained from irradiated cercariae (3 Krad), in mice

    International Nuclear Information System (INIS)

    The effect of gamma irradiation on the fertility of female mice, as well as the survival of worms in their portal system, have been observed in four groups of outbred albino mice (Mus musculus), experimentally infected with ca 450 cercariae of Schistosoma mansoni (LE and SJ strains), by transcutaneous route. The cercariae used were a) non-irradiated (control groups), and b) irradiated with 3 Krad of gamma irradiation (Co-60). From the 33rd day on, some stability in the population of surviving worm could be observed. This population remained constant till the end of the observation period (90th day), notedly in relation to the LE strain . Thus, it was concluded that gamma irradiation (at the dose of 3 Krad) is able to hinder the worm egg production in 98.1% of the infected mice. Further, it was observed that the few detected eggs were dead. Females were found to be more resistant to irradiation. The irradiation effect on the mortality of male worms was statistically significant scarcely from the 61st day on. The long period of permanence of the sterile adult irradiated worms in the portal system of mice and their probable involvement in the development of immuno-protection (the so-called concomitant immunity, without the immuno-pathological involvements for the host) are here discussed. (author)

  5. A Comparison of Molecular and Histopathological Changes in Mouse Intestinal Tissue Following Whole-Body Proton- or Gamma-Irradiation

    Science.gov (United States)

    Purgason, Ashley; Mangala, Lingegowda; Zhang, Ye; Hamilton, Stanley; Wu, Honglu

    2010-01-01

    There are many consequences following exposure to the space radiation environment which can adversely affect the health of a crew member. Acute radiation syndrome (ARS) involving nausea and vomiting, damage to radio-sensitive tissue such as the blood forming organs and gastrointestinal tract, and cancer are some of these negative effects. The space radiation environment is ample with protons and contains gamma rays as well. Little knowledge exists to this point, however, regarding the effects of protons on mammalian systems; conversely several studies have been performed observing the effects of gamma rays on different animal models. For the research presented here, we wish to compare our previous work looking at whole-body exposure to protons using a mouse model to our studies of mice experiencing whole-body exposure to gamma rays as part of the radio-adaptive response. Radio-adaptation is a well-documented phenomenon in which cells exposed to a priming low dose of radiation prior to a higher dose display a reduction in endpoints like chromosomal aberrations, cell death, micronucleus formation, and more when compared to their counterparts receiving high dose-irradiation only. Our group has recently completed a radio-adaptive experiment with C57BL/6 mice. For both this study and the preceding proton research, the gastrointestinal tract of each animal was dissected four hours post-irradiation and the isolated small intestinal tissue was fixed in formalin for histopathological examination or snap-frozen in liquid nitrogen for RNA isolation. Histopathologic observation of the tissue using standard H&E staining methods to screen for morphologic changes showed an increase in apoptotic lesions for even the lowest doses of 0.1 Gy of protons and 0.05 Gy of gamma rays, and the percentage of apoptotic cells increased with increasing dose. A smaller percentage of crypts showed 3 or more apoptotic lesions in animals that received 6 Gy of gamma-irradiation compared to mice

  6. Comparative nephrotoxicity of native or Co-60 gamma rays irradiated crotoxin in mice

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Andre Moreira; Alves, Glaucie J.; Aires, Raquel da Silva; Turibio, Thompson O.; Thomazi, Gabriela O. Coelho; Spencer, Patrick J.; Nascimento, Nanci do, E-mail: andrerocha@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Nascimento-Rocha, Josefa M.; Magalhaes Filho, Asterio Souza, E-mail: 0304@prof.itpacporto.com.br [Instituto Tocantinense Presidente Antonio Carlos Porto (ITPAC), Porto Nacional, TO (Brazil)

    2015-07-01

    Snake venoms are complex mixtures of proteins and peptides with a wide spectrum of physiological targets such as the blood coagulation and cardiovascular systems and the motor end plate among others. Acute renal failure is a common complication in accidents with the South American rattlesnake. The toxin involved in this pathology is the crotoxin, a major component of the venom in terms of concentration and toxicity. Snake venoms, when irradiated with {sup 60}Co gamma rays present a significant decrease in toxicity while the immunogenic properties of its components are preserved. The use of irradiated venom is an attractive alternative for antisera production since it might reduce the appearance of renal lesions improving the welfare and lifespan of those animals employed on antivenom production. At the present work, we have compared the effects of native and irradiated crotoxin on the mice renal function. Tubular lesions were observed in all the samples from the animal group injected with native crotoxin. Animals injected with the irradiated toxin presented alteration only after 30 minutes and 1 hour after injection. These data suggest that the onset of the renal lesions is delayed and that the severity of the lesions might be lower when using irradiated crotoxin. (author)

  7. Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice.

    Science.gov (United States)

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Barbosa, Décio S; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-24

    Ultraviolet B (UVB) irradiation may cause inflammation- and oxidative-stress-dependent skin cancer and premature aging. Naringenin (1) has been reported to have anti-inflammatory and antioxidant properties, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress are still not known. Thus, the present study aimed to investigate the potential of naringenin to mitigate UVB irradiation-induced inflammation and oxidative damage in the skin of hairless mice. Skin edema, myeloperoxidase (neutrophil marker) and matrix metalloproteinase-9 (MMP-9) activity, and cytokine production were measured after UVB irradiation. Oxidative stress was evaluated by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability, ferric reducing antioxidant power (FRAP), reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, and gp91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR. The intraperitoneal treatment with naringenin reduced skin inflammation by inhibiting skin edema, neutrophil recruitment, MMP-9 activity, and pro-inflammatory (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-12, IL-13, IL-17, IL-22, and IL-23) and anti-inflammatory (TGF-β and IL-10) cytokines. Naringenin also inhibited oxidative stress by reducing superoxide anion production and the mRNA expression of gp91phox. Therefore, naringenin inhibits UVB irradiation-induced skin damage and may be a promising therapeutic approach to control skin disease.

  8. Immunological assessment of mice hyperimmunized with native and Cobalt-60-irradiated Bothrops venoms

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira Junior, R.S.; Meira, D.A. [UNESP, Botucatu, SP (Brazil). Dept. de Doencas Tropicais; Barraviera, B. [UNESP, Botucatu, SP (Brazil). Center for the Study of Venoms and Venomous Animals - CEVAP; Nascimento, N.; Alves, J.B. [Instituto de Pesquisas Energeticas (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Martinez, J.C. [UNESP, Botucatu, SP (Brazil). Escola de Engenharia]. E-mail: rseabra@cevap.org.br

    2005-10-15

    ELISA was used to evaluate, accompany, and compare the humoral immune response of Swiss mice during hyperimmunization with native and Cobalt-60-irradiated ({sup 60}Co) venoms of Bothrops jararaca, Bothrops jararacussu and Bothrops moojeni. Potency and neutralization were evaluated by in vitro challenges. After hyperimmunization, immunity was observed by in vivo challenge, and the side effects were assessed. The animals immunization with one LD50 of each venom occurred on days 1, 15, 21, 30, and 45, when blood samples were collected; challenges happened on the 60th day. Results showed that ELISA was efficient in evaluating, accompanying and comparing mouse immune response during hyperimmunization. Serum titers produced with natural venom were similar to those produced with irradiated venom. Immunogenic capacity was maintained after {sup 60} Co-irradiation. The sera produced with native venom showed neutralizing potency and capacity similar to those of the sera produced with irradiated venom. All antibodies were able to neutralize five LD50 from these venoms. Clinical alterations were minimum during hyperimmunization with irradiated venom, however, necrosis and death occurred in animals inoculated with native venom. (author)

  9. Comparative nephrotoxicity of native or Co-60 gamma rays irradiated crotoxin in mice

    International Nuclear Information System (INIS)

    Snake venoms are complex mixtures of proteins and peptides with a wide spectrum of physiological targets such as the blood coagulation and cardiovascular systems and the motor end plate among others. Acute renal failure is a common complication in accidents with the South American rattlesnake. The toxin involved in this pathology is the crotoxin, a major component of the venom in terms of concentration and toxicity. Snake venoms, when irradiated with 60Co gamma rays present a significant decrease in toxicity while the immunogenic properties of its components are preserved. The use of irradiated venom is an attractive alternative for antisera production since it might reduce the appearance of renal lesions improving the welfare and lifespan of those animals employed on antivenom production. At the present work, we have compared the effects of native and irradiated crotoxin on the mice renal function. Tubular lesions were observed in all the samples from the animal group injected with native crotoxin. Animals injected with the irradiated toxin presented alteration only after 30 minutes and 1 hour after injection. These data suggest that the onset of the renal lesions is delayed and that the severity of the lesions might be lower when using irradiated crotoxin. (author)

  10. Immunological assessment of mice hyperimmunized with native and Cobalt-60-irradiated Bothrops venoms

    International Nuclear Information System (INIS)

    ELISA was used to evaluate, accompany, and compare the humoral immune response of Swiss mice during hyperimmunization with native and Cobalt-60-irradiated (60Co) venoms of Bothrops jararaca, Bothrops jararacussu and Bothrops moojeni. Potency and neutralization were evaluated by in vitro challenges. After hyperimmunization, immunity was observed by in vivo challenge, and the side effects were assessed. The animals immunization with one LD50 of each venom occurred on days 1, 15, 21, 30, and 45, when blood samples were collected; challenges happened on the 60th day. Results showed that ELISA was efficient in evaluating, accompanying and comparing mouse immune response during hyperimmunization. Serum titers produced with natural venom were similar to those produced with irradiated venom. Immunogenic capacity was maintained after 60 Co-irradiation. The sera produced with native venom showed neutralizing potency and capacity similar to those of the sera produced with irradiated venom. All antibodies were able to neutralize five LD50 from these venoms. Clinical alterations were minimum during hyperimmunization with irradiated venom, however, necrosis and death occurred in animals inoculated with native venom. (author)

  11. Impact of Whole Body Irradiation on the Intestinal Microbiome- Considerations for Space Flight

    Science.gov (United States)

    Karouia, Fathi; Santos, Orlando; Valdivia-Silva, Julio E.; Jones, Jeffrey; Greenberger, Joel S.; Epperly, Michael W.

    Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. Spaceflight-related changes have been reported in the musculo-skeletal, cardiovascular, neurovestibular, endocrine, and immune systems to just name a few. However, to date, radiation exposure is one of the main limiting factors for long duration space exploration missions and especially a mission to Mars. Over the past few years through advances in technology, the characterization of the microbiome has revealed a large and complex community of microorganisms living in symbiosis with the human host. However, heterogeneity of the intestinal microbial spectrum in humans has been associated with a variety of diseases and susceptibility to infectious and toxic agents. Limited information is known about the influence of space environment in general and radiation in particular on the microbiome. Furthermore, multiple spaceflight and simulated microgravity experiments have shown changes in phenotypic microbial characteristics such as microbial growth, morphology, metabolism, genetic transfer, antibiotic and stress susceptibility, and an increase in virulence factors. We now report a study of the bacterial composition of the intestine in C57BL/6NTAC mice and the types of microbes entering the body at two time points after the LD 50/30 dose of total body irradiation using microarray-based assay, G3 PhyloChip 16S rRNA, and bioinformatics methods. Bacteria and archaea taxon richness was determined at the genus level and ranged from 2 to 107 and 0 to 3 respectively. As expected, pre-exposure blood samples exhibited less bacterial and archaeal genus richness compared to all other samples. However, the study shows a significant shift in the mouse gut microbial speciation in several bacterial families, with increases in the Turicibacteraceae and Enterobacteriaceae and decreases in the Lachnospiraceae and Ruminococcaceae families. The findings most relevant to occupational

  12. EFFECT OF REGULAR GARLIC INGESTION ON BODY WEIGHT AND BLOOD GLUCOSE: A CASE STUDY IN MICE

    Directory of Open Access Journals (Sweden)

    F.T. Djankpa, A. Osonuga*, J. Ekpale, C.E. Quaye, P. Otoo, O.A. Osonuga and S.K. Amoah

    2012-05-01

    Full Text Available Garlic a perennial erect plant is known to have sulphur-containing compounds that act on the hypothalamus increasing the sensitivity of the hypothalamus to leptin which alters the set point at which satiety is reached causing an organism to eat less. Nine mice (six of which were obese were used in this study and grouped into three. Groups A and B were made of 3 obese mice each whereas group C consisted of 3 non-obese mice. For group A and group C mice, 20 ml aqueous garlic extract was added to their feed daily whereas no garlic was added to the feed of group B mice. The study was carried out over a period of 44 days. The weight and blood glucose was measured weekly and the average for each group was computed. Results indicated that Group A mice recorded a reduction in mean body weight by 46.5% (p<0.05. Group B mice had significant increase in mean body weight by 46.2% (p<0.05. The blood glucose level dropped significantly by 18.5% (p<0.05 in group A mice. Garlic had weight loss and hypoglycemic effect in obese mice. These effects were absent in non-obese mice.

  13. Protective Role Of Fresh Pomegranate Against Oxidative Damage In Whole Body Gamma Irradiated Male Albino Rats

    International Nuclear Information System (INIS)

    Twenty four male albino rats, body weight 100-130 g, were used to evaluate the protective role of fresh pomegranate fruit intake for 30 days on the damage induced by single dose of 6 Gy whole body gamma irradiation. The rats were randomly and equally divided into four groups: group (1): control, group (2): irradiated with 6 Gy, group (3): pomegranate for 30 days and group (4): pomegranate for 30 days followed by 6 Gy whole body irradiation. At the end of the experiment, all rats were sacrificed after 12 hours fasting then sera were separated for the determination of sugar, total antioxidant, lipid profile and liver and kidney functions. Results showed that gamma radiation caused significant decline (P<0.05) in serum total antioxidant, total protein, albumin, HDL-C and blood glucose with significant elevation (P<0.05) in other hepato-renal markers in addition to serum total cholesterol, triglycerides and LDL-C. These changes were significantly attenuated in irradiated animals pre-treated with whole fresh pomegranate fruit leading to the conclusion that pre-intake of pomegranate fruit had a radio- protective effect. This protection of this whole fruit may be due to the increased total antioxidant level leading to free radical scavenging

  14. Study on Fractionated Total Body Irradiation before Hematopoietic Stem Cell Transplantation

    Institute of Scientific and Technical Information of China (English)

    Tong Fang; Bo Liu; Hong Gao

    2009-01-01

    OBJECTIVE To observe the dose and the complications from total body irradiation before hematopoietic stem cell transplantation.METHODS This study involved 312 patients with total body irradiation before hematopoietic stem cell transplantation. They were entered into the treated research from May 1999 to October 2005. All patients had Received the irradiation from 60Co of an absorbed dose rate of (5.2 ± 1.13) cGy/min. The total dose of TBI was 7~12 Gy, 1 f/d × 2 d. A high-dose rate group (≥ 10 Gy) included 139 cases and a low-dose rate group (< 10 Gy) included 173 cases.RESULTS The probability of acute gastrointestinal reactions in the high-dose rate group was more compared with that in the low-dose rate group. The differences for other reactions, such as hematopoietic reconstitution and graft survival rate, between the two groups were insignificant.CONCLUSION Using fractional total body irradiation at a dose rate of 5 cGy/min, with a total dose of 7~12 Gy, 1 f/d x 2 d, with the lung receiving under 7.5 Gy is a safe and effective pretreatment for hematopoietic stem cell transplantation.

  15. Low Dietary Protein Status Potentiating Risk of Health Hazard in Whole Body Gamma Irradiated Rats

    International Nuclear Information System (INIS)

    Investigations were planned to assess the changes in certain biochemical parameters as affected by the synergistic effect of exposure to fractionated doses of rays and / or feeding on different protein levels. The date showed that animals kept on normal or low protein diet exhibited a significant decrease in serum total protein and glucose. Also , a significant increase was recorded in insulin level in rats exposed at the radiation dose level of 20 Gy. Exposure to cumulative doses of irradiation has aggrevated the hyperglycemic effect of high protein diet with a significant and marked increase of insulin at all the applied doses. Animals fed normal high or low protein diet were found to exert significant decreases in T3, T4 while a significant increase in TSH of high protein group occurred as a result of exposure to cumulative doses of gamma-irradiation. Rats kept on low protein diet exhibited losses in body weight, hypercholesterolemia, low levels of phospholipids and triglycerides as compared with the normal protein diet group. In contrast high protein diet group showed no serious effects. Irradiation has potentiated body weight losses, hypotriglyceridemia and hypercholesterolemia in animal group fed low protein diet with a significant increase in serum phospholipids due to the higher radiation dose of 20 Gy. Protein deficiency acted synergistically with gamma irradiation and increased the susceptibility of body organs to radiation damage. Such findings contributed to the knowledge which stimulated the decrease of the internationally recognized occupational dose limits from 50 down to 20 m Sv (ICRP 1991)

  16. Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules

    International Nuclear Information System (INIS)

    Protection against a Schistosoma mansoni cercarial challenge was evaluated in mice immunized with a vaccine composed of 10-krad-irradiated, cryopreserved schistosomules. The level of resistance induced in C57B1/6 or NMRI (CV) mice increased with the number of schistosomules injected. Up to 83% reduction in challenge worm burden was achieved when 5000 schistosomules were injected per mouse. Intramuscular injection of the vaccine was superior to subcutaneous. Multiple immunizations, up to 3 at 4-week intervals, did not increase the resistance induced by a single immunization. A high level of protection developed in as little as 2 weeks and was maintained through at least 12 weeks postimmunization. The vaccine irradiated with 10 krad from either a 60-cobalt or 137-cesium source induced equivalent levels of resistance, and no differences were found in the immunogenicity of vaccines comprised of organisms irradiated as cercariae or as 1- to 3-hr-old schistosomules. These findings are basic to the development of a cryopreserved, live vaccine against schistosomiasis of humans or domestic animals

  17. Kinetics of Multiplication and Differentiation of Haemopoietic Progenitor Cells Transplanted into Irradiated Mice

    International Nuclear Information System (INIS)

    The growth of colony-forming units (CFU) was followed in the spleen of normal, polycythaemic and polycythaemic erythropoietin-treated test mice after irradiation and normal bone-marrow inoculation. The number of CFU was estimated at various time intervals after inoculation of bone-marrow by retransplantation of the test spleens in irradiated mice. The results indicate that in the spleen of polycythaemic animals the number of CFU is the same as in the normal animals up to day 4 after bone-marrow inoculation. At later times the content of CFU per spleen is about half of that in normal animals, although the CFU growth rate from day 6 to day 9 is comparable in both normal and polycythaemic animals. Erythropoietin injected daily in polycythaemic animals from day 3 after bone-marrow inoculation brings the CFU growth curve back to the level of normal animals. The 7-h uptake of 59Fe in the spleen of normal, polycythaemic and polycythaemic EPO-treated irradiated animals, at various times after bone-marrow inoculation, was also followed as a measure of CFU erythropoietic differentiation. The results are discussed in the light of the available information concerning growth and differentiation of spleen colony-formers. (author)

  18. Final height and gonad function after total body irradiation during childhood.

    Science.gov (United States)

    Couto-Silva, A-C; Trivin, C; Esperou, H; Michon, J; Baruchel, A; Lemaire, P; Brauner, R

    2006-09-01

    Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak >10 microg/l. Final height was irradiated (Pirradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function.

  19. Whole body surface electron irradiation in the treatment of mycosis fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Lo, T.C.M.; Salzman, F.A.; Moschella, S.L.; Tolman, E.L.; Wright, K.A.

    1979-02-01

    The records of 200 patients with generalized cutaneous mycosis fungoides treated with whole body surface electron irradiation were reviewed. Type of skin lesion appeared to be the most important factor with respect to both survival and generalized skin disease-free interval. High-dose irradiation did not seem to influence prognosis significantly compared with a relatively conservative dose. The cure rate for the entire group was 7%. For a more homogeneous dose distribution, the eight-field technique is now used instead of the original four-field method. A new formula is proposed to standardize the reporting of doses.

  20. He-Ne Laser Auricular Irradiation Plus Body Acupuncture for Treatment of Acne Vulgaris in 36 Cases

    Institute of Scientific and Technical Information of China (English)

    Sun Lihong

    2006-01-01

    In order to observe the therapeutic effects of He-Ne laser auricular irradiation plus body acupuncture for acne vulgaris, 68 cases of acne vulgaris were randomly divided into a treatment group of 36 cases treated with He-Ne laser auricular irradiation plus body acupuncture, and a control group of 32 cases treated with body acupuncture only. The results showed that the cure rate was 77.8% in the treatment group and 46.9% in the control group (P<0.05), indicating that He-Ne laser auricular irradiation plus body acupuncture may exhibit better effects for acne vulgaris.

  1. Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation.

    Science.gov (United States)

    Valente, Marco; Denis, Josiane; Grenier, Nancy; Arvers, Philippe; Foucher, Barbara; Desangles, François; Martigne, Patrick; Chaussard, Hervé; Drouet, Michel; Abend, Michael; Hérodin, Francis

    2015-01-01

    In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hematologic support (i.e., mostly TBI victims). To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18) were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI) or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI). More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6) and PBI (n = 12), for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.

  2. Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation.

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    Marco Valente

    Full Text Available In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI and partial-body irradiation (PBI to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS and need hematologic support (i.e., mostly TBI victims. To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18 were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI. More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6 and PBI (n = 12, for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.

  3. The carcinogenic risk of high dose total body irradiation in non-human primates

    International Nuclear Information System (INIS)

    High dose total body irradiation (TBI) in combination with chemotherapy, followed by rescue with bone marrow transplantation (BMT), is increasingly used for the treatment of haematological malignancies. With the increasing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of growing concern. Studies on turnout induction in non-human primates are of relevance in this context since the response of this species to radiation does not differ much from that in man. Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marrow transplantation after irradiation with X-rays (average total body dose 6.8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which were irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened for the occurrence of neoplasms. Complete necropsies were performed after natural death or euthanasia. At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older a-e compared with those in the irradiated cohorts. The histogenesis of the tumours was diverse with a preponderance of renal carcinoma, sarcomas among which osteosarcormas, and malignant glomus tumours in the irradiated groups. When corrected for competing risks, the carcinogenic risk of TBI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a

  4. High Dose-Per-Fraction Irradiation of Limited Lung Volumes Using an Image-Guided, Highly Focused Irradiator: Simulating Stereotactic Body Radiotherapy Regimens in a Small-Animal Model

    International Nuclear Information System (INIS)

    Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.

