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Sample records for body irradiated mice

  1. Effect of bifidobacteria implantation on the survival time of whole-body irradiated mice

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    Yokokura, T.; Onoue, M.; Mutai, M. (Yakult Institute for Microbiological Research)

    1980-01-01

    Letahl dose (2 KR) of gamma-ray was irradiated on the whole bodies of mice. Survival time after irradiation was significantly longer in mice with administration of both Bifidobacterium breve YIT 4008 and transgalactosyl oligosaccharide than in mice with administration of either of the two or nothing.

  2. 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)

  3. Caffeine protects mice against whole-body lethal dose of {gamma}-irradiation

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    George, K.C.; Hebbar, S.A.; Kale, S.P.; Kesavan, P.C. [Biosciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    1999-06-01

    Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of {gamma}-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the toxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice. (author)

  4. Whole-body proton irradiation causes long-term damage to hematopoietic stem cells in mice.

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    Chang, Jianhui; Feng, Wei; Wang, Yingying; Luo, Yi; Allen, Antiño R; Koturbash, Igor; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2015-02-01

    Space flight poses certain health risks to astronauts, including exposure to space radiation, with protons accounting for more than 80% of deep-space radiation. Proton radiation is also now being used with increasing frequency in the clinical setting to treat cancer. For these reasons, there is an urgent need to better understand the biological effects of proton radiation on the body. Such improved understanding could also lead to more accurate assessment of the potential health risks of proton radiation, as well as the development of improved strategies to prevent and mitigate its adverse effects. Previous studies have shown that exposure to low doses of protons is detrimental to mature leukocyte populations in peripheral blood, however, the underlying mechanisms are not known. Some of these detriments may be attributable to damage to hematopoietic stem cells (HSCs) that have the ability to self-renew, proliferate and differentiate into different lineages of blood cells through hematopoietic progenitor cells (HPCs). The goal of this study was to investigate the long-term effects of low-dose proton irradiation on HSCs. We exposed C57BL/6J mice to 1.0 Gy whole-body proton irradiation (150 MeV) and then studied the effects of proton radiation on HSCs and HPCs in the bone marrow (BM) 22 weeks after the exposure. The results showed that mice exposed to 1.0 Gy whole-body proton irradiation had a significant and persistent reduction of BM HSCs compared to unirradiated controls. In contrast, no significant changes were observed in BM HPCs after proton irradiation. Furthermore, irradiated HSCs and their progeny exhibited a significant impairment in clonogenic function, as revealed by the cobblestone area-forming cell (CAFC) and colony-forming cell assays, respectively. These long-term effects of proton irradiation on HSCs may be attributable to the induction of chronic oxidative stress in HSCs, because HSCs from irradiated mice exhibited a significant increase in NADPH

  5. Long-Term Effects of Stem Cells on Total-Body Irradiated Mice

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    Vyalkina, M. V.; Alchinova, I. B.; Yakovenko, E. N.; Medvedeva, Yu S.; Saburina, I. N.; Karganov, M. Yu

    2017-01-01

    C57Bl/6 mice were exposed to γ-radiation in a sublethal dose of 7.5 Gy. In 3 hours injection 106/mouse of bone marrow multipotent mesenchymal stromal cells stem cells intravenously to experimental group was done. Methods used: body weight measurement, open field behavior, subfraction composition of blood serum (laser correlation spectroscopy, LCS), histological examination of the spleen, liver, and pancreas, count of T and B cells, white blood formula. After 1.5 and 3 months the general trend towards intermediate position of the parameters observed in the experimental between those in intact and irradiated controls attests to partial protective/restorative effects of the injected cells.

  6. 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.

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

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

    1981-11-01

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

  8. 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

  9. 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)

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

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    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.

  11. 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.

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

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    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.

  13. Influence of L-dopa and of thymus fraction on the survival rate of whole-body irradiated mice

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    Busse, E.; Helmholz, M. (Humboldt-Universitaet, Berlin (German Democratic Republic). Bereich Medizin (Charite))

    1982-06-01

    The survival rate of mice with exposure of the whole body (7 Gy) was hardly changed by one dose as well as several doses of the phosphodiesterase inhibitor amantadine and the interferon inductor measles vaccine. However, the survival rates were increased by one administration of L-dopa or by the long-term therapy using L-dopa at 7 and 9 Gy, resp. The survival rates were also increased at 7 and 9 Gy, resp. if the thymus factor was three times applied to the animals after irradiation. The increased survival rates gained by using L-dopa and thymus factor are correlated with the leukocyte values determined.

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

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    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.

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

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    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.

  16. Antibiotic radioprotection of mice exposed to supralethal whole-body irradiation independent of antibacterial activity. [Gamma radiation, streptomycin, kanamycin, neomycin, gentamycin

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    Mastromarino, A.; Wilson, R.

    1976-11-01

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

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

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    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.

  18. 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.

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

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    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.

  20. Differential androgenesis in gamma irradiated mice

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

    2002-07-01

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

  1. 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.

  2. Regeneration of hemopoietic and lymphoid tissues following total-body irradiation and therapeutic administration of thiamin diphosphate. [Mice, gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Vavrova, J.; Nouza, K.; Petjrek, P.

    1977-01-01

    Analysis was made of the mechanism of therapeutic application of thiamine diphosphate (TDP) in radiation sickness in mice. This agent increased the number of endogenous colonies in the spleen and incorporation of /sup 59/Fe in spleen and bone marrow with sublethal doses of radiation (500 and 600 R) and has no effect with a lethal dose (750 R). After administration of TDP to mice exposed to 500 R radiation, there is faster DNA synthesis in the spleen, thymus and bone marrow, as well as reliable increase in number of nuclear cells in femoral marrow.

  3. 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

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

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    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.

  5. 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

  6. 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 .

  7. 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.

  8. 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.

  9. Ginsan activated the antioxidant defense systems in irradiated mice

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    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.

  10. 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.

  11. 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

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    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.

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

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    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)

  13. 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.

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    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.

  14. 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.

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

    Science.gov (United States)

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

    2014-03-01

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

  16. 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.

  17. Total body irradiation for children with malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Sanuki, Eiichi; Maeno, Toshio; Kamata, Rikisaburo; Tanaka, Yoshiaki; Mugishima, Hideo [Nihon Univ., Tokyo (Japan). School of Medicine

    1995-12-01

    Total body irradiation combined with high dose chemotherapy has been performed just before bone marrow transplantation in 35 children with advanced malignancies, with the object of achieving successful transplantation and improving the prognosis. Simulation was performed as follows: back scatter, flatness, dose accumulation using randophantom and dose distribution using a thermo-luminescence dosimeter and linac-graphy. The standard error of dose distribution was within 10%. In neuroblastoma, of which there were 14 cases in stage IV and one case in stage III, the 5-year survival rate was 55%. In leukemia, of which all cases were in the high-risk group (7 cases of acute lymphoblastic leukemia and 2 of acute myeloblastic leukemia) the 5-year survival rate was 55%. The 5 cases having first remission survived disease-free while the 4 cases having non-first remission died. In malignant lymphoma (6 cases in stage IV and one case in stage III, with bulky mass) the 5-year survival rate was 67%. Four cases with other diagnoses (severe aplastic anemia, and others) all survived. As yet no side effects resulting from total body irradiation have been recognized in our cases, but a longer follow-up period is necessary to observe possible late side effects. (author).

  18. 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

  19. 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.

  20. 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.

  1. High-energy proton irradiation of C57Bl6 mice under hindlimb unloading

    Science.gov (United States)

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

    2012-07-01

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

  2. 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)

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Impairment in extinction of contextual and cued, fear following post-training whole body irradiation

    Directory of Open Access Journals (Sweden)

    Reid HJ Olsen

    2014-07-01

    Full Text Available Because of the use of radiation in cancer therapy, the risk of nuclear contamination from power plants, military conflicts, and terrorism, there is a compelling scientific and public health interest in the effects of environmental radiation exposure on brain function, in particular hippocampal function and learning and memory. Previous studies have emphasized changes in learning and memory following radiation exposure. These approaches have ignored the question of how radiation exposure might impact recently acquired memories, which might be acquired under traumatic circumstances (cancer treatment, nuclear disaster, etc.. To address the question of how radiation exposure might affect the processing and recall of recently acquired memories, we employed a fear-conditioning paradigm wherein animals were trained, and subsequently irradiated (whole-body X-ray irradiation 24 hours later. Animals were given two weeks to recover, and were tested for retention and extinction of hippocampus-dependent contextual fear conditioning. Exposure to irradiation following training was associated with reduced daily increases in body weights over the 22 days of the study and resulted in greater freezing levels and aberrant extinction 2 weeks later. This was also observed when the intensity of the training protocol was increased. Cued freezing levels and measures of anxiety 2 weeks after training were also higher in irradiated than sham-irradiated mice. In contrast to contextual freezing levels, cued freezing levels were even higher in irradiated mice receiving 5 shocks during training than sham-irradiated mice receiving 10 shocks during training. In addition, the effects of radiation on extinction of contextual fear were more profound than those on the extinction of cued fear. Thus, whole body irradiation elevates contextual and cued fear memory recall.

  8. Impairment in extinction of contextual and cued fear following post-training whole-body irradiation.

    Science.gov (United States)

    Olsen, Reid H J; Marzulla, Tessa; Raber, Jacob

    2014-01-01

    Because of the use of radiation in cancer therapy, the risk of nuclear contamination from power plants, military conflicts, and terrorism, there is a compelling scientific and public health interest in the effects of environmental radiation exposure on brain function, in particular hippocampal function and learning and memory. Previous studies have emphasized changes in learning and memory following radiation exposure. These approaches have ignored the question of how radiation exposure might impact recently acquired memories, which might be acquired under traumatic circumstances (cancer treatment, nuclear disaster, etc.). To address the question of how radiation exposure might affect the processing and recall of recently acquired memories, we employed a fear conditioning paradigm wherein animals were trained, and subsequently irradiated (whole-body X-ray irradiation) 24 h later. Animals were given 2 weeks to recover, and were tested for retention and extinction of hippocampus-dependent contextual fear conditioning or hippocampus-independent cued fear conditioning. Exposure to irradiation following training was associated with reduced daily increases in body weights over the 22-days of the study and resulted in greater freezing levels and aberrant extinction 2 weeks later. This was also observed when the intensity of the training protocol was increased. Cued freezing levels and measures of anxiety 2 weeks after training were also higher in irradiated than sham-irradiated mice. In contrast to contextual freezing levels, cued freezing levels were even higher in irradiated mice receiving 5 shocks during training than sham-irradiated mice receiving 10 shocks during training. In addition, the effects of radiation on extinction of contextual fear were more profound than those on the extinction of cued fear. Thus, whole-body irradiation elevates contextual and cued fear memory recall.

  9. 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).

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

    Energy Technology Data Exchange (ETDEWEB)

    Oshio, Shigeru; Yazaki, Tsunetada; Umeda, Takashi (Teikyo Univ., Tokyo (Japan). Faculty of Medicine); Ozaki, Satoru; Ohkawa, Isao; Tajima, Tetsuya; Yamada, Takeshi; Mohri, Hideo

    1991-12-01

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

  11. [Effects of mecobalamin on testicular dysfunction induced by X-ray irradiation in mice].

    Science.gov (United States)

    Oshio, S; Yazaki, T; Umeda, T; Ozaki, S; Ohkawa, I; Tajima, T; Yamada, T; Mohri, H

    1991-12-01

    Experimental testicular dysfunction were 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.

  12. Radioprotective effect of cimitidine on acutely irradiated mice survival and hematopoietic system

    Directory of Open Access Journals (Sweden)

    Qing-rong WANG

    2017-02-01

    Full Text Available Objective To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice. Methods The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523 group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg. Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMNPCE were determined 30d after 6.0Gy irradiation. Results After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC and bone marrow DNA content were decreased significantly (P<0.01, P<0.05 in model group, and fMNPCE was increased significantly (P<0.05. Compared with model group, WBC was significantly increased in 300mg/kg cimetidine group (P<0.01. In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 or P<0.05, and the fMNPCE was decreased significantly (P<0.01 or P<0.05and tended towards normal. Conclusion Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system. DOI: 10.11855/j.issn.0577-7402.2017.01.12

  13. Quantitative, functional and biochemical alterations in the peritoneal cells of mice exposed to whole-body gamma-irradiation. 1. Changes in cellular protein, adherence properties and enzymatic activities associated with platelet-activating factor formation and inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Steel, L.K.; Hughes, H.N.; Walden, T.L. Jr.

    1988-06-01

    Changes in total number, differentials, cell protein, adherence properties, acetyl-CoA transferase and acetylhydrolase activities, prostaglandin E/sub 2/ and leukotriene C/sub 4/ production, as well as Ca/sup 2+/ ionophore A23187 stimulation were examined in resident peritoneal cells isolated from mice 2 h to 10 days postexposure to a single dose (7, 10 or 12 Gy) of gamma-radiation. Radiation dose-related reductions in macrophage and lymphocyte numbers and increases in cellular protein and capacity to adhere to plastic surfaces were evident. In vivo irradiation also elevated the activities of acetyltransferase and acetyl-CoA hydrolase (catalysing platelet-activating factor biosynthesis and inactivation, respectively) in adherent and nonadherent peritoneal cells, particularly 3-4 days postexposure. Blood plasma from irradiated animals did not reflect the increased cellular acetyl-hydrolase activity. Prostaglandin E/sub 2/ and leukotriene C/sub 4/ synthesis were elevated postexposure, suggesting increased substrate (arachidonate) availability and increased cyclooxygenase and lipoxygenase activities. Ionophore stimulation of enzyme activities and eicosanoid release also differed in irradiated peritoneal cells.

  14. 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.

  15. 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

  16. Hemopoiesis in the splenectomized-pregnant mouse following low-dose total-body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Weinberg, S.R.; MacVittie, T.J.

    1981-09-01

    The effect of splenectomy (SPLX) and total-body irradiation (TBI) (50-200 rad) on virgin and pregnant mouse hemopoiesis was studied, using peripheral blood hemogram values and femoral marrow hemopoietic progenitor cell activity (i.e., CFUlt. slash/sub E/, BFU/sub E/, and GM-CFC). The SPLX-maternal red cell counts and hematocrit values were lower than those of SPLX-virgin mice, reflecting the anemia of pregnancy. But the white cell counts of both SPLX-virgin and SPLX-day-14.5 pregnant mice were significantly higher (P<0.005) than normal-virgin mice. Both nonirradiated and day-4 irradiated SPLX-maternal marrow Ep-independent and Ep-dependent CFU/sub E/ were higher than the nonirradiated and day-4 irradiated SPLX-virgin values (respectively, for each TBI dose studied). On the other hand, nonirradiated and day-4 irradiated SPLX-maternal GM-CFC were lower than the nonirradiated and day-4 irradiated SPLX-virgin GM-CFC values. The data demonstrate the potential of the SPLX-maternal femoral marrow to respond to the stress of low-dose TBI with effective compensatory erythropoiesis, possibly at the expense of granulopoiesis.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Total body irradiation with a reconditioned cobalt teletherapy unit.

    Science.gov (United States)

    Evans, Michael D C; Larouche, Renée-Xavière; Olivares, Marina; Léger, Pierre; Larkin, Joe; Freeman, Carolyn R; Podgorsak, Ervin B

    2006-01-01

    While the current trend in radiotherapy is to replace cobalt teletherapy units with more versatile and technologically advanced linear accelerators, there remain some useful applications for older cobalt units. The expansion of our radiotherapy department involved the decommissioning of an isocentric cobalt teletherapy unit and the replacement of a column-mounted 4-MV LINAC that has been used for total body irradiation (TBI). To continue offering TBI treatments, we converted the decommissioned cobalt unit into a dedicated fixed-field total body irradiator and installed it in an existing medium-energy LINAC bunker. This article describes the logistical and dosimetric aspects of bringing a reconditioned cobalt teletherapy unit into clinical service as a total body irradiator.

  2. Designing attenuators for total-body irradiation using virtual simulation.

    Science.gov (United States)

    Corns, R; Evans, M; Olivares, M; Dyke, L; Podgorsak, E B; Freeman, C R

    2000-01-01

    In total-body photon irradiation, the lungs are the most commonly shielded organ. Lung compensators are often designed by using high-energy portal films. Other organs, such as the kidneys and liver, are poorly visualized in portal films due to their unit-density composition. A computed tomography-based technique to design kidney and liver attenuators involves outlining these organs in a virtual simulation. The position and the shape of the attenuator are then determined from a digitally-reconstructed radiograph. Appropriate attenuator thickness is determined from measured transmission curves. This article provides a summary of this technique for total-body photon irradiation in a 4-MV photon beam.

  3. 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.

  4. 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.

  5. 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).

  6. 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)

  7. 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.

  8. Radioprotective Effect of Lyophyllum Decastes and the Effect on Immunological Functions in Irradiated Mice

    Institute of Scientific and Technical Information of China (English)

    Takashi Nakamura; Yuka Itokawa; Masayuki Tajima; Yuuichi Ukawa; Kwang-Ho Cho; Jung-Sook Choi; Torao Ishida; Yeunhwa Gu

    2007-01-01

    In this study, to explore the radiation protection effects of Lyophyllum Decastes Sing (LDS), a hot distilled-water extract of LDS was orally administered at a dosage of 250mg/kg every other day for a period of 2 weeks in irradiated mice. An automatic blood cell counter was used to measure white blood cells (lymphocytes, monocyte, and granulocytes) one day before X-ray irradiation, and 3 hours, 12 hours, 24 hours,3 days, 7 days, 15 days and 30 days after irradiation. The Dunnett test was used to examine statistical significance of differences. The peripheral blood cell counts in the Lyophyllum-administered non-irradiation group revealed an increase in the numbers of leukocytes, lymphocytes and monocytes. For 2 Gy whole body radiation, a significant statistical difference was found between the X-ray group and the Lyophyllum plus X-ray group in the numbers of leukocytes, lymphocytes and monocytes. The results suggest that Lyophyllum restrains blood cell-count falling after irradiation, which is probably mediated at least in part by hemopoietic function, and NK and LAK activities seems to play a role in preventing secondary infections associated with irradiation.

  9. Radioprotective effect of ascorbate in the liver of {gamma}-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Yun; Park, Young Soon [Sohae College, Kusan (Korea, Republic of)

    2000-06-01

    In the present study, to determine whether the ascorbate protect against radiation damage and the possible relationship among the radioprotective effects and antioxidant actions, the effects of ascorbate(240 mg/kg, i.p) pretreatment of mice on the survival ratio, splenic weight, major antioxidant enzymes(SOD, catalase and glutathione peroxidase) activities, glutathione contents and lipid peroxidation in the liver were examined for 2 weeks after whole-body {gamma}-irradiation(6.5 Gy). The 30-day survival ratio increased from 10% to 47% for mice treated with ascorbate. The ascorbate decreased the extent of loss in splenic weight and stimulated recovery of splenic weight in irradiated mice(p<0.01). On the day of 14 after {gamma}-irradiation, the ascorbate pretreatment produced a slight increase of antioxidant enzymes activities and significantly increased reduced glutathione(GSH) contents(p<0.05) in the liver compared with non-treated group. Pretreatment with the ascorbate significantly decreased GSSG/total GSH ratio(p<0.05) without the change of GSSG in the liver and inhibited the radiation-induced increase in the hepatic malondialdehyde levels(p<0.05). In these results, we found that its radioprotective effect by protecting antioxidant enzyme activities and glutathione contents from radiation induced a decrease, and thereby suppressing lipid peroxidation which is induced by free radicals.

  10. Systemic lupus erythematosus following total body irradiation for malignant lymphoma.

    Science.gov (United States)

    Spinozzi, F; Capodicasa, E; Gerli, R; Bertotto, A; Rambotti, P; Grignani, F

    1986-01-01

    A case of a 63-year old man, who developed systemic lupus erythematosus three years after an initial diagnosis of small-cleaved centrofollicular lymphoma is described. The diagnosis of SLE was made on the basis of the accepted "1982 revised criteria for the classification of SLE". The autoimmune disease arose after a cycle of total body irradiation, despite the treatment with combination chemotherapeutic doses such a CVP or COAP or Cyclophosphamide, Vincristine, VM-26 and Prednisone. Genetic, immunological and exogenous environmental factors may co-exist and might equally be implicated in the pathogenesis of SLE and malignant lymphoma. However, the onset of SLE after total body irradiation could have been caused by the inactivation of suppressor T lymphocytes, which are known to be sensitive to radiations in vitro.

  11. 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.

  12. 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...

  13. Whole Body Microwave Irradiation for Improved Dacarbazine Therapeutical Action in Cutaneous Melanoma Mouse Model

    Directory of Open Access Journals (Sweden)

    Monica Neagu

    2013-01-01

    Full Text Available A cutaneous melanoma mouse model was used to test the efficacy of a new therapeutical approach that uses low doses of cytostatics in conjunction with mild whole body microwave exposure of 2.45 GHz in order to enhance cytostatics antitumoral effect. Materials and Methods. A microwave exposure system for C57BL/6 mouse whole body microwave irradiation was designed; groups of 40 mice (males and females bearing experimental tumours were subjected to a combined therapy comprising low doses of dacarbazine in combination with mild whole body irradiation. Clinical parameters and serum cytokine testing using xMAP technology were performed. Results. The group that was subjected to combined therapy, microwave and cytostatic, had the best clinical evolution in terms of overall survival, tumour volume, and metastatic potential. At day 14 the untreated group had 100% mortality, while in the combined therapy group 40% of mice were surviving. Quantifying serum IL-1β, IL-6, IL-10, IL-12 (p70, IFN-γ, GM-CSF, TNF-α, MIP-1α, MCP-1, and KC during tumorigenesis and therapy found that the combined experimental therapy decreases all the inflammatory cytokines, except chemokine MCP-1 that was found increased, suggesting an increase of the anti-tumoral immune response triggered by the combined therapy. The overall metastatic process is decreased in the combined therapy group.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Loss of a major idiotype (CRIA) after repopulation of irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Willems, F.; Vansanten-Urbain, G.; De Wit, D.; Slaoui, M.; Urbain, J. (Universite Libre de Bruxelles (Belgium))

    1990-02-15

    The normal immune response of A/J mice against arsonate coupled to hemocyanin is characterized by a major recurrent cross-reactive Id, the CRIA. This Id is encoded by a single gene segment combination: VHidcr11-DFL16.1e-JH2 for the H chain and Vkidcr-Jk1 for the L chain. In this report, we show that lethal irradiation of A/J mice followed by reconstitution with autologous or syngeneic lymphoid cells results in loss of major CRIA Id expression in the response to arsonate. Different protocols were performed to repopulate the irradiated mice. First, lethally irradiated A/J mice were reconstituted by the transfer of syngeneic bone marrow cells. Second, A/J mice were lethally irradiated while their hind limbs were partially shielded. Third, lethally irradiated A/J mice received a transfer of syngeneic spleen cells. The three groups of mice produce high titers of antiarsonate antibodies completely devoid of CRIA DH-JH related idiotopes expression. Moreover, a lack of affinity maturation is observed in the secondary antiarsonate response of all irradiated and reconstituted mice. A transfer of syngeneic peritoneal cells or a transfer of primed T cells in irradiated and reconstituted A/J mice do not restore in a significant manner either the recurrent CRIA expression or the affinity maturation of the antiarsonate response. Our data suggest that the choice of this Id is not solely dictated by the Igh locus.

  20. 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).

  1. 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

  2. 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.

  3. 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

  4. Dosimetry Formalism and Implementation of a Homogenous Irradiation Protocol to Improve the Accuracy of Small Animal Whole-Body Irradiation Using a 137Cs Irradiator.

    Science.gov (United States)

    Brodin, N Patrik; Chen, Yong; Yaparpalvi, Ravindra; Guha, Chandan; Tomé, Wolfgang A

    2016-02-01

    Shielded Cs irradiators are routinely used in pre-clinical radiation research to perform in vitro or in vivo investigations. Without appropriate dosimetry and irradiation protocols in place, there can be large uncertainty in the delivered dose of radiation between irradiated subjects that could lead to inaccurate and possibly misleading results. Here, a dosimetric evaluation of the JL Shepard Mark I-68A Cs irradiator and an irradiation technique for whole-body irradiation of small animals that allows one to limit the between subject variation in delivered dose to ±3% are provided. Mathematical simulation techniques and Gafchromic EBT film were used to describe the region within the irradiation cavity with homogeneous dose distribution (100% ± 5%), the dosimetric impact of varying source-to-subject distance, and the variation in attenuation thickness due to turntable rotation. Furthermore, an irradiation protocol and dosimetry formalism that allows calculation of irradiation time for whole-body irradiation of small animals is proposed that is designed to ensure a more consistent dose delivery between irradiated subjects. To compare this protocol with the conventional irradiation protocol suggested by the vendor, high-resolution film dosimetry measurements evaluating the dose difference between irradiation subjects and the dose distribution throughout subjects was performed using phantoms resembling small animals. Based on these results, there can be considerable variation in the delivered dose of > ± 5% using the conventional irradiation protocol for whole-body irradiation doses below 5 Gy. Using the proposed irradiation protocol this variability can be reduced to within ±3% and the dosimetry formalism allows for more accurate calculation of the irradiation time in relation to the intended prescription dose.

  5. 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...

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

    OpenAIRE

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

    2006-01-01

    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 4...

  7. Effect of ATM heterozygosity on heritable DNA damage in mice following paternal F{sub 0} germline irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Baulch, Janet E. [University of Maryland, Baltimore, Radiation Oncology Research Laboratory, BRB 7-002, 655 West Baltimore Street, Baltimore, MD 21201 (United States)]. E-mail: jbaulch@som.umaryland.edu; Li, M.-W. [Center for Health and the Environment, University of California Davis, CA 95616 (United States); Raabe, Otto G. [Center for Health and the Environment, University of California Davis, CA 95616 (United States)

    2007-03-01

    The ataxia telangiectasia mutated (ATM) gene product maintains genome integrity and initiates cellular DNA repair pathways following exposures to genotoxic agents. ATM also plays a significant role in meiotic recombination during spermatogenesis. Fertilization with sperm carrying damaged DNA could lead to adverse effects in offspring including developmental defects or increased cancer susceptibility. Currently, there is little information regarding the effect of ATM heterozygosity on germline DNA repair and heritable effects of paternal germline-ionizing irradiation. We used neutral pH comet assays to evaluate spermatozoa 45 days after acute whole-body irradiation of male mice (0.1 Gy, attenuated {sup 137}Cs {gamma} rays) to determine the effect of ATM heterozygosity on delayed DNA damage effects of Type A/B spermatogonial irradiation. Using the neutral pH sperm comet assay, significant irradiation-related differences were found in comet tail length, percent tail DNA and tail extent moment, but there were no observed differences in effect between wild-type and ATM +/- mice. However, evaluation of spermatozoa from third generation descendants of irradiated male mice for heritable chromatin effects revealed significant differences in DNA electrophoretic mobility in the F{sub 3} descendants that were based upon the irradiated F{sub 0} sire's genotype. In this study, radiation-induced chromatin alterations to Type A/B spermatogonia, detected in mature sperm 45 days post-irradiation, led to chromatin effects in mature sperm three generations later. The early cellular response to and repair of DNA damage is critical and appears to be affected by ATM zygosity. Our results indicate that there is potential for heritable genetic or epigenetic changes following Type A/B spermatogonial irradiation and that ATM heterozygosity increases this effect00.

  8. Protected graft copolymer-formulated fibroblast growth factors mitigate the lethality of partial body irradiation injury

    Science.gov (United States)

    Castillo, Gerardo M.; Nishimoto-Ashfield, Akiko; Jones, Cynthia C.; Kabirov, Kasim K.; Zakharov, Alexander; Lyubimov, Alexander V.

    2017-01-01

    We evaluated the mitigating effects of fibroblast growth factor 4 and 7 (FGF4 and FGF7, respectively) in comparison with long acting protected graft copolymer (PGC)-formulated FGF4 and 7 (PF4 and PF7, respectively) administered to C57BL/6J mice a day after exposure to LD50/30 (15.7 Gy) partial body irradiation (PBI) which targeted the gastrointestinal (GI) system. The PGC that we developed increased the bioavailability of FGF4 and FGF7 by 5- and 250-fold compared to without PGC, respectively, and also sustained a 24 hr presence in the blood after a single subcutaneous administration. The dose levels tested for mitigating effects on radiation injury were 3 mg/kg for the PF4 and PF7 and 1.5 mg each for their combination (PF4/7). Amifostine administered prior to PBI was used as a positive control. The PF4, PF7, or PF4/7 mitigated the radiation lethality in mice. The mitigating effect of PF4 and PF7 was similar to the positive control and PF7 was better than other mitigators tested. The plasma citrulline levels and hematology parameters were early markers of recovery and survival. GI permeability function appeared to be a late or full recovery indicator. The villus length and crypt number correlated with plasma citrulline level, indicating that it can act as a surrogate marker for these histology evaluations. The IL-18 concentrations in jejunum as early as day 4 and TPO levels in colon on day 10 following PBI showed statistically significant changes in irradiated versus non-irradiated mice which makes them potential biomarkers of radiation exposure. Other colon and jejunum cytokine levels are potentially useful but require larger numbers of samples than in the present study before their full utility can be realized. PMID:28207794

  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. 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

  11. Morphological studies on the healing process of tooth extraction wounds in whole body irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, Yoichiro (Hokkaido Univ., Sapporo (Japan). School of Dentistry)

    1991-06-01

    The present studies were performed to investigate the healing process of the tooth extraction wound in whole body irradiated rats and to clarify the effect of irradiation on bone metabolism. One hundred and seven Wistar rats of about 100 g body weight were used and divided into 3 groups. Whole body irradiated rats were given single exposure with a dose of 8 Gy. The region of the left upper molars of local irradiated rats as controls, was exposed to 8 Gy. On the 7th day after irradiation, the left upper first molar of each rat was extracted. The rats were sacrificed at intervals of 1 to 14 days after extraction. Non-irradiated rats were sacrificed at the same intervals after extraction. The maxillary bone including the extraction wound was evaluated, histologically, histometrically and ultrastructurally. From the histological and histometrical findings, the difference of the healing process between non-irradiated rats and locally irradiated rats is not significant. In whole body irradiated rats, the healing process especially in the socket was disturbed. The osteoblastic new bone formation following production of granulation tissue was interfered with. Ultrastructurally, the cytoplasmic organellae were poorly developed in the osteoblast and osteoid formation was reduced in the socket. But periosteal new bone formation was the same as that of the locally irradiated rats. In whole body irradiated rats, the osteoclasts in the interradicular alveolar bone were decreased and have smaller nuclei, compared with non-irradiated and locally irradiated rats. Histometrically, the amount of bone loss was decreased in whole body irradiated rats. Ultrastructurally, the cyoplasmic organellae and ruffled border were poorly developed in the osteoclasts of whole body irradiated rats. The findings suggested that irradiation induced cytological changes not only in osteoblasts but in osteoclasts and these changes resulted in the delayed healing of extraction wound. (author) 106 refs.

  12. 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.

  13. 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

  14. Hydrogen-Rich Water Ameliorates Total Body Irradiation-Induced Hematopoietic Stem Cell Injury by Reducing Hydroxyl Radical

    Directory of Open Access Journals (Sweden)

    Junling Zhang

    2017-01-01

    Full Text Available We examined whether consumption of hydrogen-rich water (HW could ameliorate hematopoietic stem cell (HSC injury in mice with total body irradiation (TBI. The results indicated that HW alleviated TBI-induced HSC injury with respect to cell number alteration and to the self-renewal and differentiation of HSCs. HW specifically decreased hydroxyl radical (OH∙ levels in the c-kit+ cells of 4 Gy irradiated mice. Proliferative bone marrow cells (BMCs increased and apoptotic c-kit+ cells decreased in irradiated mice uptaken with HW. In addition, the mean fluorescence intensity (MFI of γ-H2AX and percentage of 8-oxoguanine positive cells significantly decreased in HW-treated c-kit+ cells, indicating that HW can alleviate TBI-induced DNA damage and oxidative DNA damage in c-kit+ cells. Finally, the cell cycle (P21, cell apoptosis (BCL-XL and BAK, and oxidative stress (NRF2, HO-1, NQO1, SOD, and GPX1 proteins were significantly altered by HW in irradiated mouse c-kit+ cells. Collectively, the present results suggest that HW protects against TBI-induced HSC injury.

  15. 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.

  16. Mutagenicity studies on alcohol extracts from gamma-irradiated potatoes. Dominant lethal test in mice

    Energy Technology Data Exchange (ETDEWEB)

    Shibuya, T.; Murora, T.; Iwahara, S.; Hashimoto, K. (Food and Drug Safety Center, Kanagawa (Japan). Hatano Research Inst.); Minegishi, A.

    1982-02-01

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

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

    Science.gov (United States)

    Sato, Tomohito; Kinoshita, Manabu; Yamamoto, Tetsuo; Ito, Masataka; Nishida, Takafumi; Takeuchi, Masaru; Saitoh, Daizoh; Seki, Shuhji; Mukai, Yasuo

    2015-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. 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)

  1. Whole-body. gamma. -irradiation in the treatment of hemoblastoses in man

    Energy Technology Data Exchange (ETDEWEB)

    Shishkova, T.V.; Danilova, N.B.; Khrushchev, V.G.; Grammatikati, V.S.

    1982-11-01

    An analysis of foreign literature on treatment acute leukoses with irradiation and transplantation of allogenic bone marrow is given. It is shown that whole-body irradiation used to increase treatment efficiency of man hemoblastosis are widely applied nowadays abroad. Bone marrow transplantation including compulsory whole-body irradiation with 10 Gy is the only practicable attempt to eradicate leukosis. Whole-body irradiation unlike chemotherapy provides more durable survival rate without recurrence; it doesn't require hospitalization and continuity of treatment following the general course; it doesn't produce toxic complications.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Secondary radiation dose during high-energy total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Janiszewska, M.; Raczkowski, M. [Lower Silesian Oncology Center, Medical Physics Department, Wroclaw (Poland); Polaczek-Grelik, K. [University of Silesia, Medical Physics Department, Katowice (Poland); Szafron, B.; Konefal, A.; Zipper, W. [University of Silesia, Department of Nuclear Physics and Its Applications, Katowice (Poland)

    2014-05-15

    The goal of this work was to assess the additional dose from secondary neutrons and γ-rays generated during total body irradiation (TBI) using a medical linac X-ray beam. Nuclear reactions that occur in the accelerator construction during emission of high-energy beams in teleradiotherapy are the source of secondary radiation. Induced activity is dependent on the half-lives of the generated radionuclides, whereas neutron flux accompanies the treatment process only. The TBI procedure using a 18 MV beam (Clinac 2100) was considered. Lateral and anterior-posterior/posterior-anterior fractions were investigated during delivery of 2 Gy of therapeutic dose. Neutron and photon flux densities were measured using neutron activation analysis (NAA) and semiconductor spectrometry. The secondary dose was estimated applying the fluence-to-dose conversion coefficients. The main contribution to the secondary dose is associated with fast neutrons. The main sources of γ-radiation are the following: {sup 56}Mn in the stainless steel and {sup 187}W of the collimation system as well as positron emitters, activated via (n,γ) and (γ,n) processes, respectively. In addition to 12 Gy of therapeutic dose, the patient could receive 57.43 mSv in the studied conditions, including 4.63 μSv from activated radionuclides. Neutron dose is mainly influenced by the time of beam emission. However, it is moderated by long source-surface distances (SSD) and application of plexiglass plates covering the patient body during treatment. Secondary radiation gives the whole body a dose, which should be taken into consideration especially when one fraction of irradiation does not cover the whole body at once. (orig.) [German] Die zusaetzliche Dosis durch sekundaere Neutronen- und γ-Strahlung waehrend der Ganzkoerperbestrahlung mit Roentgenstrahlung aus medizinischen Linearbeschleunigern wurde abgeschaetzt. Bei der Emission hochenergetischer Strahlen zur Teletherapie finden hauptsaechlich im Beschleuniger

  7. 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.

  8. 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.

  9. Total body irradiation for myasthenia gravis with thymoma: case report

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ki Mun; Choi, Ihl Bohng; Kim, In Ah [College of Medicine, Catholic Univ., Seoul (Korea, Republic of)

    1999-06-01

    Myasthenia Gravis (MG) is relatively rare occuring as one of important autoimmune disease to affect neuromuscular junction. This study was clinically to evaluate total body irradiation (TBI) against two patients including 33-year and 39-year females for chronic MG with thymoma who hospitalized in the St. Mary's Hospital, Catholic University since 1994 as well as who showed no response by thymectomy, immunotherapy and hormonal therapy. TBI designed by the dose of 150-180 cGy consisting of 10 cGy per fraction, three times a week, for 5-6 weeks using linear accelerator of 6 MV. During the treatment of TBI, they did complain acute side effect such as vomiting and also appear improved physical condition from 4-6 weeks after TBI. Through the follow-up period of 18 or 42 months after TBI, they did not have any symptomatic recurrence. Consequently, the results suggest that TBI can be used as an alternative tool for the patients concurrently for MG with thymoma who had been refractory to various conventional therapies like thymectomy, immunotherapy and hormonal therapy.

  10. 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.

  11. Modulation of in utero total body irradiation induced newborn mouse growth retardation by maternal manganese superoxide dismutase-plasmid liposome (MnSOD-PL) gene therapy.

    Science.gov (United States)

    Epperly, M W; Smith, T; Zhang, X; Goff, J P; Franicola, D; Greenberger, B; Komanduri, P; Wang, H; Greenberger, J S

    2011-06-01

    To determine the effects of manganese superoxide dismutase (MnSOD) plasmid liposome (PL) maternal radioprotection on fetal mice, timed pregnant female mice (E14 gestation) were irradiated to 3.0 Gy total body irradiation (TBI) dose, and the number, weight and growth and development over 6 months after birth of newborn mice was quantitated compared with irradiated controls. Maternal MnSOD-PL treatment at E13 improved pup survival at birth (5.4±0.9 per litter) compared with non-irradiated 3.0 Gy controls 4.9±1.1. There was no statistically significant difference in newborn abnormalities, male to female ratio in newborn litters, or other evidence of teratogenesis in surviving newborn mice from MnSOD-PL treated compared with irradiated controls. However, E14 3 Gy irradiated pups from gene therapy-treated mothers showed a significant increase in both growth and overall survival over 6 months after birth (P=0.0022). To determine if transgene product crossed the placenta pregnant E13 mice were injected intravenously with hemagglutinin-epitope-tagged MnSOD (100 μg plasmid in 100 μl liposomes), then after 24 h, fetal mice, placentas and maternal tissues were removed and tested by both immunohistochemistry and reverse transcriptase-PCR for transgene and product. There was no evidence of transgene or product in placenta or any fetal tissue while maternal liver was positive by both assays. The data provide evidence for fetal radioprotection by maternal MnSOD-PL gene therapy before irradiation, which is mediated by an indirect bystander effect and is associated with a significant improvement in both survival at birth and growth and development of newborn mice.

  12. 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.

  13. Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yani [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Leu, David [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Palo Alto Institute of Research and Education, Palo Alto, California (United States); Chui, Jennifer [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Fike, John R. [Departments of Neurosurgery and Radiation Oncology, University of California, San Francisco, California (United States); Huang, Ting-Ting, E-mail: tthuang@stanford.edu [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); VA Palo Alto Health Care System, Palo Alto, California (United States)

    2013-11-15

    Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted.

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

    Science.gov (United States)

    Espinosa-Carrasco, Gabriel; Villard, Marine; Le Saout, Cecile; Louis-Plence, Pascale; Vicente, Rita; Hernandez, Javier

    2015-01-01

    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.

  15. 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.

  16. 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.

  17. 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)

  18. 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.

  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. 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.

  1. 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.

  2. 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

  3. 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)

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

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    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)

  5. Induction and reversion process of molecular and cytological alterations after highly irradiated food ingestion in mice

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    Rojo M, M.I. (Comision Chilena de Energia Nuclear, Santiago. Dept. de Aplicaciones de los Isotopos y Radiaciones); Fernandez C, M. (Chile Univ., Santiago. Dept. de Fisica)

    1984-04-01

    The molecular and cytological alterations induced in a mammal (Mus musculus) fed ad libitum with a balanced pellet diet irradiated with 50 KGy gamma radiation from weaning, for different periods, are analyzed. The transient chromosomal changes that recall tumor-like phenomena could be the expression of the damage and repair processes induced by changed molecules present in irradiated food. The reversible alterations of DNA structure and cytoplasmatic soluble proteins observed in mice fed with irradiated pellet diet could be interpreted as a result of the enhancement of the repair processes which could also explain the significant increase of the radioresistance of DNA found at 200 days after irradiated food ingestion. Finally, our results would suggest an induction of a pseudo-neoplasia due to a prolongated and exclusive ingestion of food irradiated with sterilizing gamma dose. Moreover, the maintenance of the irradiated diet induce the reversion of the observed phenomena by an eventual activation of the repair mechanisms.

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

    Science.gov (United States)

    Oh, Sejo; Jang, Da-In; Lee, Ju-Woon; Kim, Jae-Hun; Byun, Myung-Woo; Lee, Soo-Young

    2009-07-01

    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-γ 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-γ 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.

  8. 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.

  9. Reduction of allergenicity of irradiated ovalbumin in ovalbumin-allergic mice

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Ji-Hyun; Lee, Ju-Woon; Kim, Jae-Hun [Radiation Application Research Division, Advanced Radiation Technology Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Baek [Radiation Application Research Division, Advanced Radiation Technology Institute, Jeongeup 580-185 (Korea, Republic of); Graduate School of Biotechnology, Korea University, Yeongi 339-700 (Korea, Republic of); Lee, Soo-Young [Department of Pediatrics, Ajou University School of Medicine, Suwon 442-749 (Korea, Republic of); Kang, Il-Jun [Division of Life Sciences, Hallym University, Chunchon 200-702 (Korea, Republic of); Byun, Myung-Woo [Radiation Application Research Division, Advanced Radiation Technology Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: mwbyun@kaeri.re.kr

    2007-11-15

    Egg allergy is one of the most serious of the immediate hypersensitivity reactions to foods. Such an allergic disorder is mediated by IgE antibodies stimulated by T-helper type 2 (Th2) lymphocytes. This study was undertaken to evaluate changes of allergenicity and cytokine profiles by exposure of irradiated ovalbumin (OVA), a major allergen of egg white, in the OVA-allergic mice model. OVA solutions (2 mg/ml in 0.01 M phosphate buffered saline (PBS) were gamma-irradiated to 50 and 100 kGy. The allergenicity in the OVA-allergy-induced mice model was remarkably reduced when challenged with irradiated OVA. Cultures of spleen cells harvested from OVA-sensitized mice showed a significant decrease in Th2 cytokine levels of ILs-4 and -5 with a concomitant increase in Th1 cytokine levels of IL-12 when co-cultured with irradiated OVA. However, IFN-{gamma} level decreased dependant on the radiation dose of co-cultured OVA. The levels of IgEs and Th2-cytokine were reduced dependant on the radiation dose. These data show that the irradiated OVA could downregulate the activity of Th2 lymphocytes in OVA-sensitized mice.

  10. 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.

  11. Employment of whole-body. gamma. -irradiation in chronic lymphoid leukemia and malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Danilova, N.B.; Baranov, A.E.; Khrushchev, V.G.; Grammatikati, V.S.; Murav' eva, L.I.; Strashnenko, E.S.

    1982-11-01

    There are presented data showing that whole-body therapeutic ..gamma..-irradiation is an effective method of treatment of chronic lymphoid leukosis and lymphomas. Rapid lymphopenic effect, satisfactory diminution of lymph nodes and spleen sizes testify to the effect. The necessity of further investigation of the treatment method is underlined. It is of interest to trace the fate of lymphocyte subpopulations in the course and after treatment. The urgency of working out a most rational scheme for whole-body therapeutic irradiation and for investigating indications for local irradiation of various groups of lymphatic nodes is indicated.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  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. SU-E-T-522: Investigation of Underdosage of Total Body Irradiation with Bilateral Irradiation Scheme

    Energy Technology Data Exchange (ETDEWEB)

    Lin, T; Eldib, A; Hossain, M; Price, R; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2015-06-15

    Purpose: Patient in-vivo measurements report lower readings than those predicted from TMR-based treatment planning on TBI patient knees and ankles where rice was placed to fill the gap between patient’s legs. This study is to understand and correct the under dosage of Total Body Irradiation(TBI) with rice tissue equivalent bolus placement at TBI treatment patient setup. Methods: Bilateral TBI scheme was investigated with rice bags bolus placing between patient’s two legs acting as missing tissue. In-house TMR based treatment planning system was commissioned with measurements under TBI condition at 10MV, i.e. source-to-reference distance 383.4cm with 40×40cm field size with 1cm thickness Lucite. Predictions of patient specific dose points are reported at different sites with 200cGy prescription at patient umbilicus point. Solid water and rice bag phantoms are used at TBI conditions for the attenuation factor verification and CT scanned to verify the CT number and electron density. Results: We found that the rice bag bolus overall density is 11% lower than the water; however, the attenuation factor of rice bags could become 15% lower than that of water at TBI condition. This overestimate of rice bag electron density could cause the lack of lateral scatter and the lack of backscatter. This could Result in an overestimate of dose at in-vivo dosimeter measurement points with TMR-based treatment planning systems. Observations of patient specific optically stimulated luminescent dosimeters(OSLDs) were used to confirm this overestimation. Measurements of setups with increasing the rice bag filled patient leg separation were performed to demonstrate eliminating the overdose issue. Conclusion: Rice bolus has a lower electron density than water does(11%) but results in 15% lower in attenuation factor at TBI condition. This effect was observed in patient delivery with OSLD measurements and can be corrected by increasing the filling rice bolus thickness with 15% longer of

  18. Induction of external abnormalities in offspring of male mice irradiated with [sup 252]Cf neutron

    Energy Technology Data Exchange (ETDEWEB)

    Kurishita, Akihiro; Ono, Tetsuya; Mori, Yuriko (Tohoku University School of Medicine, Sendai (Japan). Department of Radiation Research); Okada, Shigefumi (Kyoto University (Japan). Radiation Biology Center); Sawada, Syozo (Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology)

    1992-08-01

    To assess the genetic effects of fission neutron, the induction of external malformations was studied in F[sub 1] fetuses after F[sub 0] male mice were irradiated. Male mice of the ICR:MCH strain were irradiated with [sup 252]Cf neutron at doses of 0.238, 0.475, 0.95 and 1.9 Gy. They were mated with non-irradiated female mice at 71-120 days after irradiation. Pregnant females were autopsied on day 18 of gestation and their fetuses were examined for deaths and external abnormalities. No increases of pre- and post-implantation losses were noted at any dose. External abnormalities were observed at rates of 1.40% in the 0.238 Gy, 2.23% in the 0.475 Gy, 3.36% in the 0.95 and 3.26% in the 1.9 Gy groups; the rate in the control group was 1.65%. The dose-response curve was linear up to 0.95 Gy, and then flattened out; the induction rate of external abnormalities was 2.7x10[sup -4]/gamete/cGy based on the linear regression. These results indicated that fission neutron effectively induces external abnormalities in F[sub 1] fetuses after spermatogonial irradiation. (author). 29 refs.; 1 fig.; 2 tabs.