  5. Body weight is not always a good predictor of longevity in mice.

    Science.gov (United States)

    Anisimov, Vladimir N; Arbeev, Konstantin G; Popovich, Irina G; Zabezhinksi, Mark A; Rosenfeld, Svetlana V; Piskunova, Tatiana S; Arbeeva, Lyubov S; Semenchenko, Anna V; Yashin, Anatoli I

    2004-03-01

    There have been some observations that low body weight and a low level of some hormones (e.g. IGF-1) during the first half of life are predictors of longer life in mice. However, contradictions in the available data on the biomarkers of aging and predictors of longevity have shown that the research in these fields has become a controversial pursuit. In our study we addressed the following questions: (i) Can particular physiological parameters (body weight, food intake, estrus function, body temperature, incidence of chromosome aberrations in bone marrow cells) measured at the age of 3 and 12 months be a predictor of longevity and the rate of tumor development in five strains of mice? (ii) Can a heavy body weight at the age of 3 and 12 months be a predictor of longevity and high tumor risk in five strains of mice? Mice of five strains-CBA, SHR, SAMR, SAMP and transgenic HER-2/neu (FVB/N)-were under observation from the age of 2-3 months until natural death. Body weight and temperature, food consumption, and estrous cycle were longitudinally studied in all animals. Tumors discovered at autopsy were studied morphologically. We calculated the life span's parameters (mean, maximum, mortality rate, mortality rate doubling time) as well as their correlation with other parameters studied. The longest living CBA mice have the lowest body weight at the ages of 3 and 12 months, the lowest food consumption, body temperature, incidence of chromosome aberrations and spontaneous tumor incidence. In comparison with all other mouse strains they also have the latest disturbances in estrus function and highest body weight gain. The shortest living transgenic HER-2/neu mice have the lowest weight at the ages of 12 months, the lowest body weight gain, maximal body temperature, the most rapid disturbances in estrus function and the highest incidence of chromosome aberrations and tumor incidence in comparison to all other mouse strains. Our findings have shown that heavier body weight at

  6. Optimum combination of targeted 131I and total body irradiation for treatment of disseminated cancer

    International Nuclear Information System (INIS)

    Purpose: Radiobiological modeling was used to explore optimum combination strategies for treatment of disseminated malignancies of differing radiosensitivity and differing patterns of metastatic spread. The purpose of the study was to derive robust conclusions about the design of combination strategies that incorporate a targeting component. Preliminary clinical experience of a neuroblastoma treatment strategy, which is based upon general principles obtained from modelling, is briefly described. Methods and Materials: The radiobiological analysis was based on an extended (dose-rate dependent) formulation of the linear quadratic model. Radiation dose and dose rate for targeted irradiation of tumors of differing size was in part based on microdosimetric considerations. The analysis was applied to several tumor types with postulated differences in the pattern of metastatic spread, represented by the steepness of the slope of the relationship between numbers of tumors present and tumor diameter. The clinical pilot study entailed the treatment of five children with advanced neuroblastoma using a combination of 131I metaiodobenzylguanidine (mIBG) and total body irradiation followed by bone marrow rescue. Results: The theoretical analysis shows that both intrinsic radiosensitivity and pattern of metastatic spread can influence the composition of the ideal optimum combination strategy. High intrinsic radiosensitivity generally favors a high proportion of targeting component in the combination treatment, while a strong tendency to micrometastatic spread favors a major contribution by total body irradiation. The neuroblastoma patients were treated using a combination regimen with an initially low targeting component (2 Gy whole body dose from targeting component plus 12 Gy from total body irradiation). The treatment was tolerable and resulted in remissions in excess of 9 months in each of these advanced neuroblastoma patients. Conclusions: Radiobiological analysis, which

  7. Differential expression profiles of microRNAs in liver of 60Co γ-ray irradiated mice

    International Nuclear Information System (INIS)

    Objective: To investigate the differential expression profiles of microRNAs in the liver of 60Co γ-ray irradiated mice using microRNA microarray and to explore their main functions by bioinformatic analysis. Methods: After SPF C57BL/6J mice expose to 4 Gy-single whole body radiation,total number of peripheral WBC and the fMNPCE were measured at 3 d.The differentially expressed miRNAs in mouse liver were detected with miRNA microarray, miRNA-124 and miR-34a were confirmed by real time RT-PCR assay. Bioinformatic analysis was applied to explore target genes and the main functions of the differential expressed miRNAs. Results: Compared with control group, the total number of peripheral WBC decreased (t=2.87, P<0.05), while the fMNPCE in bone marrow increased (t=-2.91, P<0.05) after 4 Gy γ-ray irradiation.miRNA microarray revealed that 17 miRNAs were differentially expressed, in which 9 up-regulated, 8 down-regulated. The expression levels of miR-124 and miR-34a were coincident with the result of real time RT-PCR. GO analysis showed that some pathways including adherens junction and cell cycle were suppressed, while some immune-related pathways were activated. Conclusions: miR-34a and miR-194 were involved in the regulation of acute radiation damage, some other miRNAs including miR-124, miR-382 and miR-92a* also played important roles in radiation process. (authors)

  8. Comparison of therapeutic effects between pulsed and continuous wave 810-nm wavelength laser irradiation for traumatic brain injury in mice.

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    Takahiro Ando

    Full Text Available BACKGROUND AND OBJECTIVE: Transcranial low-level laser therapy (LLLT using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI. In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI. STUDY DESIGN/MATERIALS AND METHODS: TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm(2 for 12-minutes giving a fluence of 36-J/cm(2. Neurological severity score (NSS and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain tissue was determined immediately after laser irradiation. We examined the role of LLLT on the psychological state of the mice at 1 day and 4 weeks after TBI using tail suspension test and forced swim test. RESULTS: The 810-nm laser pulsed at 10-Hz was the most effective judged by improvement in NSS and body weight although the other laser regimens were also effective. The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover, we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim and tail suspension tests. CONCLUSION: The therapeutic effect of LLLT for TBI with an 810-nm laser was more effective at 10-Hz pulse frequency than at CW and 100-Hz. This finding may provide a new insight into biological mechanisms of LLLT.

  9. Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice

    International Nuclear Information System (INIS)

    Ultraviolet radiation is known to induce a transient defect in epidermal antigen presentation which leads to the generation of antigen-specific suppression of the delayed-type hypersensitivity (DTH) response. The putative receptor in skin for the primary event in UV-suppression is urocanic acid (UCA) which may then interact locally, or systemically, with antigen presenting cells or initiate a cascade of events resulting in suppression. We present the first direct evidence that UCA, when irradiated with a dose (96 mJ/cm2) of UVB radiation known to suppress the DTH response to herpes simplex virus, type 1 (HSV-1) in mice, can induce suppression following epidermal application or s.c. injection of the irradiated substance. This suppression is transferable with nylon wool-passed spleen cells

  10. Tissue air ratio in total body irradiation. An in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Scarpati, D.; Mancini, G.; Corvo, R.; Franzone, P.

    1989-01-01

    On the basis of dose readings in 102 patients treated with total body irradiation (TBI), a 'tissue air ratio (TAR) curve' has been produced. It could be useful to precalculate treatment time in TBI, for dose prescription to a specific point, provided the same source (/sup 60/Co) and treatment setting (lateral irradiation; 3 m source-axis distance; reference point at thighs bifurcation, neat the perineum) is used. The TAR curve produced, and the formula relating tissue depth to TAR value, are presented, and compared to preexisting data for 'magna fields' treatments. This curve is exponential, and in semilog representation becomes straight, as every classic TAR curve; it is lower than others, reflecting non full-scatter situation in patient irradiation. (orig.).

  11. Asymptotic weight and maturing rate in mice selected for body conformation

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    Di Masso Ricardo J.

    2000-01-01

    Full Text Available Growth patterns of four lines of mice selected for body conformation were analyzed with the logistic function, in order to provide baseline information about the relationship between asymptotic weight and maturing rate of body weight. Two lines were divergently selected favoring the phenotypic correlation between body weight and tail length (agonistic selection: CBi+, high body weight and long tail; CBi-, low body weight and short tail, whereas the other two lines were generated by a disruptive selection performed against the correlation between the aforementioned traits (antagonistic selection: CBi/C, high body weight and short tail; CBi/L, low body weight and long tail. The logistic parameters A (asymptotic weight and k (maturing rate behaved in CBi/C and CBi- mice and in CBi+ females as expected in terms of the negative genetic relationship between mature size and earliness of maturing. An altered growth pattern was found in CBi/L mice and in CBi+ males, because in the former genotype, selected for low body weight, the time taken to mature increased, whereas in the latter, selected for high body weight, there was a non-significant increase in the same trait. In accordance with the selective criterion, different sources of genetic variation for body weight could be exploited: one inversely associated with earliness of maturing (agonistic selection, and the other independent of maturing rate (antagonistic selection, showing that genetic variation of A is partly independent of k.

  12. Response of mice liver to continuous beta-irradiation from tritiated water

    International Nuclear Information System (INIS)

    The low-level toxicity of the tritium has been studied on the adult mice liver. A group of adult mice was irradiated continuously at the radioactivity of 1.25 μCi/ml of drinking water up to 30 days and the liver was studied on 1, 5, 7, 15 and 30 days after initiation of treatment. In early intervals, a gradual increase in the degree of damage in the form of histopathological lesions like cytoplasmic vacuolation and degranulation, pycnosis, hemorrhage and lymphocytic infiltration etc. was noticed which reaches to maximum on day 7, after which it was found a bit repaired on the following interval (15 days) and on 30th day exhibited almost a near-normal hepatic architecture with a few histopathological lesions viz. edema and leukocytic infiltration. (author)

  13. Dose-effect relationships in total body irradiation on the healing of cutaneous wounds

    Institute of Scientific and Technical Information of China (English)

    冉新泽; 程天民; 林远; 屈纪富; 刘都户; 艾国平; 阎国和; 王文昌; 许汝福

    2003-01-01

    ObjectiveTo study the effects of dosages of total body irradiation on the healing process of cutaneous wounds and to observe the changes of wound area at different periods after injury.star rats. The single dosage varied from 1 to 8 Gy. Within 1 h after irradiation, two whole thickness circular cutaneduced on the back of the animals (combined injury groups). Same wounds were produced on rats with no irradiation (single wound group). Wound healing was observed at different points after injury. ResultsAfter total body irradiation with the dose of 1,2,3,4,5,6, 7 or 8 Gy, the wound healing was obviously retarded as the dosages increased. The wound area remained was larger in the large dosage groups than in the small dosage groups. Seven days after injury, there was 33.5% wound surface left unhealed in the single wound group, whereas in the combined injury groups, 35.4%, 38.1%, 41.6%, 48.8%, 53.9%, 63.7%, 69.2% and 73.9% of the wound surfaces remained unhealed, respectively. Statistical analysis showed marked correlations between the varioustimes after total body irradiation and various dosages to the percentage of unhealed wound surface. Nine dose-effect relation formulae were deduced according to the statistical results.ConclusionsIn soft tissue trauma combined with radiation injury, the delay of wound healingis related to the dose of radiation inflicted. It is also related to the time between injury and time of observation.

  14. DNA damage focus analysis in blood samples of minipigs reveals acute partial body irradiation.

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    Andreas Lamkowski

    Full Text Available Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs. The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI with 49 Gy (± 6% Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL of 49 Gy partial body irradiated minipigs were found to display 1-8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available

  15. Human granulocytopoietic colonies in diffusion chambers in mice: Growth of colonies and the effect of host irradiation

    International Nuclear Information System (INIS)

    Normal human non-separated bone marrow cells were cultured in fibrin clots in diffusion chambers implanted intraperitoneally in mice, and harvested at different intervals by a previously described chamber centrifugation technique. This method demonstrates the presence of cell aggregates in the diffusion chambers. When the chambers are implanted in irradiated mice (450 R) and retransplantated into newly irradiated mice every seventh day, a continous increase in number of cells per granulocytopoietic aggregate is observed from day 8 to day 21. This is compatible with the view that the aggregates are colonies. The term 'colony forming unit diffusion chamber' (CFUD) is suggested to denote the ancestor(s) of the colonies. However, formal proof that one colony is derived from one cell is lacking. Preirradiation of mice with 450 R significantly increases the number of neutrophilic granulocytopoietic colonies at day 14, provided the chambers are retransplantated to newly irradiated mice at day 7, indicating that the neutrophilic colony forming unit or its progeny is involved as at least one of the targets of the stimulating effect of host irradiation. In contrast, no effect of host irradiation on the numbers of eosinophilic colonies was observed. Aggregates of megakaryocytic cells were present during the entire culture period. (author)

  16. Characteristics of macrophages in irradiation chimeras in mice reconstituted with allogeneic bone marrow cells

    International Nuclear Information System (INIS)

    Biological and immunological characteristics of the reticuloendothelial system of irradiation bone marrow chimeric mice and macrophages collected from various tissue sources of the mice were studied. The chimeras showed comparable activities in carbon clearance to those of normal donor or recipient mice. The macrophages from spleen, lymph node, bone marrow, peripheral blood, liver, peritoneal cavity, and lung were demonstrated to be of donor marrow origin. They showed almost the same enzyme activities and phagocytic capability of sheep erythrocytes (SRBC, E), SRBC sensitized with anti-SRBC IgG (EA), and SRBC sensitized with anti-SRBC IgM and coated with complement (EAC) as those of normal mice. Proportions of Fc receptor and complement receptor-positive cells are also in normal range. In addition, the antigen-presenting capability of the chimeric macrophages for in vitro primary antibody response to SRBC was intact. These observations suggest that the reticuloendothelial system and macrophages of allogeneic bone marrow chimeras where donor and recipient differ at the major histocompatibility complex have no defect so far as could be ascertained by the present study

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

    International Nuclear Information System (INIS)

    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)

  18. Anorexia in rats after protracted whole-body irradiation with low doses

    International Nuclear Information System (INIS)

    In our experiments, carried out hitherto, concerning the effect of incorporated and radioactive substances, weight behaviour and food uptake have proved to be a sensitive test. With regard to these experiments and the half-life of the radionuclides used, it is reported about trial series in Wistar rats. These rats were applied, with Co-60 gamma irradiation, different whole-body doses protracted over 48 hours. A total of 32 groups of experimental animals (20 animals each) was exposed to irradiation doses of lethal, medium lethal, and sublethal ranges, control and pseudo-irradiation series included. The experiments were carried out under observance of constant irradiation and attitude conditions, night and day changes, as conditioned by the season, included. Even in the inferior sublethal range (12 to 24 R), a significant trend of decreased food uptake is registered. This trend remains for a short period after the end of irradiation, but then it returns to normal conditions. Furthermore, a new decrease with subsequent increase seems to become evident - about ten days after termination of the radiotherapy (especially after several hundred R); report about these items will be made later on. (orig.)

  19. Effects of supralethal total body irradiation and bone marrow reconstitution upon immunologic memory

    International Nuclear Information System (INIS)

    The transplantation of bone marrow from prospectively selected genotypically and pedigree DLA-identical donors into supralethally irradiated littermate and nonlittermate recipients within the Copperstown beagle colony has regularly resulted in the establishment of long-term chimerism, with no evidence of graft-versus-host disease in the recipients. It has been demonstrated that irradiated recipients exhibit significant decreases in their ability to muster primary immunological responses during the first months after reconstitution with bone marrow. Beyond the documented capacity of preirradiation blood transfusions to interfere with subsequent engraftment of allogeneic marrow, however, there have been no systematic studies of the possible effects of irradiation and bone marrow transplantation upon immunologic memory. The present study was designed in order to assess this question in greater detail, with particular regard to the effects of irradiation and bone marrow reconstitution upon host sensitization to skin allografts. The results indicate that, within the experimental limitations described, the state of sensitivity produced by first set skin allograft rejection is not affected significantly by supralethal total body irradiation and reconstitution of the recipient with allogeneic bone marrow

  20. Kidney and lung injury in irradiated rats protected from acute death by partial-body shielding

    International Nuclear Information System (INIS)

    Ninety-six CD-1 male rats were exposed to gamma-ray doses (0-25 Gy) in increments of 5 Gy. One femur, the surgically exteriorized GI tract, and the oral cavity were shielded during irradiation to protect against acute mortality from injury to the hematopoietic system, small intestine, and oral cavity. In addition, the thoraxes of half of the animals from each dose group were shielded. At approximately monthly intervals from 2 to 10 months after irradiation the hematocrit, plasma urea nitrogen (PUN), and 51Cr-EDTA clearance were measured. During the study 20 thorax-shielded and 19 thorax-irradiated animals died. All rats whose thoraxes received 25 Gy irradiation and three out of seven rats whose thoraxes received 20 Gy died 1 to 3 months postirradiation with massive pleural fluid accumulation. Shielding the thoraxes prevented this mode of death at these doses. Kidney injury was judged to be the primary cause of death of all thorax-shielded animals and 15- and 20-Gy thorax-irradiated animals. Animals with kidney damage had elevated PUN and reduced 51Cr-EDTA clearance and hematocrits. The relative merits of each of these end points in assessing radiation-induced kidney injury after total-body exposure are discussed

  1. Low-dose irradiation affects expression of inflammatory markers in the heart of ApoE -/- mice.

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    Daniel Mathias

    Full Text Available Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min or high dose rate (150 mGy/min. The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45 and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025-0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM at 0.025-2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05-2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen and decreases (sICAM, sVCAM, sE-selectin of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and

  2. Technical modifications in hyperfractionated total body irradiation for T-lymphocyte deplete bone marrow transplant

    International Nuclear Information System (INIS)

    The Medical College of Wisconsin implemented a major bone marrow transplant (BMT) program in July 1985. The type of transplants to be focused on were allogeneic T-lymphocyte deplete. Total body irradiation (TBI) was initially patterned after the Memorial method. Patients received total body irradiation in a sitting position at a dose rate of 20-25 cGy/minute with 50% attenuation lung blocks used both anterior/posterior and posterior/anterior. Electron boosting was utilized for the ribs beneath the lung blocks. Occasionally, lower extremity boosting was required because of the sitting position. A dose of 14 Gy was chosen since T-lymphocyte deplete bone marrow transplant data suggest the need for higher total doses to consistently obtain engraftment. This dose was given in 3 equal daily fractions over 3 days following conditioning chemotherapy. Six of 11 patients treated in this manner developed lethal pulmonary events. In response to the pulmonary toxicity, partial lung shielding was increased to 60% attenuation. In the next 107 patients receiving this program of total body irradiation there was a reduced incidence of fatal pulmonary events (10 cases of fatal idiopathic interstitial pneumonitis and 12 cases of fatal pulmonary infections) after a median follow-up of 9 months. This was an obvious improvement over the initial group. A significant level of hepato-renal toxicity was also observed with 14 Gy total body irradiation when no liver or kidney blocking was used. Of the first 20 patients treated, three cases of fatal veno-occlusive disease resulted. Subsequently, a 10% attenuation right sided liver block was added. Five of 98 patients treated with this block have developed fatal hepatic dysfunction, (median follow-up of 7.2 months)

  3. An Acute Transverse Myelitis Attack after Total Body Irradiation: A Rare Case

    OpenAIRE

    Ali Unal; Bulent Eser; Mustafa Cetin; Cigdem Pala; Serife Cingoz; Celalettin Eroglu; Serdar Sivgin; Leylagul Kaynar; Afra Yildirim; Muzaffer Keklik

    2013-01-01

    Total body irradiation (TBI) combined with chemotherapy is widely used as a pretreatment regimen of bone marrow transplantation (BMT) in hematologic disorders. Late complications related to TBI as part of the conditioning regimen for hematopoietic stem cell transplantation have been revealed. Acute transverse myelitis (ATM) is a neurological syndrome characterized by disorder of motor, sensorial, and autonomic nerves, and tracts at medulla spinalis, which is resulted from involvement of spina...

  4. CALHM1 Deletion in Mice Affects Glossopharyngeal Taste Responses, Food Intake, Body Weight, and Life Span.

    Science.gov (United States)

    Hellekant, Göran; Schmolling, Jared; Marambaud, Philippe; Rose-Hellekant, Teresa A

    2015-07-01

    Stimulation of Type II taste receptor cells (TRCs) with T1R taste receptors causes sweet or umami taste, whereas T2Rs elicit bitter taste. Type II TRCs contain the calcium channel, calcium homeostasis modulator protein 1 (CALHM1), which releases adenosine triphosphate (ATP) transmitter to taste fibers. We have previously demonstrated with chorda tympani nerve recordings and two-bottle preference (TBP) tests that mice with genetically deleted Calhm1 (knockout [KO]) have severely impaired perception of sweet, bitter, and umami compounds, whereas their sour and salty tasting ability is unaltered. Here, we present data from KO mice of effects on glossopharyngeal (NG) nerve responses, TBP, food intake, body weight, and life span. KO mice have no NG response to sweet and a suppressed response to bitter compared with control (wild-type [WT]) mice. KO mice showed some NG response to umami, suggesting that umami taste involves both CALHM1- and non-CALHM1-modulated signals. NG responses to sour and salty were not significantly different between KO and WT mice. Behavioral data conformed in general with the NG data. Adult KO mice consumed less food, weighed significantly less, and lived almost a year longer than WT mice. Taken together, these data demonstrate that sweet taste majorly influences food intake, body weight, and life span. PMID:25855639

  5. Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation

    International Nuclear Information System (INIS)

    One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30 had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients

  6. Immunizing effect of irradiated homogenate of schistosomal cercariae against bilharzial ultrastructural damage in mice intestinal epithelium

    International Nuclear Information System (INIS)

    The present study is a parasitological and electron microscopical investigation on the immunizing effect of normal and gamma irradiated homogenate cercariae of Schistosoma Mansoni against Bilharzial complications in the fine structure of the intestinal epithelium of mice. A group of mice was exposed, through tail immersion to live wild cercariae and was used as a control, (1st group), whereas the two other groups were injected with either unirradiated (400 Gy) (2nd group) or irradiated homogenate (3rd group) of schistosoma Mansoni cercariae and challenged with wild cercariae. All group were sacrificed 6 weeks post infection and the intestinal tissues were examined by the electron microscope. The Ist group showed considerable alterations in the different organelles of the cells. Abnormalities in epithelial cells appeared in goblet cells being deformed, shorter and adhering to microvilli, with degenerative cytoplasm and nuclei. In 2nd group, the intestinal epithelial cells were injured showing dark goblet cells. swollen mitochondria whereas microvilli and nuclei appeared normal. The 3rd group displayed epithelial cells with a relatively normal ultrastructure

  7. Chloroquine Engages the Immune System to Eradicate Irradiated Breast Tumors in Mice

    International Nuclear Information System (INIS)

    Purpose: This study used chloroquine to direct radiation-induced tumor cell death pathways to harness the antitumor activity of the immune system. Methods and Materials: Chloroquine given immediately after tumor irradiation increased the cure rate of MCaK breast cancer in C3H mice. Chloroquine blocked radiation-induced autophagy and drove MCaK cells into a more rapid apoptotic and more immunogenic form of cell death. Results: Chloroquine treatment made irradiated tumor vaccines superior at inducing strong interferon gamma-associated immune responses in vivo and protecting mice from further tumor challenge. In vitro, chloroquine slowed antigen uptake and degradation by dendritic cells, although T-cell stimulation was unaffected. Conclusions: This study illustrates a novel approach to improve the efficacy of breast cancer radiation therapy by blocking endosomal pathways, which enhances radiation-induced cell death within the field and drives antitumor immunity to assist therapeutic cure. The study illuminates and merges seemingly disparate concepts regarding the importance of autophagy in cancer therapy

  8. Chloroquine Engages the Immune System to Eradicate Irradiated Breast Tumors in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Ratikan, Josephine Anna [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Sayre, James William [Public Health Biostatistics/Radiology at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, California (United States); Schaue, Dörthe, E-mail: dschaue@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

    2013-11-15

    Purpose: This study used chloroquine to direct radiation-induced tumor cell death pathways to harness the antitumor activity of the immune system. Methods and Materials: Chloroquine given immediately after tumor irradiation increased the cure rate of MCaK breast cancer in C3H mice. Chloroquine blocked radiation-induced autophagy and drove MCaK cells into a more rapid apoptotic and more immunogenic form of cell death. Results: Chloroquine treatment made irradiated tumor vaccines superior at inducing strong interferon gamma-associated immune responses in vivo and protecting mice from further tumor challenge. In vitro, chloroquine slowed antigen uptake and degradation by dendritic cells, although T-cell stimulation was unaffected. Conclusions: This study illustrates a novel approach to improve the efficacy of breast cancer radiation therapy by blocking endosomal pathways, which enhances radiation-induced cell death within the field and drives antitumor immunity to assist therapeutic cure. The study illuminates and merges seemingly disparate concepts regarding the importance of autophagy in cancer therapy.

  9. Prenatal irradiation and spatial memory in mice: investigation of dose-response relationship

    Energy Technology Data Exchange (ETDEWEB)

    Sienkiewicz, Z.J.; Haylock, R.G.E.; Saunders, R.D. (National Radiological Protection Board, Chilton (United Kingdom))

    1994-05-01

    Pregnant CD1 mice were exposed on gestational day 18 to 250 kV X-rays at 0.1, 0.25, 0.35 and 0.5 Gy. The performances of 10 adult male offspring from each exposure condition were investigated on a spatial discrimination learning task in a radial arm maze. An impairment in the performance of this task was found which showed a correlation with dose. Compared with sham exposed control mice, performance was not significantly affected with irradiation at 0.1 Gy and was slightly but non-significantly reduced at 0.25 Gy. Irradiation at 0.35 Gy caused a significant impairment in performance, and exposure at 0.5 Gy resulted in a still larger impairment. The overall association between dose and behavioural impairment was best described by a linear relationship without a threshold, although at doses lower than about 0.25 Gy any impairment would appear to be too small to be detectable. (Author).

  10. Gamma residual radioactivity measurements on rats and mice irradiated in the thermal column of a TRIGA Mark II reactor for BNCT.

    Science.gov (United States)

    Protti, Nicoletta; Manera, Sergio; Prata, Michele; Alloni, Daniele; Ballarini, Francesca; di Tigliole, Andrea Borio; Bortolussi, Silva; Bruschi, Piero; Cagnazzo, Marcella; Garioni, Maria; Postuma, Ian; Reversi, Luca; Salvini, Andrea; Altieri, Saverio

    2014-12-01

    The current Boron Neutron Capture Therapy (BNCT) experiments performed at the University of Pavia, Italy, are focusing on the in vivo irradiations of small animals (rats and mice) in order to evaluate the effectiveness of BNCT in the treatment of diffused lung tumors. After the irradiation, the animals are manipulated, which requires an evaluation of the residual radioactivity induced by neutron activation and the relative radiological risk assessment to guarantee the radiation protection of the workers. The induced activity in the irradiated animals was measured by high-resolution open geometry gamma spectroscopy and compared with values obtained by Monte Carlo simulation. After an irradiation time of 15 min in a position where the in-air thermal flux is about 1.2 × 10(10) cm(-2) s(-1), the specific activity induced in the body of the animal is mainly due to 24Na, 38Cl, 42K, 56Mn, 27Mg and 49Ca; it is approximately 540 Bq g(-1) in the rat and around 2,050 Bq g(-1) in the mouse. During the irradiation, the animal body (except the lung region) is housed in a 95% enriched 6Li shield; the primary radioisotopes produced inside the shield by the neutron irradiation are 3H by the 6Li capture reaction and 18F by the reaction sequence 6Li(n,α)3H → 16O(t,n)18F. The specific activities of these products are 3.3 kBq g(-1) and 880 Bq g(-1), respectively. PMID:25353239

  11. Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X-Irradiation.

    Science.gov (United States)

    Farese, Ann M; Hankey, Kim G; Cohen, Melanie Veirs; MacVittie, Thomas J

    2015-11-01

    Recovery from severe immunosuppression requires hematopoietic stem cell reconstitution and effective thymopoiesis to restore a functional immune cell repertoire. Herein, a model of immune cell reconstitution consequent to potentially lethal doses of irradiation is described, which may be valuable in evaluating potential medical countermeasures. Male rhesus macaques were total body irradiated by exposure to 6.00 Gy 250 kVp x-radiation (midline tissue dose, 0.13 Gy min), resulting in an approximate LD10/60 (n = 5/59). Animals received medical management, and hematopoietic and immune cell recovery was assessed (n ≤ 14) through 370 d post exposure. A subset of animals (n ≤ 8) was examined through 700 d. Myeloid recovery was assessed by neutrophil and platelet-related parameters. Lymphoid recovery was assessed by the absolute lymphocyte count and FACS-based phenotyping of B- and T-cell subsets. Recent thymic emigrants were identified by T cell receptor excision circle quantification. Severe neutropenia, lymphopenia, and thrombocytopenia resolved within 30 d. Total CD3+ cells μL required 60 d to reach values 60% of normal, followed by subsequent slow recovery to approximately normal by 180 d post irradiation. Recovery of CD3+4+ and CD3+8+ cell memory and naïve subsets were markedly different. Memory populations were ≥ 100% of normal by day 60, whereas naïve populations were only 57% normal at 180 d and never fully recovered to baseline post irradiation. Total (CD20+) B cells μL were within normal levels by 77 d post exposure. This animal model elucidates the variable T- and B-cell subset recovery kinetics after a potentially lethal dose of total-body irradiation that are dependent on marrow-derived stem and progenitor cell recovery, peripheral homeostatic expansion, and thymopoiesis.

  12. Dominant cataract mutations induced by γ-irradiation of male mice

    International Nuclear Information System (INIS)

    To improve the knowledge of the phenotypic damage caused by mutational events occurring in the first generation the authors initiated an experiment to study the induction of radiation-induced hereditary cataracts. To determine the frequency of dominant mutations affecting the lens, the authors examine the offspring of irradiated and control (101xC3H)F1 hybrid male mice which had been mated to untreated females. The observation of the induction of specific-locus mutations served as a positive control of the effectiveness of the exposure. The males of the irradiated group were exposed at the age of 11 weeks to 455 R+455 R 137Cs γ-rays (55 R/min) with a 24-h fractionation interval. The eyes of the F1 offspring, as well as of the animals of the parental generation, were examined biomicroscopically. The F1 offspring were 3 weeks old at the time of examination. The frequency of specific-locus mutations (9 mutations in 5231 offspring) derived from irradiated spermatogonia was 2.7x10-7 mutations/locus/R in this experiment, which is in accord with data discussed elsewhere. (Auth.)

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

    International Nuclear Information System (INIS)

    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.)

  14. Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice

    International Nuclear Information System (INIS)

    We studied the effects of intraperitoneal injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) according to various administration schedules on the recovery of spleen colony-forming units (CFU-S) and peripheral blood counts, and on the survival of irradiated mice. The sooner and more frequently the mice were injected with rhG-CSF after irradiation, the more enhanced the recovery of CFU-S in bone marrow was obtained on day 7. Twice-daily injections of rhG-CSF from day 0 to day 2 significantly enhanced the recovery of platelets and hematocrit, but two injections of rhG-CSF on only day 0 did not. Twice-daily injections of rhG-CSF from day 0 to day 6 enhanced the recovery of platelets more effectively than twice-daily injections of rhG-CSF from day 1 to day 7, and increased the survival of irradiated mice more effectively than any other examined administration schedules. Twice-daily injections of rhG-CSF from day 0 to day 6 were significantly effective in enhancing the survival of mice irradiated with 8.5-, 9.0-, and 9.5-Gy x-rays, although not effective after irradiation of 10.5-Gy x-rays

  15. Chromosome aberrations and micronucleus in continuously irradiated mice for a low dose rate of {sup 137}Cs {gamma}-rays

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Jun; Yanai, Takanori; Shirata, Katsutoshi; Tanaka, Kimio; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)

    2002-07-01

    Delayed chromosomal instability is developed by radiation after several cell divisions in cultured rodent and human cells. The genetic instability might be related to cancer development and it has been mainly found in cultured rodent and human cells irradiated at high dose rate. It has not been well studied whether the genetic instability is induced by prolonged irradiation with low dose rate in vivo or not. Mice irradiated with 20 mGy/day for 5-8 Gy were analyzed by FISH to estimate the chromosome aberration rate and micronucleus incidence in spleen and bone marrow cells. Spleen cells in mice exposed to 8 Gy have higher incidence of monosomy and trisomy than non-exposed mice. The number of cells with 2-4 micronuclei in 10,000 scored spleen cells is also higher in 5-8 Gy exposed mice. These numerical chromosome aberrations are not induced directly by radiation exposure. These results indicate that prolonged {sup 137}Cs {gamma} ray-irradiation with low dose rates of 20 mGy/day induces delayed chromosome instability in mice. (author)

  16. Dose estimation in B16 tumour bearing mice for future irradiation in the thermal column of the TRIGA reactor after B/Gd/LDL adduct infusion.

    Science.gov (United States)

    Protti, N; Ballarini, F; Bortolussi, S; Bruschi, P; Stella, S; Geninatti, S; Alberti, D; Aime, S; Altieri, S

    2011-12-01

    To test the efficacy of a new (10)B-vector compound, the B/Gd/LDL adduct synthesised at Torino University, in vivo irradiations of murine tumours are in progress at the TRIGA Mark II reactor of the Pavia University. A localised B16 melanoma tumour is generated in C57BL/6 mice and subsequently infused with the adduct. During the irradiation, the mouse will be put in a shield to protect the whole body except the tumour in the back-neck area. To optimise the treatment set-up, MCNP simulations were performed. A very simplified mouse model was built using MCNP geometry capabilities, as well as the geometry of the shield made of 99% (10)B enriched boric acid. A hole in the shield is foreseen in correspondence of the back-neck region. Many configurations of the shield were tested in terms of neutron flux, dose distribution and mean induced activity in the tumour region and in the radiosensitive organs of the mouse. In the final set-up, up to five mice can be treated simultaneously in the reactor thermal column and the neutron fluence in the tumour region for 10 min of irradiation is of about 5×10(12) cm(-2). PMID:21459587

  17. Influence of radioprotectors on total body weight evolution and on oxygen consumption in lethal dose irradiated animals. (Preliminary study)

    International Nuclear Information System (INIS)

    Comparison of total body weight evolution and oxygen consumption in lethal dose irradiated animals, protected by various well known radioprotective substances, isolated or in mixture, with evolution and consumption of non protected animals irradiated at the same dose and with these of check animals

  18. Short-term endocrine consequences of total body irradiation and bone marrow transplantation in children treated for leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Ryalls, M.; Tait, D.M.; Meller, S.T. (Royal Marsden Hospital, Sutton (United Kingdom)); Spoudeas, H.A.; Hindmarsh, P.C.; Brook, C.G.D. (Middlesex Hospital, London (United Kingdom)); Matthews, D.R. (Radcliffe Infirmary, Oxford (United Kingdom). Diabetes Research Lab.)

    1993-02-01

    We studied 24-h hormone profiles and hormonal responses to insulin-induced hypoglycaemia prospectively in 23 children of similar age and pubertal stage, nine of whom had received prior cranial irradiation and fourteen of whom had not before and 6-12 months after total body irradiation (TBI) for bone marrow transportation in leukaemia. (Author).

  19. Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates

    NARCIS (Netherlands)

    Opländer, C.; Volkmar, C.M.; Paunel-Görgülü, A.; van Faassen, E.E.H.; Heiss, C.

    2009-01-01

    Rationale: Human skin contains photolabile nitric oxide derivates like nitrite and S-nitroso thiols, which after UVA irradiation, decompose and lead to the formation of vasoactive NO. Objective: Here, we investigated whether whole body UVA irradiation influences the blood pressure of healthy volunte

  20. Rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Afifi, M.S.H.

    1985-01-01

    The objective of this study was to investigate the mechanisms of rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice, in part by investigating the hypothesis that two or more cell types are involved in recognition and rejection of hemopoietic cells. Interferon (IFN) was used as a tool for investigating such mechanisms. IFN alpha/beta stimulated the rejection of normal hemopoietic marrow cell grafts in Fl hybrid and in allogeneic host mice but did not affect the growth of cells in syngeneic mice. IFN alpha/beta was effective in hosts pretreated with silica but not in hosts pretreated with cyclophosphamide (Cy) or with anti-asialoGMI serum. Rabbit anti-IFN alpha/beta, but not anti-IFN gamma, serum inhibited genetic resistance to bone marrow cells. These results indicated that IFN alpha/beta was acting indirectly during the rejection of normal hemopoietic cells. It is proposed that four events occur in succession: a host cell recognizes the hemopoietic histocompatibility (Hh) antigens expressed on the surface of incompatible stem cells; this recognition leads to secretion of IFN; IFN activates natural killer (NK) cells; NK cells lyse donor stem cells. Silica interrupts one or both of the first two events. i.e., recognition and/or interrupts one or both of the first two events, i.e. recognition and/or IGN secretion.

  1. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    International Nuclear Information System (INIS)

    Mitochondrial DNA (mtDNA) alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD), are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI) treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL) patients as well as to take them as predictors for radiation toxicity. Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively). Extracted DNA was analyzed by real-time PCR method. Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048). Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. mtDNA and CD content may be considered as predictive factors to radiation toxicity

  2. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    Directory of Open Access Journals (Sweden)

    Ji Fuyun

    2011-10-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD, are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL patients as well as to take them as predictors for radiation toxicity. Methods Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively. Extracted DNA was analyzed by real-time PCR method. Results Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048. Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. Conclusions mtDNA and CD content may be considered as predictive factors to radiation toxicity.

  3. Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

    1996-12-01

    We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

  4. The influence of recombinant granulocytic and macrophagic colony-stimulating factor on halmopoiesis recovery and survival rate of irradiated mice

    International Nuclear Information System (INIS)

    A human recombinant granulocytic-and-macrophagic colony-stimulating factor (rGM-CSF) administered repeatedly to irradiated (10 Gy) CBA mice increased CFUs and CFUGM content, the number of bone marrow granulocytes and erythronormoblasts, and spleen and peripharal blood cellularity. The survival rate of exposed (9.7 Gy) mice repeatedly injected with rGM-CSF increased from 25% (control) to 90%

  5. Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training

    Science.gov (United States)

    Raber, Jacob; Weber, Sydney J.; Kronenberg, Amy; Turker, Mitchell S.

    2016-06-01

    The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to 28Si ions (263 MeV/n, LET = 78keV / μ m ; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to 48Ti ions (1 GeV/n, LET = 107keV / μ m ; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used 40Ca ion beams (942 MeV/n, LET = 90keV / μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. 40Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to 40Ca ions had sex-dependent effects on response to shock. 40Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, 40Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus 40Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of 40Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions.

  6. Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training.

    Science.gov (United States)

    Raber, Jacob; Weber, Sydney J; Kronenberg, Amy; Turker, Mitchell S

    2016-06-01

    The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to (28)Si ions (263 MeV/n, LET=78keV/μm; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to (48)Ti ions (1 GeV/n, LET=107keV/μm; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used (40)Ca ion beams (942 MeV/n, LET=90keV/μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. (40)Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to (40)Ca ions had sex-dependent effects on response to shock. (40)Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, (40)Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus (40)Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of (40)Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions. PMID:27345201

  7. Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Ricard, Clement; Fernandez, Manuel [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Requardt, Herwig [European Synchrotron Radiation Facility, Grenoble (France); Wion, Didier [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France); Vial, Jean-Claude [Université Joseph Fourier, Grenoble (France); Laboratoire Interdisciplinaire de Physique, St Martin d’Hères (France); Segebarth, Christoph; Sanden, Boudewijn van der, E-mail: boudewijn.vandersanden@ujf-grenoble.fr [Grenoble Institut des Neurosciences, Grenoble (France); Université Joseph Fourier, Grenoble (France)

    2013-09-01

    Synchrotron photoactivation therapy of cisplatin relies on a synergistic effect of synchrotron X-rays and platinum and leads to tumor-cell-killing effects and reduction of the tumor blood perfusion. Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.

  8. Study of uptake and endocytosis of gamma rays-irradiated crotoxin by mice peritoneal macrophages

    International Nuclear Information System (INIS)

    The purpose was to investigate the uptake and endocytosis of 2000 Gy 60Co irradiated crotoxin through mouse peritoneal macrophages, correlating with native one and another non related protein, the ovalbumin. Native (CTXN) or 2000 Gy 60 Co γ-rays (dose rate 540 Gy/hour) irradiated crotoxin (CTXI) or ovalbumin processed of same manner (OVAN - OVAI) were offered to mouse peritoneal macrophages and their uptake was evaluated by immunohistochemistry and quantitative in situ ELISA. The involvement of scavenger receptors (ScvR) was evaluated by using blockers drugs (Probuco-PBC or Dextran Sulfate - SD) or with nonspecific blocking using fetal calf serum (FBS). The morphology and viability of macrophages were preserved during the experiments. CTXI showed irradiation-induced aggregates and formation of oxidative changing were observed on this protein after gamma rays treatment. By immunohistochemistry we could observe heavy stained phagocytic vacuole on macrophages incubated with CTXI, as compared with CTXN. Quantitatively by in situ ELISA, the sema pattern was observed, displaying a 2-fold CTXI incorporation. In presence of PBC or SD we could find a significant decrease of CTXI uptake but not of CTXN. However the CTXN uptake was depressed by FBS, not observed with CTXI. OVA, after gamma rays treatment, underwent a high degradation suffering a potent incorporation and metabolism by macrophages, with a major uptake of OVAI in longer incubation (120 minutes). Gamma rays (60 Co) produced oxidative changes on CTX molecule, leading to a uptake by ScvR-mice peritoneal macrophages, suggesting that the relation antigen-presenting cells and gamma rays-modified proteins are responsible for the better immune response presented by irradiated antigens. (author)

  9. Variable maturation and oviposition by female Schistosoma japonicum in mice: the effects of irradiation of the host prior to infection

    Energy Technology Data Exchange (ETDEWEB)

    Cheever, A.W.; Duvall, R.H.

    1987-11-01

    The maturation of female Schistosoma japonicum was found to vary greatly within each of two Philippine strains of this parasite and some females did not contain uterine eggs 7 to 15 weeks after infection while others contained numerous eggs before the fifth week of infection. It was found that female worms containing less than 20 uterine eggs contributed little to the accumulation of eggs in the tissues of infected mice. Such worms also generally appeared to be immature. The variable rate of maturation of worms is likely to have profound effects on the immune reactions of mice as well as on the pathologic response to infection. Systematic delay in oviposition was serendipitously found in worms from mice which had been irradiated for other purposes prior to exposure to S. japonicum, and from the fourth to the sixth week after infection egg production by worms in irradiated mice lagged well behind that in intact mice. Seven to 10 weeks after infection these worms were laying normal numbers of eggs, as judged by egg passage per worm pair in the feces and the accumulation of eggs in the tissues. S. mansoni developed normally in irradiated mice.

  10. Early biochemical changes in rat lungs following whole-body exposure to external ionizing irradiation

    International Nuclear Information System (INIS)

    Some biochemical and cytological parameters were followed up in broncho-alveolar lavage fluid and in lung homogenate from albino rats, exposed to single whole-body ionizing irradiation with 4, 8, and 15 Gy. Infectious complications were ruled out by addition of 2 g/l tetracycline in the drinking water before and after irradiation. Dose-dependent increase in the number of cells and lactatedehydrogenase and acid phosphate activities in the broncho-alveolar lavage fluid was observed on the first day and a tendency toward decrease in the period between the 5th and 15th day. These parameters are of the definite value as early diagnostic tests in radiation lung injury. These is evidence of inhibition of the antioxidative protective system in this organ - a dose-dependent decrease in the enzymatic activities of superoxyde dismutase and glucose-6-phosphatedehydrogenase and in the content of nonprotein sulfhydryl groups in the pulmonary homogenate

  11. Meningioma: The role of a foreign body and irradiation in tumor formation

    Energy Technology Data Exchange (ETDEWEB)

    Saleh, J.; Silberstein, H.J.; Salner, A.L.; Uphoff, D.F. (Hartford Hospital, CT (USA))

    1991-07-01

    A case of meningioma is reported. At the age of 18 years, the patient had undergone insertion of a Torkildsen shunt through a posteroparietal burr hole for obstructive hydrocephalus secondary to a tumor of the pineal region, of which no biopsy had been made. After the hydrocephalus was relieved, he underwent irradiation of the tumor. Thirty years later, he was treated for an intracranial meningioma wrapped around the shunt. The tumor followed the shunt in all of its intracranial course. Microscopy disclosed pieces of the shunt tube within the meningioma. The role of a foreign body and irradiation in the induction of meningiomas is discussed, and a comprehensive review of the literature is presented. 47 references.

  12. Dehydroepiandrosterone Supplementation Combined with Whole-Body Vibration Training Affects Testosterone Level and Body Composition in Mice

    Science.gov (United States)

    Chen, Wen-Chyuan; Chen, Yi-Ming; Huang, Chi-Chang; Tzeng, Yen-Dun

    2016-01-01

    Dehydroepiandrosterone (DHEA), the most abundant sex steroid, is primarily secreted by the adrenal gland and a precursor hormone used by athletes for performance enhancement. Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults. However, the potential effects of DHEA supplementation combined with WBV training on to body composition, exercise performance, and hormone regulation are currently unclear. The objective of the study is to investigate the effects of DHEA supplementation combined with WBV training on body composition, exercise performance, and physical fatigue-related biochemical responses and testosterone content in young-adult C57BL/6 mice. In this study, male C57BL/6 mice were divided into four groups (n = 8 per group) for 6-weeks treatment: sedentary controls with vehicle (SC), DHEA supplementation (DHEA, 10.2 mg/kg), WBV training (WBV; 5.6 Hz, 2 mm, 0.13 g), and WBV training with DHEA supplementation (WBV+DHEA; WBV: 5.6 Hz, 2 mm, 0.13 g and DHEA: 10.2 mg/kg). Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time, as well as changes in body composition and anti-fatigue levels of serum lactate, ammonia, glucose, creatine kinase (CK), and blood urea nitrogen (BUN) after a 15-min swimming exercise. In addition, the biochemical parameters and the testosterone content were measured at the end of the experiment. Six-week DHEA supplementation alone significantly increased mice body weight (BW), muscle weight, testosterone level, and glycogen contents (liver and muscle) when compared with SC group. DHEA supplementation alone had no negative impact on all tissue and biochemical profiles, but could not improve exercise performance. However, WBV+DHEA supplementation also significantly decreased BW, testosterone level and glycogen content of liver, as well as serum

  13. Biodistribution of gold nanoparticles synthesized by γ-irradiation after intravenous administration in mice

    Science.gov (United States)

    Luan Le, Quang; Phuong Linh Do, Thi; Phuong Uyen Nguyen, Huynh; Phu Dang, Van; Hien Nguyen, Quoc

    2014-06-01

    In the present research work we evaluate the in vivo distribution of gold nanoparticles (AuNPs) at different time durations after intravenous administration in mice. AuNPs with size of about 20 nm and concentration of 1 mM were synthesized by gamma irradiation method using 0.5% alginate as a stabilizer. AuNPs were characterized by UV-Vis spectrum and transmission electron microscope (TEM) image. The as-synthesized AuNPs solution was centrifuged to concentrate to 2 mg AuNPs/1 ml solution. Intravenous administration of AuNPs in mice was done at the tail with 1 mg AuNPs (0.5 ml). After 1, 3, 6 and 12 h of injection, blood was collected, mice were sacrificed and various tissues/organs were removed. The blood haematology and serum clinical chemistry indexes of mice intravenously injected with AuNPs were not significantly different compared to those of the control ones. In addition, gold content in the samples was quantitatively determined by k0-neutron activation analysis (k0-NAA) at nuclear research reactor, Da Lat Vietnam. Results showed that after 1 h of administration, AuNPs were mainly accumulated in blood (41.56%), in liver (51.60.%), in lung (6.16%) and in kidney (0.53%). After that the content of AuNPs in blood was decreased to nearly normal at 6 h while the content of AuNPs in liver, lung and kidney was accumulatively increased. After 6 h of administration AuNPs were mainly accumulated in organs like liver (76.33%), lung (11.86%) and kidney (2.23%). Thus, the obtained results are practically useful for using AuNPs as x-ray contrast agent, especially for blood and liver.

  14. Experimental foreign body infections in mice challenged with slime-producing Staphylococcus epidermidis.

    OpenAIRE

    Christensen, G D; Simpson, W A; Bisno, A L; Beachey, E H

    1983-01-01

    The virulence of two previously described Staphylococcus epidermidis strains was examined in an experimental model of foreign body infection in mice. Animals challenged with the slime-producing strain developed three times as many infections as animals challenged with the strain that did not produce slime (P less than 0.001). Bacterial isolates recovered from the infected sites retained the characteristics of the inoculated strain. Animals without foreign bodies but challenged in a similar ma...

  15. Feasibility of intrafraction whole-body motion tracking for total marrow irradiation

    Science.gov (United States)

    Sharma, Manju; Santos, Troy Dos; Papanikolopoulos, Nikolaos P.; Hui, Susanta Kumar

    2011-05-01

    With image-guided tomotherapy, highly targeted total marrow irradiation (TMI) has become a feasible alternative to conventional total body irradiation. The uncertainties in patient localization and intrafraction motion of the whole body during hour-long TMI treatment may pose a risk to the safety and accuracy of targeted radiation treatment. The feasibility of near-infrared markers and optical tracking system (OTS) is accessed along with a megavoltage scanning system of tomotherapy. Three near-infrared markers placed on the face of a rando phantom are used to evaluate the capability of OTS in measuring changes in the markers' positions as the rando is moved in the translational direction. The OTS is also employed to determine breathing motion related changes in the position of 16 markers placed on the chest surface of human volunteers. The maximum uncertainty in locating marker position with the OTS is 1.5 mm. In the case of normal and deep breathing motion, the maximum marker position change is observed in anterior-posterior direction with the respective values of 4 and 12 mm. The OTS is able to measure surface changes due to breathing motion. The OTS may be optimized to monitor whole body motion during TMI to increase the accuracy of treatment delivery and reduce the radiation dose to the lungs.