  19. Effect of methergoline on body temperature in mice.

    Science.gov (United States)

    Cardano, C; Strocchi, P; Gonni, D; Walsh, M; Agnati, L F

    1977-03-01

    Serotonin (5-HT) involvement in body temperature regulation has been studied in mice by means of a 5-HT-selective blocking agent (methergoline). This drug causes an effect on body temperature which is dependent on environmental temperature. At environmental temperatures of 25 degrees C and 11 degrees C methergoline has a hypothermic effect, while at 36 degrees C environmental temperature, methergoline has a hyperthermic effect. At 25 degrees C environmental temperature, the hypothermic effect induced by 125 mug/kg i.p. of methergoline could be antagonized by low doses of LAE-32 (80 mug/kg s.c.), while there was not such an antagonism using higher doses of LAE-32 (100 and 300 mug/kg s.c.). This has been explained using Jalfre's hypothesis of the existence of 5-HT inhibitory and excitatory receptors.

  20. Effect of antimicrobial therapy on bowel flora and bacterial infection in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Brook, Itzhak; Walker, R.I.; MacVittie, T.J.

    1988-05-01

    Mice exposed to 10 Gy cobalt-60 radiation were given intramuscular antimicrobial therapy of gentamicin, metronidazole, or a combination. Mortality in mice treated with metronidazole alone or in combination with gentamicin occurred earlier than in controls (P < 0.001). Microorganisms were recovered from blood, spleen, and liver of the metronidazole-treated mice earlier than from other groups. Predominant organisms recovered from these animals were Enterobacteriaceae. Quantitative cultures of ileal flora showed decrease in aerobic, facultative anaerobic and strict anaerobic bacteria after irradiation, and a subsequent increase only in the number of strict aerobic bacteria. Compared to untreated mice, a rapid decrease (by 8.8 logs) in anaerobic flora occurred in mice treated with metronidazole 5 days after irradiation, followed by a rapid increase in the number of aerobic organisms which coincided with the earlier mortality in this group. Data suggest that antimicrobial agents decreasing the number of the strict anaerobic component of the gut flora enhance systemic infection by aerobic or facultative anaerobic bacteria, facilitating post-irradiation mortality.

  1. Quantitative, functional, and biochemical alterations in the peritoneal cells of mice exposed to whole-body gamma irradiation. 1. Changes in cellular protein, adherence properties, and enzymatic activities associated with platelet-activating factor formation and inactivation, and arachidonate metabolism. Scientific report

    Energy Technology Data Exchange (ETDEWEB)

    Steel, L.K.; Hughes, H.N.; Walden, T.L.

    1988-01-01

    Changes in total number, differentials, cell protein, adherence properties, acetyltransferase and acetylhydrolase activities, prostaglandin E2 and leukotriene C4 production, as well as calcium (2+) ionophore A23187 stimulation were examined in resident peritoneal cells isolated from mice 2h to 10 days postexposure to a single dose (7,10 or 12 Gy) of gamma radiation. Radiation dose-related reductions in macrophage and lymphocyte numbers and increases in cellular protein and capacity to adhere to plastic surfaces were evident. In-vitro irradiation also elevated the activities of acetyltransferase and acetylhydrolase (catalyzing platelet-activating factor biosynthesis and inactivation, respectively) in adherent and nonadherent peritoneal cells, particularly 3-4 days postexposure. Blood plasma from irradiated animals did not reflect the increased cellular acetylhydrolase activity. Prostaglandin E2 and leukotriene C4 synthesis were elevated postexposure, suggesting increased substrate (arachidonate) availability and increased cyclooxygenase and lipoxygenase activities. Ionospheric stimulation of enzyme activities and eicosanoid release also differed in irradiated peritoneal cells. While the properties of adherence, platelet-activating factor synthesis/inactivation-associated enzyme activities, and eicosanoid production are generally characterized as those of macrophages, lymphocytes or their products may influence or contribute to the observed radiation-induced changes.

  2. Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Girinsky, T.; Benhamou, E.; Bourhis, J.H.; Dhermain, F.; Guillot-Valls, D.; Ganansia, V.; Luboinski, M.; Perez, A.; Cosset, J.M.; Socie, G.; Baume, D.; Bouaouina, N.; Briot, E.; Baudre, A.; Bridier, A.; Pico, J.L

    2001-02-01

    The efficiency of the two irradiation modes are similar, but the hyperfractionated irradiation seems superior in term of global and specific survival. The incidence rates of pneumopathies are not different between the two groups but the incidence rate of the liver vein-occlusive illness is superior in the group treated by non fractionated whole body irradiation. The cost of the hyperfractionated whole body irradiation is superior to this one of the non fractionated whole body irradiation around a thousand dollars. (N.C.)

  3. Automatic nonrigid registration of whole body CT mice images.

    Science.gov (United States)

    Li, Xia; Yankeelov, Thomas E; Peterson, Todd E; Gore, John C; Dawant, Benoit M

    2008-04-01

    Three-dimensional intra- and intersubject registration of image volumes is important for tasks that include quantification of temporal/longitudinal changes, atlas-based segmentation, computing population averages, or voxel and tensor-based morphometry. While a number of methods have been proposed to address this problem, few have focused on the problem of registering whole body image volumes acquired either from humans or small animals. These image volumes typically contain a large number of articulated structures, which makes registration more difficult than the registration of head images, to which the majority of registration algorithms have been applied. This article presents a new method for the automatic registration of whole body computed tomography (CT) volumes, which consists of two main steps. Skeletons are first brought into approximate correspondence with a robust point-based method. Transformations so obtained are refined with an intensity-based nonrigid registration algorithm that includes spatial adaptation of the transformation's stiffness. The approach has been applied to whole body CT images of mice, to CT images of the human upper torso, and to human head and neck CT images. To validate the authors method on soft tissue structures, which are difficult to see in CT images, the authors use coregistered magnetic resonance images. They demonstrate that the approach they propose can successfully register image volumes even when these volumes are very different in size and shape or if they have been acquired with the subjects in different positions.

  4. Fluid and sodium loss in whole-body-irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.

    1987-09-01

    Whole-body and organ fluid compartment sizes and plasma sodium concentrations were measured in conventional, GI decontaminated, bile duct ligated, and choledochostomized rats at different times after various doses of gamma radiation. In addition, sodium excretion was measured in rats receiving lethal intestinal radiation injury. After doses which were sublethal for 3-5 day intestinal death, transient decreases occurred in all the fluid compartments measured (i.e., total body water, extracellular fluid space, plasma volume). No recovery of these fluid compartments was observed in rats destined to die from intestinal radiation injury. The magnitude of the decreases in fluid compartment sizes was dose dependent and correlated temporally with the breakdown and recovery of the intestinal mucosa but was independent of the presence or absence of enteric bacteria or bile acids. Associated with the loss of fluid was an excess excretion of 0.83 meq of sodium between 48 and 84 h postirradiation. This represents approximately 60% of the sodium lost from the extracellular fluid space in these animals during this time. The remaining extracellular sodium loss was due to redistribution of sodium to other spaces. It is concluded that radiation-induced breakdown of the intestinal mucosa results in lethal losses of fluid and sodium as evidenced by significant decreases in total body water, extracellular fluid space, plasma volume, and plasma sodium concentration, with hemoconcentration. These changes are sufficient to reduce tissue perfusion leading to irreversible hypovolemic shock and death.

  5. The Persistence of FISH Translocations for Retrospective Biological Dosimetry after Simulated Whole or Partial Body Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero-Carbajal, Y.C.; Moquet, J.E.; Edwards, A.A.; Lloyd, D.C

    1998-07-01

    High acute whole and partial body accidental irradiations were simulated by in vitro irradiation of blood. Lymphocyte culture times were extended from 48 h to 72 h and 96 h to simulate the elimination of chromosomal damage that occurs over time in vivo following successive cell divisions. The yields of stable translocations involving chromosomes 2, 3 and 5 were scored by the FISH method together with full genome dicentrics. With simulated whole body irradiation the yieldsof dicentrics fell sharply with successive cell divisions whilst translocation frequencies remained constant. With partial irradiation both dicentric and translocation yields reduced. This may be explained by the hypothesis that with homogeneous irradiation at high doses the distributions of stable and unstable aberrations are Poisson and independent whilst with partial exposure their distributions are linked because both types are confined to the irradiated fraction of cells. This has highlighted a possible limitation in the use of FISH for retrospective dosimetry and may explain instances where the method has been reported to underestimate dose when compared with contemporary dosimetry. (author)

  6. 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.

  7. 2nd Tuebingen radiotherapy symposium: Whole body, large field and whole skin irradiation. Introduction

    Energy Technology Data Exchange (ETDEWEB)

    Huebener, K.H.; Frommhold, W.

    1987-04-01

    The symposium which took place on the 11th and 12th April 1986 set itself the task of discussing three different groups of radiotherapy topics. The chief issue was whole-body irradiation prior to bone marrow transplants, in which all the therapy centres in West Germany, Austria, East Germany and German-speaking Switzerland made clinical and radiophysical contributions. The second part of the Symposium consisted mainly of talks and discussions on large-field irradiation, more precisely half-body and sequential partial body irradiation. This topic was chosen because this type of therapy is scarcely practised at all, particularly in West Germany, whereas in the United States, East Germany, Switzerland and a number of other countries it has long since become one of the established methods. The last talk at the Symposium explained clinical and radiophysical aspects of whole-skin irradiation. Here too, one was impressed by the wide diversity of the equipment and methods of irradiation used which, nevertheless, all demonstrated satisfactory practical solutions in their common aim of distributing the dose as homogeneously as possible.

  8. Clinical aspects of accidents resulting in acute total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cronkite, E.P.

    1988-01-01

    That the management of whole body radiation injury involves: (1) watchful waiting, (2) observation of the hematologic parameters, (3) use of antibiotics, platelet red cell and possibly granulocyte transfusions, (4) administration of hemopoietic molecular regulators of granulopoiesis, and (5) bone marrow transplantation as the last line of defense. The clinical indication for the preceding will not be discussed, since this will be a subject of later speakers in this conference. Certainly, if a radiation casualty is fortunate enough to have an identical twin, a marrow transplant may be lifesaving and certainly can do no harm to the patient, and there is little risk to the donor.

  9. Effects of γ-ray total body irradiation from a 60Co source on expression level of intrathymic forkhead box protein N1 in mice%60Coγ射线全身照射对小鼠胸腺中叉状头转录因子N1表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    孙玉琦; 武育菁; 刘洁; 潘彬; 徐开林

    2016-01-01

    delta样配体(DLL)4、自身免疫调节蛋白(Aire)与骨形成蛋白(BMP)4 mRNA相对表达水平相比,差异均有统计学意义(CCL25 mRNA相对表达水平:11.2±1.5、11.4±1.2、1.0±0.1,DLL4 mRNA相对表达水平:7.3±0.9、6.3±0.3、1.0±0.1,Aire mRNA相对表达水平:5.1±1.0、5.0±0.1、1.0±0.1,BMP4 mRNA相对表达水平:4.4±1.4、3.6±0.5、1.0±0.1;F=148.862、197.667、73.911、21.471,P=0.000、0.000、0.000、0.000);3组中Foxn1上游基因同源框蛋白(Hox)a3 mRNA相对表达水平相比,差异却无统计学意义(1.4±0.4、0.8±0.3、1.0±0.1相比;F=5.368,P=0.221).与对照组相比,L-TBI 5 d组中Foxn1下游基因CCL25、DLL4与Aire的mRNA相对表达水平均显著增高(p=0.000、0.000、0.000);SL-TBI 5 d组中CCL25、DLL4与Aire mRNA相对表达水平亦显著增高(P=0.000、0.000、0.000).同时,与对照组相比,L-TBI 5 d组、SL-TBI 5 d组中BMP4mRNA相对表达水平存在一定程度的增高,且差异亦有统计学意义(P=0.000、0.000).结论 60C0γ射线TBI可导致小鼠胸腺中Foxn1mRNA表达水平增高,Foxn1表达水平上调及其相关基因表达水平的变化与胸腺受损程度的关系密切.%Objectives To explore the influence of γ-ray total body irradiation (TBI) from a 60Co source induced mice thymus injury on expression levels of forkhead box protein N (Foxn) 1 and related genes,and to analyze the correlation between expression levels of Foxn1,related genes and thymus injury.Methods Sixty five male C57BL/6 mice were chosen as subjects during November and December 2014.Inclusion criteria for choosing mice:all these mice are 6-8 weeks old specific pathogen free (SPF) animals,and weighting between 18.0-21.0 g.Thirty-five mice were randomly devided into 4 groups:① Lethal total body irradiation (L-TBI) 5 d group (n=10),mice received a total dose of 7.5 Gy γ-ray TBI from a 60Co source;② Sublethal total body irradiation (SL-TBI) 5 d group (n=10),mice received a total dose of 5.5 Gy TBI;③SL-TBI 24 d group (n =10),mice

  10. [Effect of antibiotics and bifiodobacterium preparations on the intestinal microflora of mice irradiated with gamma quanta].

    Science.gov (United States)

    Korshunov, V M; Pinegin, B V; Mal'tsev, V N; Kissina, E V; Ikonnikova, T B

    1980-07-01

    The treatment of CBA mice, irradiated in a dose of 700 Gy with antibiotics (penicillin V, oxytetracycline, streptomycin) in combination with bacterial therapy (B. bifidum, strain 75-41) or with antibiotics alone led to the increased percentage of survivors among them in comparison with the control animals. At the same time the medical prognosis was better in cases of the combined treatment with antibiotics and bifidobacteria. This circumstance was due to the fact that the combined treatment with antibiotics and bifidobacteria, considerably facilitated the normalization of the microbial picture of the intestine; in this case the "eubiosis" of the intestinal tract was almost completely restored by the 22nd day after the irradiation, whereas in the treatment with antibiotics alone the inhibitory effect on the development of the opportunistic flora at a later period of the development of dysbacteriosis was less pronounced, while the number of lactic acid bacteria remained at the same low level as in the untreated mice.

  11. [Comparison of different G-CSF treatment effectiveness in experiments on irradiated mice].

    Science.gov (United States)

    Rozhdestvenskiĭ, L M; Shchegoleva, R A; Deshevoĭ, Iu B; Lisina, N I; Titov, B A

    2012-01-01

    In the experiments on F1 (CBA x C57BL) and BALB mice irradiated by 137Cs gamma-rays, preparations of unglycosilated G-SCF such as Neupogen and their domestic analogs Leucostim and Neupomax were investigated. The tests such as 9-day bone marrow cellularity (BMC) and endogenous CFUs, the neutrophile number restoration, the 30-day survival index have shown that all three preparations have an approximately equal effectiveness relating to acute radiation disease treatment and granulopoiesis stimulation after a 5-10 day consecutive administration following irradiation of mice at lethal and sublethal doses. We have come to the conclusion that Leucostim and Neupomax can be regarded as adequate substitutes for Neupogen.

  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. Irradiation of protoporphyric mice induces down-regulation of epidermal eicosanoid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    He, D.; Lim, H.W. (Department of Veterans Affairs Medical Center, New York, NY (USA))

    1991-09-01

    This study investigated the effect of radiation on clinical and histologic changes, and on cutaneous eicosanoid metabolism, in Skh:HR-1 hairless albino mice rendered protoporphyric by the administration of collidine. At 0.1-18 h after exposure to 12 kJ/m2 of 396-406 nm irradiation, thicknesses of back skin and ears were measured, and histologic changes were evaluated by using hematoxylin and eosin (H-E) and Giemsa's stains. Activities of eicosanoid-metabolizing enzymes in epidermal and dermal homogenates were assessed by incubating the tissue homogenates with 3H-AA, followed by quantitation of the eicosanoids generated by radio-TLC. In irradiated protoporphyric mice, an increase of back-skin thickness was noted at 0.1 h, reaching a peak at 18 h, whereas maximal increase in ear thickness was observed at 12 h. Histologic changes included dermal edema, increased mast cell degranulation, and mononuclear cells in the dermis. In these irradiated protoporphyric animals, generations of 6 keto-PGF1a, PGF2a, PGE2, PGD2, and HETE by epidermal eicosanoid-metabolizing enzymes were markedly suppressed at all the timepoints studied. Dermal eicosanoid-metabolizing enzymes of irradiated protoporphyric mice generated increased amounts of PGE2 and HETE at 18 h, probably reflecting the presence of dermal cellular infiltrates. The suppression of the activities of epidermal eicosanoid-metabolizing enzymes was prevented by intraperitoneal injection of WR-2721, a sulfhydryl group generator, prior to irradiation, suggesting that the suppression was secondary to photo-oxidative damage of the enzymes during the in vivo phototoxic response. These results suggest that the effect of protoporphyrin and radiation on cutaneous eicosanoid metabolism in this animal model in vivo is that of a down regulation of the activities of epidermal eicosanoid-metabolizing enzymes.

  14. 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

  15. Early changes in vascular reactivity in response to 56Fe irradiation in ApoE-/- mice

    Science.gov (United States)

    White, C. Roger; Yu, Tao; Gupta, Kiran; Babitz, Stephen K.; Black, Leland L.; Kabarowski, Janusz H.; Kucik, Dennis F.

    2015-03-01

    Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE-/- mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4-5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

  16. Acid base balance in the rabbit following whole-body gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bassant, M.H.; Touchard, F.; Court, L. (CEA Centre d' Etudes Nucleaires de Fontenay-aux-Roses, 92 (France). Dept. de Recherches sur la Fusion Controlee)

    1981-07-06

    2 hrs. after whole-body gamma irradiation (doses of 1.5 and 4.5 Gy) a metabolic acidosis developed in curarised rabbits placed under artificial respiration in order to eliminate radiation-induced respiratory effect. The metabolic acidosis was evaluated by measurement of the negative base excess. The results were compared to others obtained under different experimental procedures.

  17. 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.

  18. 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)

  19. 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.

  20. The effect of UV-B irradiation on secondary epidermal infection of mice with herpes simplex virus type 1

    Energy Technology Data Exchange (ETDEWEB)

    El-Ghorr, A.A.; Norval, Mary [Edinburgh Univ. Medical School (United Kingdom). Dept. of Medical Microbiology

    1996-03-01

    Previous studies have indicated that suberythemal ultraviolet B (UV-B) irradiation of C3H mice before primary infection with herpes simplex virus (HSV) type 1 does not result in increased morbidity or mortality, but a suppressed delayed type hypersensitivity (DH) to the virus can be demonstrated. Any effect of UV radiation on pathogenesis during secondary epidermal HSV infection has not been previously examined. Mice were immunized by subcutaneous injection of inactivated HSV and, 5 days later, one group was UV-B-irradiated. The next day all mice were challenged epidermally with HSV. Most of the mice (92%) in the irradiated group developed severe lesions, whilst 59% of the non-irradiated group had mild lesions and 30% no lesions. Infectious virus was not isolated from the adrenal glands after challenge in either group. In addition, the DH to the virus was not affected by the UV exposure. (author).

  1. 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.

  2. B lymphocyte differentiation in lethally irradiated and reconstituted mice. I. The effect of strontium-89 induced bone marrow aplasia on the recovery of the B cell compartment in the spleen

    Energy Technology Data Exchange (ETDEWEB)

    Rozing, J.; Buurman, W.A.; Benner, R.

    1976-06-01

    The influence of /sup 89/Sr-treatment on the recovery of the B cell compartment in lethally irradiated, fetal liver reconstituted mice was studied by means of membrane fluorescence, /sup 89/Sr is a bone-seeking radio-isotope which causes in a dose of 3 ..mu..Ci /sup 89/Sr/g body weight a depletion of all nucleated cells, including immunoglobulin-bearing (B) cells, of the bone marrow. Treatment of irradiated and fetal liver reconstituted mice with 3 ..mu..Ci /sup 89/Sr/g body weight immediately and at 17 days after irradiation and reconstitution prevented recovery of the nucleated cell population, including B cells, in the bone marrow. In the spleen of such mice both nucleated cells and B cells reappeared at day 7 and 14 respectively. The B cell population in the spleen did not recover up to normal values during the experimental period of 45 days. It is concluded that B cell differentiation in lethally irradiated, fetal liver reconstituted mice can take place outside the bone marrow. The efficiency of this extra-medullary differentiation is discussed. The conclusion was drawn that mice with a /sup 89/Sr-induced bone marrow aplasia are able to generate B lymphocytes. Consequently the bone marrow microenvironment seems not to be obligate to the differentiation of B lymphocytes. The peripheral lymphoid organs of such mice were found to be unable to compensate completely for the absence of B lymphocyte production in the bone marrow.

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

    Science.gov (United States)

    Zhang, Lei; Yuan, Hong; Burk, Laurel M.; Inscoe, Christy R.; Hadsell, Michael J.; Chtcheprov, Pavel; Lee, Yueh Z.; Lu, Jianping; Chang, Sha; Zhou, Otto

    2014-03-01

    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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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)

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

    Directory of Open Access Journals (Sweden)

    R. S. Ferreira Junior

    2005-12-01

    Full Text Available 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 60Co-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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Late effects from whole body irradiation and protection by chemical and biological agents. A review

    Energy Technology Data Exchange (ETDEWEB)

    Maisin, J.R. [Catholic Univ. of Louvain, Brussels (Belgium); Gerber, G.B.