  16. Changes in plasma apolipoproteins following whole-body irradiation in rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Feliste, R. (INSERM, Toulouse, France); Dousset, N.; Carton, M.; Douste-Blazy, L.

    1981-09-01

    Male New Zealand white rabbits were whole-body-irradiated with a linear electron accelerator at 800 rad (LD/sub 50/ in 30 days). This treatment induced a pronounced hypertriglyceridemia. The apoprotein composition of very low density lipoproteins (VLDL, d < 1.006 g/ml) and high-density lipoproteins (HDL, d = 1.063 - 1.21 g/ml) from irradiated rabbits was studied and compared to those of normal rabbits. Significant changes were observed in both very low density apolipoproteins and high-density apolipoproteins. (1) In the VLDL fraction from irradiated rabbits, there appeared in high proportion two apolipoproteins with electrophoretic mobility in urea/polyacrylamide gels similar to apoA-I and A-II but which were distinctly different in their apparent molecular weights, their isoelectric points, and their amino acid composition from these latter proteins. These proteins had apparent molecular weights of about 10,000. They focused into three bands with pI values of 6.1, 6.4, and 6.6. Their amino acid composition was characterized by a very low content of threonine and serine and a high content of aspartic acid, glycine, alanine, and arginine. In addition, a marked increase of an apolipoprotein with an apparent molecular weight of about 43,000 and with an amino acid composition similar to rat apoA-IV was also observed in rabbit VLDL after irradiation. Apolipoprotein C constituents with slowmobility decreased significantly. (2) The irradiated rabbit HDL apolipoproteins showed an important increase of the proteins with molecular weight 10,000 and isoelectric points 6.1, 6.4, and 6.6. Compared to normal rabbit HDL apolipoproteins, a significant decrease of apoA-IV occurred. These modifications were also observed with lower radiation doses (200 and 400 rad).

  17. Lipid metabolism and body composition in Gclm(−/−) mice

    International Nuclear Information System (INIS)

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate–cysteine ligase modifier subunit gene (Gclm(−/−)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(−/−) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(−/−) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(−/−) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(−/−) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(−/−) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(−/−) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(−/−) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: ► A high fat diet does not produce body weight and fat gain in Gclm(−/−) mice. ► A high fat diet does not induce steatosis or insulin resistance in Gclm(−/−) mice. ► Gclm(−/−) mice have high basal metabolism and mitochondrial oxygen consumption.

  18. An experimental model of acute encephalopathy after total body irradiation in the rat: effect of Ginkgo biloba extract (EGb 761)

    International Nuclear Information System (INIS)

    To define the therapeutic effect of Ginkgo biloba extract (EGb 761) in an experimental model of acute encephalopathy following total body irradiation in rats. Ninety four-month-old rats received 4.5 Gy total body irradiation (TBI) at day 1 while 15 rats received sham irradiation. A behavioural study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed test, was performed after irradiation. Orally treatment was started one day (study A) or twenty two days (study B) after irradiation and repeated daily for twelve days. In the irradiated group, three subgroups were defined according to the treatment received: EGb 761 (50 mg/kg), EGb 761 (100 mg/kg), water. This work comprised two consecutive studies. In study A (45 rats) the one-way avoidance test was administered daily from day 7 to day 14. In study B (45 rats) the behavioural test was performed from day 28 to day 35. Study A (three groups of 15 rats): following TBI, irradiated rats treated with water demonstrated a significant delay in a learning the one-way avoidance test in comparison with sham-irradiated rats (P < 0.0002) or irradiated rats treated with EGb 761 (50 mg/kg; P < 0.007) or EGb 761 (100 mg/kg; P < 0.0002). The irradiated rats, treated with EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. Study B (three groups of 15 rats): the irradiated rats, treated with water of EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. (authors)

  19. Locomotor behavior in mice following exposure to fission-neutron irradiation and trauma

    International Nuclear Information System (INIS)

    Locomotor activity, body weights, and food and water consumption were monitored in female mice for 35 d following a sublethal wound (W), burn (B), exposure to 3 Gray fission neutron radiation (R), or combination of these injuries: radiation-wound (RW) and radiation-burn (RB). Activity in groups W and RW was depressed immediately after injury, with recovery to control levels after 5 and 14 d, respectively. Mice that received radiation alone showed a biphasic response with decrements in activity on days 0-4 and 9-11. Groups B and RB exhibited depressed activity levels that differed significantly from control levels until day 17. Food intake was reduced for about 6 d in groups R, W, RW, and RB. Body weights decreased for 4 d in groups R, W, RW, and RB, but returned to control levels by the end of the experiment. Animals in group B did not show significant reduction in food intake or body weight. Water consumption was reduced for 5-6 d in groups R and RB and was increased in groups W, RW, and B. The data suggest that behavioral responses to fission-neutron radiation are exacerbated by tissue trauma

  20. Idiopathic interstitial pneumonia following bone marrow transplantation: the relationship with total body irradiation

    International Nuclear Information System (INIS)

    Interstitial pneumonia is a frequent and often fatal complication of allogenic bone marrow transplantation. Thirty to 40 percent of such cases are of unknown etiology and have been labelled as cases of idiopathic interstitial pneumonia. Idiopathic cases are more commonly associated with the use of total body irradiation; their occurrence appears to be independent of immunosupression or graft versus host disease. Evidence is presented from the literature suggesting that the development of idiopathic interstitial pneumonia is related to the absolute absorbed dose of radiation to lung. The similarity of idiopathic pneumonia to radiation pneumonitis seen in a different clinical setting is described

  1. An Acute Transverse Myelitis Attack after Total Body Irradiation: A Rare Case

    Directory of Open Access Journals (Sweden)

    Muzaffer Keklik

    2013-01-01

    Full Text Available Total body irradiation (TBI combined with chemotherapy is widely used as a pretreatment regimen of bone marrow transplantation (BMT in hematologic disorders. Late complications related to TBI as part of the conditioning regimen for hematopoietic stem cell transplantation have been revealed. Acute transverse myelitis (ATM is a neurological syndrome characterized by disorder of motor, sensorial, and autonomic nerves, and tracts at medulla spinalis, which is resulted from involvement of spinal cord. In this paper, we presented an ATM attack developed after TBI in a patient with acute lymphoblastic leukemia (ALL as it is a rarely seen case.

  2. Basal Cell Skin Cancer after Total-Body Irradiation and Hematopoietic Cell Transplantation

    OpenAIRE

    Schwartz, Jeffrey L.; Kopecky, Kenneth J.; Robert W. Mathes; Leisenring, Wendy M; Friedman, Debra L.; Deeg, H. Joachim

    2009-01-01

    Previous studies identified radiation therapy as a key modifier of basal cell carcinoma (BCC) risk in survivors of hematopoietic cell transplantation (HCT). In the present analysis, risk of BCC was analyzed in relation to age at transplant, attained age, race, total-body irradiation (TBI), and radiation fractionation in 6,306 patients who received HCT at ages 0–65 years after conditioning regimens with (n = 3870) or without (n = 2436) TBI, and who were followed from 100 days to 36.2 years aft...

  3. Total body irradiation with volumetric modulated arc therapy: Dosimetric data and first clinical experience

    International Nuclear Information System (INIS)

    To implement total body irradiation (TBI) using volumetric modulated arc therapy (VMAT). We applied the Varian RapidArc™ software to calculate and optimize the dose distribution. Emphasis was placed on applying a homogenous dose to the PTV and on reducing the dose to the lungs. From July 2013 to July 2014 seven patients with leukaemia were planned and treated with a VMAT-based TBI-technique with photon energy of 6 MV. The overall planning target volume (PTV), comprising the whole body, had to be split into 8 segments with a subsequent multi-isocentric planning. In a first step a dose optimization of each single segment was performed. In a second step all these elements were calculated in one overall dose-plan, considering particular constraints and weighting factors, to achieve the final total body dose distribution. The quality assurance comprised the verification of the irradiation plans via ArcCheck™ (Sun Nuclear), followed by in vivo dosimetry via dosimeters (MOSFETs) on the patient. The time requirements for treatment planning were high: contouring took 5–6 h, optimization and dose calculation 25–30 h and quality assurance 6–8 h. The couch-time per fraction was 2 h on day one, decreasing to around 1.5 h for the following fractions, including patient information, time for arc positioning, patient positioning verification, mounting of the MOSFETs and irradiation. The mean lung dose was decreased to at least 80 % of the planned total body dose and in the central parts to 50 %. In two cases we additionally pursued a dose reduction of 30 to 50 % in a pre-irradiated brain and in renal insufficiency. All high dose areas were outside the lungs and other OARs. The planned dose was in line with the measured dose via MOSFETs: in the axilla the mean difference between calculated and measured dose was 3.6 % (range 1.1–6.8 %), and for the wrist/hip-inguinal region it was 4.3 % (range 1.1–8.1 %). TBI with VMAT provides the benefit of satisfactory dose

  4. Comparison between combination chemotherapy and total body irradiation plus combination chemotherapy in non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Thirty-nine untreated patients with either lymphocytic or nodular mixed/nodular histiocytic non-Hodgkin's lymphoma, stage II-IV, were randomized to treatment with total body irradiation (TBI), 100 rads in 10 fractions over 12 days, plus combination chemotherapy with either cyclophosphamide, vincristine and prednisone (CVP) or cyclophosphamide, vincristine, procarbazine and prednisone (C-MOPP) or to treatment with combination chemotherapy (CVP or C-MOPP) alone. Remission rate and duration were comparable for both treatment groups; thus the use of both treatment modalities ab initio provides no therapeutic advantage

  5. Changes of proliferation kinetics after X-irradiation of a human malignant melanoma grown in nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Vindeløv, L L

    1984-01-01

    A human malignant melanoma grown in nude mice was exposed to single-dose X-irradiation and the effect on the proliferation kinetics was investigated by two methods. Flow cytometric DNA analysis was performed on tumour tissue obtained by sequential fine-needle aspirations after the treatment to mo......-related increasing proportion of radiation-inactivated tumour cells....

  6. Beta-carotene reduces body adiposity of mice via BCMO1.

    Directory of Open Access Journals (Sweden)

    Jaume Amengual

    Full Text Available Evidence from cell culture studies indicates that β-carotene-(BC-derived apocarotenoid signaling molecules can modulate the activities of nuclear receptors that regulate many aspects of adipocyte physiology. Two BC metabolizing enzymes, the BC-15,15'-oxygenase (Bcmo1 and the BC-9',10'-oxygenase (Bcdo2 are expressed in adipocytes. Bcmo1 catalyzes the conversion of BC into retinaldehyde and Bcdo2 into β-10'-apocarotenal and β-ionone. Here we analyzed the impact of BC on body adiposity of mice. To genetically dissect the roles of Bcmo1 and Bcdo2 in this process, we used wild-type and Bcmo1(-/- mice for this study. In wild-type mice, BC was converted into retinoids. In contrast, Bcmo1(-/- mice showed increased expression of Bcdo2 in adipocytes and β-10'-apocarotenol accumulated as the major BC derivative. In wild-type mice, BC significantly reduced body adiposity (by 28%, leptinemia and adipocyte size. Genome wide microarray analysis of inguinal white adipose tissue revealed a generalized decrease of mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ target genes. Consistently, the expression of this key transcription factor for lipogenesis was significantly reduced both on the mRNA and protein levels. Despite β-10'-apocarotenoid production, this effect of BC was absent in Bcmo1(-/- mice, demonstrating that it was dependent on the Bcmo1-mediated production of retinoids. Our study evidences an important role of BC for the control of body adiposity in mice and identifies Bcmo1 as critical molecular player for the regulation of PPARγ activity in adipocytes.

  7. Predicting changes of body weight, body fat, energy expenditure and metabolic fuel selection in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Juen Guo

    Full Text Available The mouse is an important model organism for investigating the molecular mechanisms of body weight regulation, but a quantitative understanding of mouse energy metabolism remains lacking. Therefore, we created a mathematical model of mouse energy metabolism to predict dynamic changes of body weight, body fat, energy expenditure, and metabolic fuel selection. Based on the principle of energy balance, we constructed ordinary differential equations representing the dynamics of body fat mass (FM and fat-free mass (FFM as a function of dietary intake and energy expenditure (EE. The EE model included the cost of tissue deposition, physical activity, diet-induced thermogenesis, and the influence of FM and FFM on metabolic rate. The model was calibrated using previously published data and validated by comparing its predictions to measurements in five groups of male C57/BL6 mice (N = 30 provided ad libitum access to either chow or high fat diets for varying time periods. The mathematical model accurately predicted the observed body weight and FM changes. Physical activity was predicted to decrease immediately upon switching from the chow to the high fat diet and the model coefficients relating EE to FM and FFM agreed with previous independent estimates. Metabolic fuel selection was predicted to depend on a complex interplay between diet composition, the degree of energy imbalance, and body composition. This is the first validated mathematical model of mouse energy metabolism and it provides a quantitative framework for investigating energy balance relationships in mouse models of obesity and diabetes.

  8. Ethanolic Extract of Taheebo Attenuates Increase in Body Weight and Fatty Liver in Mice Fed a High-Fat Diet

    OpenAIRE

    Won Hee Choi; Min Young Um; Jiyun Ahn; Chang Hwa Jung; Myung Kyu Park; Tae Youl Ha

    2014-01-01

    We evaluated whether intake of an ethanolic extract of Taheebo (TBE) from Tabebuia avellanedae protects against body weight increase and fat accumulation in mice with high-fat diet (HFD)-induced obesity. Four-week old male C57BL/6 mice were fed a HFD (25% fat, w/w) for 11 weeks. The diet of control (HFD) mice was supplemented with vehicle (0.5% sodium carboxymethyl cellulose by gavage); the diet of experimental (TBE) mice was supplemented with TBE (150 mg/kg body weight/day by gavage). Mice a...

  9. The behaviour of the endocrinological parameters cortisol, testosterone, growth hormone and prolactin after UVA and UVB whole-body irradiation

    International Nuclear Information System (INIS)

    With two groups, each with 8 healthy subjects UV whole-body irradiation was carried out with uniformly 30 J/cm2 UVA or respectively UVB at the level of the individual minimal erythema dose. Every subject received serial irradiations once a day for four days. The determination of the serum hormone level was accomplished by means of radioimmunoassays. The results show a weakly significant decline of cortisol 4 and 24 hours after 2 serial UVB irradiations. 3,5 and 7 days after the end of the irradiation series the cortisol values have increased, but by the seventh day statistically only weakly significant. With UVA irradiation there was also a weakly significant increase in cortisol levels three days after the end of the irradiation series. The serum levels of the other hormones showed no statistically significant changes. (orig./MG)

  10. Microbiota prevents cholesterol loss from the body by regulating host gene expression in mice.

    Science.gov (United States)

    Zhong, Chun-Yan; Sun, Wei-Wei; Ma, Yinyan; Zhu, Hongling; Yang, Pan; Wei, Hong; Zeng, Ben-Hua; Zhang, Qian; Liu, Yu; Li, Wen-Xia; Chen, Yixin; Yu, Liqing; Song, Zhi-Yuan

    2015-05-27

    We have previously observed that knockout of Niemann-Pick C1-Like 1 (NPC1L1), a cholesterol transporter essential for intestinal cholesterol absorption, reduces the output of dry stool in mice. As the food intake remains unaltered in NPC1L1-knockout (L1-KO) mice, we hypothesized that NPC1L1 deficiency may alter the gut microbiome to reduce stool output. Consistently, here we demonstrate that the phyla of fecal microbiota differ substantially between L1-KO mice and their wild-type controls. Germ-free (GF) mice have reduced stool output. Inhibition of NPC1L1 by its inhibitor ezetimibe reduces stool output in specific pathogen-free (SPF), but not GF mice. In addition, we show that GF versus SPF mice have reduced intestinal absorption and increased fecal excretion of cholesterol, particularly after treatment with ezetimibe. This negative balance of cholesterol in GF mice is associated with reduced plasma and hepatic cholesterol, and likely caused by reduced expression of NPC1L1 and increased expression of ABCG5 and ABCG8 in small intestine. Expression levels of other genes in intestine and liver largely reflect a state of cholesterol depletion and a decrease in intestinal sensing of bile acids. Altogether, our findings reveal a broad role of microbiota in regulating whole-body cholesterol homeostasis and its response to a cholesterol-lowering drug, ezetimibe.

  11. Effects of low-dose carbon ion irradiation on the proliferation of splenocytes and the concentration of interferon in mice

    Science.gov (United States)

    Li, Ning

    AIM: To investigate the changes in the proliferation response of splenic lymphocytes and the concentration of serum interferon (IFN-γ) in mice induced by low doses carbon ion irradiation. METHODS: The experiment was carried out in the laboratory of physical medicine, Institute of Modern Physics, Chinese Academy of Sciences in November 2006. 1. Thirty Kunming mice were randomly divided into five groups with six animals in each group and irradiated with 0, 0.01, 0.03, 0.05 and 0.10 Gy carbon ion at Heavy Ion Research Facility Laboratory of Lanzhou. Twenty-four hours after irradiation, the eyeballs of mice were taken out under anesthesia and blood was harvested. 2. The concentration of IFN-γ in serum was detected by ELISA kit. After the mice were executed, the spleen was harvested under sterile condition to prepare spleen mononuclear cell suspension. The effects of concanavalin A(ConA) and lipopolysaccharide(LPS) on the proliferations of mononuclear cells was tested by MTT assay. RESULTS: All thirty mice were involved in the result analysis. 1. The concentration of IFN-γ in serum remarkably increased after irradiation with 0.01 Gy and 0.03 Gy compared with that in controls (p<0.05). However, the concentration of IFN-γ decreased after irradiation with 0.05 Gy and 0.1 Gy. 2. Compared with control group, the proliferation of T lymphocytes induced by ConA and B lymphocytes induced by LPS remarkably increased after irradiation with 0.01 Gy (p<0.001) and the effect was of significant difference compared with that of 0.03 Gy (p<0.01). The irradiation with 0.05 Gy presented an inhibition to the proliferation of splenic lymphocytes. This inhibition was also obvious when irradiated with 0.10 Gy. CONCLUSION: 0.01 Gy and 0.03 Gy carbon ion irradiation can stimulate the proliferation of splenocytes, induce the secretion of IFN-γ and, in consequence, enhance the immune function.

  12. The effect of preirradiation application of aspartic acid salts on hemopoietic recovery in X-irradiated mice

    International Nuclear Information System (INIS)

    The possibility of radioprotective action of K and Mg aspartate administered in tap water for ten days prior to X-irradiation was investigated in male mice of the strain C 57 Bl/10. In normal animals, thymus weight was found to be increased by 10-day treatment with K and Mg aspartate. The postirradiation regeneration of spleen weight and incorporation of radioactive iron into the spleen and femoral marrow following sublethal irradiation was favorably modified by the treatment used. Pretreatment of mice with K and Mg aspartate delays the onset of early deaths at irradiation with an absolutely lethal X-ray exposure and raises the percentage of surviving animals after nearly lethal exposures. (orig.)

  13. 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)

  14. Topical Administration of Manuka Oil Prevents UV-B Irradiation-Induced Cutaneous Photoaging in Mice

    Directory of Open Access Journals (Sweden)

    Oh Sook Kwon

    2013-01-01

    Full Text Available Manuka tree is indigenous to New Zealand, and its essential oil has been used as a traditional medicine to treat wounds, fever, and pain. Although there is a growing interest in the use of manuka oil for antiaging skin care products, little is known about its bioactivity. Solar ultraviolet (UV radiation is the primary environmental factor causing skin damage and consequently premature aging. Therefore, we evaluated manuka oil for its effects against photoaging in UV-B-irradiated hairless mice. Topical application of manuka oil suppressed the UV-B-induced increase in skin thickness and wrinkle grading in a dose-dependent manner. Application of 10% manuka oil reduced the average length, depth, and % area of wrinkles significantly, and this was correlated with inhibition of loss of collagen fiber content and epidermal hyperplasia. Furthermore, we observed that manuka oil could suppress UV-B-induced skin inflammation by inhibiting the production of inflammatory cytokines. Taken together, this study provides evidence that manuka oil indeed possesses antiphotoaging activity, and this is associated with its inhibitory activity against skin inflammation induced by UV irradiation.

  15. Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lucarelli, G.; Izzi, T.; Porcellini, A.; Delfini, C.; Galimberti, M.; Moretti, L.; Polchi, P.; Agostinelli, F.; Andreani, M.; Manna, M. (Haematological Department, Pesaro Hospital, Pesaro, Italy)

    1982-01-01

    2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20 % of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haemotopoietic recovery and the appearance of red cell isoenzyme phenotypes of donor origin. Survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.

  16. Effect of the lipid fraction of Listeria monocytogenes cells on the immune response of irradiated mice. Pt. 1. Effect of lipids administered prior to irradiation

    International Nuclear Information System (INIS)

    Stimulation of the immune mechanisms by Listeria monocytogenes lipides, given prior to irradiation, was tested for its effect on the rate of the immune response of mice to sheep erythrocytes given as the antigen. Cellular and humoral response was evaluated each time on the fourth day after immunization, which was performed 5, 15, and 30 days after exposure to X rays in doses of 250 or 500 R. The administration of lipids prior to irradiation was found to decrease in some measure the immuno-suppresive effect of X rays. The observed protective effect was greatly related to the lipid dose given, as well as to time interval between the lipid administration and irradiation. (author)

  17. Conjugated linoleic acid reduces body weight gain in ovariectomized female C57BL/6J mice

    OpenAIRE

    Kanaya, Noriko; Chen, Shiuan

    2010-01-01

    Estrogen is an important protective factor against obesity in females. Therefore, postmenopausal women have a higher rate of obesity than premenopausal women, which is associated with age-related loss of ovary function. It has been reported that a diet containing conjugated linoleic acid (CLA) reduced body weight and body fat mass in the animal model as well as in human trials. We hypothesized that ingestion of CLA would reduce body weight gain in ovariectomized (OVX) female C57BL/6J mice whi...

  18. Effects of Pre-exposure Mouse Pituitary with Low-dose 60Co γ-ray on Growth Hormone (GH) and Body Mass Induced by Subsequent High-dose Irradiation

    Institute of Scientific and Technical Information of China (English)

    ZhangHong; LiWenjian; JingXiaodong; LiuBing; MinFengling; ZhouQingming; XieYi

    2003-01-01

    The pituitary of the B6C3F1 hybrid strain mice were irradiated with 0.05 Gy of 60Co γ-ray as the pre-exposure dose (D1), and were then irradiated with 2 Gy of 60Co γ-ray as challenging irradiation dose (D2) at 4h after per-exposure. Body weight and serum growth hormone (GH) were measured at 35th day after irradiation. The results showed that irradiation of mouse testes with 2 Gy of 60Co γ-ray significantly diminished mousebody weight and level of serum GH (Table). Pre-exposure with a low-dose (0.05 Gy) of 60Co γ-ray significantly alleviated reductions of mouse body weight and level of serum GH induced by subsequent a high-dose (2 Gy) irradiation (Table). The data suggested that low-dose ionizing irradiation can induce adaptive responses to the harmful effects of pituitary by subsequent high-dose exposure.

  19. Altered natural killer cell biology in C57BL/6 mice after leukemogenic split-dose irradiation. [/sup 137/Cs

    Energy Technology Data Exchange (ETDEWEB)

    Parkinson, D.R.; Brightman, R.P.; Waksal, S.D.

    1981-04-01

    Natural killer (NK) cell activity was examined in the spleens of C57BL/6 mice given leukemogenic split-dose irradiation. The radiation protocol resulted in severe depression of spontaneous NK cell activity; this activity was not fully restored after treatment with the interferon inducer poly I:C. In vitro mixing studies provided no evidence for active suppression in vivo as a mechanism for this decrease in activity. In addition, spontaneous activity was restored towards control levels after bone marrow transfusion from nonirradiated mice. The results are most compatible with the radiation-induced loss of a cell with normal NK activity from spleen and bone marrow after the split-dose radiation protocol. In addition, a population of cells able to competitively block normal NK cell lysis of YAC-1 tumor cells is found in the bone marrow, spleen, and thymus of the irradiated mice lacking NK cell activity.