    2000-07-01

    This review described studies attempting to reduce damage of exposure to ionizing radiation with an application of chemical or biological agents by illustrating authors' data to point out which possibilities such protectors might hold in future. Authors described their studies on mice exposed to a single or fractionated dose of X-rays at the Belgian Atomic Center at Mol. Mice were irradiated with 250 kV of X-rays at a dose rate of 1 Gy/min or underwent the fractionated irradiation of 1-week intervals with total dose of 2-25 Gy. Before irradiation, some animals were given glutathione, mercaptoethylamine, cystein, serotonine-creatine, 2{beta}-aminoethylisothiuronium, and other agents, alone or as a mixture. Results indicated that radioprotectors reduced many specific late diseases to different degrees together with protection against tumor induction which other investigators had shown. Future prospects were considered for ideal radioprotectors and searches for new radioprotectors and for combination of biological agents (e.g., cytokines with polysaccharides or prostaglandins) were described. (K.H.)

  20. Effect of ultra-low dose whole-body-irradiation on patients with severe myasthenia gravis

    Energy Technology Data Exchange (ETDEWEB)

    Arimori, Shigeru; Koriyama, Kenji (Tokai Univ., Isehara, Kanagawa (Japan). School of Medicine)

    1982-12-01

    An ultra-low dose whole body irradiation therapy was given to 5 patients with intractable bulbar syndrome, in a dose of 10 rad/fraction, 2 times a week for 5 weeks, with a total of 100 rad; and effects of this therapy on their clinical symptoms and immunological ability were discussed. In 3 of them, bulbar syndrome was improved, and the other one, the first irradiation was effective. The peripheral leukocyte count and lymphocyte count became lowest immediately after completion of the irradiation, and returned to the normal level within 1 to 2 months. The function of T-cells, especially suppressive T-cells, was recovered; and decrease in B-cells, resulted in a decrease in the AChR antibody titer.

  1. Late effects of total-head gamma irradiation in mice. 2. Pathomorphological analysis of organic changes with regard to the role of the hypophysis - adrenal gland axis and of the thymolymphatic system

    Energy Technology Data Exchange (ETDEWEB)

    Tkadlecek, L.; Viklicka, S.; Karpfel, Z.; Pospisil, M.; Netikova, J. (Ceskoslovenska Akademie Ved, Brno. Biofysikalni Ustav)

    1985-01-01

    Relations between late manifestations of wasting of C57BL/10 mice whose heads were irradiated with a dose of 16 Gy of /sup 60/Co gamma rays, and some pathomorphological findings in the organs of animals in the late period after irradiation were studied. A close correlation was found between the fall in body weight of animals during the period of the 6th month after irradiation and involution of the thymolymphatic system. Adenohypophysis and adrenal cortex of wasting animals revealed clear signs of structural defects, indicating failure of their hormonal functions. Morphological examination of brain, cerebellum, duodenum and liver did not exhibit signs of damage.

  2. Eight years of whole body irradiation at Verone: clinical and physical experience in 115 patients (june 2000-december 2008); Huit ans d'irradiation corporelle totale a verone: experience clinique et physique chez 115 patients (juin 2000-decembre 2008)

    Energy Technology Data Exchange (ETDEWEB)

    Palazzi, M.; Benedetti, F.; Romano, M.; Maluta, S.; Compri, C.; Giri, M.G.; Meliado, G. [Azienda Ospedaliera, Verona (Italy)

    2009-10-15

    The multi fractionated whole-body irradiation has today replaced the technique of whole-body irradiation in single dose, that was at the origin of acute and delayed effects, especially pneumonia and cataract. The results and the tolerance of our whole-body irradiation pattern are similar to these ones mentioned in the national register of allogeneic marrow transplants. (N.C.)

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  5. Protective value of piroxicam on the enhanced inflammatory response after whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    el-Ghazaly, M.; Saleh, S.; Kenawy, S.; Roushdy, H.M.; Khayyal, M.T.

    1986-06-01

    The anti-inflammatory activity of piroxicam was assessed after whole body irradiation in rats. Two models of inflammation, the carrageenan-induced edema and the adjuvant-induced arthritis in rats have been utilised. Piroxicam at doses of 1, 5 and 10 mg kg-1 i.p. was effective in inhibiting the paw edema produced in both models of inflammation. The inflammatory response in irradiated was significantly higher than that produced in normal animals and was dependent on the radiation dose level used (0.5-2 Gy). The effect of piroxicam on the late inflammatory response produced by exposure to 2 Gy was studied by measuring the carrageenan-induced edema 4 h after irradiation and on the third and seventh day thereafter. The increase in paw volume was significantly suppressed in animals receiving the drug. Administration of piroxicam (5 mg kg-1) one hour before irradiation of animals at 0.5 Gy, produced inhibition to the exaggerated inflammatory response in irradiated animals. This suggests that piroxicam possibly owes its protective value to prevention of the increase in cellular permeability induced by radiation. Alternatively, the drug may exert this effect by inhibiting PG synthesis, thereby reducing their potentiating influence on the other mediators of inflammation. Furthermore, the inhibition of lysosomal enzyme release possibly induced by the drug may contribute to the probable reduction in the release of inflammatory mediators.

  6. Histomorphological and angiogenic analyzes of skin epithelium after low laser irradiation in hairless mice.

    Science.gov (United States)

    Leão, Juliane Caroline; Issa, João Paulo Mardegan; Pitol, Dimitrius Leonardo; Rizzi, Ellen Camargo; Dias, Fernando José; Siéssere, Selma; Regalo, Simone Cecílio Hallak; Iyomasa, Mamie Mizusaki

    2011-09-01

    It is not well-understood how low-laser therapy affects the skin of the applied area. This study analyzes skin of the masseteric region of mice from the HRS/J strain after three different application regimens (three, six or ten applications per regimen) of low intensity laser at 20 J/cm(2) and 40 mW for 20 sec on alternate days. Three experimental groups according to the number of laser applications (three, six or ten) and three control groups (N = 5 animals for each group) were used. On the third day after the last irradiation, all animals were sacrificed and the skin was removed and processed to analyze the relative occupation of the test area by each epithelial layer and the aspects of neovascularization. Data were submitted to statistical analyzes. The irradiated groups compared to their respective controls at each period of time, showed no significant difference in relative occupation of the test area by the layers and epithelium areas for three and six applications, but for ten applications, a significant decrease (P epithelium areas were found. From the comparisons of the three irradiated groups together, the group with six laser applications showed statistical difference (P epithelium and on the layers. Vascular endothelial growth factor (VEGF) and VEGFR-2 immunoreactivities were similar for the control and irradiated groups. Results suggested a biostimulatory effect with low risks associated with superficial tissues, when the treatment aims the deeper layers after six applications.

  7. [Effect of lactobacillus and bifidobacteria preparations on the intestinal microflora of mice irradiated with gamma quanta].

    Science.gov (United States)

    Korshunov, V M; Kissina, E V; Ikonnikova, T B; Mal'tsev, V N; Goncharova, G I

    1980-06-01

    Lactobacilli (strain B12G) and bifidobacteria (strain 75-41), administered orally in a dose of 5 x 10 cells to CBA mice on days 1, 3, 5 and 10 after irradiation with gamma quanta in a dose of 700 rad, restored the "eubiosis" of the intestinal tract, specifically suppressing opportunistic bacteria and facilitating the normalization of the quantitative and qualitative correlation between microbial associations constituting the obligatory intestinal flora. For one thing, the preparations of lactobacilli and bifidobacteria, used for treatment, restored the amount of lactobacilli in the intestinal tract of the irradiated animals to the level, characteristic of the intact animals; for another, these preparations prevented the dissemination of Escherichia, Proteus, Enterococcus in the small intestine and considerably decreased the amount of these microorganisms, as well as Clostridium, in the large intestine.

  8. 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...... on the patients' global quality of life. CONCLUSION: Single fraction HBI is safe and effective providing long lasting pain reduction in 76% of patients with multiple bone metastases....

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Michal Barshishat-Kupper

    2015-08-01

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

  11. Orally administered betaine reduces photodamage caused by UVB irradiation through the regulation of matrix metalloproteinase-9 activity in hairless mice.

    Science.gov (United States)

    Im, A-Rang; Lee, Hee Jeong; Youn, Ui Joung; Hyun, Jin Won; Chae, Sungwook

    2016-01-01

    Betaine is widely distributed in plants, microorganisms, in several types of food and in medical herbs, including Lycium chinense. The administration of 100 mg betaine/kg body weight/day is an effective strategy for preventing ultraviolet irradiation‑induced skin damage. The present study aimed to determine the preventive effects of betaine on ultraviolet B (UVB) irradiation‑induced skin damage in hairless mice. The mice were divided into three groups: Control (n=5), UVB‑treated vehicle (n=5) and UVB‑treated betaine (n=5) groups. The level of irradiation was progressively increased between 60 mJ/cm2 per exposure at week 1 (one minimal erythematous dose = 60 mJ/cm2) and 90 mJ/cm2 per exposure at week 7. The formation of wrinkles significantly increased following UVB exposure in the UVB‑treated vehicle group. However, treatment with betaine suppressed UVB‑induced wrinkle formation, as determined by the mean length, mean depth, number, epidermal thickness and collagen damage. Furthermore, oral administration of betaine also inhibited the UVB‑induced expression of mitogen‑activated protein kinase kinase (MEK), extracellular signal‑regulated kinase (ERK), and matrix metalloproteinase‑9 (MMP‑9). These findings suggested that betaine inhibits UVB‑induced skin damage by suppressing increased expression of MMP‑9 through the inhibition of MEK and ERK.

  12. Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

    Science.gov (United States)

    Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

    2001-01-01

    The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

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

    Directory of Open Access Journals (Sweden)

    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

  14. Effect of Ligustrazine on Bone Marrow Microenvironment and Signal Transduction Path in Irradiation Injured Mice

    Institute of Scientific and Technical Information of China (English)

    孙岚; 刘文励; 孙汉英; 任天华; 李登举; 徐惠珍; 路武

    2002-01-01

    Objective:To evaluate the effect of ligustrazine on bone marrow hematopoietic microenvi-ronment and signal transduction in irradiation injured mice. Methods:After being irradiated by 6.0 Gy 60Coγ-ray, the mice in the ligustrazine group were orally given ligustrazine 4 mg/mouse twice a day to the endof the experiment. For the control group, normal saline was given instead of ligustrazine and the mice inthe normal group was untreated. The mice were sacrificed separately on the 3rd, 7th and 14th day after ra-diation, bone marrow of them was taken and managed as follows: (1) Make stromal cell culture to observethe growth state and the expression of focal adhesion kinase (FAK) of the cells; (2) Make the bone mar-row section to examine the pathological and immunohistochemistry changes, including the expression of fe-tal liver kinase-1 (Flk-1) and Fvm: RAg. The data were recorded and compared among groups. Results:Af-ter radiation, the hematopoietic cells in bone marrow decreased and the micro-vessels dilated and congestedwith bleeding; bone marrow became thinner, red colored with cells of irregular shape and few cells adhereto the bottom of culture flask. These changes began to recover at the 7th day and approached to normalwithin 2 weeks. The recovery was better, earlier and quicker in the ligustrazine group than that in the con-trol group. The expression levels of Flk-1 decreased significantly. Conclusion: Ligustrazine could promotethe recovery of hematopoietic function of radiation damaged bone marrow, the mechanisms might bethrough improving the microenvironment and signal transduction path for recovery.

  15. 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.

  16. The effect of bamboo (Phyllostachys nigra var. henenis Strapf) leaf extract on epidermal melanocytes in ultraviolet B-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae June; Chae, Se Lim; Kim, Sung Ho [Chonnam National Univ., Gwangju (Korea, Republic of)

    2007-06-15

    We induced the activation of melanocytes in the epidermis of C57BL/6 mice by ultraviolet B (UVB) irradiation and observed the effect of bamboo (phyllostachys nigra var. henenis strapf) Leaf Extract (BLE) on the formation, and decrease of UVB-induced epidermal melanocytes. C57BL/6 mice were irradiated by UVB 80 mJ/cm{sup 2} (0.5 mW/sec) daily for 7 days, and BLE was intraperitoneally 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 11-16 melanocytes/mm{sup 2}, and one week after UV irradiation, the applied areas show an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal or topical treatment with BLE before each irradiation interrupted UVB-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to radiation 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 BLE at 3rd and 6th weeks after irradiation. The results of present study indicate that BLE is likely to be useful as inhibitor of UVB-induced pigmentation and depigmenting agent.

  17. The effect of Bu-Zhong-Yi-Qi-Tang 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, Hwan Sung; Park, Young Jong; Kim, Joong Sun; Moon, Chang Jong; Kim, Jong Choon; Bae, Chun Sik; Kim, Sung Ho [Chonnam National University, Gwangju (Korea, Republic of); Jo, Sung Kee [KAERI, Daejeon (Korea, Republic of)

    2008-09-15

    We induced the activation of melanocytes in the epidermis of C57BL/6 mice by UltraViolet B (UVB) irradiation and observed the effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) on the formation, and decrease of UVB-induced epidermal melanocytes. C57BL/6 mice were irradiated by UVB 80 mJ/cm{sup 2} (0.5 mW/sec) daily for 7 days, and BZYQT was intraperitoneally 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 11-16 melanocytes/mm{sup 2}, and one week after UV irradiation, the applied areas show an increased number of strongly DOPA-positive melanocytes with stout dendrites. But intraperitoneal or topical treatment with BZYQT before each irradiation interrupted UVB-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to radiation 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 BZYQT at 3rd and 6th weeks after irradiation. The present study suggests the BZYQT as inhibitor of UVB-induced pigmentation and depigmenting agent.

  18. Energetic proton irradiation history of the HED parent body regolith and implications for ancient solar activity

    Science.gov (United States)

    Rao, M. N.; Garrison, D. H.; Palma, R. L.; Bogard, D. D.

    1997-07-01

    Previous studies have shown that the Kapoeta howardite, as well as several other meteorites, contain excess concentrations of cosmogenic neon in the darkened, solar-irradiated phase compared to the light, non-irradiated phase. The two explanations offered for the nuclear production of these Ne excesses in the parent body regolith are either from galactic particle (GCR) irradiation or from a greatly enhanced flux of energetic solar protons (SCR), as compared to the recent solar flux. Combining new isotopic data we obtained on acid-etched, separated feldspar from Kapoeta light and dark phases with literature data, we show that the cosmogenic 21Ne /22Ne ratio of light phase feldspar (0.80) is consistent with only GCR irradiation in space for ~3 Myr. However, the 21Ne/22Ne ratio (0.68) derived for irradiation of dark phase feldspar in the Kapoeta regolith indicates that cosmogenic Ne was produced in roughly equal proportions from galactic and solar protons. Considering a simple model of an immature Kapoeta parent body regolith, the duration of this early galactic exposure was only ~3-6 Myr, which would be an upper limit to the solar exposure time of individual grains. Concentrations of cosmogenic 21Ne in pyroxene separates and of cosmogenic 126Xe in both feldspar and pyroxene are consistent with this interpretation. The near-surface irradiation time of individual grains in the Kapoeta regolith probably varied considerably due to regolith mixing to an average GCR irradiation depth of ~10 cm. Because of the very different depth scales for production of solar ~Fe tracks, SCR Ne, and GCR Ne, the actual regolith exposure times for average grains probably differed correspondingly. However, both the SCR 21Ne and solar track ages appear to be longer because of enhanced production by early solar activity. The SCR/GCR production ratio of 21Ne inferred from the Kapoeta data is larger by a at least a factor of 10 and possibly as much as a factor of ~50 compared to recent solar

  19. 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.

  20. 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)

  1. 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.

  2. Effect of helium-neon laser irradiation on hair follicle growth cycle of Swiss albino mice.

    Science.gov (United States)

    Shukla, S; Sahu, K; Verma, Y; Rao, K D; Dube, A; Gupta, P K

    2010-01-01

    We report the results of a study carried out to investigate the effect of helium-neon (He-Ne) laser (632.8 nm) irradiation on the hair follicle growth cycle of testosterone-treated and untreated mice. Both histology and optical coherence tomography (OCT) were used for the measurement of hair follicle length and the relative percentage of hair follicles in different growth phases. A positive correlation (R = 0.96) was observed for the lengths of hair follicles measured by both methods. Further, the ratios of the lengths of hair follicles in the anagen and catagen phases obtained by both methods were nearly the same. However, the length of the hair follicles measured by both methods differed by a factor of 1.6, with histology showing smaller lengths. He-Ne laser irradiation (at approximately 1 J/cm(2)) of the skin of both the control and the testosterone-treated mice was observed to lead to a significant increase (p < 0.05) in % anagen, indicating stimulation of hair growth. The study also demonstrates that OCT can be used to monitor the hair follicle growth cycle, and thus hair follicle disorders or treatment efficacy during alopecia.

  3. 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).

  4. Thread Embedding Acupuncture Inhibits Ultraviolet B Irradiation-Induced Skin Photoaging in Hairless Mice

    Directory of Open Access Journals (Sweden)

    Yoon-Jung Kim

    2015-01-01

    Full Text Available Thread embedding acupuncture (TEA is an acupuncture treatment applied to many diseases in Korean medical clinics because of its therapeutic effects by continuous stimulation to tissues. It has recently been used to enhance facial skin appearance and antiaging, but data from evidence-based medicine are limited. To investigate whether TEA therapy can inhibit skin photoaging by ultraviolet B (UVB irradiation, we performed analyses for histology, histopathology, in situ zymography and western blot analysis in HR-1 hairless mice. TEA treatment resulted in decreased wrinkle formation and skin thickness (Epidermis; P=0.001 versus UV in UVB irradiated mice and also inhibited degradation of collagen fibers (P=0.010 versus normal by inhibiting proteolytic activity of gelatinase matrix-metalloproteinase-9 (MMP-9. Western blot data showed that activation of c-Jun N-terminal kinase (JNK induced by UVB (P=0.002 versus normal group was significantly inhibited by TEA treatment (P=0.005 versus UV with subsequent alleviation of MMP-9 activation (P=0.048 versus UV. These results suggest that TEA treatment can have anti-photoaging effects on UVB-induced skin damage by maintenance of collagen density through regulation of expression of MMP-9 and related JNK signaling. Therefore, TEA therapy may have potential roles as an alternative treatment for protection against skin damage from aging.

  5. 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.

  6. Activation of "eclipsed" lymphoid cells from advanced tumor-bearing mice through adoptive transfer to sublethally irradiated syngeneic hosts.

    Science.gov (United States)

    Youn, J K; Le Francois, D; Hue, G; Santillana, M; Barski, G

    1975-10-15

    Immunologically inactive or "eclipsed" lymphoid cells from advanced tumor-bearing mice were investigated following their adoptive transfer to irradiated syngeneic hosts. Experiments were performed with two syngeneic tumor-host system: the T5-BALB/c tumor line chronically infected with a low-leukemogenic Rauscher virus variant and the TM1-C3H tumor line developed from a spontaneous C3H/He mouse mammary tumor. In confirmation of our previous data, peritoneal cells (PC) from advanced tumor-bearing mice (EPC) appeared to have lost any capacity to inhibit specifically the growth of corresponding tumor target cells in vitro colony inhibition (CI) tests, whereas PC from immunized mice (IPC) were perfectly active. When these EPC were adoptively transferred by intraperitoneal inoculation into sublethally irradiated (450 R) syngeneic mice in association with respective tumor extracts (TE), the PC from such recipient mice, taken 5 to 13 days later, were nearly as active in in vitro CI tests as were PC from parallel IPC-recipient mice. For this recovery of specific immunological activity following the adoptive transfer of EPC the adjunction of the TE and irradiation of the recipient animals seem important and may be necessary. On the other hand, no specific immunological activity was seen in PC from irradiated mice to which PC from normal mice had been transferred with TE. In addition to the in vitro results, an effect of adoptive transfer of EPC (retardation of tumor growth) was also observed in vivo. It is concluded that the "eclipsed" immunologically inactive state of the EPC in mice bearing advanced tumor is not irreversible and that activation of these cells can occur in vivo under certain conditions helped by the presence of tumor-specific antigenic stimulus.

  7. Distinct Expression of Various Angiogenesis Factors in Mice Brain After Whole-Brain Irradiation by X-ray.

    Science.gov (United States)

    Deng, Zhezhi; Huang, Haiwei; Wu, Xiaohong; Wu, Mengmeng; He, Guoyong; Guo, Junjie

    2017-02-01

    Radiation-induced brain injury (RBI) is the most serious complication after radiotherapy. However, the etiology of RBI remains elusive. In order to evaluate the effect of X-rays on normal brain tissue, adult male BALB/C mice were subjected to whole-brain exposure with a single dose of 10 Gy or sham radiation. The structure and number of mice brain vessels were investigated 1, 7, 30, 90 and 180 days after irradiation by H&E staining and immune-fluorescence staining. Compared with sham control mice, in addition to morphological changes, a significant reduction of microvascular density was detected in irradiated mice brains. Whole-brain irradiation also caused damage in tight junction (TJ). Increased expression of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was observed in irradiated mouse brains showed by Western Blot. Immune-fluorescence staining results also verified the co-labeling of GFAP and VEGF after whole-brain irradiation. Furthermore, the protein expression levels of other angiogenesis factors, angiopoietin-1 (Ang-1), endothelial-specific receptor tyrosine kinase (Tie-2), and angiopoietin-2 (Ang-2) in brain were determined by Western Blot. Increased expression of Ang-2 was shown in irradiated mouse brains. In contrast, whole-brain irradiation significantly decreased Ang-1 and Tie-2 expression. Our data indicated that X-rays induced time-dependent microvascular injury and activation of astrocytes after whole-brain irradiation in mouse brain. Distinct regulation of VEGF/Ang2 and Ang-1/Tie-2 are closely associated with RBI, suggesting that angiogenesis interventions might be beneficial for patients with RBI.

  8. 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.

  9. Craniomandibular dysfunction in children treated with total-body irradiation and bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Dahlloef, G.; Krekmanova, L.; Kopp, S.; Borgstroem, B.; Forsberg, C.M.; Ringden, O. (Huddinge Univ. Hospital (Sweden))

    1994-01-01

    The prevalence of pain and dysfunction in the stomatognathic system was studied in a group of 19 long-term survivors after pediatric bone marrow transplantation (BMT), conditioned with total-body irradiation (TBI). Compared with the control group, the children and adolescents in the BMT group had a significantly reduced mouth opening capacity. A reduced translation movement of the condyles was diagnosed in 53% of children treated with TBI, compared with 5% in the control group. Signs of craniomandibular dysfunction were found in 84% of children in the BMT group, compared with 58% in the control group. Both irradiation and chemotherapy induce long-term alterations in connective and muscle tissues resulting in inflammation and eventually fibrosis. These changes in tissue homeostasis and concomitant growth retardation may lead to the observed malocclusion and reduced mobility of the temporomandibular joint, with subsequent muscle pain and headaches, which were found in this study. 29 refs., 3 tabs., 2 figs.