  20. Jeju ground water containing vanadium induced immune activation on splenocytes of low dose γ-rays-irradiated mice.

    Science.gov (United States)

    Ha, Danbee; Joo, Haejin; Ahn, Ginnae; Kim, Min Ju; Bing, So Jin; An, Subin; Kim, Hyunki; Kang, Kyung-goo; Lim, Yoon-Kyu; Jee, Youngheun

    2012-06-01

    Vanadium, an essential micronutrient, has been implicated in controlling diabetes and carcinogenesis and in impeding reactive oxygen species (ROS) generation. γ-ray irradiation triggers DNA damage by inducing ROS production and causes diminution in radiosensitive immunocytes. In this study, we elucidate the immune activation capacities of Jeju water containing vanadium on immunosuppression caused by γ-ray irradiation, and identify its mechanism using various low doses of NaVO(3). We examined the intracellular ROS generation, DNA damage, cell proliferation, population of splenocytes, and cytokine/antibody profiles in irradiated mice drinking Jeju water for 180 days and in non-irradiated and in irradiated splenocytes both of which were treated with NaVO(3). Both Jeju water and 0.245 μM NaVO(3) attenuated the intracellular ROS generation and DNA damage in splenocytes against γ-ray irradiation. Splenocytes were significantly proliferated by the long-term intake of Jeju water and by 0.245 μM NaVO(3) treatment, and the expansion of B cells accounted for the increased number of splenocytes. Also, 0.245 μM NaVO(3) treatment showed the potency to amplify the production of IFN-γ and total IgG in irradiated splenocytes, which correlated with the expansion of B cells. Collectively, Jeju water containing vanadium possesses the immune activation property against damages caused by γ-irradiation.

  1. Induction of genomic instability after an acute whole-body exposure of mice to 56Fe ions

    Science.gov (United States)

    Rithidech, Kanokporn; Supanpaiboon, Wisa; Whorton, Elbert

    collected from CBA/CaJ and C57BL/6J mice at different times up to 3 months following an acute whole-body exposure to various doses of 1 GeV/amu 56 Fe ions (0, 0.1, 0.5 and 1.0 cGy) or 137 Cs gamma rays (0, 0.5, 1.0 and 3.0 cGy, as a reference radiation). These strains of mouse are known to be sensitive (CBA/CaJ) or resistant (C57BL/6J) to radiation-induced chromosomal damage and AML. At 2 days after the exposure, our data indicated that there was no increase in the frequency of MN-PCEs in CBA/CaJ mice exposed to 56 Fe ions while the frequency of MN-PCEs elevated as a function of dose in the C57BL/6J mice. At day 4, there was no dose related increase in either strain of mouse exposed to either 56 Fe ions or 137 Cs gamma rays. We also found that at the early sacrifice times (2 and 4 days) the 56 Fe ions were slightly more effective, per unit dose, in inducing MN-NCEs than 137 Cs gamma rays in both strains. Likewise, no increase in the frequency of MN-NCEs was found at late times after an acute exposure to either type of radiation. In contrast, both types of radiation induced increased MN-PCE frequencies in irradiated CBA/CaJ mice, but not C57BL/6J mice, at late times post-exposure. This finding indicates the potential induction of genomic instability in hematopoietic cells of CBA/CaJ mice by both types of radiation. The finding also demonstrates the influence of genetic background on radiation-induced genomic instability in vivo. Research funded by NASA Grant #NAG9- 1 52 .

  2. Protective Effect Of Avocado Oil Against Biochemical And Histological Changes In Whole Body Gamma Irradiation In Albino Rats

    International Nuclear Information System (INIS)

    Avocado oil, extracted from the pulp of the fruit, is rich in poly-unsaturated fatty acids, linoleic, linolenic, oleic acids and the monounsaturated fatty acid. It also contains B-sitosterol, B-carotene, lecithin, minerals and vitamins A, C, D and E. Avocado oil lowers the blood levels of serum lipids and has antioxidant properties as a free radical scavenger. Male albino rats were divided into 5 groups. 1- Control group: rats not subjected to any treatment, 2- Avocado treated group: rats received avocado oil (0.1 ml/kg/day) via intraperitoneal injection during 21 days, 3- Irradiated group: rats were whole body gamma irradiated with 7 Gy, 4- Avocado + irradiated group: rats received avocado oil for 21 days then exposed to whole body gamma irradiation with 7 Gy and 5- Radiation + avocado group: rats were exposed to 7 Gy whole body gamma irradiation then received avocado oil for 21 days. Avocado oil (0.1 ml/kg/day) was given to rats, receiving a standard diet, for 21 days before exposure to 7 Gy whole body gamma irradiation then the treatment was continued for 10 days after irradiation. Several investigations were carried out such as superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), lipid profile and blood sugar. High significant increase in MDA was observed and treatment with avocado before irradiation caused significant increase in GSH, CAT and SOD and significant decrease in MDA as compared to the irradiated groups. The results also showed that treatment with avocado oil significantly diminished the radiation-induced alterations observed in the levels of lipid profile and glucose. The results demonstrated that whole body gamma irradiated rats showed significant increase in alanine aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP) and glucose. By studying the lipid profile, significant increases in cholesterol, triglycerides and LDL-C levels were recorded while significant decrease was

  3. A Cajal body-independent pathway for telomerase trafficking in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tomlinson, Rebecca L.; Li, Jian; Culp, Bradley R.; Terns, Rebecca M., E-mail: rterns@bmb.uga.edu; Terns, Michael P., E-mail: mterns@bmb.uga.edu

    2010-10-15

    The intranuclear trafficking of human telomerase involves a dynamic interplay between multiple nuclear sites, most notably Cajal bodies and telomeres. Cajal bodies are proposed to serve as sites of telomerase maturation, storage, and assembly, as well as to function in the cell cycle-regulated delivery of telomerase to telomeres in human cells. Here, we find that telomerase RNA does not localize to Cajal bodies in mouse cells, and instead resides in separate nuclear foci throughout much of the cell cycle. However, as in humans, mouse telomerase RNA (mTR) localizes to subsets of telomeres specifically during S phase. The localization of mTR to telomeres in mouse cells does not require coilin-containing Cajal bodies, as mTR is found at telomeres at similar frequencies in cells from wild-type and coilin knockout mice. At the same time, we find that human TR localizes to Cajal bodies (as well as telomeres) in mouse cells, indicating that the distinct trafficking of mTR is attributable to an intrinsic property of the RNA (rather than a difference in the mouse cell environment such as the properties of mouse Cajal bodies). We also find that during S phase, mTR foci coalesce into short chains, with at least one of the conjoined mTR foci co-localizing with a telomere. These findings point to a novel, Cajal body-independent pathway for telomerase biogenesis and trafficking in mice.

  4. A Cajal body-independent pathway for telomerase trafficking in mice

    International Nuclear Information System (INIS)

    The intranuclear trafficking of human telomerase involves a dynamic interplay between multiple nuclear sites, most notably Cajal bodies and telomeres. Cajal bodies are proposed to serve as sites of telomerase maturation, storage, and assembly, as well as to function in the cell cycle-regulated delivery of telomerase to telomeres in human cells. Here, we find that telomerase RNA does not localize to Cajal bodies in mouse cells, and instead resides in separate nuclear foci throughout much of the cell cycle. However, as in humans, mouse telomerase RNA (mTR) localizes to subsets of telomeres specifically during S phase. The localization of mTR to telomeres in mouse cells does not require coilin-containing Cajal bodies, as mTR is found at telomeres at similar frequencies in cells from wild-type and coilin knockout mice. At the same time, we find that human TR localizes to Cajal bodies (as well as telomeres) in mouse cells, indicating that the distinct trafficking of mTR is attributable to an intrinsic property of the RNA (rather than a difference in the mouse cell environment such as the properties of mouse Cajal bodies). We also find that during S phase, mTR foci coalesce into short chains, with at least one of the conjoined mTR foci co-localizing with a telomere. These findings point to a novel, Cajal body-independent pathway for telomerase biogenesis and trafficking in mice.

  5. Blood-brain barrier permeability after gamma whole-body irradiation: an in vivo microdialysis study

    Energy Technology Data Exchange (ETDEWEB)

    Diserbo, M.; Agin, A.; Lamproglou, I.; Mauris, J.; Staali, F.; Multon, E.; Amourette, C

    2002-07-01

    The effects of total-body irradiation on the permeability of rat striatal blood-brain barrier (BBB) to [{sup 3}H]{alpha}-aminoisobutyric acid (AIBA) and [{sup 14}C] sucrose were investigated using the microdialysis technique. Seven days, 3 and 6 weeks, and 3, 5, and 8 months after gamma exposure at a dose of 4.5 Gy, no modification of the permeability to both [{sup 3}H]AIBA and [{sup 14}C] sucrose was observed. But, in the course of the initial syndrome, we observed a significant but transient increase in the BBB permeability to the two markers between 3 and 17 h after exposure. A secondary transient 'opening' of the BBB to [{sup 14}C] sucrose was noticed about 28 h following irradiation without the corresponding increase in BBB permeability to [{sup 3}H]AIBA. On the contrary, the transport of [{sup 3}H]AIBA through the BBB was decreased between 33 and 47 h postradiation. In conclusion, our experiments showed early modifications of BBB permeability after a moderate-dose whole-body exposure. Confirmation of these results with other tracers, in another experimental model or in humans, would have clinical applications for designing appropriate pharmacotherapy in radiotherapy and treatment of accidental overexposure. (author)

  6. Dose calculation method with 60-cobalt gamma rays in total body irradiation

    CERN Document Server

    Scaff, L A M

    2001-01-01

    Physical factors associated to total body irradiation using sup 6 sup 0 Co gamma rays beams, were studied in order to develop a calculation method of the dose distribution that could be reproduced in any radiotherapy center with good precision. The method is based on considering total body irradiation as a large and irregular field with heterogeneities. To calculate doses, or doses rates, of each area of interest (head, thorax, thigh, etc.), scattered radiation is determined. It was observed that if dismagnified fields were considered to calculate the scattered radiation, the resulting values could be applied on a projection to the real size to obtain the values for dose rate calculations. In a parallel work it was determined the variation of the dose rate in the air, for the distance of treatment, and for points out of the central axis. This confirm that the use of the inverse square law is not valid. An attenuation curve for a broad beam was also determined in order to allow the use of absorbers. In this wo...

  7. Changes of pulmonary function in patients treated with bone marrow transplantation after total body irradiation

    International Nuclear Information System (INIS)

    Changes of pulmonary functions were studied with time in 10 patients who underwent bone marrow transplantation (BMT) after total body irradiation (TBI, total lung dose, 3 to 12 Gy; dose rate, 5.3 to 10.0 cGy/min). Regardless of the total lung dose and the dose rate of irradiation or the period after BMT, the percent vital capacity (%VC) and the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1.0%) were kept within normal limits, whereas the diffusion capacity of carbon monoxide (%DLco) tended to decrease within 100 days after BMT in all of our patients. From the possibility that respiratory insufficiency will rapidly occur due to infection, it seems unfavorable for the patients to return to routine life during this period after BMT, even if in states without any clinical manifestations. It was found that the %DLco began to decrease prior to the onset of interstitial pneumonia (IP) and that the degree was more marked in patients who progressed to IP than in those who did not. Therefore, it is possible to predict the occurrence of IP by frequently measuring pulmonary function. In patients with IP, the %DLco rapidly improved with steroid administration, and it tended to improve gradually even after discontinuing the administration of the drug. But regardless of the total lung dose and dose rate of irradiation, the %DLco in patients with chronic graft-versus-host disease (GVHD) did not recover completely when compared with that in patients without chronic GVHD. Thus, it is considered that this persistant pulmonary dysfunction is caused mainly by chronic GVHD rather than by irradiation. (author)

  8. Late ophthalmological complications after total body irradiation in non-human primates

    Science.gov (United States)

    Niemer-Tucker, M. M.; Sterk, C. C.; de Wolff-Rouendaal, D.; Lee, A. C.; Lett, J. T.; Cox, A.; Emmanouilidis-van der Spek, K.; Davelaar, J.; Lambooy, A. C.; Mooy, C. M.; Broerse, J. J.

    1999-01-01

    PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

  9. Adoptive transfer of Mammaglobin-A epitope specific CD8 T cells combined with a single low dose of total body irradiation eradicates breast tumors.

    Science.gov (United States)

    Lerret, Nadine M; Rogozinska, Magdalena; Jaramillo, Andrés; Marzo, Amanda L

    2012-01-01

    Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80% of human breast tumors. Here we evaluated the use of adoptively transferred Mammaglobin-A specific CD8 T cells in combination with low dose irradiation to induce breast tumor rejection and prevent relapse. We show Mammaglobin-A specific CD8 T cells generated by DNA vaccination with all epitopes (Mammaglobin-A2.1, A2.2, A2.4 and A2.6) and full-length DNA in vivo resulted in heterogeneous T cell populations consisting of both effector and central memory CD8 T cell subsets. Adoptive transfer of spleen cells from all Mammaglobin-A2 immunized mice into tumor-bearing SCID/beige mice induced tumor regression but this anti-tumor response was not sustained long-term. Additionally, we demonstrate that only the adoptive transfer of Mammaglobin-A2 specific CD8 T cells in combination with a single low dose of irradiation prevents tumors from recurring. More importantly we show that this single dose of irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and reduces lipid uptake by tumor resident dendritic cells potentially enabling the dendritic cells to present tumor antigen more efficiently and aid in tumor clearance. These data reveal the potential for adoptive transfer combined with a single low dose of total body irradiation as a suitable therapy for the treatment of established breast tumors and the prevention of tumor recurrence.

  10. Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

    International Nuclear Information System (INIS)

    Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocytes, and resultant apoptosis of β-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect

  11. Effects of stochastic food deprivation on energy budget, body mass and activity in Swiss mice

    Directory of Open Access Journals (Sweden)

    Zhi-Jun ZHAO, Jing CAO, Ye TIAN, Rui-Rui WANG, Gui-Ying WANG

    2009-08-01

    Full Text Available When small animals are faced with an unpredictable food supply, they can adapt by altering different components of their energy budget such as energy intake, metabolic rate, rate of non-shivering thermogenesis (NST or behaviour. The present study examined the effect of stochastic food deprivation (FD on body mass, food intake, resting metabolic rate (RMR, NST and behaviour in male Swiss mice. During a period of 4 weeks’ FD, animals were fed ad libitum for a randomly assigned 4 days each week, but were deprived of food for the other 3 days. The results showed that body mass significantly dropped on FD days compared to controls. Food intake of FD mice increased significantly on ad libitum days, ensuring cumulative food intake, final body mass, fat mass, RMR and NST did not differ significantly from controls. Moreover, gastrointestinal tract mass increased in FD mice, but digestibility decreased. In general, activity was higher on deprived days, and feeding behaviour was higher on ad libitum days suggesting that Swiss mice are able to compensate for stochastic FD primarily by increasing food intake on ad libitum days, and not by reducing energy expenditure related to RMR or NST [Current Zoology 55(4: 249–257, 2009].

  12. Ethanolic extract of Taheebo attenuates increase in body weight and fatty liver in mice fed a high-fat diet.

    Science.gov (United States)

    Choi, Won Hee; Um, Min Young; Ahn, Jiyun; Jung, Chang Hwa; Park, Myung Kyu; Ha, Tae Youl

    2014-01-01

    We evaluated whether intake of an ethanolic extract of Taheebo (TBE) from Tabebuia avellanedae protects against body weight increase and fat accumulation in mice with high-fat diet (HFD)-induced obesity. Four-week old male C57BL/6 mice were fed a HFD (25% fat, w/w) for 11 weeks. The diet of control (HFD) mice was supplemented with vehicle (0.5% sodium carboxymethyl cellulose by gavage); the diet of experimental (TBE) mice was supplemented with TBE (150 mg/kg body weight/day by gavage). Mice administered TBE had significantly reduced body weight gain, fat accumulation in the liver, and fat pad weight, compared to HFD mice. Reduced hypertrophy of fat cells was also observed in TBE mice. Mice administered TBE also showed significantly lower serum levels of triglycerides, insulin, and leptin. Lipid profiles and levels of mRNAs and proteins related to lipid metabolism were determined in liver and white adipose tissue of the mice. Expression of mRNA and proteins related to lipogenesis were decreased in TBE-administered mice compared to mice fed HFD alone. These results suggest that TBE inhibits obesity and fat accumulation by regulation of gene expression related to lipid metabolism in HFD-induced obesity in mice. PMID:25299819

  13. Ethanolic Extract of Taheebo Attenuates Increase in Body Weight and Fatty Liver in Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Won Hee Choi

    2014-10-01

    Full Text Available We evaluated whether intake of an ethanolic extract of Taheebo (TBE from Tabebuia avellanedae protects against body weight increase and fat accumulation in mice with high-fat diet (HFD-induced obesity. Four-week old male C57BL/6 mice were fed a HFD (25% fat, w/w for 11 weeks. The diet of control (HFD mice was supplemented with vehicle (0.5% sodium carboxymethyl cellulose by gavage; the diet of experimental (TBE mice was supplemented with TBE (150 mg/kg body weight/day by gavage. Mice administered TBE had significantly reduced body weight gain, fat accumulation in the liver, and fat pad weight, compared to HFD mice. Reduced hypertrophy of fat cells was also observed in TBE mice. Mice administered TBE also showed significantly lower serum levels of triglycerides, insulin, and leptin. Lipid profiles and levels of mRNAs and proteins related to lipid metabolism were determined in liver and white adipose tissue of the mice. Expression of mRNA and proteins related to lipogenesis were decreased in TBE-administered mice compared to mice fed HFD alone. These results suggest that TBE inhibits obesity and fat accumulation by regulation of gene expression related to lipid metabolism in HFD-induced obesity in mice.

  14. The effect of local irradiation on the immune response in mice. II. Alterations due to low dose scattering

    International Nuclear Information System (INIS)

    The effect of localized irradiation given as single dose on the immune response of tumour-bearing mice was evaluated using the CRT. The tumour system (MBL2 on C57BL/6 females) was regularly lethal, although presence of CTL was demonstrated 15 days after transplantation (50,000 cells in the left hind limb). This T-dependent, antigen-specific cytotoxic activity observed on day 15 in the non-irradiated tumour-bearing group was abolished in the irradiated group (but not in the sham-irradiated group) and their CTL were incapable to mount a secondary response in MLTC-CML. The scattering of the 1,600 rad-single dose was sufficient to provoke this inhibition

  15. Recombinant human tumor necrosis factor induces acute reductions in food intake and body weight in mice

    OpenAIRE

    1988-01-01

    We examined the effects of treatment with rHuTNF on food consumption and body weight in C3H/HeJ mice. rHuTNF was administered intraperitoneally either by injections of 3, 12, or 24 micrograms twice a day or by implantation of osmotic pumps that released 0.75, 3, or 12 micrograms per day. Dose-dependent reductions in both food intake and weight were induced by rHuTNF. However, in spite of continued exposure to rHuTNF, the mice developed a resistance to rHuTNF and resumed their pretreatment foo...

  16. Toxoplasma gondii vs ionizing radiation: intestinal immunity induced in C57bl/6j mice by irradiated tachyzoites

    International Nuclear Information System (INIS)

    We study the oral route for the development of a vaccine for toxoplasmosis, using parasites irradiated with 60 Cobalt, as an alternative for vaccine development to this worldwide parasitic infection. We evaluated the development of immunity at serum or mucosal levels, and their efficiency in protect the mice against challenge with oral cysts of the Me-49 strain. C57Bl/6j isogenic mice were immunized by oral route with 107 255 Gy irradiated tachyzoites from RH strain, at several protocols using milk as anti-peptic adjuvant and alum hydroxide as antacid. The preparations of irradiated tachyzoites induced production of serum IgG and IgA in immunized mice, as determined by ELISA, with IgG2a as the dominant subclass, similar to chronic infection. Their use with adjuvant allowed the excretion of significant amounts of IgA in stools also IgG, despite a lesser extent. There are suggestion of tolerance induction at mucosal level, with lower antigen induced proliferation and lower in vitro antibody production by spleen and gut lymphocytes, with the latter doses, specially when milk was used as adjuvant. All oral preparations induced some quantitative protection against challenge, which was similar to the parenteral route only isolated alum hydroxide was used as adjuvant. All these data support the possibility of the development of an oral vaccine against toxoplasmosis, using irradiated tachyzoites, which would be possible tool in near future for use in field baits, for immunizing either domestic or wild felines. (author)

  17. Correlation analysis on MN-RET from peripheral blood and MN-PCE bone marrow in mice following exposure to irradiation

    International Nuclear Information System (INIS)

    Objective: To study the changes of reticulocyte micronucleus (MN-RET)from peripheral blood and polychromatic erythrocyte micronucleus (MN-PCE) from bone marrow in mice following exposure to X-rays in order to provide an experimental basis for exploring possible high-throughput radiation biodosimeter. Methods: Male ICR mice were whole-body irradiated with 0, 0.5, 1, 2, 4 and 5 Gy at a dose rate of 0.488 Gy/min. MN-RET from peripheral blood wag scored with FCM and MN-PCE from bone marrow was scored with manual microscopy at 24, 48 and 72 h post-irradiation. Results: Both MN-RET and MN-PCE rates increased with doses in the range of 0-5 Gy at 24, 48 and 72 h after WBI. The dose-response relationship can be fit with linear equations (t=10.26-25.77, P<0.05). The correlation coefficients between MN-RET from peripheral blood and MN-PCE from bone mallow were highly significant (r=0.986-0.996, P<0.05). Conclusions: In view of its simplicity,accuracy and high throughput capacity, FCM scoring of peripheral blood MN-RET may be a candidate for radiation biodosimetry, More work should be carried out on human specimens to investigate this possibility. (authors)

  18. Bone marrow transplantation across major histocompatibility barriers in mice: II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    International Nuclear Information System (INIS)

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatability barriers.Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then given to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 100-rad TLI. In TLI plus CY-conditioned recipients, it was also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for these findings are discussed

  19. Bronchial neuroendocrine elements in late post-radiation stage in humans after total body irradiation

    International Nuclear Information System (INIS)

    It is not known how long-term total body irradiation affects the neuroendocrine cells (Nc) and peptidergic innervation in the bronchial wall. This study examined, by immunohistochemical and radioimmunoassay (RIA) techniques, the distribution of NC and neuropeptide-containing nerve fibres in the large bronchi of Chernobyl nuclear accident cleanup workers displaying pulmonary fibrosis and metaplastic epithelium. Bronchial mucous and submucous layers from 16 Chernobyl patients and 6 control subjects were examined by conventional light microscopy and immunohistochemical techniques for determination of protein gene product 9.5 (PGP), chromogranin A, chromogranin A and B (CAB), calcitonin gene-related peptide (CGRP), calcitonin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), helospectin I, neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP), serotonin (5-hydroxyltryptamine, 5-HT), and substance P (SP). Additionally, bronchial biopsies from 6 Chernobyl cleanup workers and 3 control patients were examined by RIA for VIP and NPY/peptideYY-Ievels. The Chernobyl patients were examined 10 years after exposure during the cleanup works in the Chernobyl Atomic Electric Power Station. PGP immunoreactive nerve fibres appeared to be more frequent in the bronchial wall after long term irradiation as compared with controls. However, no specific alterations in the amounts of NPY-, PACAP-, helospectin-, SP- and CGRP-immunoreactive nerve fibres were seen in bronchi of control and Chernobyl patients. 5-HT -immunoreactive NC appeared to be more numerous in normal bronchial epithelium adjacent to metaplastic epithelium, in which numerous CAB- immunoreactive NC were seen in Chernobyl patients. RIA for VIP and NPY/PYY showed individual variations in the levels of these peptides in the bronchial tissue. In two cases (one Chernobyl patient and one control patient) there was a high concentration of VIP in parallel with a high concentration of NPY

  20. Modification of immunological potential by ultraviolet radiation. I. Immune status of short-term uv-irradiated mice

    International Nuclear Information System (INIS)

    C3Hf/HeN mice support the progressive growth of most transplanted syngeneic ultraviolet (uv) light-induced tumors following short-term uv exposure whereas nonexposed mice reject these tumors. Because an immunosuppressive role in uv-mediated tumor susceptibility might be suggested by these observations, a comparison of several immunological parameters has been conducted. These include antibody production, proliferation in response to antigenic and mitogenic stimulation, and the generation of cytotoxic effector cells by normal or short-term uv-exposed mice. The results indicate that short-term uv irradiation of mice does not result in any readily detectable alterations of the host's immune system other than the consistent loss of the antitumor response mediating rejection of the transplanted uv-induced tumor

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

    International Nuclear Information System (INIS)

    '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. (author)

  2. Deletion of running-induced hippocampal neurogenesis by irradiation prevents development of an anxious phenotype in mice.