  10. Analysis of dose-LET distribution in the human body irradiated by high energy hadrons.

    Science.gov (United States)

    Sato, T; Tsuda, S; Sakamoto, Y; Yamaguchi, Y; Niita, K

    2003-01-01

    For the purposes of radiological protection, it is important to analyse profiles of the particle field inside a human body irradiated by high energy hadrons, since they can produce a variety of secondary particles which play an important role in the energy deposition process, and characterise their radiation qualities. Therefore Monte Carlo calculations were performed to evaluate dose distributions in terms of the linear energy transfer of ionising particles (dose-LET distribution) using a newly developed particle transport code (Particle and Heavy Ion Transport code System, PHITS) for incidences of neutrons, protons and pions with energies from 100 MeV to 200 GeV. Based on these calculations, it was found that more than 80% and 90% of the total deposition energies are attributed to ionisation by particles with LET below 10 keV microm(-1) for the irradiations of neutrons and the charged particles, respectively.

  11. 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.

  12. 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.

  13. 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)

  14. 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.

  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. Discoidin domain receptor 2 (DDR2) regulates body size and fat metabolism in mice.

    Science.gov (United States)

    Kawai, Ikuma; Matsumura, Hirokazu; Fujii, Wataru; Naito, Kunihiko; Kusakabe, Ken; Kiso, Yasuo; Kano, Kiyoshi

    2014-02-01

    Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens, which act as its endogenous ligand. DDR2 regulates cell proliferation, cell adhesion, migration, extracellular matrix remodeling and reproductive functions. Both DDR2 null allele mice and mice with a recessive, loss-of-function allele for Ddr2 exhibit dwarfing and a reduction in body weight. However, the detailed mechanisms by which DDR2 exerts its positive systemic regulation of whole body size, local skeletal size and fat tissue volume remain to be clarified. To investigate the systemic role of DDR2 in body size regulation, we produced transgenic mice in which the DDR2 protein is overexpressed, then screened the transgenic mice for abnormalities using systematic mouse abnormality screening. The modified-SHIPRA screen revealed that only the parameter of body size was significantly different among the genotypes. We also discovered that the body length was significantly increased, while the body weight was significantly decreased in transgenic mice compared to their littermate controls. We also found that the epididymal fat pads were significantly decreased in transgenic mice compared to normal littermate mice, which may have been the cause of the leptin decrement in the transgenic mice. The new insight that DDR2 might promote metabolism in adipocyte cells is very interesting, but more experiments will be needed to elucidate the direct relation between DDR2 and adipose-derived hormones. Taken together, our data demonstrated that DDR2 might play a systemic role in the regulation of body size thorough skeletal formation and fat metabolism.

  17. 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.

  18. Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

    1985-01-01

    The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae.

  19. 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.

  20. 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.

  1. [Effects of mesenchymal stem cells on cell cycle and apoptosis of hematopoietic tissue cells in irradiated mice].

    Science.gov (United States)

    Hu, Kai-Xun; Zhao, Shi-Fu; Guo, Mei; Ai, Hui-Sheng

    2007-12-01

    The aim of this study was to investigate the effect of mesenchymal stem cells (MSCs) on cell cycle and apoptosis of thymus, spleen and bone marrow cells in mice totally irradiated with sublethal dose, and to explore its mechanisms. BALB/c mice irradiated with 5.5 Gy 60Co gamma-ray were randomly divided into control group and MSC group. Mice in MSC group were infused with 0.4 ml containing 2.5x10(7)/kg of MSCs through tail vein at 1 hour after irradiation. Mice in control group were infused with 0.4 ml normal saline. The cell apoptosis and cell cycle of thymus, spleen and bone marrow cells were detected by flow cytometry at 6, 12, 24 and 72 hours after irradiation and the P53 protein expressions in thymus and bone marrow cells were assayed by immunohistochemistry at 12 hours after irradiation. The results showed that the arrest of cells in G0/G1 and G2/M phase, and decrease of cells in S phase appeared at 6 hours after irradiation, those reached peak respectively at 12 hours in thymus cells, 6 hours in spleen and 24 hours in bone marrow, then the cell counts in G0/G1 phase decreased and the cell counts in S and G2/M phases increased. At 72 hours the cell counts in G0/G1 phase were less than the normal level and the cell counts in S phase were more than the normal level. The above changes of cell cycle in thymus and spleen were more rapid in spleen and more obvious in amplitude than that in bone marrow, the change of cell cycle in MSC group was more rapid and obvious than those in control group. After irradiation the apoptosis cells increased from 6 hours, reached the highest level at 12 hours and decreased to the normal level gradually after 24 hours in two groups; the apoptosis rates in spleen and thymus cells were higher than that in bone marrow cells. In comparison with the control group, the apoptosis rate in thymus cells at 12 hours, in spleen cells at 12 and 24 hours, and in bone marrow cells at 24 hours were fewer in MSC group. The cells expressing P53

  2. Assessment of Routine Procedure Effect on Breathing Parameters in Mice by Using Whole-Body Plethysmography

    Science.gov (United States)

    Raşid, Orhan; Chirita, Daniel; Iancu, Adina D; Stavaru, Crina; Radu, Dorel L

    2012-01-01

    We used whole-body plethysmography to investigate the effect of restraint, ear marking, tail vein and retroorbital blood sampling, and tail clipping on respiration in Balb/c × TCR-HA+/– F1 hybrid mice (F1h). Baseline values of breathing parameters were determined. During the experiment, mice experienced a procedure and then plethysmographic recordings were obtained immediately and at 4, 24, and 48 h afterward. Baseline breathing parameters showed significant differences between sexes. Restraint affected minute volume differently than did handling in male mice and to a lesser extent in female mice. Ear marking significantly changed minute volume compared with handling but not restraint in male mice and in the opposite manner in female mice. Tail vein blood sampling changed minute volume in a significant manner compared with restraint but not compared with handling in both sexes. Retroorbital blood sampling significantly changed minute volume compared with values for both handling and restraint in male mice but only compared with handling in female mice. Tail clipping modified minute volume significantly compared with handling in male mice and compared with restraint in both sexes. Analysis of data showed that routine procedures affect minute volume in mice depending on invasiveness of maneuver and in a sex-biased manner for as long as 24 h after the procedure. Our experiment shows that procedures performed on laboratory mice can change respiratory parameters and can be investigated by plethysmography. PMID:23043813

  3. 3-aminobenzamide, a poly (ADP ribose) polymerase inhibitor, enhances wound healing in whole body gamma irradiated model.

    Science.gov (United States)

    El-Hamoly, Tarek; El-Denshary, Ezzeddin S; Saad, Shokry Mohamed; El-Ghazaly, Mona A

    2015-09-01

    The custom use of radiotherapy was found to participate in the development of chronic unhealed wounds. In general, exposure to gamma radiation stimulates the production of reactive oxygen species (ROS) that eventually leads to damaging effect. Conversely, overexpression of a nuclear poly (ADP-ribose) polymerase enzyme (PARP) after oxidative insult extremely brings about cellular injury due to excessive consumption of NAD and ATP. Here, we dedicated our study to investigate the role of 3-aminobenzamide (3-AB), a PARP inhibitor, on pregamma irradiated wounds. Two full-thickness (6 mm diameter) wounds were created on the dorsum of Swiss albino mouse. The progression of wound contraction was monitored by capturing daily photo images. Exposure to gamma radiation (6Gy) exacerbated the normal healing of excisional wounds. Remarkably, topical application of 3-AB cream (50 µM) revealed a marked acceleration in the rate of wound contraction. Likewise, PARP inhibition ameliorated the unbalanced oxidative/nitrosative status of granulated skin tissues. Such effect was significantly revealed by the correction of the reduced antioxidant capacity and the enhanced lipid peroxidation, hydrogen peroxide, and myeloperoxidase contents. Moreover, application of 3-AB modified the cutaneous nitrite content throughout healing process. Conversely, the expressions of pro-inflammatory cytokines were down-regulated by PARP inhibition. The mitochondrial ATP content showed a lower consumption rate on 3-AB-treated wound bed as well. In parallel, the mRNA expressions of Sirt-1 and acyl-COA oxidase-2 (ACOX-2) were up-regulated; whom functions control the mitochondrial ATP synthesis and lipid metabolism. The current data suggested that inhibition of PARP-1 enzyme may accelerate the delayed wound healing in whole body gamma irradiated mice by early modifying the oxidative stress as well as the inflammatory response.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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

    BACKGROUND: Ultraviolet (UV) radiation induces non-melanoma skin cancer (NMSC), and UV prophylaxis is essential to prevent skin cancer. It is unclear whether patients diagnosed with squamous cell carcinomas (SCC) may benefit from reduced UV exposures in terms of delaying the development of new...... 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.......0001) and 44 days (2 SED, P = 0.111). CONCLUSION: This suggests that patients with SCC may benefit from reduced UV exposure....

  8. 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.

  9. 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....

  10. Macroarray analysis of gene expression in hematopoietic tissues from mice continuously irradiated by low dose-rate ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Saitou, Mikio; Nakamura, Shingo; Shirata, Katsutoshi; Yanai, Takanori; Izumi, Jun; Sugihara, Takashi; Tanaka, Satoshi; Tanaka, Kimio; Otsu, Hiroshi; Sato, Fumiaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)

    2002-07-01

    We found that the number of hematopoietic progenitor cells in bone marrow and spleen from 4 - 8 Gy-irradiated mice decreased about 50%, in spite of no change in the number of peripheral blood cells. To evaluate the effects of chronic irradiation by low dose-rate ionizing radiation on the gene expression in mice hematopoietic cells from bone marrow and spleen, the RNA expressions of more than 500 genes such as cytokine genes and oncogenes were measured on the membranes by the RNA macroarray analysis method at accumulated doses at 4.7 and 8 Gy in specific-pathogen-free (SPF) C3H/HeN female mice irradiated by {sup 137}Cs {gamma}-rays with the dose rate of 20 mGy/day. The RNA macroarray analysis in spleens from 8 Gy-irradiated mice showed that the expressions in 16 genes including noggin were more than 1.5 times larger than that of control, while those in 64 genes including shh (sonic hedgehog) and BMP-4 (bone morphogenesis protein 4) were more than 1.5 times smaller than that of control. (author)

  11. 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...

  12. 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)

  13. 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.

  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. Analysis of hematopoiesis in mice irradiated with 500 mGy of X rays at different stages of development

    Energy Technology Data Exchange (ETDEWEB)

    Grande, T.; Bueren, J.A. [U. de Biologia Molecular y Celular, Madrid (Spain)

    1995-09-01

    We have investigated whether a relatively low dose of 500 mGy of X rays given as a single acute irradiation at different stages of pre-and postnatal development induces significant changes in the content of femoral hematopoietic progenitores during a 1-year period after irradiation. Data obtained show that, in the case of 4-day-old embryos as well as in 2-day, 8-day and 12-week-old mice, this dose is below the threshold capable of inducing a long-term impairment of hematopoiesis in the mouse. Nevertheless, in mice irradiated at the 13th or the 17th day postconception, a hematopoietic dysfunction consisting of a significant reduction in the proportion of femoral granulocyte-macrophage colony-forming units (CFU-GM) was manifested 1 year after irradiation. Our study confirms that, for most stages of development in the mouse, a single acute X irradiation of 500 mGy is below the threshold dose capable of inducing deterministic effects in the mouse hematopoietic system, although it reveals the induction of a significant impairment in the CFU-GM population when irradiation is given at the late stages of embryonic development. 24 refs., 4 figs.

  16. Partial depletion of regulatory T cells does not influence the inflammation caused by high dose hemi-body irradiation.

    Directory of Open Access Journals (Sweden)

    Shihong Ma

    Full Text Available There is clinical interest in the modulation of regulatory T cells for cancer therapy. The safety of these therapies in combination with conventional anti-cancer therapies, including radiation therapy, can be studied in animal models. The effects of partial depletion of regulatory T (Treg cells with an anti-CD25 antibody in conjunction with ionizing radiation on inflammation and tissue injury were analyzed in C57BL/6 mice. An anti-CD25 antibody (PC61 was administered 3 days prior to 13 Gy lower-half hemi-body irradiation (HBI. The blood, spleen, mesenteric lymph nodes (mLNs and inguinal lymph nodes (iLNs were harvested at various times thereafter. Alterations in the proportion of leukocyte subsets including CD4(+ T cells, CD8(+ T cells, Treg cells, B cells, NK cells, NK1.1(+ T cells, macrophages and granulocytes were analyzed by FACS. The lungs, liver, pancreas, stomach, jejunum, duodenum, ileum, colon and kidney were harvested and studied by H&E staining. Expression of inflammatory mediators in plasma and tissue were investigated by ELISA. HBI significantly decreased the leukocyte pool though the various leukocyte subsets had different sensitivities to HBI. The administration of PC61 significantly decreased the proportion of Treg cells in spleen, iLN, mLN and blood (reduction of approximately 60%. Irradiation significantly increased the proportion of Treg cells in the spleen, iLN and mLN. HBI induced a systemic inflammatory reaction as demonstrated by increased plasma levels of IL-6, KC/CXCL1 and circulating granulocytes in the blood. Neutrophils also infiltrated the small bowel. The same general patterns were observed whether or not Treg cells were partially depleted with PC61 prior to HBI. These data demonstrate that partial depletion of Treg cells in these mice does not influence HBI-induced inflammatory response and tissue injury, and that combining anti-CD25 therapy with radiation may be safe and well tolerated in a clinical setting.

  17. Partial Depletion of Regulatory T Cells Does Not Influence the Inflammation Caused by High Dose Hemi-Body Irradiation

    Science.gov (United States)

    Ma, Shihong; Richardson, James A.; Bitmansour, Andrew; Solberg, Timothy D.; Pidikiti, Rajesh; Song, Kwang; Stojadinovic, Strahinja; Vitetta, Ellen S.; Meyer, Jeffrey J.

    2013-01-01

    There is clinical interest in the modulation of regulatory T cells for cancer therapy. The safety of these therapies in combination with conventional anti-cancer therapies, including radiation therapy, can be studied in animal models. The effects of partial depletion of regulatory T (Treg) cells with an anti-CD25 antibody in conjunction with ionizing radiation on inflammation and tissue injury were analyzed in C57BL/6 mice. An anti-CD25 antibody (PC61) was administered 3 days prior to 13 Gy lower-half hemi-body irradiation (HBI). The blood, spleen, mesenteric lymph nodes (mLNs) and inguinal lymph nodes (iLNs) were harvested at various times thereafter. Alterations in the proportion of leukocyte subsets including CD4+ T cells, CD8+ T cells, Treg cells, B cells, NK cells, NK1.1+ T cells, macrophages and granulocytes were analyzed by FACS. The lungs, liver, pancreas, stomach, jejunum, duodenum, ileum, colon and kidney were harvested and studied by H&E staining. Expression of inflammatory mediators in plasma and tissue were investigated by ELISA. HBI significantly decreased the leukocyte pool though the various leukocyte subsets had different sensitivities to HBI. The administration of PC61 significantly decreased the proportion of Treg cells in spleen, iLN, mLN and blood (reduction of approximately 60%). Irradiation significantly increased the proportion of Treg cells in the spleen, iLN and mLN. HBI induced a systemic inflammatory reaction as demonstrated by increased plasma levels of IL-6, KC/CXCL1 and circulating granulocytes in the blood. Neutrophils also infiltrated the small bowel. The same general patterns were observed whether or not Treg cells were partially depleted with PC61 prior to HBI. These data demonstrate that partial depletion of Treg cells in these mice does not influence HBI-induced inflammatory response and tissue injury, and that combining anti-CD25 therapy with radiation may be safe and well tolerated in a clinical setting. PMID:23409194

  18. 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)

  19. A systematic proteomic study of irradiated DNA repair deficient Nbn-mice.

    Directory of Open Access Journals (Sweden)

    Anna Melchers

    Full Text Available BACKGROUND: The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs. The NBN gene is essential in mammals. METHODOLOGY/PRINCIPAL FINDINGS: We have used a conditional null mutant mouse model in a proteomics approach to identify proteins with modified expression levels after 4 Gy ionizing irradiation in the absence of nibrin in vivo. Altogether, amongst approximately 8,000 resolved proteins, 209 were differentially expressed in homozygous null mutant mice in comparison to control animals. One group of proteins significantly altered in null mutant mice were those involved in oxidative stress and cellular redox homeostasis (p<0.0001. In substantiation of this finding, analysis of Nbn null mutant fibroblasts indicated an increased production of reactive oxygen species following induction of DSBs. CONCLUSIONS/SIGNIFICANCE: In humans, biallelic hypomorphic mutations in NBN lead to Nijmegen breakage syndrome (NBS, an autosomal recessive genetic disease characterised by extreme radiosensitivity coupled with growth retardation, immunoinsufficiency and a very high risk of malignancy. This particularly high cancer risk in NBS may be attributable to the compound effect of a DSB repair defect and oxidative stress.

  20. Regulation of cellular marker modulated upon irradiation of low power laser light in burn injured mice

    Science.gov (United States)

    Rathnakar, Bharath; Prabhu, Vijendra; Rao, Bola Sadashiva Satish; Chandra, Subhash; Rai, Sharada; Mahato, Krishna Kishore

    2016-12-01

    The present study intends to understand the importance of cellular marker in tissue regeneration regulated upon irradiation of low power laser light in burn inflicted mice. Under anesthetic conditions, the thermal injury was induced on Swiss albino mice of either sex. Following injury, the animals were randomly divided into three groups; i. e., un-illuminated control, the group treated with 5% Povidone iodine (reference standard) and single exposure of 3 J/cm2 (830 nm). Burn tissue samples from each group were excised at day 6 post burn injury upon euthanization and used for histological and immunohistochemical analysis. Haematoxylin and Eosin (H and E) staining was performed on the selected sections to asses proliferation and angiogenesis at day 6 post-injury. For immunohistochemical analysis, tissue sections from all the three treatment groups on day 6 were stained using specific antibody against Proliferating cell nuclear antigen (PCNA). The results of the histological and immunohistochemical analysis showed improved tissue restoration in animals treated with optimal laser influence as compared to un-illuminated controls. The findings of present study clearly demonstrated the beneficial effects of 830 nm laser in burn wound healing and its influence in regulating the cellular marker.

  1. 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.

  2. 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.

  3. Effects of GABA agonists on body temperature regulation in GABA(B(1))-/- mice.

    Science.gov (United States)

    Quéva, Christophe; Bremner-Danielsen, Marianne; Edlund, Anders; Ekstrand, A Jonas; Elg, Susanne; Erickson, Sven; Johansson, Thore; Lehmann, Anders; Mattsson, Jan P

    2003-09-01

    1. Activation of GABA(B) receptors evokes hypothermia in wildtype (GABA(B(1))+/+) but not in GABA(B) receptor knockout (GABA(B(1))-/-) mice. The aim of the present study was to determine the hypothermic and behavioural effects of the putative GABA(B) receptor agonist gamma-hydroxybutyrate (GHB), and of the GABA(A) receptor agonist muscimol. In addition, basal body temperature was determined in GABA(B(1))+/+, GABA(B(1))+/- and GABA(B(1))-/- mice. 2. GABA(B(1))-/- mice were generated by homologous recombination in embryonic stem cells. Correct gene targeting was assessed by Southern blotting, PCR and Western blotting. GABA(B) receptor-binding sites were quantified with radioligand binding. Measurement of body temperature was done using subcutaneous temperature-sensitive chips, and behavioural changes after drug administration were scored according to a semiquantitative scale. 3. GABA(B(1))-/- mice had a short lifespan, probably caused by generalised seizure activity. No histopathological or blood chemistry changes were seen, but the expression of GABA(B(2)) receptor protein was below the detection limit in brains from GABA(B(1))-/- mice, in the absence of changes in mRNA levels. 4. GABA(B) receptor-binding sites were absent in brain membranes from GABA(B(1))-/- mice. 5. GABA(B(1))-/- mice were hypothermic by approximately 1 degrees C compared to GABA(B(1))+/+ and GABA(B(1))+/- mice. 6. Injection of baclofen (9.6 mg kg-1) produced a large reduction in body temperature and behavioural effects in GABA(B(1))+/+ and in GABA(B(1))+/- mice, but GABA(B(1))-/- mice were unaffected. The same pattern was seen after administration of GHB (400 mg kg-1). The GABA(A) receptor agonist muscimol (2 mg kg-1), on the other hand, produced a more pronounced hypothermia in GABA(B(1))-/-mice. In GABA(B(1))+/+ and GABA(B(1))+/- mice, muscimol induced sedation and reduced locomotor activity. However, when given to GABA(B(1))-/- mice, muscimol triggered periods of intense jumping and wild

  4. Gamma irradiation or CD4+-T-cell depletion causes reactivation of latent Salmonella enterica serovar Typhimurium infection in C3H/HeN mice.

    Science.gov (United States)

    van Diepen, Angela; van de Gevel, Joke S; Koudijs, Margaretha M; Ossendorp, Ferry; Beekhuizen, Henry; Janssen, Riny; van Dissel, Jaap T

    2005-05-01

    Upon infection with Salmonella, a host develops an immune response to limit bacterial growth and kill and eliminate the pathogen. Salmonella has evolved mechanisms to remain dormant within the body, only to reappear (reactivate) at a later time when the immune system is abated. We have developed an in vivo model for studying reactivation of Salmonella enterica serovar Typhimurium infection in mice. Upon subcutaneous infection, C3H/HeN (Ity(r)) mice showed an increase in bacterial numbers in livers and spleens, which reached a peak on day 19. After full recovery from the infection, these mice were irradiated or depleted of CD4(+) T cells. The mice displayed a secondary infection peak in livers and spleens with a course similar to that of the primary infection. We concluded that CD4(+) T cells are involved in active suppression of S. enterica serovar Typhimurium during latency. The role of CD4(+) T cells during primary infection with S. enterica serovar Typhimurium is well established. This is the first study to describe a role of CD4(+) T cells during the latent phase of S. enterica serovar Typhimurium infection.

  5. 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.

  6. The dose and dose-rate effects of paternal irradiation on transgenerational instability in mice: a radiotherapy connection.

    Directory of Open Access Journals (Sweden)

    Safeer K Mughal

    Full Text Available The non-targeted effects of human exposure to ionising radiation, including transgenerational instability manifesting in the children of irradiated parents, remains poorly understood. Employing a mouse model, we have analysed whether low-dose acute or low-dose-rate chronic paternal γ-irradiation can destabilise the genomes of their first-generation offspring. Using single-molecule PCR, the frequency of mutation at the mouse expanded simple tandem repeat (ESTR locus Ms6-hm was established in DNA samples extracted from sperm of directly exposed BALB/c male mice, as well as from sperm and the brain of their first-generation offspring. For acute γ-irradiation from 10-100 cGy a linear dose-response for ESTR mutation induction was found in the germ line of directly exposed mice, with a doubling dose of 57 cGy. The mutagenicity of acute exposure to 100 cGy was more pronounced than that for chronic low-dose-rate irradiation. The analysis of transgenerational effects of paternal irradiation revealed that ESTR mutation frequencies were equally elevated in the germ line (sperm and brain of the offspring of fathers exposed to 50 and 100 cGy of acute γ-rays. In contrast, neither paternal acute irradiation at lower doses (10-25 cGy, nor low-dose-rate exposure to 100 cGy affected stability of their offspring. Our data imply that the manifestation of transgenerational instability is triggered by a threshold dose of acute paternal irradiation. The results of our study also suggest that most doses of human exposure to ionising radiation, including radiotherapy regimens, may be unlikely to result in transgenerational instability in the offspring children of irradiated fathers.

  7. 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.

  8. Androgens Attenuate Vitamin D Production Induced by UVB Irradiation of the Skin of Male Mice by an Enzymatic Mechanism.

    Science.gov (United States)

    Xue, Yingben; Ying, Lee; Horst, Ronald L; Watson, Gordon; Goltzman, David

    2015-12-01

    Cutaneous exposure to UVB irradiation is an important source of vitamin D. Here, we examined sex-specific differences in cutaneous vitamin D production in mice. Both male and female mice on a vitamin D-deficient diet manifested vitamin D deficiency, with mineral abnormalities, secondary hyperparathyroidism, and osteomalacia. UVB irradiation significantly increased vitamin D levels in the skin of female mice and normalized serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels, as well as mineral and skeletal abnormalities. However, in male mice, the vitamin D response to UVB was attenuated and mineral and skeletal abnormalities were not normalized. The vitamin D precursor, 7-dehydrocholesterol (7DHC), was significantly lower in the skin of male than female mice. This reduction was due to local androgen action in the skin as demonstrated by castration studies and skin-specific androgen receptor deletion in male mice, both of which reversed the male phenotype. Local androgen regulation in the skin of the CYP11A1 gene, which encodes a crucial enzyme that metabolizes cholesterol, 7DHC, and vitamin D, appeared to contribute to the gender differences in UVB-induced vitamin D production and to its reversal of vitamin D deficiency. Sex-specific, enzymatically regulated differences in cutaneous production of vitamin D may therefore be of importance to ensure vitamin D sufficiency.

  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. 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.

  11. 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.

  12. 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.

  13. Dietary Milk Sphingomyelin Prevents Disruption of Skin Barrier Function in Hairless Mice after UV-B Irradiation.

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    Chisato Oba

    Full Text Available Exposure to ultraviolet-B (UV-B irradiation causes skin barrier defects. Based on earlier findings that milk phospholipids containing high amounts of sphingomyelin (SM improved the water content of the stratum corneum (SC in normal mice, here we investigated the effects of dietary milk SM on skin barrier defects induced by a single dose of UV-B irradiation in hairless mice. Nine week old hairless mice were orally administrated SM (146 mg/kg BW/day for a total of ten days. After seven days of SM administration, the dorsal skin was exposed to a single dose of UV-B (20 mJ/cm2. Administration of SM significantly suppressed an increase in transepidermal water loss and a decrease in SC water content induced by UV-B irradiation. SM supplementation significantly maintained covalently-bound ω-hydroxy ceramide levels and down-regulated mRNA levels of acute inflammation-associated genes, including thymic stromal lymphopoietin, interleukin-1 beta, and interleukin-6. Furthermore, significantly higher levels of loricrin and transglutaminase-3 mRNA were observed in the SM group. Our study shows for the first time that dietary SM modulates epidermal structures, and can help prevent disruption of skin barrier function after UV-B irradiation.

  14. Effect of antimicrobial therapy on the gastrointestinal bacterial flora, infection and mortality in mice exposed to different doses of irradiation

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    Brook, I.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

    1994-01-01

    The effect of antimicrobial therapy on gut flora, sepsis, and mortality was investigated in C[sub 3]H/HeN female mice irradiated with 7.0, 8.0 or 8.5 Gy or [sup 60]Co. The antimicrobial agents tested were metronidazole, penicillin, imipenem, gentamicin and ofloxacin. In control mice, the greatest reduction of lactose fermenting organisms (1.7-2.8 logs) occurred on day 8 after irradiation and were related directly to radiation doses. After day 8 lactose fermenting organism levels increased and the increases were associated with mortality due to Enterobacteriaceae sepsis. Irradiation reduced the populations of strict anaerobic bacteria in control mice by 2-8 logs, and these remained at low levels. Treatment with either metronidazole or penicillin resulted in greater reductions of strict anaerobic bacteria than occurred in the controls and induced earlier and greater increases in lactose fermenting organisms and associated mortality. Therapies with either gentamicin or ofloxacin resulted in lesser reductions of strict anaerobic bacteria (1.1-2.2 logs) than occurred in controls, and caused greater decreases in lactose fermenting organisms and mortality. The changes in the bacterial flora and mortality following imipenem treatment were similar to controls. These data demonstrate that in animals exposed to irradiation, antimicrobial agents effective against strict anaerobic bacteria can be deleterious, but antimicrobial agents effective against lactose fermenting organsims may be beneficial. (Author).

  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. Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys

    Science.gov (United States)

    Lucas, J. N.; Hill, F. S.; Burk, C. E.; Cox, A. B.; Straume, T.

    1996-01-01

    Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

  17. Enhancing effect by electron beam irradiation on immunomodulating and antitumor activity of b-glucan in mice

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, A Reum; Lee, Jung Lim; Park, Seok Rae; Yoo, Yung Choon [Konyang Univ., Daejeon (Korea, Republic of); Kim, Jae Hoon; Lee, Ju Woon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-07-01

    In this study, in order to investigated the effect of electron beam irradiation to b-glucan on its biological activities, we compared anti-allergic and antitumor activity between non-irradiated and electron beam-irradiated b-glucan. EDB-glucan was irradiated by electron beam with 50 kGy. Treatment of EDB-glucan, but not NCI-glucan also significantly inhibited T cell proliferation and cytokine production in response to the same allergen Ova. However EDB-glucan did not affect the production of Ova-specific IgG, IgA and IgM. In experiments of antitumor activity, EDB-glucan treated with 50 kGy prior to tumor inoculation inhibited an experimental lung metastasis produced by B/E-B/L melanoma cells in mice. The same effect of EDB-glucan treated with 50 kGy induced a decrease of tumor growth in tumor-bearing mice. Collective, these results indicates that electron beam irradiation to b-glucan leads to inhibit allergic responses, and enhance antitumor activity.

  18. Dose homogeneity of the total body irradiation in vivo and in vitro confirmed with thermoluminescent dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Chie, E.K.; Park, S.W.; Kang, W.S.; Kim, I.H.; Ha, S.W.; Park, C.I. [Seoul National University College of Medicine, Department of Therapeutic Radiology, Seoul (Korea)

    2000-05-01

    Total body irradiation (TBI) or whole body irradiation is used to acquire immune suppression, to treat malignant lymphoma and leukemia, and as a conditioning regimen for bone marrow transplantation. The objective of this study was to analyze and confirm the accuracy and the homogeneity of the treatment setup, the parallel opposed lateral technique, currently used in Seoul National University Hospital. Surface dose data, measured with a thermoluminescent dosimeter in 8 patients among 10 patients, who were given total body irradiation with the parallel opposed lateral technique between September 1996 to August 1998, in Seoul National University Hospital was analyzed. Surface doses were measured at the head, neck, axilla, thigh, and ankle level. Surface and midline doses of head, neck, axilla, abdomen, and hip level were measured with similar set-up and technique in the Humanoid phantom, as well. Measured surface doses relative to prescribed dose for the head, neck, axilla, thigh, and ankle level were 91.3{+-}7.8%, 98.3{+-}7.5%, 95.1{+-}6.3%, 98.3{+-}5.5%, and 95.3%{+-}6.3%, respectively in patients. Measured surface doses and midline doses relative to prescribed dose for the head, neck, axilla, abdomen, and thigh level were 85.0{+-}4.0%, 86.6{+-}5.8%, 83.9{+-}4.9%, 94.8{+-}2.8%, and 96.6{+-}2.2%, 95.3{+-}3.2%, 80.4{+-}1.9%, 100.0{+-}3.1%, 90.5{+-}2.2%, respectively. The surface-to-midline dose conversion ratio obtained from the Humanoid phantom study were 1.14{+-}0.06, 1.10{+-}0.09, 0.96{+-}0.05, 1.06{+-}0.06, 0.95{+-}0.02 for head, neck, axilla, abdomen, and hip level, respectively. The midline doses of the head, neck, axilla, thigh, and ankle in patients estimated from the surface-to-midline conversion ratios were 103.4{+-}9.0%, 107.8{+-}10.5%, 91.1{+-}6.1%, 93.8{+-}4.5%, and 104.5{+-}9.3%, respectively. Measured surface doses and estimated midline doses ranged from -8.9% to +7.8%. Midline doses at the neck and the axilla level deviated more than 5% from the

  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. 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.

  1. 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.)

  2. 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

  3. SU-E-T-664: Radiobiological Modeling of Prophylactic Cranial Irradiation in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D; Debeb, B; Woodward, W [MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Prophylactic cranial irradiation (PCI) is a clinical technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with ALL and SCLC, and we have shown the potential of PCI in select breast cancer patients through a mouse model (manuscript in preparation). We developed a computational model using our experimental results to demonstrate the advantage of treating brain micro-metastases early. Methods: MATLAB was used to develop the computational model of brain metastasis and PCI in mice. The number of metastases per mouse and the volume of metastases from four- and eight-week endpoints were fit to normal and log-normal distributions, respectively. Model input parameters were optimized so that model output would match the experimental number of metastases per mouse. A limiting dilution assay was performed to validate the model. The effect of radiation at different time points was computationally evaluated through the endpoints of incidence, number of metastases, and tumor burden. Results: The correlation between experimental number of metastases per mouse and the Gaussian fit was 87% and 66% at the two endpoints. The experimental volumes and the log-normal fit had correlations of 99% and 97%. In the optimized model, the correlation between number of metastases per mouse and the Gaussian fit was 96% and 98%. The log-normal volume fit and the model agree 100%. The model was validated by a limiting dilution assay, where the correlation was 100%. The model demonstrates that cells are very sensitive to radiation at early time points, and delaying treatment introduces a threshold dose at which point the incidence and number of metastases decline. Conclusion: We have developed a computational model of brain metastasis and PCI in mice that is highly correlated to our experimental data. The model shows that early treatment of subclinical disease is highly advantageous.

  4. Improved cerebral energetics and ketone body metabolism in db/db mice.

    Science.gov (United States)

    Andersen, Jens V; Christensen, Sofie K; Nissen, Jakob D; Waagepetersen, Helle S

    2017-03-01

    It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate for cerebral glucose hypometabolism and unravel the functionality of cerebral mitochondria in type 2 diabetes mellitus. Acutely isolated cerebral cortical and hippocampal slices of db/db mice were incubated in media containing [U-(13)C]glucose, [1,2-(13)C]acetate or [U-(13)C]β-hydroxybutyrate and tissue extracts were analysed by mass spectrometry. Oxygen consumption and ATP synthesis of brain mitochondria of db/db mice were assessed by Seahorse XFe96 and luciferin-luciferase assay, respectively. Glucose hypometabolism was observed for both cerebral cortical and hippocampal slices of db/db mice. Significant increased metabolism of [1,2-(13)C]acetate and [U-(13)C]β-hydroxybutyrate was observed for hippocampal slices of db/db mice. Furthermore, brain mitochondria of db/db mice exhibited elevated oxygen consumption and ATP synthesis rate. This study provides evidence of several changes in brain energy metabolism in type 2 diabetes mellitus. The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism.

  5. 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.

  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. Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling

    Energy Technology Data Exchange (ETDEWEB)

    Edmondson, Elijah F., E-mail: elijah.edmondson@colostate.edu [Environmental and Radiological Health Sciences Department, Colorado State University, Fort Collins, Colorado (United States); Hunter, Nancy R. [Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Weil, Michael M. [Environmental and Radiological Health Sciences Department, Colorado State University, Fort Collins, Colorado (United States); Mason, Kathryn A. [Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

    2015-07-15

    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

  8. 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).

  9. 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.

  10. 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.

  11. Phosphorylation and cytoplasmic localization of MAPK p38 during apoptosis signaling in bone marrow granulocytes of mice irradiated in vivo and the role of amifostine in reducing these effects.

    Science.gov (United States)

    Segreto, Helena R C; Oshima, Celina T F; Franco, Marcello F; Silva, Maria Regina R; Egami, Mizue I; Teixeira, Vicente P C; Segreto, Roberto A

    2011-05-01

    We studied p38 phosphorylation and its intracellular localization during p53 and Puma (a p53 upregulated modulator of apoptosis) apoptotic signaling pathway in bone marrow granulocytes in mice irradiated in vivo and the role of the radioprotector amifostine in ameliorating these responses. Sixty-four C57BL mice were randomly assigned in two non-irradiated (Ami-/rad- and Ami+/rad-) and two irradiated (Ami-/rad+ and Ami+/rad+) groups. Animals received 400mg/kg of amifostine i.p. 30 min prior to a single whole body radiation dose of 7Gy. The experiments were performed using immunohistochemistry for caspase-3, cleaved caspase-3, p53, p-p53 (Ser 15), Puma, p38 and p-p38 (Thr 180/Tyr 182) protein expression. In addition transmission electron microscopy was used for ultrastructural characterization of apoptosis. Data showed that: (i) amifostine significantly reduced the number of apoptotic cells, (ii) p-p53 and Puma proteins were strongly immunostained in granulocytes after irradiation (Ami-/rad+), (iii) amifostine decreased the immunostaining of the proteins (Ami+/rad+), (iv) p38 was immunolocalized in physiological conditions in the nucleus and cytoplasm of granulocytes and neither radiation nor amifostine changed the protein immunostaining or its subcellular distribution, but influenced its activation, (v) radiation-induced p38 phosphorylation and its cytoplasmic accumulation during apoptosis signaling in granulocytes after whole body high radiation dose and amifostine markedly reduced these effects.

  12. 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.

  13. Transcription and activity of antioxidant enzymes after ionizing irradiation in radiation-resistant and radiation-sensitive mice

    OpenAIRE

    Hardmeier, Rosmarie; Hoeger, Harald; Fang-Kircher, Susanne; Khoschsorur, Ali; Lubec, Gert

    1997-01-01

    The involvement of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in radiobiological processes has been described at the enzyme activity level. We irradiated radiation-resistant (RR) and radiation-sensitive (RS) mice and studied antioxidant enzymes at the transcriptional and activity level. In addition, aromatic hydroxylation and lipid peroxidation parameters were determined to study radiation resistance at the oxidation level. RS BALB/c/J Him m...

  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. Activation of endogenous C-type retroviral genomes by internal alpha-irradiation of mice with /sup 224/Radium

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, J.; Erfle, V.; Mueller, W.A.

    1985-01-01

    Sensitive co-cultivation techniques were applied to study the radiation-induced activation of endogenous retroviral genomes in different mouse strains by the alpha-emitting radionuclide /sup 224/Radium. Activated infectious C-type retroviruses were detected in spleen, bone marrow and bone tissues of C57BL/6-, BALB/c- and NMRI mice. The titres of high-dose-irradiated animals were higher than those found in low-dose-irradiated animals. Infectious retrovirus could be detected with a dose of 13.2 rad (maximum dose rate 0.9 rad/day) in the skeleton, and a dose of 4.2 rad (maximum dose rate 0.3 rad/day) in the spleen. The virus activation pattern was different in the three mouse strains. These data indicate that activation of endogenous retroviral genomes by alpha-irradiation shows a dose-effect relationship and a dependence on the genetic background of the mouse.

  16. 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],

  17. 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.

  18. 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.

  19. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

    Science.gov (United States)

    Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

    2017-02-01

    We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21(CIP/WAF1))-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21(CIP/WAF1))-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21(CIP/WAF1))-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21(CIP/WAF1))-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

  20. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation

    Science.gov (United States)

    Vendetti, Frank P.; Leibowitz, Brian J.; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F.; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O’Connor, Mark J.; Yu, Jian; Beumer, Jan H.; Bakkenist, Christopher J.

    2017-01-01

    We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21CIP/WAF1)−/− mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21CIP/WAF1)−/− mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21CIP/WAF1)−/−, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21CIP/WAF1)−/− mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI. PMID:28145510

  1. Critical care of sub-lethal irradiated transgenic mice using a complete soft food formula-DietGel76A™.

    Science.gov (United States)

    Jumanca, Ovidiu I; Palmer, Jay

    2015-01-01

    The objective of this research is to determine whether the administration of a complete soft food formula to sub-lethal irradiated animals from three different transgenic mouse strains over a period of 21 consecutive days will have a significant impact on the clinical signs, and the general survival rate of the animals. Our hypothesis is that using DietGel76A™, along with an antibiotic treatment, strict handling and manipulation procedures, the general mortality rate, as well as the onset of the clinical signs between the treated animals and the control animals, will be significantly lower. This hypothesis was confirmed for the C57BL/6 mice. However, the treatment with DietGel76A™ had only a very limited impact on the recovery of more irradiation sensitive strains (CD45.1 and mostly NRG). Further studies must be conducted on mice from these strains in order to assess whether mice belonging to more sensitive strains should be on DietGel76A™ for a longer period of time (at least 42days post irradiation).

  2. Metabolism and aging: effects of cold exposure on metabolic rate, body composition, and longevity in mice.

    Science.gov (United States)

    Vaanholt, Lobke M; Daan, Serge; Schubert, Kristin A; Visser, G Henk

    2009-01-01

    The proposition that increased energy expenditure shortens life has a long history. The rate-of-living theory (Pearl 1928 ) states that life span and average mass-specific metabolic rate are inversely proportional. Originally based on interspecific allometric comparisons between species of mammals, the theory was later rejected on the basis of comparisons between taxa (e.g., birds have higher metabolic rates than mammals of the same size and yet live longer). It has rarely been experimentally tested within species. Here, we investigated the effects of increased energy expenditure, induced by cold exposure, on longevity in mice. Longevity was measured in groups of 60 male mice maintained at either 22 degrees C (WW) or 10 degrees C (CC) throughout adult life. Forty additional mice were maintained at both of these temperatures to determine metabolic rate (by stable isotope turnover, gas exchange, and food intake) as well as the mass of body and organs of subsets of animals at four different ages. Because energy expenditure might affect longevity by either accumulating damage or by instantaneously affecting mortality rate, we included a third group of mice exposed to 10 degrees C early in life and to 22 degrees C afterward (CW). Exposure to cold increased mean daily energy expenditure by ca. 48% (from 47.8 kJ d(-1) in WW to 70.6 kJ d(-1) in CC mice, with CW intermediate at 59.9 kJ d(-1)). However, we observed no significant differences in median life span among the groups (WW, 832 d; CC, 834 d; CW, 751 d). CC mice had reduced body mass (lifetime mean 30.7 g) compared with WW mice (33.8 g), and hence their lifetime energy potential (LEP) per gram whole-body mass had an even larger excess than per individual. Greenberg ( 1999 ) has pointed out that the size of the energetically costly organs, rather than that of the whole body, may be relevant for the rate-of-living idea. We therefore expressed LEP also in terms of energy expenditure per gram dry lean mass or per gram

  3. 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)

  4. A Cajal body-independent pathway for telomerase trafficking in mice.

    Science.gov (United States)

    Tomlinson, Rebecca L; Li, Jian; Culp, Bradley R; Terns, Rebecca M; Terns, Michael P

    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.

  5. 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.

  6. Influence of radiation field and fractionation schedule of total lymphoid irradiation (TLI) on the induction of suppressor cells and stable chimerism after bone marrow transplantation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-02-01

    When BALB/c mice received 17 daily fractions of 2 Gy each of total lymphoid irradiation (TLI, total dose 34 Gy) and 30 x 10/sup 6/ C/sub 57/ B1 bone marrow cells (BM) on the day after the last fraction, stable bone marrow chimerism without signs of graft-vs-host disease (GVHD) was obtained in 84% of the animals. On the contrary, in BALB/c mice receiving only seven fractions of TLI (total dose 14 Gy), all bone marrow grafts were rejected. When the last two fractions of a 14-Gy TLI course were given without shielding the extra lymphatic tissues (combined total lymphoid + total body irradiation, TLBI), chimerism could be induced in 53% of the animals. When this 14-Gy TLBI schedule was used, it was even possible to administer four fractions per day (multiple fractions per day schedule, MFD), thus reducing the overall treatment time to 2 consecutive days. After this concentrated form of TLBI, chimerism was detected in 35% of the animals. As in the 34-Gy TLI schedule, graft-vs-host reaction could not be prevented in the 14-Gy TLBI schedule when spleen lymphocytes (10 x 10/sup 6/) were added to the BM inocolum. Leucopenia or suppression of the phytohaemagglutinin (PHA)-induced blastogenesis could not predict which schedule would result in a successful allogeneic bone marrow take. Suppressor cells of the mixed lymphocyte reaction, on the other hand, were only found in the spleen of BALB/c mice treated with the TLI or TLBI schedules, which also resulted in stable bone marrow chimerism.

  7. Sepsis-induced morbidity in mice: effects on body temperature, body weight, cage activity, social behavior and cytokines in brain.

    Science.gov (United States)

    Granger, Jill I; Ratti, Pietro-Luca; Datta, Subhash C; Raymond, Richard M; Opp, Mark R

    2013-07-01

    Infection negatively impacts mental health, as evidenced by the lethargy, malaise, and cognitive deficits experienced during illness. These changes in central nervous system processes, collectively termed sickness behavior, have been shown in animal models to be mediated primarily by the actions of cytokines in brain. Most studies of sickness behavior to date have used bolus injection of bacterial lipopolysaccharide (LPS) or selective administration of the proinflammatory cytokines interleukin-1β (IL-1β) or IL-6 as the immune challenge. Such models, although useful for determining mechanisms responsible for acute changes in physiology and behavior, do not adequately represent the more complex effects on central nervous system (CNS) processes of a true infection with replicating pathogens. In the present study, we used the cecal ligation and puncture (CLP) model to quantify sepsis-induced alterations in several facets of physiology and behavior of mice. We determined the impact of sepsis on cage activity, body temperature, food and water consumption and body weights of mice. Because cytokines are critical mediators of changes in behavior and temperature regulation during immune challenge, we also quantified sepsis-induced alterations in cytokine mRNA and protein in brain during the acute period of sepsis onset. We now report that cage activity and temperature regulation in mice that survive are altered for up to 23 days after sepsis induction. Food and water consumption are transiently reduced, and body weight is lost during sepsis. Furthermore, sepsis decreases social interactions for 24-48 h. Finally, mRNA and protein for IL-1β, IL-6, and tumor necrosis factor-α (TNFα) are upregulated in the hypothalamus, hippocampus, and brain stem during sepsis onset, from 6h to 72 h post sepsis induction. Collectively, these data indicate that sepsis not only acutely alters physiology, behavior and cytokine profiles in brain, but that some brain functions are impaired for

  8. Retroviral vector integration in post-transplant hematopoiesis in mice conditioned with either submyeloablative or ablative irradiation.