    Directory of Open Access Journals (Sweden)

    Johannes Fuss

    Full Text Available Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box. Reducing neurogenesis by focalized irradiation of the hippocampus abolished this exercise-induced increase of anxiety, suggesting a direct implication of hippocampal neurogenesis in this phenotype. On the other hand, irradiated mice explored less frequently the lit compartment of the dark-light box test irrespective of wheel running, suggesting that irradiation per se induced anxiety as well. Thus, our data suggest that intermediate levels of neurogenesis are related to the lowest levels of anxiety. Moreover, using c-Fos immunocytochemistry as cellular activity marker, we observed significantly different induction patterns between runners and sedentary controls when exposed to a strong anxiogenic stimulus. Again, this effect was altered by irradiation. In contrast, the well-known induction of brain-derived neurotrophic factor (BDNF by voluntary exercise was not disrupted by focal irradiation, indicating that hippocampal BDNF levels were not correlated with anxiety under our experimental conditions. In summary, our data demonstrate to our knowledge for the first time that increased neurogenesis has a causative implication in the induction of anxiety.

  3. Comparison of total body irradiation-based or non-total body irradiation-based conditioning regimens for allogeneic stem cell transplantation in pediatric leukemia patients

    Directory of Open Access Journals (Sweden)

    Sang Jeong Kim

    2010-04-01

    Full Text Available Purpose : This study aims to compare the outcome of total body irradiation (TBI- or non-TBI-containing conditioning regimens for leukemia in children. Methods : We retrospectively evaluated 77 children conditioned with TBI (n=40 or non-TBI (n=37 regimens, transplanted at Chonnam National University Hospital between January 1996 and December 2007. The type of transplantation, disease status at the time of transplant, conditioning regimen, engraftment kinetics, development of graft-versus-host disease (GVHD, complications, cause of deaths, overall survival (OS, and event-free survival (EFS were compared between the 2 groups. Results : Among 34 patients with acute lymphoblastic leukemia (ALL, 28 (82.4% were in the TBI group, while 72.7% (24/33 of patients with myeloid leukemia were in the non-TBI group. Although the 5-year EFS of the 2 groups was similar for all patients (62% vs 63%, the TBI group showed a better 5-year EFS than the non-TBI group when only ALL patients were analyzed (65% vs 17%; P =0.005. In acute myelogenous leukemia patients, the non-TBI group had better survival tendency (73% vs 38%; P=0.089. The incidence of GVHD, engraftment, survival, cause of death, and late complications was not different between the 2 groups. Conclusion : The TBI and non-TBI groups showed comparable results, but the TBI group showed a significantly higher 5-year EFS than the non-TBI group in ALL patients. Further prospective, randomized controlled studies involving larger number of patients are needed to assess the late-onset complications and to compare the socioeconomic quality of life.

  4. Renal damage in mice after sequential cisplatin and irradiation; The influence of prior irradiation on platinum elimination

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, F.A.; Bartelink, H.; Voet, G.B. van der (Nederlands Kanker Inst. ' Antoni van Leeuwenhoekhuis' , Amsterdam (Netherlands)); Wolff, F.A. de (Rijksuniversiteit Leiden (Netherlands). Academisch Ziekenhuis)

    1991-08-01

    Doses of 4-6 mg kg{sup -1} c-DDP given 6 months before renal irradiation caused only a modest increase in functional radiation damage (DEF 1.1). These effects could be explained by additive toxicities and the damage was much less than when c-DDP was given 3-6 months after irradiation. Pharmacokinetic studies did not demonstrate any decrease in the rate of platinum elimination after previous low-dose renal irradiation. (author). 23 refs.; 2 figs.; 1 tab.

  5. Effect of DNA-loaded erythrocyte ghosts and DNA on some parameters of hematopoiesis and peripheral blood in irradiated mice

    International Nuclear Information System (INIS)

    The effect of DNA-loaded erythrocyte ghosts (DNA-LEs) on hematopoiesis, concentration of nucleic acids and electrophoretic mobility is studied in peripheral blood cells from mice irradiated with gamma rays at dose 4-8 Gy. Native exogenous thymus DNA studied as DNA-Les and DNA solution reduces the damage inflicted to hematopoietic organs assayed by the quantity of endogenous spleen and bone marrow. Simultaneously, it has a positive therapeutic effect on nucleic acids in the leukocytes and on electrophoretic mobility of erythrocytes in the post-irradiation recovery period. 1 tab., 2 figs., 14 refs. (orig.)

  6. Effect of sex and age on the frequency of tumors arising in non-linear mice exposed to total gamma irradiation

    International Nuclear Information System (INIS)

    The effect of sex and age of nonlinear mice on the frequency of tumours was studied. Nonlinear mice of the SHK colony of both sexes were gamma-irradiated with 137Cs. The histological material, frequency and time of tumour appearance were investigated in dependence on age. Single exposure accelerated the appearance of tumours of the hemopoietic tissue in females and lung and liver tumours in males. The irradiation increased the frequency of tumour appearance in females. The frequency of mammary gland tumours increased under irradiation of females of older age. Ovary tumours developed irrespective of mouse age by the time of irradiation. Average longevity reduced only in young females

  7. Development and clinical application of a length-adjustable water phantom for total body irradiation.

    Science.gov (United States)

    Chen, Zhi-Wei; Yao, Sheng-Yu; Zhang, Tie-Ning; Zhu, Zhen-Hua; Hu, Zhe-Kai; Lu, Xun

    2012-08-01

    A new type of water phantom which would be specialised for the absorbed dose measurement in total body irradiation (TBI) treatment is developed. Ten millimetres of thick Plexiglas plates were arranged to form a square cube with 300 mm of edge length. An appropriate sleeve-type piston was installed on the side wall, and a tabular Plexiglas piston was positioned inside the sleeve. By pushing and pulling the piston, the length of the self-made water phantom could be varied to meet the required patients' physical sizes. To compare the international standard water phantom with the length-adjustable and the Plexiglas phantoms, absorbed dose for 6-MV X ray was measured by an ionisation chamber at different depths in three kinds of phantoms. In 70 cases with TBI, midplane doses were metered using the length-adjustable and the Plexiglas phantoms for simulating human dimensions, and dose validation was synchronously carried out. There were no significant statistical differences, p > 0.05, through statistical processing of data from the international standard water phantom and the self-designed one. There were significant statistical differences, p body width. Obviously, the difference had a positive correlation with the body width. The results proved that the new length-adjustable water phantom is more accurate for simulating human dimensions than Plexiglas phantom.

  8. Patient dose analysis in total body irradiation through in vivo dosimetry

    Directory of Open Access Journals (Sweden)

    K Ganapathy

    2012-01-01

    Full Text Available Total body irradiation (TBI is a special radiotherapy technique, administered prior to bone marrow transplantation. Due to the complex nature of the treatment setup, in vivo dosimetry for TBI is mandatory to ensure proper delivery of the intended radiation dose throughout the body. Lithium fluoride (LiF TLD-100 chips are used for the TBI in vivo dosimetry. Results obtained from the in vivo dosimetry of 20 patients are analyzed. Results obtained from forehead, abdomen, pelvis, and mediastinum showed a similar pattern with the average measured dose from 96 to 97% of the prescription dose. Extremities and chest received a dose greater than the prescription dose in many instances (more than 20% of measurements. Homogeneous dose delivery to the whole body is checked by calculating the mean dose with standard deviation for each fraction. Reasons for the difference between prescription dose and measured dose for each site are discussed. Dose homogeneity within ±10% is achieved using our in-house TBI protocol.

  9. In pediatric leukemia, dose evaluation according to the type of compensators in total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Yeon [Dongnam Inst. of Radiological and Medical science, Busan (Korea, Republic of); Kim, Chang Soo; Kim, Jung Hoon [Dept. of Radiological Science, College of Health Science, Catholic University of Busan, Busan (Korea, Republic of)

    2015-04-15

    Total body irradiation (TBI) and chemotherapy are the pre-treatment method of a stem cell transplantations of the childhood leukemia. in this study, we evaluate the Quantitative human body dose prior to the treatment. The MCNPX simulation program evaluated by changing the material of the tissue compensators with imitation material of pediatric exposure in a virtual space. As a result, first, the average skin dose with the material of the tissue compensators of Plexiglass tissue compensators is 74.60 mGy/min, Al is 73.96 mGy/min, Cu is 72.26 mGy/min and Pb 67.90 mGy/min respectively. Second, regardless of the tissue compensators material that organ dose were thyroid, gentile, digestive system, brain, lungs, kidneys higher in order. Finally, the ideal distance between body compensator and the patient were 50 cm aparting each other. In conclusion, tissue compensators Al, Cu, Pb are able to replace of the currently used in Plexiglass materials.

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

    International Nuclear Information System (INIS)

    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)

  11. Enhanced reconstitution of hematopoietic organs in irradiated mice, following their transplantation with bone marrow cells pretreated with recombinant interleukin 3

    International Nuclear Information System (INIS)

    Lethally irradiated C3H/eb mice were injected with syngeneic bone marrow cells that had been exposed for 4 h in vitro to purified bacterially synthesized interleukin 3 (rIL-3). Control mice were injected with cells exposed to incubation medium only. Mice injected with rIL-3-treated cells exhibited, on day 10 after transplantation an 8.2-fold and 2.7-fold increase in number of myeloid progenitors in their spleen and bone marrow, respectively, but the in vitro differentiation pattern of the myeloid progenitors was not affected. There was, however, an increase in the number of cells per individual in vitro myeloid colony (CFU-C) of the rIL-3-treated mice. The latter mice also showed a 1.6-fold increase in the number of splenic colony-forming units (CFU-S), a higher self-renewal capacity of hematopoietic progenitors, and a higher number of leukocytes in the peripheral blood. These results indicate that the injection into lethally irradiated recipients of bone marrow cells briefly pretreated in vitro with rIL-3 significantly enhances the reconstitution of their hematopoietic organs, and suggest that the in vitro pretreatment of bone marrow cells with appropriate stimulating factors could be useful in bone marrow transplantation

  12. Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni

    Energy Technology Data Exchange (ETDEWEB)

    Aitken, R.; Coulson, P.S.; Wilson, R.A.

    1988-05-15

    Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means.

  13. Stimulation of hematopoietic stem cells by interferon inducer in nonhuman primates receiving fractionated total body irradiation

    International Nuclear Information System (INIS)

    Interferon response and hematopoietic stem cells (spleen colony forming units-CFU-S) were studied in rhesus monkeys subjected to fractionated total body irradiation (FTBI). An interferon inducer, a nuclease resistant complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxmethylcellulose[-poly(ICLC)] was used. Poly(ICLC) at 3.75 mg/m2 was given I.V. to 7 monkeys, 5 of which, starting 24 hours later, received 50 rad of 4 MV X rays twice a week for 2.5 weeks (total of 250 rad). Another group of 4 monkeys received FTBI only. Although the initial interferon response was similar in both groups treated with poly(ICLC)-800 international units (IU), the animals receiving FTBI showed reduced interferon levels after 100 rad. These animals, however, did not develop the hyporesponsiveness to subsequent poly(ICLC) injections that was observed in non-irradiated monkeys. Stabile interferon response (30-100 IU) in the FTBI group paralleled the prolonged persistence of the drug in their serum. Bone marrow (BM) aspirates from animals receiving FTBI and poly(ICLC) contained more CFU-S per 106 nucleated cells than those treated with poly(ICLC) alone or FTBI alone. FTBI with and without poly(ICLC) led to thrombocytopenia and leukopenia. Lower white blood cell (WBC) count was found in irradiated animals treated with poly(ICLC). Partial alopecia was observed in animals receiving poly(ICLC). Two animals--one in the poly(ICLC) and FTBI group and the other receiving FTBI alone, died with thrombocytopenia and leukopenia

  14. Stimulation of hematopoietic stem cells by interferon inducer in nonhuman primates receiving fractionated total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lvovsky, E.A. (George Washington Univ. Medical Center, Washington, DC); Levine, P.H.; Bengali, Z.; Leiseca, S.A.; Cicmanec, J.L.; Robinson, J.E.; Bautro, N.; Levy, H.B.; Scott, R.M.

    1982-10-01

    Interferon response and hematopoietic stem cells (spleen colony forming units--CFU-S) were studied in rhesus monkeys subjected to fractionated total body irradiation (FTBI). An interferon inducer, a nuclease resistant complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxmethylcellulose(-poly(ICLC)) was used. Poly(ICLC) at 3.75 mg/m/sup 2/ was given I.V. to 7 monkeys, 5 of which, starting 24 hours later, received 50 rad of 4 MV X rays twice a week at 2.5 weeks (total of 250 rad). Another group of 4 monkeys received FTBI only. Although the initial interferon response was similar in both groups treated wih poly(ICLC)--800 international units (IU), the animals that receiving FTBI showed reduced interferon levels after 100 rad. These animals, however, did not develop the hyporesponsiveness to subsequent poly(ICLC) injections that was observed in non-irradiated monkeys. Stabile interferon response (30-100 IU) in the FTBI group paralleled the prolonged persistence of the drug in their serum. Bone marrow (BM) aspirates from animals receiving FTBI and poly(ICLC) contained more CFU-S per 10/sup 6/ nucleated cells than those treated with poly(ICLC) along or FTBI with and without poly(ICLC) lead to thrombocytopenia and leukopenia. Lower white blood cell (WBC) count was found in irradiated animals treated with poly(ICLC). Partial alopecia was observed in animals receiving poly(ICLC). Two animals--one in the poly(ICLC) and FTBI group and the other receiving FTBI along, died with thrombocytopenia and leukopenia.

  15. Dosimetry and verification of Co total body irradiation with human phantom and semiconductor diodes.

    Science.gov (United States)

    Allahverdi, Mahmoud; Geraily, Ghazale; Esfehani, Mahbod; Sharafi, Aliakbar; Haddad, Peyman; Shirazi, Alireza

    2007-10-01

    Total Body Irradiation (TBI) is a form of radiotherapy used for patients prior to bone marrow or stem cell transplant to destroy any undetectable cancer cells. The dosimetry characteristics of a (60)Co unit for TBI were studied and a simple method for the calculation of the prescribed dose for TBI is presented. Dose homogeneity was verified in a human phantom. Dose measurements were made in water phantom (30 × 30 × 30 cm(3)), using farmer ionization chamber (0.6 cc, TM30010, PTW) and a parallel plate ionization chamber (TM23343, PTW). Point dose measurements for AP/PA irradiation were measured in a human phantom using silicon diodes (T60010L, PTW). The lung dose was measured with an ionization chamber (0.3 cc, TM31013). The validity of the proposed algorithm was checked at TBI distance using the human phantom. The accuracy of the proposed algorithm was within 3.5%. The dose delivered to the mid-lobe of the lung was 14.14 Gy and it has been reduced to 8.16 Gy by applying the proper shield. Dose homogeneity was within ±7% for all measured points. The results indicate that a good agreement between the total prescribed and calculated midplane doses can be achieved using this method. Therefore, it could be possible to use calculated data for TBI treatments.

  16. Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Ki Mun; Kim, In Ah; Shinn, Kyung Sub; Kim, Choon Choo; Kim, Dong Jip [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1994-06-15

    Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

  17. Allogeneic bone marrow transplantation in adults after fractionated body irradiation and high dose cyclophosphamide

    International Nuclear Information System (INIS)

    The authors present short and long-term results of allogeneic bone marrow transplantation after hyper-fractionated total body irradiation and high dose cyclophosphamide in ten patients treated for leukaemia during th period 1985-89. Three patients died from complications connected to the transplantation, while seven are living free from leukaemia 18 to 59 months after transplantation. Two patients need treatment for chronic graft versus host disease. Allogeneic bone marrow transplantation is expensive and risky. Close cooperation between clinicians and laboratory specialists is essential. The treatment increases long term survival and probably cures certain patients with leukaemia. Some of the patients will need treatment for chronic graft versus host disease and other late sequelae. 19 refs., 2 tabs

  18. Simple technique for fabrication of shielding blocks for total body irradiation at extended treatment distances

    Directory of Open Access Journals (Sweden)

    Ravichandran R

    2009-01-01

    Full Text Available Techniques are being standardized in our department for total body irradiation (TBI with six MV photons in linear accelerator for preconditioning to bone marrow transplantation (BMT. Individualized shields with low melting point alloy are to be fabricated for shielding critical organs such as lungs, kidneys etc. A method to mount diminished dimension of shields in a tray at 3.75m is designed in the department for a teletreatment distance of four meters with magna field with A simulator image taken with the patient′s midplane (MP at one meter distance is used to mark the dimensions of lung, scaled down by a factor of 3.75/4.0. These lung dimensions are reprinted from the digital simulator image for making the shield. The methodology of the technique using digitized minification in radiography is the first of its kind to be used for shield cutting in magna field radiotherapy.

  19. Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern.

    Science.gov (United States)

    Meerwaldt, J H; Carde, P; Burgers, J M; Monconduit, M; Thomas, J; Somers, R; Sizoo, W; Glabbeke, M V; Duez, N; de Wolf-Peeters, C

    1991-10-01

    The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36%--TBI and 55%--CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo-radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population.

  20. Interstitial pneumonitis after allogeneic bone marrow transplantation following total body irradiation

    International Nuclear Information System (INIS)

    The records of 40 patients who received allogeneic bone marrow transplantation (BMT) at Hyogo College of Medicine under the same conditioning regimen using cyclophosphamide and total body irradiation (TBI) from January 1984 to August 1989 were analyzed. The dose rate of TBI was 10 cGy per minute, and the total dose was 10 Gy (2.5 Gy daily for 4 days). Interstitial pneumonitis (IP) occurred in 13 of 40 patients, and was fatal in five patients. The probability of developing IP during the first year was 31%. We performed univariate analysis on the following factors but did not find any significant risk factors for IP: age and sex of patient, sex mismatch, ABO mismatch, grade of acute graft-versus-host disease, post immunosuppression regimen, and number of marrow cells transfused. (author)

  1. Half body irradiation of patients with multiple bone metastases: A phase II trial

    DEFF Research Database (Denmark)

    Berg, Randi; Yilmaz, Mette; Høyer, Morten;

    2009-01-01

    AIM OF STUDY: The primary aim of this study was to evaluate the effect of half-body irradiation (HBI) on pain and quality of life in cancer patients with multiple bone metastases. The secondary aim was to evaluate side effects of the treatment. PATIENTS AND METHODS: A total of 44 patients received...... lower (n = 37), upper (n = 5), or sequential HBI (n = 2). The dose for lower HBI was 8 Gy in one fraction and for upper HBI 7 Gy in one fraction, with reduction of the lung dose to 6 Gy in one fraction by partial shielding. The majority of patients (n = 41) were males with prostate cancers (93...... after treatment. RESULTS: Relief of pain was observed in 76% of the patients receiving HBI with 8.8% of the patients experiencing complete pain relief with no residual pain in the treated field. For most patients, the pain relief was lasting throughout the follow-up period. About one third...

  2. Effects of chronic whole-body gamma irradiation on cell mediated immunity

    International Nuclear Information System (INIS)

    The whole blood lymphocyte stimulation test has been used to estimate the effects of chronic, whole-body, gamma irradiation in the dog. At lower dose levels, 0.07 and 0.33 R/day to cumulative dose of about 50 and 250 R, there was no change in cell mediated immunity. Dogs at high dose levels were affected. Dogs which succumbed to aplastic anemia at high doses had reduced immunological responses. Dogs which survived these high doses showed a temporary depression. When aplastic anemia was initially noted, there was a differential response to PHA and Con-A stimulation. The response to the former mitogen was profoundly reduced, but Con-A stimulated cells were unaffected, indicative of the development of radioresistant cell lines. As the dogs progressed toward aplastic anemia, all T lympocytes were negatively affected

  3. Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling

    International Nuclear Information System (INIS)

    Purpose: To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single-dose or clinically relevant, fractioned-dose γ-ray radiation. Methods and Materials: C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2-Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days after irradiation, and all tumors were characterized histologically. Results: A total of 210 tumors were induced within the radiation field in 788 mice. An overall decrease in tumor incidence was observed after fractionated irradiation (16.4%) in comparison with single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation tumor observed (n=201), with carcinomas occurring less frequently (n=9). The proportion of mice developing tumors increased significantly with total dose for both single-dose and fractionated schedules, and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice after single-dose irradiation; however, significant differences in tumor susceptibilities after fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common after fractionated irradiation, whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common after single-dose irradiation. Conclusions: This study investigated the tumorigenic effect of acute large doses in comparison with fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiation therapy. Differences in tumor histotype after single-dose or fractionated radiation exposures provide novel in vivo evidence for differences in tumor

  4. Growth of Theileria annulata and Theileria parva macroschizont-infected bovine cells in immunodeficient mice: effect of irradiation and tumour load on lymphocyte subsets

    Energy Technology Data Exchange (ETDEWEB)

    Fell, A.H.; Preston, P.M. (Edinburgh Univ. (United Kingdom))

    1992-07-01

    Bovine cells infected with macroschizonts of the protozoan parasites Theileria annulata and Theileria parva formed solid tumours when injected into irradiated Balb/c and irradiated Balb/c nude mice. T. annulata tumours grew more vigorously than T. parva tumours, when initiated with similar doses of infected cells in mice exposed to the same doses of gamma-irradiation. In irradiated Balb/c mice, tumours of both species of parasites began to regress 2-3 weeks after injection of cells but grew without regression in irradiated Balb/c nude mice. Haemorrhage and necrosis of tumours, induced by macrophages and neutrophils, were seen in both mouse strains but were insufficient to cause regression in Balb/c nude mice. Theileria-infected bovine cells failed to establish in C57 beige mice, which lack functional natural killer (NK) cells. Flow cytometry, using monoclonal antibodies to murine leukocyte/lymphocyte antigens, showed that the radiation dose required to allow establishment of T. annulata tumours in Balb/c mice caused a severe depletion of splenic lymphocytes. B cells, helper T and cytotoxic T cells showed differing levels of susceptibility to irradiation. (Author).

  5. Involvement of the Gli3 (Extra-Toes Gene Region in Body Weight in Mice

    Directory of Open Access Journals (Sweden)

    Benoît Martin

    2007-01-01

    Full Text Available The mutation extra-toes (Gli3Xt-J on chromosome (Chr 13 of the mouse is known to be involved in the development of the skeleton. The only visible manifestation is the presence of an extra digit on each hind foot. Here we report evidence from several experiments that Gli3XtJ/+ mice weigh more than littermate Gli3+/+ mice, suggesting an effect on body weight of Gli3 or of a gene tightly linked to it on Chr 13. Four independent experiments in different environments were conducted on mice with different genetic backgrounds derived from the C3XtEso Gli3Xt-J/+ Eso/+ linkage testing strain and the JE/Le strain at adult age. The analyses have shown an association between the Gli3Xt-J allele and a body weight increase of about 6.5%. This effect is genetically dominant. It would appear that if the gene of interest is not Gli3 itself, it must be very close to this locus. Indeed, the expected size for this fragment is 7.9 ± 5.3 cM. The manifestation of this gene, observed in two animal facilities and on different genetic backgrounds, is consistent with the idea that the effect of the gene(s is displayed in a stable manner. It accounts for a variation of 6.5% of body weight.

  6. Chondrosarcoma arising within a radiation-induced osteochondroma several years following childhood total body irradiation: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Shuji [Kurume University Hospital, Department of Radiology, Fukuoka (Japan); Shen, Robert K. [Mayo Clinic, Department of Surgery, Rochester, MN (United States); Laack, Nadia N. [Mayo Clinic, Department of Radiation Oncology, Rochester, MN (United States); Inwards, Carrie Y. [Mayo Clinic, Department of Pathology, Rochester, MN (United States); Wenger, Doris E.; Amrami, Kimberly K. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2013-08-15

    Malignant degeneration arising in radiation-induced osteochondromas is extremely rare. We report a case of a 34-year-old man with a chondrosarcoma arising from an osteochondroma of the left posterior eighth rib that developed following total body irradiation received as part of the conditioning regimen prior to bone marrow transplantation at age 8. To our knowledge, this is only the fourth reported case of a chondrosarcoma arising within a radiation-induced osteochondroma and the first case occurring following childhood total body irradiation. (orig.)

  7. Comparison of endpoints relevant to toxicity assessments in 3 generations of CD-1 mice fed irradiated natural and purified ingredient diets with varying soy protein and isoflavone contents.

    Science.gov (United States)

    Camacho, Luísa; Lewis, Sherry M; Vanlandingham, Michelle M; Juliar, Beth E; Olson, Greg R; Patton, Ralph E; Gamboa da Costa, Gonçalo; Woodling, Kellie; Sepehr, Estatira; Bryant, Matthew S; Doerge, Daniel R; Basavarajappa, Mallikarjuna S; Felton, Robert P; Delclos, K Barry

    2016-08-01

    Diet is an important variable in toxicology. There are mixed reports on the impact of soy components on energy utilization, fat deposition, and reproductive parameters. Three generations of CD-1 mice were fed irradiated natural ingredient diets with varying levels of soy (NIH-41, 5K96, or 5008/5001), purified irradiated AIN-93 diet, or the AIN-93 formulation modified with ethanol-washed soy protein concentrate (SPC) or SPC with isoflavones (SPC-IF). NIH-41 was the control for pairwise comparisons. Minimal differences were observed among natural ingredient diet groups. F0 males fed AIN-93, SPC, and SPC-IF diets had elevated glucose levels and lower insulin levels compared with the NIH-41 group. In both sexes of the F1 and F2 generations, the SPC and SPC-IF groups had lower body weight gains than the NIH-41 controls and the AIN-93 group had an increased percent body fat at postnatal day 21. AIN-93 F1 pups had higher baseline glucose than NIH-41 controls, but diet did not significantly affect breeding performance or responses to glucose or uterotrophic challenges. Reduced testes weight and sperm in the AIN-93 group may be related to low thiamine levels. Our observations underline the importance of careful selection, manufacturing procedures, and nutritional characterization of diets used in toxicological studies. PMID:27234134

  8. Comparison of 32P therapy and sequential hemibody irradiation (HBI) for bony metastases as methods of whole body irradiation

    International Nuclear Information System (INIS)

    We report a retrospective study of 15 patients with prostate carcinoma and diffuse bone metastases treated with sodium 32P for palliation of pain at Downstate Medical Center and Kings County Hospital from 1973 to 1978. The response rates, duration of response, and toxicities are compared with those of other series of patients treated with 32P and with sequential hemibody irradiation. The response rates and duration of response are similar with both modalities ranging from 58 to 95% with a duration of 3.3 to 6 months with 32P and from 75 to 86% with a median duration of 5.5 months with hemibody irradiation. There are significant differences in the patterns of response and in the toxicities of the two treatment methods. Both methods cause significant bone marrow depression. Acute radiation syndrome, radiation pneumonitis, and alopecia are seen with sequential hemibody irradiation and not with 32P, but their incidence can be reduced by careful treatment planning. Hemibody irradiation can provide pain relief within 24 to 48 h, while 32P may produce an initial exacerbation of pain. Lower hemibody irradiation alone is less toxic than either upper hemibody irradiation or 32P treatment

  9. Comparison of /sup 32/P therapy and sequential hemibody irradiation (HBI) for bony metastases as methods of whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Aziz, H.; Choi, K.; Sohn, C.; Yaes, R.; Rotman, M.

    1986-06-01

    We report a retrospective study of 15 patients with prostate carcinoma and diffuse bone metastases treated with sodium /sup 32/P for palliation of pain at Downstate Medical Center and Kings County Hospital from 1973 to 1978. The response rates, duration of response, and toxicities are compared with those of other series of patients treated with /sup 32/P and with sequential hemibody irradiation. The response rates and duration of response are similar with both modalities ranging from 58 to 95% with a duration of 3.3 to 6 months with /sup 32/P and from 75 to 86% with a median duration of 5.5 months with hemibody irradiation. There are significant differences in the patterns of response and in the toxicities of the two treatment methods. Both methods cause significant bone marrow depression. Acute radiation syndrome, radiation pneumonitis, and alopecia are seen with sequential hemibody irradiation and not with /sup 32/P, but their incidence can be reduced by careful treatment planning. Hemibody irradiation can provide pain relief within 24 to 48 h, while /sup 32/P may produce an initial exacerbation of pain. Lower hemibody irradiation alone is less toxic than either upper hemibody irradiation or /sup 32/P treatment.

  10. Comparing the biological washout of β+-activity induced in mice brain after 12C-ion and proton irradiation

    International Nuclear Information System (INIS)

    In clinical ion beam therapy, protons as well as heavier ions such as carbon are used for treatment. For protons, β+-emitters are only induced by fragmentation reactions in the target (target fragmentation), whereas for heavy ions, they are additionally induced by fragmentations of the projectile (further referred to as autoactivation). An approach utilizing these processes for treatment verfication, by comparing measured Positron Emission Tomography (PET) data to predictions from Monte Carlo simulations, has already been clinically implemented. For an accurate simulation, it is important to consider the biological washout of β+-emitters due to vital functions. To date, mathematical expressions for washout have mainly been determined by using radioactive beams of 10C- and 11C-ions, both β+-emitters, to enhance the counting statistics in the irradiated area. Still, the question of how the choice of projectile (autoactivating or non-autoactivating) influences the washout coefficients, has not been addressed. In this context, an experiment was carried out at the Heidelberg Ion Beam Therapy Center with the purpose of directly comparing irradiation-induced biological washout coefficients in mice for protons and 12C-ions. To this aim, mice were irradiated in the brain region with protons and 12C-ions and measured after irradiation with a PET/CT scanner (Siemens Biograph mCT). After an appropriate waiting time, the mice were sacrificed, then irradiated and measured again under similar conditions. The resulting data were processed and fitted numerically to deduce the main washout parameters. Despite the very low PET counting statistics, a consistent difference could be identified between 12C-ion and proton irradiated mice, with the 12C data being described best by a two component fit with a combined medium and slow washout fraction of 0.50 ± 0.05 and the proton mice data being described best by a one component fit with only one (slow) washout fraction of 0.73 ± 0

  11. Reduced ultraviolet irradiation delays subsequent squamous cell carcinomas in hairless mice

    DEFF Research Database (Denmark)

    Togsverd-Bo, Katrine; Lerche, Catharina M; Poulsen, Thomas;

    2009-01-01

    time of appearance of the first skin tumor. RESULTS: The development of new tumors was delayed, corresponding to the degree of reductions in UV dose in an inversely linear manner. Discontinuation of UV doses delayed the median times to the second tumor by 24 days (2 SED, P = 0.0549) and 33.5 days (4...... tumors. The objective was to evaluate the significance of discontinued or reduced UV exposure for the development of subsequent skin tumors. METHODS: Seven groups of mice (n = 175) were irradiated with UV doses of 2 and 4 standard erythema doses (SED) that were continued, reduced or discontinued at the...... SED, P < 0.0001), and when reduced to 1 SED, the median delays were 18 days (2 SED, P = 0.0469) and 33 days (4 SED, P < 0.0001). The median delay to the third tumor was after UV reduction 47 days (4 SED, P < 0.0001) and 35 days (2 SED, P = 0.151), and after UV discontinuation 49 days (4 SED, P < 0...

  12. The onset of hemoglobin synthesis in spleens of irradiated mice after bone marrow transplantation

    International Nuclear Information System (INIS)

    Messenger RNA (mRNA) for globin was isolated from spleens of irradiated mice in which erythroid differentiation was induced by a bone marrow graft. The globin mRNA was isolated either by means of sucrose gradients of reticulocyte polysomal RNA or by affinity chromatography of total spleen RNA on poly (U)-sepharose. The globin mRNA was tested in a wheat embryo cell-free system. The appearance of mRNA in the spleen erythroid colonies was correlated with other parameters of erythroid differentiation such as globin synthesis, activity of delta-aminolevulinic acid synthetase and iron uptake. Poly(A) containing mRNA did appear already on the 3rd day after grafting. However, significant translational activity of globin mRNA could be demonstrated only one day later together with increase in globin synthesis and delta-aminolevulinic acid synthetase and enhanced iron uptake. In the second part of this study mouse spleen cells rich in erythroid elements were incubated with a specific heme synthesis inhibitor (isonicotinic acid hydrazide, INH) and the synthesis of 9 S RNA was estimated. It was found that a 40-minute incubation with INH reduced uridine incorporation into 9 S RNA fraction by about 40%. (author)

  13. Impact of fractionated local irradiation on lung metastasis in H22-bearing mice and exploration of its mechanism

    International Nuclear Information System (INIS)

    Objective: To study the impact of local fractionated irradiation on lung metastasis in H22-bearing ice, and to explore its mechanism involved. Methods: Subcutaneous transplantation tumor model bearing with H22 was established. Mice were divided into three groups as healthy control, tumor control and irradiation groups. The size of subcutaneous tumors was measured and lung metastasis was observed. The expressions of PCNA, VEGF and MVD were detected immunohistochemically. The plasma levels of CD4 and CD8 were determined by using flow cytometry. Results: The tumor size in irradiated group was smaller than that in tumor control group. The tumor inhibition rate in irradiated group was 30%. Lung metastasis in irradiated group was more severe than that in tumor control group (χ2=8.31, 4.48, 9.60, P<0.05). The expressions of PCNA, VEGF and MVD in two groups were statistically different (t=23.78, -2.47, -6.43, P<0.05). The levels of CD4 and CD8 in irradiated group were statistically different compared to healthy control group (t=4.72 and 3.31, P<0.05). Conclusions: For the H22 model, radiation might inhibit the local transplantation tumor, but increase the risk of lung metastasis. (authors)

  14. Pilot-Scale Pulsed UV Light Irradiation of Experimentally Infected Raspberries Suppresses Cryptosporidium parvum Infectivity in Immunocompetent Suckling Mice.

    Science.gov (United States)

    Le Goff, L; Hubert, B; Favennec, L; Villena, I; Ballet, J J; Agoulon, A; Orange, N; Gargala, G

    2015-12-01

    Cryptosporidium spp., a significant cause of foodborne infection, have been shown to be resistant to most chemical food disinfectant agents and infective for weeks in irrigation waters and stored fresh vegetal produce. Pulsed UV light (PL) has the potential to inactivate Cryptosporidium spp. on surfaces of raw or minimally processed foods or both. The present study aimed to evaluate the efficacy of PL on viability and in vivo infectivity of Cryptosporidium parvum oocysts present on raspberries, a known source of transmission to humans of oocyst-forming apicomplexan pathogens. The skin of each of 20 raspberries was experimentally inoculated with five 10-μl spots of an oocyst suspension containing 6 × 10(7) oocysts per ml (Nouzilly isolate). Raspberries were irradiated by PL flashes (4 J/cm(2) of total fluence). This dose did not affect colorimetric or organoleptic characteristics of fruits. After immunomagnetic separation from raspberries, oocysts were bleached and administered orally to neonatal suckling mice. Seven days after infection, mice were euthanized, and the number of oocysts in the entire small intestine was individually assessed by immunofluorescence flow cytometry. Three of 12 and 12 of 12 inoculated mice that received 10 and 100 oocysts isolated from nonirradiated raspberries, respectively, were found infected. Four of 12 and 2 of 12 inoculated mice that received 10(3) and 10(4) oocysts from irradiated raspberries, respectively, were found infected. Oocyst counts were lower in animals inoculated with 10(3) and 10(4) oocysts from irradiated raspberries (92 ± 144 and 38 ± 82, respectively) than in animals infected with 100 oocysts from nonirradiated raspberries (35,785 ± 66,221, P = 0.008). PL irradiation achieved oocyst reductions of 2 and 3 log for an inoculum of 10(3) and 10(4) oocysts, respectively. The present pilot-scale evaluation suggests that PL is an effective mode of decontamination for raspberries and prompts further applicability

  15. Relative effect of radiation dose rate on hemopoietic and nonhemopoietic lethality of total-body irradiation

    International Nuclear Information System (INIS)

    Experiments were undertaken to determine the influence of dose rate on the toxicity of total-body irrdiation (TBI) with and without syngeneic bone-marrow rescue in mice. The results showed a much greater dose-rate dependence for death from nonhemopoietic toxicity than from bone-marrow ablation, with the ratio of LD50's increasing from 1.73 at 25 cGy/min to 2.80 at 1 cGy/min. At the higher dose rates, dose-limiting nonhemopoietic toxicity resulted from late organ injury, affecting the lungs, kidneys, and liver. At 1 cGy/min the major dose-limiting nonhemopoietic toxicity was acute gastrointestinal injury. The implications of these results in the context of TBI in preparation for bone-marrow transplantation are discussed. 15 refs., 4 figs

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

    International Nuclear Information System (INIS)

    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

  17. Dermal dysplasia, hypotrichosis, and dorsal skin ulcers in adult NMRI-mice after X-irradiation in utero

    International Nuclear Information System (INIS)

    Prenatal X-irradiation in mice leads to a marked incidence of hypotrichosis and alopecia in offspring, when irradiation occurs during the stage of late organogenesis (day 11-13 p.c.). In addition, severe ulcerative dermatitis occurs in offspring starting at 2 months of age, with marked preference for those animals which have been irradiated at least during days 11-13 p.c. This occurs without any dose dependence; application of doses between 2.4 Gy and 7.2 Gy results in approximately similar incidence rates of skin ulcers (range between 39.1 and 48.0%). There is no sex preference and no dependence on housing. At autopsy no special abnormalities were found in the internal organs with the exception of frequent signs of amyloidosis. This disease pattern could also be produced in germ-free animals. The intracutanous administration of skin extracts from affected animals into unirradiated mice leads to a marked infiltration of leukocytes. It is therefore suggested that prenatal X-irradiation induces a distinct dysplasia of the epidermis, which is followed by an endogenous leukotactic activity. (orig.)

  18. Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Hofer, M.; Pospisil, M.; Netikiva, J.; Hola, J. [Institute of Biophysics, Academy of Sciences of the Czech Republic (Czech Republic)

    1997-03-01

    Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 {mu}g/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

  19. Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

    International Nuclear Information System (INIS)

    Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 μg/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

  20. Biochemical and histological changes in whole body gamma-irradiated rats feed on wheat, barely and corn bran

    International Nuclear Information System (INIS)

    The present work aims to study the effect of adding 3 different of dietary fibers (wheat, barley or corn bran) to normal balanced diet on liver function, blood, cholesterol, triglycerides and blood glucose level to counteract their elevation in whole body gamma irradiation rats. The experimental diets (balanced diet + fibre additive) were fed for 4 weeks. Samples (blood and tissue) were collected at intervals of times 7, 14 and 28 days post exposure to single dose (7 Gy) gamma irradiation. The control group consumed a fibre diet for 4 weeks, but not irradiated. The minimum aspartate amino-transferase (AST) and alanine aminotransferase (ALT) activities and the lowest blood total cholestrol, triglycerides and blood glucose were observed in rats (irradiated and non-irradiated rats) fed on wheat bran experimental diet (barley or corn bran). It could be concluded that wheat fibers were more effective, as compared with other fibers contained in balanced diet, in improving the investigated parameters observed after whole body gamma irradiation exposure

  1. Protective Effects of Ibuprofen and L-Carnitine Against Whole Body Gamma Irradiation-Induced Duodenal Mucosal Injury

    Directory of Open Access Journals (Sweden)

    Meryem Akpolat

    2011-03-01

    Full Text Available Objective: Ibuprofen and L-carnitine have been demonstrated to provide radioprotective activity to the hamster against whole body sublethal irradiation. The purpose of this study is to test those antioxidant drugs, each of which has the capacity of inhibiting mucosal injury, as topical radioprotectants for the intestine. Material and Methods: The male hamsters were divided into the following four groups (n=6: group 1: control group, received saline, 1 ml/100 g by gavage, as placebo. Group 2: irradiated-control group, received whole body irradiation of 8 Gy as a single dose plus physiological saline. The animals in groups 3 and 4 were given a daily dose of 10 mg/kg of ibuprofen and 50 mg/kg of L-carnitine for 15 days respectively, before irradiation with a single dose of 8 Gy. Twenty-four hours after radiation exposure, the hamsters were sacrificed and samples were taken from the duodenum, and the histopatological determinations were carried out. Results: Morphologically, examination of the gamma irradiated duodenum revealed the presence of shortening and thickening of villi and flattening of enterocytes, massive subepithelial lifting. Pretreatment of ibuprofen and L-carnitine with irradiation reduced these histopathological changes. Conclusion: Ibuprofen and L-carnitine administrated by the oral route may be a good radioprotector against small intestinal damage in patients undergoing radiotherapy.

  2. A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Yao Rui; Bernard, Damian; Turian, Julius; Abrams, Ross A.; Sensakovic, William; Fung, Henry C.; Chu, James C. H. [Department of Radiation Oncology, Rush University Medical Center, 500 South Paulina Street, Chicago, Illinois 60612 (United States); Sections of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Rush University Medical Center, 500 South Paulina Street, Chicago, Illinois 60612 (United States); Department of Radiation Oncology, Rush University Medical Center, 500 South Paulina Street, Chicago, Illinois 60612 (United States)

    2012-04-15

    Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lung dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.

  3. Recovery of the Erythropoietin-Sensitive Stem-Cell Population following Total-Body X-Irradiation

    International Nuclear Information System (INIS)

    Erythropoietin acts upon haemopoietic stem cells to initiate their differentiation into the erythroid series. This effect may be used in polycythaemic mice to estimate changes in the erythropoietin-sensitive stem-cell population following total-body irradiation (TBR). Generally, single doses of erythropoietin, less than that needed for maximum stem-cell response, are used to estimate changes in the stem-cell population. The validity of results using this test is based upon accepting several assumptions regarding erythropoietin kinetics. These are: (a) the contribution of endogenous erythropoietin is always negligible; (b) the origin of the dose-response curve to erythropoietin alters only because of changes in stem-cell numbers; (c) the proportion of stem cells responding to a given concentration of erythropoietin is independent of stem-cell numbers; (d) the slope of the dose-response curve does not alter; and (e) competition between erythropoietin and other factors for the stem cells remains unchanged. The studies to be reported indicate that some of these assumptions m a y not always be valid. Following 150 rad TBR, changes in erythropoietin dose-response curves were not always due to changes in the size of the stem-cell population, but also due to changes in erythropoietin kinetics. Changes in erythropoietin kinetics could be corrected for by using doses of erythropoietin which at any particular time after TBR gave maximum stem-cell response; through full dose-response studies, the nature of changes in erythropoietin kinetics following TBR could be established. These studies appear to explain discrepancies in results obtained in different laboratories using the erythropoietin test. The effect of 150 rad TBR on the erythropoietin-sensitive stem-cell population is an initial depression within 30 min to 20% of normal followed by a second depression (post-irradiation dip) at about 12 h. Twenty-four hours after TBR there is a recovery to the initial depression. This

  4. Inability of donor total body irradiation to prolong survival of vascularized bone allografts: Experimental study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.; Weiland, A.J. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1990-07-01

    At the present time, the toxic side effects of recipient immunosuppression cannot be justified for human non-vital organ transplantation. Total body irradiation has proven effective in ablating various bone-marrow-derived and endothelial immunocompetent cellular populations, which are responsible for immune rejection against donor tissues. Irradiation at a dose of 10 Gy was given to donor rats six days prior to heterotopic transplantation of vascularized bone allografts to host animals. Another group of recipient rats also received a short-term (sixth to fourteenth day after grafting), low dose of cyclosporine. Total body irradiation was able merely to delay rejection of grafts across a strong histocompatibility barrier for one to two weeks, when compared to nonirradiated allografts. The combination of donor irradiation plus cyclosporine did not delay the immune response, and the rejection score was similar to that observed for control allografts. Consequently, allograft viability was quickly impaired, leading to irreversible bone damage. This study suggest that 10 Gy of donor total body irradiation delivered six days prior to grafting cannot circumvent the immune rejection in a vascularized allograft of bone across a strong histocompatibility barrier.

  5. Investigation on using high-energy proton beam for total body irradiation (TBI).

    Science.gov (United States)

    Zhang, Miao; Qin, Nan; Jia, Xun; Zou, Wei J; Khan, Atif; Yue, Ning J

    2016-01-01

    This work investigated the possibility of using proton beam for total body irradia-tion (TBI). We hypothesized the broad-slow-rising entrance dose from a monoen-ergetic proton beam can deliver a uniform dose to patient with varied thickness. Comparing to photon-based TBI, it would not require any patient-specific com-pensator or beam spoiler. The hypothesis was first tested by simulating 250 MeV, 275 MeV, and 300 MeV protons irradiating a wedge-shaped water phantom in a paired opposing arrangement using Monte Carlo (MC) method. To allow ± 7.5% dose variation, the maximum water equivalent thickness (WET) of a treatable patient separation was 29 cm for 250 MeV proton, and > 40 cm for 275 MeV and 300 MeV proton. The compared 6 MV photon can only treat patients with up to 15.5 cm water-equivalent separation. In the second step, we simulated the dose deposition from the same beams on a patient's whole-body CT scan. The maximum patient separation in WET was 23 cm. The calculated whole-body dose variations were ± 8.9%, ± 9.0%, ± 9.6%, and ± 14% for 250 MeV proton, 275 MeV proton, 300 MeV proton, and 6 MV photon. At last, we tested the current machine capability to deliver a monoenergetic proton beam with a large uniform field. Experiments were performed on a compact double scattering single-gantry proton system. With its C-shaped gantry design, the source-to-surface distance (SSD) reached 7 m. The measured dose deposition curve had 22 cm relatively flat entrance region. The full width half maximum field size was measured 105 cm. The current scatter filter had to be redesigned to produce a uniform intensity at such treatment distance. In con-clusion, this work demonstrated the possibility of using proton beam for TBI. The current commercially available proton machines would soon be ready for such task. PMID:27685117

  6. Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine

    Directory of Open Access Journals (Sweden)

    Y. Guney

    2007-10-01

    Full Text Available We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB or abdominopelvic (AP irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset or evening (activity span - 13 h after light onset. Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively to the irradiated rats. AP (P < 0.05 and TB (P < 0.05 irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS levels. Melatonin treatment in the morning (P < 0.05 or evening (P < 0.05 decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05. Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

  7. Targeted microbubbles for imaging tumor angiogenesis: assessment of whole-body biodistribution with dynamic micro-PET in mice

    DEFF Research Database (Denmark)

    Willmann, Jürgen K; Cheng, Zhen; Davis, Corrine;

    2008-01-01

    To evaluate in vivo whole-body biodistribution of microbubbles (MBs) targeted to tumor angiogenesis-related vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by using dynamic micro-positron emission tomography (PET) in living mice....