    Science.gov (United States)

    Sadat, M A; Dirscherl, S; Sastry, L; Dantzer, J; Pech, N; Griffin, S; Hawkins, T; Zhao, Y; Barese, C N; Cross, S; Orazi, A; An, C; Goebel, W S; Yoder, M C; Li, X; Grez, M; Cornetta, K; Mooney, S D; Dinauer, M C

    2009-12-01

    X-linked chronic granulomatous disease (X-CGD) is an inherited immunodeficiency with absent phagocyte NADPH-oxidase activity caused by defects in the gene-encoding gp91(phox). Here, we evaluated strategies for less intensive conditioning for gene therapy of genetic blood disorders without selective advantage for gene correction, such as might be used in a human X-CGD protocol. We compared submyeloablative with ablative irradiation as conditioning in murine X-CGD, examining engraftment, oxidase activity and vector integration in mice transplanted with marrow transduced with a gamma-retroviral vector for gp91(phox) expression. The frequency of oxidase-positive neutrophils in the donor population was unexpectedly higher in many 300 cGy-conditioned mice compared with lethally irradiated recipients, as was the fraction of vector-marked donor secondary CFU-S12. Vector integration sites in marrow, spleen and secondary CFU-S12 DNA from primary recipients were enriched for cancer-associated genes, including Evi1, and integrations in or near cancer-associated genes were more frequent in marrow and secondary CFU-S12 from 300 cGy-conditioned mice compared with fully ablated mice. These findings support the concept that vector integration can confer a selection bias, and suggest that the intensity of the conditioning regimen may further influence the effects of vector integration on clonal selection in post-transplant engraftment and hematopoiesis.

  9. Study of the radioprotective effects of TMG on teratogenic malformations in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Yeunhwa; Hasegawa, Takeo; Suzuki, Ikukatsu; Mori, Takehiko; Yamamoto, Youichi [Suzuka Univ. of Medical Science, Mie (Japan); Kim, Hwakon

    2000-12-01

    ICR mice fetuses in the organogenesis stage were used to clarify experimentally the mechanism of the protective effect of vitamin E derivant (TMG: 2- ({alpha}-D-Glucopyranosyl) methyl-2, -5, -7, -8-Teramethylchorman-6-working woman) on the effects of radiation. The authors paid careful attention to radiation, and the radioprotective effects of TMG on the induction of malformations was examined. Radiation is an important consideration because of its widespread use in the areas of medicine, nuclear energy, and industry. Malformations induced by radiation at the organogenesis stage, skeletal malformations, and the effects at the cellular level of embryos were examined in this research. Further, the mechanism of the protection effect of TMG against radiation-induced malformations was analyzed and observed experimentally. Thus, this study was done to provide fundamental data on the radioprotective agent TMG. It was clear that TMG exerted radioprotective effects against embryonic death and the rate of teratogenesis when administered before exposure. Such effects were also exerted against skeletal malformations and fetal body weight. In summary, radioprotective effects were observed at the whole-body level as well as at the cellular level. (author)

  10. 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.

  11. A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems

    Science.gov (United States)

    Brodin, N. Patrik; Velcich, Anna; Guha, Chandan

    2017-01-01

    Background and Purpose: Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). Materials and Methods: The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury. Results: A steep dose–response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation. Conclusion: The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation. PMID:28203121

  12. 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.

  13. Benefits of online in vivo dosimetry for single-fraction total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Eaton, David J., E-mail: davideaton@nhs.net [Department of Radiotherapy, Royal Free Hospital, London (United Kingdom); Warry, Alison J. [Department of Radiotherapy Physics, University College London Hospital, London (United Kingdom); Trimble, Rachel E.; Vilarino-Varela, Maria J.; Collis, Christopher H. [Department of Radiotherapy, Royal Free Hospital, London (United Kingdom)

    2014-01-01

    Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.

  14. Conditioning with total body irradiation for autologous bone marrow transplantation in patients with advanced neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Motoaki; Mugishima, Hideo; Nagata, Toshihito; Shichino, Hiroyuki; Takamura, Mayumi; Shimada, Toshiaki; Suzuki, Takashi; Fujisawa, Takahito; Harada, Kensuke [Nihon Univ., Tokyo (Japan). School of Medicine

    1996-12-01

    We administered a combination of chemotherapy, autologous bone marrow purged with magnet immunobeads and total body irradiation (TBI) for advanced neuroblastoma (NB). The effect of TBI was retrospectively studied with regard to hematological recovery and complications after autologous bone marrow transplantation (A-BMT). The bone marrow was engrafted in all patients, both recipients and non-recipients of TBI. In patients receiving TBI, the average number or days after A-BMT required for the white blood cell count to exceed 1,000/{mu}l, the neutrophile count to exceed 500/{mu}l and the platelet count to exceed 5.0 x 10{sup 4}/{mu}l was 15.0{+-}6.5, 16.0{+-}6.4 and 59.7{+-}24.4, respectively. In patients not receiving TBI, the corresponding figures were 12.2{+-}6.2, 12.9{+-}6.9 and 43.2{+-}17.8 days, respectively. During hematological recovery after A-BMT, there was no statistical difference between patients having received TBI and those who did not receive TBI. Hemolytic uremic syndrome (HUS) was observed in four patients while receiving TBI, but no HUS developed after shielding the kidney from TBI. In terms or engraftment and complications, A-BMT can be performed on patients receiving TBI as safely as on those patients not receiving TBI. (author)

  15. Fractionated half body irradiation for palliation of multiple symptomatic bone metastases from solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sekiguchi, Kenji; Hayashi, Shinya; Sunagawa, Yoshimitsu; Sougawa, Mitsuharu; Nakazawa, Masanori; Yamashita, Takashi (Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital)

    1992-06-01

    This was a phase I-II nonrandomized study that explored the toxicity and response of fractionated half-body irradiation (F-HBI) in patients with multiple symptomatic osseous metastases. The patients had no premedication and received 10 Gy in 5 fractions with a dose rate of 15 cGy/min. At the Cancer Institute Hospital, 9 patients were treated by this technique (1 upper and lower F-HBI, 6 upper F-HBI, 2 lower F-HBI). All patients were female and had adenocarcinomas (8 breast and 1 lung). Adverse effects were myelosuppression, vomiting and partial alopecia. But hematologic toxicity was treated with blood transfusion or G-CSF. All toxicity was transient, and no pneumonitis nor radiation-related deaths occurred. When given as palliation, F-HBI was found to relieve pain in 80% of the patients. In 10% of the patients the pain relief was complete. The mean time to achieve pain relief in responders after F-HBI was 9 days. The pain relief was long-lasting and continued without need of reirradiation for 40% of the remaining patient's life. This treatment modality appears to be well tolerated and effective in patients with multiple symptomatic osseous metastases. The optimal indications, dose and fractionation for F-HBI should be further explored in randomized trials. (author).

  16. Renal dysfunction after total-body irradiation. Significance of selective renal shielding blocks

    Energy Technology Data Exchange (ETDEWEB)

    Igaki, Hiroshi [Tokyo Metropolitan Komagome Hospital (Japan). Dept. of Radiation Center; University of Tsukuba, Ibaraki (Japan). Proton Medical Research Center; University of Tokyo (Japan). Dept. of Radiology; Karasawa, Katsuyuki [Tokyo Metropolitan Komagome Hospital (Japan). Dept. of Radiation Center; Sakamaki, Hisashi [Tokyo Metropolitan Komagome Hospital (Japan). Dept. of Hematology; Saito, Hiroshi [Tokyo Metropolitan Komagome Hospital (Japan). Dept. of Nephrology; Nakagawa, Keiichi; Ohtomo, Kuni [University of Tokyo (Japan). Dept. of Radiology; Tanaka, Yoshiaki [Nihon University School of Medicine, Tokyo (Japan). Dept. of Radiology

    2005-11-01

    Purpose: A retrospective analysis was conducted on the outcome of total-body irradiation (TBI) followed by bone marrow transplantation (BMT) on leukemia patients. Also studied was the risk of renal dysfunction after TBI/BMT with or without the use of selective renal shielding blocks. Patients and Methods: The cases of 109 leukemia patients who received TBI as a component of the conditioning regimen for their BMT were reviewed. They received 12 Gy of TBI in six fractions over 3 consecutive days. Doses to eyes and lungs were reduced to 7 Gy and 8 Gy, respectively, but customized organ shielding blocks. After March 1999, renal shielding blocks were used to constrain the renal dose to 10 Gy. The patients were followed for a median period of 16.6 months (range: 0.3-180.1 months). Results: The 2-year and 5-year overall survival rates were 55.4% and 43.2%, respectively. Renal dysfunction-free rates were different between those with and without renal shielding blocks: 100% and 78.5%, respectively, at 2 years. Overall survivals were not significantly different among these patients: 60.4% and 52.9%, respectively, at 2 years in patients with and without renal shielding blocks (p=0.53). Conclusion: The use of selective renal shielding blocks provided evidence for reducing radiation-induced renal toxicities without decreasing the overall survival rate. (orig.)

  17. Interstitial pneumonitis following total body irradiation for bone marrow transplantation using two different dose rates

    Energy Technology Data Exchange (ETDEWEB)

    Kim, T.H.; Rybka, W.B.; Lehnert, S.; Podgorsak, E.B.; Freeman, C.R.

    1985-07-01

    A total of 22 patients with leukemia have undergone allogeneic bone marrow transplantation (BMT) by the Quebec Co-operative Group for Marrow Transplantation from 1980 to 1982. All patients received 900 cGy total body irradiation (TBI), in a single fraction, on the day preceding BMT. The first 11 patients were treated on a cobalt unit at a constant dose rate of 4.7 to 6.3 cGy/min. Six of these patients developed interstitial pneumonitis (IP). The clinical course of three patients, two with idiopathic and one with drug-induced pneumonitis, was mild and recovery was complete in all. The other three patients developed severe infectious IP and two died. The next 11 patients were treated with a sweeping beam technique on a 4 MV linear accelerator delivering a total tumor dose of 900 cGy at an average dose rate of 6.0 to 6.5 cGy/min but an instantaneous dose rate of 21.0 to 23.5 cGy/min. Eight patients developed severe IP. Five of these were idiopathic and four died. Three were infectious and all died. The fatality of interstitial pneumonitis appeared to be greater in the group treated with the sweeping beam technique.

  18. Clinical application of glass dosimeter for in vivo dose measurements of total body irradiation treatment technique

    Energy Technology Data Exchange (ETDEWEB)

    Rah, Jeong-Eun; Hwang, Ui-Jung; Jeong, Hojin; Lee, Sang-Yeob; Lee, Doo-Hyun; Shin, Dong Ho; Yoon, Myonggeun; Lee, Se Byeong [Proton Therapy Center, National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang-si, Gyeonggi-do, 410-769 (Korea, Republic of); Lee, Rena [Department of Radiation Oncology, Mokdong Hospital, Ewha Womans University College of Medicine (Korea, Republic of); Park, Sung Yong, E-mail: cool_park@ncc.re.k [Proton Therapy Center, National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang-si, Gyeonggi-do, 410-769 (Korea, Republic of)

    2011-01-15

    The commercially available glass dosimeter (model GD-301) was investigated for its dosimetric characteristics, in order to evaluate its use for in vivo dosimetry. We specifically assessed overall precision of dosimetric dose data in patients who received treatment with the total body irradiation (TBI). Uniformity obtained in this study was within 1.2% (1 SD). The dose-response was linear in the range of 0.5-10 Gy with R of 0.999. Dose rate, SSD, field size, angular and energy dependence were found to be within 3.0%. In vivo skin dosimetry for TBI was performed for 3 patients. For all patients, the glass dosimeter was exposed and measured dose recorded for one fraction in addition to conventional used TLD and MOSFET. Overall uncertainty of the glass dosimeter for in vivo dose measurement was estimated at 2.4% (68.3% confidence level). The measured doses of the glass dosimeter were well within {+-}5.0% of the prescription dose at all sites expect mediastinum of one patient, for which it is within {+-}5.7%. Agreement of measured doses between glass dosimeter and TLD, MOSFET was within {+-}6.3% and {+-}6.6%, respectively. Results show that the glass dosimeter can be used as an accurate and reproducible dosimeter for TBI treatment skin dose measurements. The glass dosimeter is a practical alternative to TLD or MOSFET as an in vivo dosimeter.

  19. Benefits of online in vivo dosimetry for single-fraction total body irradiation.

    Science.gov (United States)

    Eaton, David J; Warry, Alison J; Trimble, Rachel E; Vilarino-Varela, Maria J; Collis, Christopher H

    2014-01-01

    Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.

  20. An anti-apoptotic peptide improves survival in lethal total body irradiation.

    Science.gov (United States)

    McDunn, Jonathan E; Muenzer, Jared T; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C; Davis, Christopher G; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 microM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  1. Monte Carlo optimization of total body irradiation in a phantom and patient geometry

    Science.gov (United States)

    Chakarova, R.; Müntzing, K.; Krantz, M.; Hedin, E.; Hertzman, S.

    2013-04-01

    The objective of this work is to apply a Monte Carlo (MC) accelerator model, validated by experimental data at isocentre distances, to a large-field total body irradiation (TBI) technique and to develop a strategy for individual patient treatment on the basis of MC dose distributions. Calculations are carried out using BEAMnrc/DOSXYZnrc code packages for a 15 MV Varian accelerator. Acceptable agreement is obtained between MC data and measurements in a large water phantom behind a spoiler at source-skin distances (SSD) = 460 cm as well as in a CIRS® thorax phantom. Dose distributions in patients are studied when simulating bilateral beam delivery at a distance of 480 cm to the patient central sagittal plane. A procedure for individual improvement of the dose uniformity is suggested including the design of compensators in a conventional treatment planning system (TPS) and a subsequent update of the dose distribution. It is demonstrated that the dose uniformity for the simple TBI technique can be considerably improved. The optimization strategy developed is straightforward and suitable for clinics where the TPS available is deficient to calculate 3D dose distributions at extended SSD.

  2. ACPSEM ROSG TBI working group recommendations for quality assurance in total body irradiation.

    Science.gov (United States)

    Nelligan, Raelene; Bailey, Michael; Tran, Thu; Baldwin, Zoë

    2015-06-01

    The Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) radiation oncology specialty group (ROSG) formed a series of working groups in 2011 to develop recommendations for guidance of radiation oncology medical physics practice within the Australasian setting. These recommendations are intended to provide guidance for safe work practices and a suitable level of quality control without detailed work instructions. It is the responsibility of the medical physicist to ensure that locally available equipment and procedures are sufficiently sensitive to establish compliance to these recommendations. The recommendations are endorsed by the ROSG, and have been subject to independent expert reviews. For the Australian audience, these recommendations should be read in conjunction with the tripartite radiation oncology practice standards [1, 2]. This publication presents the recommendations of the ACPSEM total body irradiation working group (TBIWG) and has been developed in alignment with other international associations. However, these recommendations should be read in conjunction with relevant national, state or territory legislation and local requirements, which take precedence over the ACPSEM recommendations. It is hoped that the users of this and other ACPSEM recommendations will contribute to the development of future versions through the ROSG of the ACPSEM. This document serves as a guideline for calibration and quality assurance of equipment used for TBI in Australasia.

  3. ACPSEM ROSG TBE working group recommendations for quality assurance in total body electron irradiation.

    Science.gov (United States)

    Nelligan, Raelene; Baldwin, Zoë; Ostwald, Trish; Tran, Thu; Bailey, Michael

    2015-09-01

    The Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) Radiation Oncology Specialty Group (ROSG) formed a series of working groups in 2011 to develop recommendations for guidance of radiation oncology medical physics practice within the Australasian setting. These recommendations are intended to provide guidance for safe work practices and a suitable level of quality control without detailed work instructions. It is the responsibility of the medical physicist to ensure that locally available equipment and procedures are sufficiently sensitive to establish compliance to these recommendations. The recommendations are endorsed by the ROSG, and have been subject to independent expert reviews. For the Australian readers, these recommendations should be read in conjunction with the Tripartite Radiation Oncology Reform Implementation Committee Quality Working Group: Radiation Oncology Practice Standards (2011), and Radiation Oncology Practice Standards Supplementary Guide (2011). This publication presents the recommendations of the ACPSEM ROSG Total Body Electron Irradiation Working Group and has been developed in alignment with other international associations. However, these recommendations should be read in conjunction with relevant national, state or territory legislation and local requirements, which take precedence over the ACPSEM recommendations. It is hoped that the users of this and other ACPSEM recommendations will contribute to the development of future versions through the Radiation Oncology Specialty Group of the ACPSEM. This document serves as a guideline for calibration and quality assurance of equipment used for TBE in Australasia.

  4. A Monte Carlo evaluation of beam characteristics for total body irradiation at extended treatment distances.

    Science.gov (United States)

    Chakarova, Roumiana; Krantz, Marcus

    2014-05-08

    The aim is to study beam characteristics at large distances when focusing on the electron component. In particular, to investigate the utility of spoilers with various thicknesses as an electron source, as well as the effect of different spoiler-to-surface distances (STSD) on the beam characteristics and, consequently, on the dose in the superficial region. A MC model of a 15 MV Varian accelerator, validated earlier by experimental data at isocenter and extended distances used in large-field total body irradiation, is applied to evaluate beam characteristics at distances larger than 400 cm. Calculations are carried out using BEAMnrc/DOSXYZnrc code packages and phase space data are analyzed by the beam data processor BEAMdp. The electron component of the beam is analyzed at isocenter and extended distances, with and without spoilers as beam modifiers, assuming vacuum or air surrounding the accelerator head. Spoiler thickness of 1.6 cm is found to be optimal compared to thicknesses of 0.8 cm and 2.4 cm. The STSD variations should be taken into account when treating patients, in particular when the treatment protocols are based on a fixed distance to the patient central sagittal plane, and also, in order to maintain high dose in the superficial region.

  5. Total body irradiation therapy for thymectomized myasthenic patients and immunological evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, Nobukazu; Tanaka, Masayuki; Kurihara, Teruyuki (Miyazaki Medical College (Japan))

    1983-06-01

    Three patients with intractable myasthenia gravis (MG) were treated with total body irradiation (TBI). All the three patients had been unstable after extended thymectomy and poorly responding to prednisolone therapy. Radiation therapy consisted of 10 doses of 10 rads/day given over five weeks. After the radiation therapy the three patients improved clinically, and an objective parameter, area of M-waves also improved. No significant side effects were noted. TBI therapy can be considered as a safe method to induce selective reduction of circulating lymphocytes. This was indeed achieved, as evidenced by a drop of the lymphocyte counts to the levels of 20-40 % of the pretreatment level. The effects were persistent over twelve weeks. Early radiosensitivity of B lymphocytes were recognized. The levels of T..gamma.. cells were low before TBI therapy, increasing gradually during TBI therapy and returned to normal range after twelve weeks. Serum anti-AChR antibody titers decreased in all the cases, but it was impossible to determine whether the decrement was due to the therapy or natural course after thymectomy. Two of our three cases had a significant percentage decrement of the titers after TBI therapy. We suggest that TBI therapy is a safe method of immunosupperssive treatment for the myasthenic patients after thymectomy.

  6. Induction of systemic bone changes by preconditioning total body irradiation for bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Osamu; Okamoto, Reiko; Masaki, Hidekazu [National Centre for Child Health and Development, Department of Radiology, Tokyo (Japan); Nishimura, Gen [Tokyo Metropolitan Kiyose Children' s Hospital, Department of Radiology, Tokyo (Japan); Kumagai, Masaaki; Shioda, Yoko [National Centre for Child Health and Development, Department of Oncology, Tokyo (Japan); Nozawa, Kumiko [Saitama Children' s Medical Centre, Department of Radiology, Saitama (Japan); Kitoh, Hiroshi [Nagoya University Hospital, Department of Orthopaedic Surgery, Nagoya, Aichi (Japan)

    2009-01-15

    Preconditioning total body irradiation (TBI) prior to bone marrow transplantation (BMT) has been believed to be a safe procedure that does not cause late morbidity; yet, a recent report raises the suspicion that TBI-induced chondroosseous abnormalities do occur. To evaluate the radiological manifestations of TBI-induced skeletal alterations and their orthopaedic morbidity. Subjects included 11 children with TBI-induced skeletal changes, including 9 in our hospital and 2 in other hospitals. The former were selected from 53 children who had undergone TBI with BMT. Radiographic examinations (n=11), MRI (n=3), CT (n=2), and medical records in the 11 children were retrospectively reviewed. The skeletal alterations included abnormal epiphyseal ossification and metaphyseal fraying (8/11), longitudinal metaphyseal striations (8/11), irregular metaphyseal sclerosis (6/11), osteochondromas (4/11), slipped capital femoral epiphysis (2/10), genu valgum (3/10), and platyspondyly (2/3). MRI demonstrated immature primary spongiosa in the metaphysis. Of the 11 children, 9 had clinical symptoms. TBI can induce polyostotic and/or generalized bone changes, mainly affecting the epiphyseal/metaphyseal regions and occasionally the spine. The epi-/metaphyseal abnormalities represent impaired chondrogenesis in the epiphysis and growth plate and abnormal remodelling in the metaphysis. Generalized spine changes may lead to misdiagnosis of a skeletal dysplasia. (orig.)

  7. Monoallelic loss of the imprinted gene Grb10 promotes tumor formation in irradiated Nf1+/- mice.

    Directory of Open Access Journals (Sweden)

    Rana Mroue

    2015-05-01

    Full Text Available Imprinted genes are expressed from only one parental allele and heterozygous loss involving the expressed allele is sufficient to produce complete loss of protein expression. Genetic alterations are common in tumorigenesis but the role of imprinted genes in this process is not well understood. In earlier work we mutagenized mice heterozygous for the Neurofibromatosis I tumor suppressor gene (NF1 to model radiotherapy-associated second malignant neoplasms that arise in irradiated NF1 patients. Expression analysis of tumor cell lines established from our mouse models identified Grb10 expression as widely absent. Grb10 is an imprinted gene and polymorphism analysis of cell lines and primary tumors demonstrates that the expressed allele is commonly lost in diverse Nf1 mutant tumors arising in our mouse models. We performed functional studies to test whether Grb10 restoration or loss alter fundamental features of the tumor growth. Restoring Grb10 in Nf1 mutant tumors decreases proliferation, decreases soft agar colony formation and downregulates Ras signaling. Conversely, Grb10 silencing in untransformed mouse embryo fibroblasts significantly increased cell proliferation and increased Ras-GTP levels. Expression of a constitutively activated MEK rescued tumor cells from Grb10-mediated reduction in colony formation. These studies reveal that Grb10 loss can occur during in vivo tumorigenesis, with a functional consequence in untransformed primary cells. In tumors, Grb10 loss independently promotes Ras pathway hyperactivation, which promotes hyperproliferation, an early feature of tumor development. In the context of a robust Nf1 mutant mouse model of cancer this work identifies a novel role for an imprinted gene in tumorigenesis.