  8. Chemical protection against long-term effects of whole-body exposure of mice to ionizing radiation. III. The effects of fractionated exposure to C57Bl mice

    International Nuclear Information System (INIS)

    Mice of the C57Bl/Cnb strain were exposed to four fractionated doses delivered at weekly intervals (total doses from 4 x 50 to 4 x 375 R). One group of mice received a mixture of radioprotectors. The animals were followed to their natural death and investigated for histopathology. Life-shortening showed a sigmoid dependency on the dose in nonprotected and protected mice with a dose reduction factor of 2.1 at 50% life-shorteining. Thymic lymphoma was the most predominant cause of death in irradiated C57Bl mice. Radioprotectors diminished significantly the incidence of this disease but apparently did not reduce other causes of death. Reticulum cell sarcoma B also increased at the same low doses as thymic lymphoma. Both thymic lymphoma and reticulum cell sarcoma B increased in frequency after a fractionated dose compared to a single exposure with doses of 600 to 700 R and 300 to 400 R, respectively

  9. Protection of mouse hematopoietic stem cells by a preparation of herb mixture (hemoHIM) against whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Jung, W. H.; Park, H. R.; Oh, H.; Jung, I. Y.; Cho, S. K. [KAERI, Taejon (Korea, Republic of)

    2002-10-01

    A preparation of herb mixture (HemoHIM) was designed from three medicinal herbs including Angelica gigantis Radix to protect gastrointestine, hematopoietic organs and immune system against radiation damage. In the present study, we investigated the radioprotective effects of HemoHIM on hematopoietic stem cells in {gamma}-irradiated mice and the underlying mechanisms. The administration of HemoHIM significantly increased the formation of endogenous spleen colony and reduced apoptosis of bone marrow cells in {gamma}-irradiated mice. These results showed that HemoHIM protected hematopoietic stem cells from irradiation. To investigate the mechanism of the protection, the effects of HemoHIM on expression of radioprotective cytokines was examined. HemoHIM increased the mRNA levels of IL-1{beta}, TNF-{alpha}, SCF and IL-6 in bone marrow cells and peritoneal macrophages in vitro. In vivo administration of HemoHIM increased the mRNA levels of IL-1{beta}, TNF-{alpha} in spleen. The examination of radical scavenging activity of HemoHIM as another mechanism revealed that HemoHIM was effective at scavenging DPPH radicals and hydroxyl radicals. From these results, it is suggested that HemoHIM exerts these radioprotective effects through the induction of radioprotective cytokines and/or through directly scavenging radicals produced by {gamma}-irradiation.

  10. The effects of whole-body irradiation on the serum levels and kinetics of thyroid hormones in rats

    International Nuclear Information System (INIS)

    The effects of a single whole-body dose of X-rays on the serum levels and kinetics of thyroid hormones in rats were studied. The influence of radiation-induced anorexia was monitored by using pair fed control groups. A dose of 800 rad caused a reduction in T4 levels and 750 rad had a similar effect on T3; in each case the control group showed a smaller reduction. The kinetic results indicated that, in the control groups, the early reduction in hormone concentrations was caused by decreased production, whereas, in the irradiated groups, it was caused by a change in the distribution of the hormone; however the continuing reduction in hormone levels in the irradiated rats appeared to result from decreased production. The results suggest that the thyroid system may play an active part in the early metabolic changes which follow whole-body irradiation. (author)

  11. In vivo dosimetry for total body irradiation: five-year results and technique comparison.

    Science.gov (United States)

    Patel, Reshma P; Warry, Alison J; Eaton, David J; Collis, Christopher H; Rosenberg, Ivan

    2014-07-08

    The aim of this work is to establish if the new CT-based total body irradiation (TBI) planning techniques used at University College London Hospital (UCLH) and Royal Free Hospital (RFH) are comparable to the previous technique at the Middlesex Hospital (MXH) by analyzing predicted and measured diode results. TBI aims to deliver a homogeneous dose to the entire body, typically using extended SSD fields with beam modulation to limit doses to organs at risk. In vivo dosimetry is used to verify the accuracy of delivered doses. In 2005, when the Middlesex Hospital was decommissioned and merged with UCLH, both UCLH and the RFH introduced updated CT-planned TBI techniques, based on the old MXH technique. More CT slices and in vivo measurement points were used by both; UCLH introduced a beam modulation technique using MLC segments, while RFH updated to a combination of lead compensators and bolus. Semiconductor diodes were used to measure entrance and exit doses in several anatomical locations along the entire body. Diode results from both centers for over five years of treatments were analyzed and compared to the previous MXH technique for accuracy and precision of delivered doses. The most stable location was the field center with standard deviations of 4.1% (MXH), 3.7% (UCLH), and 1.7% (RFH). The least stable position was the ankles. Mean variation with fraction number was within 1.5% for all three techniques. In vivo dosimetry can be used to verify complex modulated CT-planned TBI, and demonstrate improvements and limitations in techniques. The results show that the new UCLH technique is no worse than the previous MXH one and comparable to the current RFH technique.

  12. COMPROMISING EFFECT OF LOW DOSE-RATE TOTAL-BODY IRRADIATION ON ALLOGENEIC BONE-MARROW ENGRAFTMENT

    NARCIS (Netherlands)

    VANOS, R; KONINGS, AWT; DOWN, JD

    1993-01-01

    The protraction of total body irradiation (TBI) to a continuous low dose-rate has been investigated for its effect on donor marrow engraftment in murine bone marrow transplant (BMT) models of varying histocompatibility. Three different BMT combinations were used: syngeneic [B6-Gpi-1a --> B6-Gpi-1b],

  13. 60Coγ射线损伤后小鼠造血系统生理指标的动态变化%Changes of Physiological Indexes in Hematopoietic System of Mice after 60Coγ Ray Irradiation

    Institute of Scientific and Technical Information of China (English)

    侯新然; 王晓波; 袭荣刚; 李忠亮; 高慧媛; 吴立军; 马晓梅

    2012-01-01

    Objective To explore the physiological variation of the hematopoietic system in mice after C07 ray irradiation. Methods Body weight, peripheral blood cell counts,the immune organ index and pathological changes in femoral bone marrow of mice were measured at different times after whole-body irradiation with C07 ray. The doses were 2,4,6 Gy respectively. Results The changes of peripheral blood of mice were different. The white blood cell counts declined most rapidly and obviously,followed by the platelet count,with a dose-effect relationship. Three days after radiation, the immune organ index of mice decreased significantly compared with the immune organ index in mice unirradiated. Myeloid elements in bone marrow were reduced and bone marrow hematopoiesis was depressed. Body weight of irradiated mice grew slowly, without significant difference with mice unirradiated. Conclusion 60Coγ ray radiation can decrease peripheral blood cells, decrease the immune organ index and inhibit bone marrow cell proliferation in mice.%目的 探索小鼠60Coγ射线损伤后造血系统各项生理指标的变化规律.方法 采用60Coγ射线对小鼠进行一次性全身照射,剂量分别为2、4、6 Gy,在不同时间分别测定小鼠体质量,外周血细胞计数,免疫器官指数及股骨骨髓的病理变化.结果 照射后小鼠的外周血象有变化,其中白细胞下降最迅速且明显,其次是血小板,且具有剂量效应关系.照射后3d免疫器官指数下降明显,与对照组比较具有显著性差异;骨髓造血细胞数目迅速减少,出现造血抑制;照射后小鼠体质量增加缓慢,但与对照组比较无显著性差异.结论 60Coγ射线照射可引起小鼠外周血细胞下降,免疫器官指数下降,并抑制骨髓造血细胞增生.

  14. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    Science.gov (United States)

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome. PMID:27356057

  15. Calorie restriction reduces the incidence of myeloid leukemia induced by a single whole-body radiation in C3H/He mice.

    Science.gov (United States)

    Yoshida, K; Inoue, T; Nojima, K; Hirabayashi, Y; Sado, T

    1997-03-18

    Dietary restriction, especially caloric restriction, is a major modifier in experimental carcinogenesis and is known to decrease significantly the incidence of neoplasms. Gross and Dreyfuss [Gross, L. & Dreyfuss, Y. (1984) Proc. Natl. Acad. Sci. USA 81, 7596-7598; Gross, L. & Dreyfuss, Y. (1986) Proc. Natl. Acad. Sci. USA 83, 7928-7931] reported that a 36% restriction in caloric intake dramatically decreased the radiation-induced solid tumors and/or leukemias. Their protocol predominantly produced lymphatic neoplasms. It is of interest to observe the effect of caloric restriction on radiation-induced myeloid leukemia, because the disease was observed to have been increased in the survivors of the atomic bombs in Hiroshima and Nagasaki. The spontaneous incidence of myeloid leukemia in C3H/He male mice is 1%, and the incidence increased to 23.3% when 3 Gy of whole-body x-ray irradiation was given. However, the incidence of myeloid leukemia was found to be significantly decreased by caloric restriction; it was reduced to 7.9% and 10.7% when restriction was started before (6 weeks old) and after (10 weeks old) irradiation, respectively. In addition, the onset of the myeloid leukemia in both restricted groups was prolonged to a greater extent as compared with the control diet group. Caloric restriction demonstrated a significant prolongation of the life span in the groups on a restricted diet after having been exposed to irradiation, either before or after dietary restriction, in comparison with mice that were only irradiated. PMID:9122244

  16. Characterization and clonality of prelymphoma cells of B10 mice treated with fractionated X-irradiation (FX)

    International Nuclear Information System (INIS)

    With a combined use of cell separation by cell sorter and intrathymic injection assay, it was shown that prelymphoma cells existed in the subpopulation of thymocytes expressing TL-2 antigen which is not expressed on normal thymocytes of B10. Thy 1.2 or B10. Thy 1.1 mice. We then addressed a question whether all TL-2+ cells undergo neoplastic initiation or pre-neoplastic cells develop infrequently from TL-2+ cells. To investigate this problem and to examine the clonality of prelymphoma cells, thymocytes from individual B10. Thy 1.1 mice at various times after FX were stained with anti TL-2 mAb and the content of TL-2+ cells was evaluated. A graded amount of TL-2+ thymocytes from individual mice was injected into the thymuses of B10. Thy 1.2 mice. Although various numbers of TL-2+ cells appeared in the thymus of individual mice 14 - 28 days after FX, the donor type T cell lymphomas developed when 102 - 105 of TL-2+ cells from 7 individuals out of 20 mice were injected into the recipient mice. On the other hand, injection of TL-2+ cells from other mice (13 out of 20) did not develop donor type T cell lymphoma in spite of TL-2+ cells appearing in the thymus. These results indicate that all TL-2+ cells did not always undergo neoplastic initiation, and prelymphoma cells might develop infrequently from TL-2+ cells. To evaluate the clonality of prelymphoma cells, high molecular weight DNAs were isolated from the donor-derived T cell lymphomas and the rearrangement of T cell receptors examined by Southern blot analysis. The nucleotide sequences of V-J junctions were also determined by polymerase chain reaction techniques. The results indicated that after irradiation neoplastic initiation might occur oligoclonally in some of the TL-2+ cells. (author)

  17. The formation of tigroid substance during postnatal maturation of the brain of mice after pre- and perinatal X-irradiation

    International Nuclear Information System (INIS)

    Using Nissl stained slices of postnatal brain, tigroid formation in neurons of the cortex, thalamus, cerebellum, hippocampus, gyrus dentatus and nucleus mot. trigemini was examined in X-irradiated mice. Following exposure on days 13, 16, 18,5 or 22 post conception with doses ranging grom 0.5 Gy to 3.0 Gy tigroid formation was studied by means of a selective microphotometrical measurement technique. After irradiation, a fluctuating diminution in the tigroid density was observed in relation to the controls. It was dependent both on the dose and on the stage of development during exposure. In several brain regions fluctuating tigroid responses, being most pronounced during the critical periods of postnatal brain maturation, resulted in a longterm compensation of a deficit in the tigroid density after irradiation with 0.5 Gy. After the higher doses the density diminution was either not compensated or was progressive. The late tigroid responses decrease from irradiation on day 13 p.c. to irradiation day 22 p.c. Hence, this type of late maturation impairment was either extended through several cell generations or it was induced to a lesser degree in the early postmitotic neurons. Changes in the total RNA-content of the brain are concomitant with the third week after birth. The tigroid reactions were interpreted as a chain of interdependent processes of retardation and stabilization. Accordingly, to obtain a better understanding of long-term maturation defects, a comprehensive evaluation of the whole chain of events will be required. (orig.)

  18. Pulmonary changes induced by combined mouse β-interferon (rMuIFN-β) and irradiation in normal mice

    International Nuclear Information System (INIS)

    This study in normal mice was undertaken to investigate possible enhancement of pulmonary toxicity by interferon - beta (IFN) combined with single doses of irradiation. A pharmacokinetic study preceded the toxicity study to determine the optimal timing of IFN administration. Graded single doses of radiation were combined with graded doses of IFN. Pulmonary toxicity was determined using endpoints of alveolar surfactant and procollagen in lung lavage fluid at 7 days, breathing frequency lethality and histology. Increased lethality was seen when IFN was combined with irradiation at 12.5 Gy vs. irradiation alone. This occurred between 20 and 30 weeks post treatment with no increased breathing frequency or surfactant release, suggesting independent mechanism of injury. Increased breathing frequency after 40 weeks, usually associated with fibrosis, was less pronounced for IFN treated vs. irradiation only controls. Ultrastructural studies at 72 weeks suggest reduced fibrosis in lungs of IFN treated vs. irradiation only controls. Supporting this was the finding that Procollagen III, a biosynthetic precursor of collagen, was increased in lavage fluid at 7 days for all radiation doses but decreased with the addition of IFN at 12.5 and 15 Gy. Interferons can act either as sensitizers or radioprotectors, depending on the biological system and type of interferon. Our study suggests that IFN-β may increase the acute effects of radiation in the mouse lung, some protection from radiation-induced fibrosis, possibly related to alteration of immune mechanisms, may exist

  19. Effect of a whole-body gamma irradiation on glycemia and ATP blood level in rats

    International Nuclear Information System (INIS)

    An attempt was made to establish possible correlations, during gamma irradiation, between glucose and ATP. The variations in their blood levels were studied, using specific enzymatic methods. The results obtained after a low dose irradiation (150 roentgens) demonstrated an increase of glycemia during the hours following the irradiation and a parallel decrease of ATP blood level

  20. Radioprotection effect on irradiation mice of haemopoietic cell of echinacea purpurea(north American herb) by the celiac medication

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Kiyoto; Gu, Yeunhwa; Ukawa, Yuuichi; Park, Sangrea; Trai, Kaoru; Tanaka, Kenichirou; Tajima, Masayuki; Hasegawa, Takeo; Suzuki, Ikukatsu [Suauka Univ. of Medical Science, Suzuka (Japan); Mishima, Satoshi [Api Co., LTD., Kifu (Japan)

    2002-07-01

    The medicine that suspension made phosphoric acid saline make the dryness leaf powder of Echinacea purpurea which is typical north American herb in medical herb with the multiple seeds muddy, in the ICR male mouse (age of five weeks). It period in three times a week, eight weeks, and Celiac Medication was given. (360mg/kg/mouse). 2Gy irradiated it by the X-ray irradiation device (200kV, 0.35Gy/min) for the Echinacea purpurea medication the third week. Collecting blood was done in the sutra time target from the day before X-ray irradiation, and a change in the corpuscle number (the number of the leukocyte, the number of the lymphocyte, the number of the granulocytes, the number of monocyte) was observed. The number of the leukocytes of the non-medication control group faced, and increase in the number of the leukocytes in the medication group wasn't recognized with the thing before the X-ray irradiation as a result. It faced though the number of the leukocytes decreased remarkably due to the radiation irradiation in the non-medication control group, and the decrease was controlled as for the medication group. The recovery of the number of the leukocytes of the medication group in the group after the X-ray irradiation showed a tendency of becoming early in comparison with the non-medication control group. As for the number of the lymphocyte except for the leukocyte, the number of the granulocyte, the number of monocyte as well, it could get the same result as the number of the leukocytes. Than the above result, Echinacea purpurea toward the mice blood cell. Effect on radiation protection along with effect on repression of a blood number decrease due to the irradiation manufactured by was suggested.

  1. Repeated 0.5 Gy gamma-ray irradiation attenuates autoimmune disease in MRL-lpr/lpr mice with up-regulation of regulatory T cells

    International Nuclear Information System (INIS)

    Complete text of publication follows. MRL-lpr/lpr mice present a single gene mutation on the Fas (CD95) gene that leads to reduced signaling for apoptosis. With aging, these mice spontaneously develop autoimmune disease and are used as a model of systemic lupus erythematosus. We previously reported attenuation of autoimmune disease in MRL-lpr/lpr mice by repeated γ-ray irradiation (0.5 Gy each time). In this study, we investigated the mechanisms of this attenuation focusing the highly activated CD3+CD4-CD8-B220+ T cells, which are characteristically involved in autoimmune pathology in these mice. We measured the weight of the spleen and the population of CD3+CD4-CD8-B220+ T cells. Splenomegaly and increase in percentage of CD3+CD4-CD8-B220+ T cells, which occur with aging in non-irradiated mice, were suppressed in irradiated mice. To investigate the function of CD3+CD4-CD8-B220+ T cells, we isolated these cells from splenocytes by magnetic cell sorting. Isolated CD3+CD4-CD8-B220+ T cells were more resistant to irradiation-induced cell death than isolated CD4+ T cells. Although high proliferation rate and IL-6 production were observed in isolated CD3+CD4-CD8-B220+ T cells, the proliferation rate and IL-6 production were lower in the cells isolated from the irradiated mice. Moreover, the production of autoantibodies (anti-collagen antibody and anti-single strand DNA antibody) was also lowered by irradiation. These results indicate that activation of CD3+CD4-CD8-B220+ T cells and progression of pathology would be suppressed by repeated 0.5 Gy γ-ray irradiation. To uncover the mechanism of the immune suppression, we analyzed population of regulatory T cells (CD4+CD25+Foxp3+), which suppress activated T cells and excessive autoimmune responses. Intriguingly, significant increase of the percentage of regulatory T cells was observed in irradiated mice. In conclusion, we found that repeated 0.5 Gy γ-ray irradiation suppresses proliferation rate of CD3+CD4-CD8-B220+ T

  2. Effects of a granulocyte colony stimulating factor, Neulasta, in mini pigs exposed to total body proton irradiation

    Science.gov (United States)

    Sanzari, Jenine K.; Krigsfeld, Gabriel S.; Shuman, Anne L.; Diener, Antonia K.; Lin, Liyong; Mai, Wilfried; Kennedy, Ann R.

    2015-04-01

    Astronauts could be exposed to solar particle event (SPE) radiation, which is comprised mostly of proton radiation. Proton radiation is also a treatment option for certain cancers. Both astronauts and clinical patients exposed to ionizing radiation are at risk for loss of white blood cells (WBCs), which are the body's main defense against infection. In this report, the effect of Neulasta treatment, a granulocyte colony stimulating factor, after proton radiation exposure is discussed. Mini pigs exposed to total body proton irradiation at a dose of 2 Gy received 4 treatments of either Neulasta or saline injections. Peripheral blood cell counts and thromboelastography parameters were recorded up to 30 days post-irradiation. Neulasta significantly improved WBC loss, specifically neutrophils, in irradiated animals by approximately 60% three days after the first injection, compared to the saline treated, irradiated animals. Blood cell counts quickly decreased after the last Neulasta injection, suggesting a transient effect on WBC stimulation. Statistically significant changes in hemostasis parameters were observed after proton radiation exposure in both the saline and Neulasta treated irradiated groups, as well as internal organ complications such as pulmonary changes. In conclusion, Neulasta treatment temporarily alleviates proton radiation-induced WBC loss, but has no effect on altered hemostatic responses.

  3. The enhancement of haemopoietic stem cell recovery in irradiated mice by prior treatment with cyclophosphamide

    International Nuclear Information System (INIS)

    Studies are reported of the enhancement of stem cell recovery following whole body irradiation as a result of prior administration of cyclophosphamide. It is shown that the much larger enhancement of regeneration observed for the hosts own surviving stem cells, compared to the regeneration of injected bone marrow stem cells, is due to the different numbers of stem cells initiating the regeneration in conjunction with the time course of stem cell regeneration. The results show that the environmental changes produced by cyclophosphamide greatly enhance haemopoietic recovery even though at the dose used this agent is relatively toxic to stem cells. Furthermore it has been shown that the level of stem cell regeneration is nearly independent of the γ-ray dose in the range 3-8 gray (300-800 rad). If human bone marrow should respond similarly it follows that regeneration produced by cytotoxic drugs administered prior to radiation embodies a considerable safety factor as far as recovery of the haemopoietic system is concerned. (author)

  4. Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice

    DEFF Research Database (Denmark)

    Gustafsson, E; Brakebusch, C; Hietanen, K;

    2001-01-01

    the production and screening of multiple transgenic lines we used embryonic stem cell and embryoid body technology to identify recombinant embryonic stem cell clones with high, endothelial-specific Cre activity. One embryonic stem cell clone that showed high Cre activity in endothelial cells was used to generate...... germline chimeras. The in vivo efficiency and specificity of the transgenic Cre was analysed by intercrossing the tie-1-Cre line with the ROSA26R reporter mice. At initial stages of vascular formation (E8-9), LacZ staining was detected in almost all cells of the forming vasculature. Between E10 and birth...

  5. Successful treatment of autoimmune manifestations in MRL/l and MRL/n mice using total lymphoid irradiation (TLI)

    International Nuclear Information System (INIS)

    The autoimmune manifestations of MRL-+/+ (MRL/n) and MRL/Mp-lpr/lpr (MRL/l) murine models of systemic lupus erythematosus (SLE) were successfully reversed following total lymphoid irradiation (TLI) therapy consisting of 8-12 daily fractions of 200 rad. Following radiotherapy the characteristic lymphadenopathy of MRL/l disappeared, proteinuria was 334 mg% compared to a peak of 2272 mg% in untreated controls, and the median survival time was prolonged to 423 days compared to 214 days in untreated mice. The albuminuria of TLI-treated MRL/n mice was 194 mg% compared to 1180 mg% in untreated controls. The survival of treated MRL/n mice was prolonged to a median of 389 as compared to 190 days in untreated controls. The effect of TLI on antiDNA antibodies in both MRL/l and MRL/n was less remarkable. However, the antiDNA activity reached normal levels in most long-living mice. The most impressive finding was complete reversal and/or prevention of the SLE-like glomerulonephritis in MRL/l mice as documented by light and electron microscopy. Immunomanipulation with TLI should be further evaluated as a possible treatment modality in intractable human autoimmune disorders

  6. Successful treatment of autoimmune manifestations in MRL/l and MRL/n mice using total lymphoid irradiation (TLI)

    Energy Technology Data Exchange (ETDEWEB)

    Moscovitch, M.; Rosenmann, E.; Neeman, Z.; Slavin, S.

    1983-02-01

    The autoimmune manifestations of MRL-+/+ (MRL/n) and MRL/Mp-lpr/lpr (MRL/l) murine models of systemic lupus erythematosus (SLE) were successfully reversed following total lymphoid irradiation (TLI) therapy consisting of 8-12 daily fractions of 200 rad. Following radiotherapy the characteristic lymphadenopathy of MRL/l disappeared, proteinuria was 334 mg% compared to a peak of 2272 mg% in untreated controls, and the median survival time was prolonged to 423 days compared to 214 days in untreated mice. The albuminuria of TLI-treated MRL/n mice was 194 mg% compared to 1180 mg% in untreated controls. The survival of treated MRL/n mice was prolonged to a median of 389 as compared to 190 days in untreated controls. The effect of TLI on antiDNA antibodies in both MRL/l and MRL/n was less remarkable. However, the antiDNA activity reached normal levels in most long-living mice. The most impressive finding was complete reversal and/or prevention of the SLE-like glomerulonephritis in MRL/l mice as documented by light and electron microscopy. Immunomanipulation with TLI should be further evaluated as a possible treatment modality in intractable human autoimmune disorders.

  7. Transfer of 109Cd in the mother's body to the suckling infant mice through the milk and its distribution in their whole bodies

    International Nuclear Information System (INIS)

    To point out the transfer of injected 109Cd in mothers, body to suckled infant mice through the milk and its distribution in their whole bodies, the following experiments were performed. Pregnant mice received 8μ Ci of 109Cd by intravenous injection 7 days before parturition. After the delivery, the suckled infant mice were killed and fixed by momentary freezing in the refrigerated room of -15 deg C every day from 1 to 5 days an