  8. 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.

  9. Chronic UVA (365-nm) irradiation induced scratching in hairless mice: dose-time dependency and the effect of ketanserin

    Energy Technology Data Exchange (ETDEWEB)

    Laat, J.M.T. de; Groenendijk, M.; Vloten, W.A. van; Gruijl, F.R. de [Univ. Hospital Utrecht, Dept. of Dermatology (Netherlands); Seite, S. [L`Oreal-Centre de Recherche Charles Zviak, Recherche Avancee Biologie (France)

    1997-12-31

    In a study on the dose-response relationship for longwave UVA (UVA1; 340-400 nm) carcinogenesis in hairless mice scratch marks appeared after months of daily exposure as an unwanted side effect. Tumor induction in the highest of the 4 tested dose groups (receiving a daily dose of 430 kJ/m{sup 2} of 365-nm radiation) could not be determined because extensive scarification occurred prior to the development of any tumors. The induction of scratch marks could be scored and quantified in all 4 dose groups tested. The UVA1 dose-dependencies for the induction of tumors and scratch marks were compared. We found that the induction of scratch marks depended mainly on the cumulative UVA1 exposure, whereas tumor induction showed a lesser dose-dependency. An attempt was made to prevent the apparent pruritogenic effect of UVA1 irradiation and to understand its mechanism. The influence of ketanserin, a serotonin/histamine antagonist, on the UVA1 induction of scratch marks was tested in groups of 8 mice daily irradiated with 430 kJ/m{sup 2}. No difference was found between treated and untreated animals. Histological examination of skin biopsies from irradiated mice from the 430-kJ/m{sup 2} dose group from the UVA1 carcinogenic experiment, showed no changes in numbers of mast cells or other inflammatory features when compared to skin biopsies from unirradiated control mice. This indicated that UVA1-induced scratching is not mediated through mast cell release of serotonin and/or histamine. An adequate therapeutic treatment which can prevent UVA1-induced scratching would enable us to test tumor induction with UVA1 over a larger dose range, and may provide additional insight in how this radiation damages the skin. It remains conjectural whether there exists and analogous UVA-induced pruritus in human skin. (au) 26 refs.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-03-01

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

  11. Total Body Irradiation in the "Hematopoietic" Dose Range Induces Substantial Intestinal Injury in Non-Human Primates.

    Science.gov (United States)

    Wang, Junru; Shao, Lijian; Hendrickson, Howard P; Liu, Liya; Chang, Jianhui; Luo, Yi; Seng, John; Pouliot, Mylene; Authier, Simon; Zhou, Daohong; Allaben, William; Hauer-Jensen, Martin

    2015-11-01

    The non-human primate has been a useful model for studies of human acute radiation syndrome (ARS). However, to date structural changes in various parts of the intestine after total body irradiation (TBI) have not been systematically studied in this model. Here we report on our current study of TBI-induced intestinal structural injury in the non-human primate after doses typically associated with hematopoietic ARS. Twenty-four non-human primates were divided into three groups: sham-irradiated control group; and total body cobalt-60 (60Co) 6.7 Gy gamma-irradiated group; and total body 60Co 7.4 Gy gamma-irradiated group. After animals were euthanized at day 4, 7 and 12 postirradiation, sections of small intestine (duodenum, proximal jejunum, distal jejunum and ileum) were collected and fixed in 10% formalin. The intestinal mucosal surface length, villus height and crypt depths were assessed by computer-assisted image analysis. Plasma citrulline levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total bone marrow cells were counted and hematopoietic stem/progenitor cells in bone marrow were analyzed by flow cytometer. Histopathologically, all segments exhibited conspicuous disappearance of plicae circulares and prominent atrophy of crypts and villi. Intestinal mucosal surface length was significantly decreased in all intestinal segments on day 4, 7 and 12 after irradiation (P 0.05). Crypt depth was also significantly reduced in all segments on day 4, 7 and 12 after irradiation (P irradiation, consistent with intestinal mucosal injury. Both 6.7 and 7.4 Gy TBI reduced total number of bone marrow cells. And further analysis showed that the number and function of CD45(+)CD34(+) hematopoietic stem/progenitors in bone marrow decreased significantly. In summary, TBI in the hematopoietic ARS dose range induces substantial intestinal injury in all segments of the small bowel. These findings underscore the importance of maintaining the

  12. 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.

  13. Late Effects of Total-Body Roentgen Irradiation. Longevity and Incidence of Nephrosclerosis as Influenced by Partial-Body Shielding

    Science.gov (United States)

    1959-05-01

    postirradiation with complete obliteration oi the capillary developed this lesion (table III). Nephrosclero- tufts (3). sis was nearly absent during the 17.5...the human species. We have not ob- these organs are not yet complete. Possiblyserved significant arteriosclerosis of large irradiation of the kidneys

  14. Dose and dose rate effects of irradiation on blood count and cytokine assay in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joong Sun [Research center, Dongnam institute of radiological and Medical Sciences (DIRAMS), Busan (Korea, Republic of)

    2013-11-15

    The possible role of exposure to radiation as a risk factor for human health has been of increasing public concern in the series of explosions at earthquake damaged nuclear reactors on the Japan. Current events throughout the world underscore the growing threat of different forms of accidental exposure to radiation including nuclear accidents, atomic weapons use and testing, and the side effects of cancer therapy. A large range of dose rates of ionizing radiations could be encountered in accidental radiation situations. Nevertheless, most of the studies related to radiation effects have only examined a high dose rate. In this study, we investigated the blood count and the cytokine levels in the serum of mice exposed to a high or low dose rate of radiation. In this study, the precise molecular mechanism underlying the low dose rate of radiation remains unclear, but differential hematopoietic effects of radiation exposed at a high dose rate versus low dose rate were observed using the number of peripheral blood count and serum cytokines. These data suggest that chronic low dose rate exposure caused a stimulation of heamatopoietic system occurrence, unlike those observed after higher dose rate exposure. Our data suggest that the dose rate, rather than the total dose, may be more critical in causing damage to the cellular hematopoietic compartments of the body.

  15. Correlation of plasma FL expression with bone marrow irradiation dose.

    Directory of Open Access Journals (Sweden)

    Mary Sproull

    Full Text Available PURPOSE: Ablative bone marrow irradiation is an integral part of hematopoietic stem cell transplantation. These treatment regimens are based on classically held models of radiation dose and the bone marrow response. Flt-3 ligand (FL has been suggested as a marker of hematopoiesis and bone marrow status but the kinetics of its response to bone marrow irradiation has yet to be fully characterized. In the current study, we examine plasma FL response to total body and partial body irradiation in mice and its relationship with irradiation dose, time of collection and pattern of bone marrow exposure. MATERIALS/METHODS: C57BL6 mice received a single whole body or partial body irradiation dose of 1-8 Gy. Plasma was collected by mandibular or cardiac puncture at 24, 48 and 72 hr post-irradiation as well as 1-3 weeks post-irradiation. FL levels were determined via ELISA assay and used to generate two models: a linear regression model and a gated values model correlating plasma FL levels with radiation dose. RESULTS: At all doses between 1-8 Gy, plasma FL levels were greater than control and the level of FL increased proportionally to the total body irradiation dose. Differences in FL levels were statistically significant at each dose and at all time points. Partial body irradiation of the trunk areas, encompassing the bulk of the hematopoietically active bone marrow, resulted in significantly increased FL levels over control but irradiation of only the head or extremities did not. FL levels were used to generate a dose prediction model for total body irradiation. In a blinded study, the model differentiated mice into dose received cohorts of 1, 4 or 8 Gy based on plasma FL levels at 24 or 72 hrs post-irradiation. CONCLUSION: Our findings indicate that plasma FL levels might be used as a marker of hematopoietically active bone marrow and radiation exposure in mice.

  16. Assessment of population external irradiation doses with consideration of Rospotrebnadzor bodies equipment for monitoring of photon radiation dose

    Directory of Open Access Journals (Sweden)

    I. P. Stamat

    2016-01-01

    Full Text Available This paper provides review of equipment and methodology for measurement of photon radiation dose; analysis of possible reasons for considerable deviation between the Russian Federation population annual effective external irradiation doses and the relevant average global value. Data on Rospotrebnadzor bodies dosimetry equipment used for measurement of gamma radiation dose are collected and systematized. Over 60 kinds of dosimeters are used for monitoring of population external irradiation doses. Most of dosimeters used in the country have gas-discharge detectors (Geiger-Mueller counters, minor biochemical annunciators, etc. which have higher total values of own background level and of space radiation response than the modern dosimeters with scintillation detectors. This feature of dosimeters is apparently one of most plausible reasons of a bit overstating assessment of population external irradiation doses. The options for specification of population external irradiation doses assessment are: correction of gamma radiation dose measurement results with consideration of dosimeters own background level and space radiation response, introduction of more up-to-date dosimeters with scintillation detectors, etc. The most promising direction of research in verification of population external irradiation doses assessment is account of dosimetry equipment.

  17. Expression of pulmonary mRNA encoding ICAM-1, VCAM-1, and P-selectin following thoracic irradiation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tsujino, Kayoko; Kodama, Akihisa; Nanaoka, Noriyoshi; Maruta, Tsutomu; Kono, Michio [Kobe Univ. (Japan). School of Medicine

    1999-08-01

    Recent studies have revealed that ionizing radiation induces the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin in vitro. The purpose of this study was to investigate the expression of these adhesion molecules in mouse lung following whole thoracic irradiation. C57BL/6J mice were irradiated with a single dose of 12 Gy to the thoraces and sacrificed at 4, 12, 24, and 48 hours and 1, 2, 4, and 8 weeks after irradiation. Expression of total lung mRNA for ICAM-1, VCAM-1, and P-selectin was quantified by the Northern blot method and normalized to {beta}-actin. There were increases in mRNA for ICAM-1 of 42% at 4 hours (p<0.05), 76% at 24 hours (p<0.01), and 51% at 48 hours (p<0.05) compared with the controls. There returned to the control level at 1 week. The expression of VCAM-1 mRNA was also increased by 49% (p<0.01) at 12 hours and was still increased by 25% at 1 week. P-selectin mRNA was transiently increased by 59% at 12 hours. These early inductions of mRNA for ICAM-1, VCAM-1, and P-selectin in mouse lung following thoracic irradiation were transient but significant, and are one of the most immediate changes reported in vivo. (author)

  18. Enact of Glutathione(GSH/GSSG) Contents of Fermented Ginseng on the {gamma}-irradiated Liver of Mice

    Energy Technology Data Exchange (ETDEWEB)

    Ko, In Ho [Dept. of Radiology Technology, Jeju Halla College, Jeju (Korea, Republic of)

    2006-03-15

    The radioprotective effects of white and fermented ginseng on liver damage induced by {sup 60}Co {gamma}-ray were investigated. To one group of ICR male mice were given white(150 mg/kg/day for 7 days, orally) and fermented ginseng(150 mg/kg/day for 7 days, orally) before {sup 60}Co {gamma}--ray irradiation. To another group were irradiated by 5 Gy(1.01 Gy/min) dose of {sup 60}Co {gamma}--ray. Contrast group were given with saline(0.1 mL). The levels of reduced(GSH) and oxidized(GSSG) glutathione in liver tissue were measured. In the fermented(150 mg/kg) and white ginseng(150 mg/kg) groups than irradiation group, the GSH levels were significantly increased, but the GSSG levels were significantly decreased. The ratio of GSSG/total GSH was significantly decreased in the fermented(150 mg/kg) and white ginseng(150 mg/kg) groups than irradiation group. In the fermented(150 mg/kg) groups than white ginseng(150 mg/kg) groups the GSH levels were significantly increased. The radioprotective effects of fermented(150 mg/kg) groups than white ginseng(150 mg/kg) groups were increased.

  19. SU-E-T-275: Dose Build Up and Bolusing Characteristics for Total Body Irradiation Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Butson, M; Pope, D; Whitaker, M [Chris O’Brien LifeHouse, Sydney, NSW (Australia)

    2015-06-15

    Purpose: Total Body Irradiation (TBI) treatments are mainly used in a preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. Our standard regimen is a 12 Gy / 6 fraction bi-daily technique. To evaluate the delivered dose homogeneity to the patient, EBT3 Gafchromic film is positioned at the head, neck, chest, pelvis and groin for all fractions. This work investigates and quantifies the build-up dose characteristics at TBI distances and requirements for in-vivo dosimetry bolusing. Methods: Percentage dose build up characteristics of photon beams have been investigated at large extended SSD’s using parallel plate ionisations chambers (Attix) and EBT3 Gafchromic film. Measurements were made to open fields at different field sizes as well as large 40cm × 40cm fields with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point. Results: Percentage surface dose measured values for open fields at 300 cm SSD were found to range from 20 % up to 65.5 % for fields of 5 cm × 5 cm to 40 cm × 40 cm. With the introduction of 1cm Perspex scattering plates used in TBI treatments the surface dose values increased up to 83% to 90%, depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 3mm water equivalent bolus / scatter material should be placed over the EBT3 for accurate dose assessment for TBI treatments. Conclusion: Build up dose characteristics exist at long (300cm) SSD’s including treatments using Perspex scattering plates placed at various distances form the patient during TBI treatment. Top accurately assess the applied dose during treatment, in-vivo dosimeters such as Gafchromic EBT3 should have at least 3mm bolus / scatter material placed over them to measure actual applied doses.

  20. Long-term results of low dose total body irradiation for advanced non-Hodgkin lymphoma.

    Science.gov (United States)

    Lybeert, M L; Meerwaldt, J H; Deneve, W

    1987-08-01

    Sixty-eight patients received fractionated low dose total body irradiation (LTBI) as treatment for non-Hodgkin lymphoma (NHL) at the Rotterdamsch Radio-Therapeutisch Instituut (RRTI) in the period 1973-1979. Ninety percent (61/68) of these patients had advanced disease (Stage III + IV). According to current malignancy grade classifications, 34 patients had low grade NHL, 10 intermediate, and 19 high grade. In 5 cases no exact grading was possible. LTBI was given 3 times a week, midline dose 0.1 Gy, using 6 or 25 MeV photons to a mean total dose of 1.78 Gy. Initial response rate for low, intermediate, and high grade NHL was resp. 84, 42, and 40%. The main prognostic factor for survival and recurrence-free survival (RFS) was malignancy grade. Probability of uncorrected survival at 10 years for low, intermediate, and high grade was resp. 34, 0 and 0%. Probability of RFS at 10 years was resp. 19, 0, and 0%. Neither stage nor sex had any influence on survival. Age was reversely correlated with survival, but was not correlated with RFS. Influence of prior therapy (18 patients) on survival and RFS was separately analyzed. Neither survival nor RFS of unfavorable histologic type NHL (high and intermediate grade) was influenced. On the other hand patients with a favorable histologic type NHL (low grade) had a significantly (p less than 0.05) better RFS if they received LTBI as initial treatment, but survival was not significantly influenced. RFS at 5 and 10 years of patients who received LTBI as first treatment was respectively 32% and 27%. No treatment related complications were noted. Subsequent chemotherapy in case of relapse was not hampered by previous LTBI. The high response rate and extended RFS, without maintenance therapy, makes LTBI a preferable first line treatment for patients with advanced stage low grade NHL.

  1. Half body irradiation of patients with multiple bone metastases: A phase II trial

    Energy Technology Data Exchange (ETDEWEB)

    Berg, Randi S.; Yilmaz, Mette K. (Dept. of Oncology, Aalborg Hospital, Aarhus Univ., Aalborg (Denmark)); Hoeyer, Morten; Nielsen, Ole S. (Dept. of Oncology, Aarhus Univ. Hospital, Aarhus (Denmark)); Keldsen, Nina (Dept. of Oncology, Herning Hospital, Herning (Denmark)); Ewertz, Marianne (Dept. of Oncology, Odense Univ. Hospital, Odense (Denmark))

    2009-05-15

    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%). Outcome and side effects were measured by the EORTC Quality of Life Questionnaire C30 (QLQ-C30), and by the doctors' toxicity scores in the medical record. Pain relief was defined as a reduction of more than 10 points on the QLQ-C30 scale. Evaluations were performed before and 2, 4, 8, 16, and 24 weeks 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 of the patients were able to reduce their intake of analgesics. Grade 1-2 diarrhoea was the most common side effect observed in 49% of the patients two weeks after treatment. Mild pulmonary symptoms (grade 1-2) were observed in four of seven patients receiving upper HBI. No clear effect was observed on the patients' global quality of life.Conclusion. Single fraction HBI is safe and effective providing long lasting pain reduction in 76% of patients with multiple bone metastases.

  2. Retrospective, monocentric analysis of late effects after total body irradiation (TBI) in adults

    Energy Technology Data Exchange (ETDEWEB)

    Boelling, Tobias [Universitaetsklinikum Muenster (Germany). Dept. of Radiotherapy; Paracelsus Clinic Osnabrueck (Germany). Dept. of Radiotherapy; Kreuziger, David Christoph; Ernst, Iris; Elsayed, Hassan; Willich, Normann [Universitaetsklinikum Muenster (Germany). Dept. of Radiotherapy

    2011-05-15

    Purpose: Total body irradiation (TBI) is a standard treatment modality within the multidisciplinary approach for allogeneous stem cell or bone marrow transplantation. However, surviving patients are at risk for developing a variety of late sequelae. This analysis aimed to retrospectively characterize late effects after TBI in adults treated in a single center. Patients and Methods: Patients {>=} 18 years treated with fractionated TBI (4-12 Gy) between 1996 and 2008 were included in this study. Treatment data were collected retrospectively from the treating departments. Late effects were evaluated using the clinic charts and/or were obtained from the general practitioners using a standardized questionnaire. Analyses were performed by calculation of the cumulative incidences using the Kaplan-Meier method and the log rank test. Results: A total of 308 patients {>=} 18 years were treated including a TBI of whom 78 patients were excluded from further analysis due to death within less than 1 year after TBI. Patients suffered from leukemia in most cases. Late toxicity follow-up was available in 120 patients (mean age 46.1 years; range, 18-70 years) after a mean follow-up of 23 months (range, 12-96 months). The cumulative incidences (CI) at 3 years were 28% for pulmonary event, 8% for pulmonary toxicity, 25% for kidney toxicity, 8% for cataract, 17% for bone toxicity, and 10% for secondary malignancy. The CI of bone toxicity was higher in female than in male patients (p = 0.019). Conclusion: Late effects after TBI in the context of allogeneous stem cell or bone marrow transplantation can frequently be observed. Regular follow-up examinations are advised for the early registration and treatment of adverse effects. (orig.)

  3. Build-up material requirements in clinical dosimetry during total body irradiation treatments.

    Science.gov (United States)

    Butson, Martin; Pope, Dane; Haque, Mamoon; Chen, Tom; Song, Guangli; Whitaker, May

    2016-01-01

    Total body irradiation (TBI) treatments are mainly used in a preparative regimen for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy/6 fraction bi-daily technique using 6MV X-rays at a large extended source to surface distance (SSD). This work investigates and quantifies the dose build-up characteristics and thus the requirements for bolus used for in vivo dosimetry for TBI applications. Percentage dose build-up characteristics of photon beams have been investigated at large extended SSDs using ionization chambers and Gafchromic film. Open field measurements at different field sizes and with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point were made in an effort to determine the required bolus/build-up material required for accurate determination of applied dose. Percentage surface dose values measured for open fields at 300 cm SSD were found to range from 20% up to 65.5% for fields 5 cm × 5 cm to 40 cm × 40 cm, respectively. With the introduction of 1 cm Perspex scattering plates used in TBI treatments, the surface dose values increased up to 83-90% (93-97% at 1 mm depth), depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 5 mm water equivalent bolus/scatter material should be placed over the EBT3 film for accurate dose assessment for TBI treatments. Results also show that a small but measurable decrease in measured dose occurred with 5 mm water equivalent thick bolus material of areas '3 cm(2). As such, we recommend that 3 cm × 3 cm × 5 mm bolus build-up is the smallest size that should be placed over EBT3 Gafchromic film when used for accurate in vivo dosimetry for TBI applications.

  4. Whole Body Irradiation Induces Cutaneous Dendritic Cells Depletion via NF-κB Activation

    Directory of Open Access Journals (Sweden)

    Yanyong Yang

    2013-07-01

    Full Text Available Background: Effect of ionizing radiation on cutaneous dendritic cells (cDC is critical to its influence on immune status of the skin, which plays an important role in the progression and recovery of radiation skin sickness. This study was to study the influence of whole body irradiation (WBI on the cDC. Methods: Density of epidermal and dermal DC was determined with a fluorescent microscopy and the DC numbers in lymph node were measured by flow cytometry. A FITC induced migration assay was also used to study the migration of DC. The expressions of cytokines and chemokines were evaluated by Realtime PCR, and the protein level of was measured by Western blot. Results: WBI caused depletion of cDC in epidermal as well as dermal and augmented FITC-induced migration of DC to the draining lymph node (LN. The number of DC migrated from ear explants to the CCL19-containing medium also increased after exposure to WBI. It was also found that WBI increased mRNA level of CCL19/CCL21 as well as CCR7 in LN and skin tissue. The expressions of TNFa, IL-1a, IL-1ß, and IL-6 in skin tissues were also greatly induced by WBI in a dose dependent manner. Finally, we found that WBI induced translocation of nuclear factor κB (NF-κB and that the radiation-induced migration of DC was blocked by NF-κB inhibitor or TLR4 knockout. Conclusion: WBI caused cDC depletion through induction of DC migration to the draining LN, which might result from the activation of NF-κB and the induction of inflammatory microenvironment within the skin.

  5. Time-course of micronucleated erythrocytes in response to whole-body gamma irradiation in a model mammalian species, the bank vole (Clethrionomys glareolus, Schreber).

    Science.gov (United States)

    Smolich, Igor I; Savina, Natalya V; Ryabokon, Nadezhda I

    2011-01-01

    The time course of the formation of micronucleated polychromatic (MNPCEs) and normochromatic erythrocytes (MNNCEs) in the bone marrow of the bank vole (Clethrionomys glareolus, Schreber), a model mouse-like species, was studied using the standard micronucleus test at 0, 6, 12, 18, 24, 30, 36 and 48 hr following whole-body acute γ-irradiation at a dose of 0.5 Gy. Based on the existing literature on laboratory mice, it was suggested that such a dose will not have significant effect on erythroid cell proliferation in the bank vole and hence on the time course of the rise of micronucleated cells. In total, ∼905,000 polychromatic (PCEs) and normochromatic erythrocytes (NCEs) from 82 adult bank voles were analyzed. Although the mean frequencies of MNNCEs were too low to allow for the correct assessment of their time course, an analysis of PCEs showed an increasing rate of MNPCE appearance at 6 hr that reached a maximum at 18-24 hr after irradiation and subsequently decreased. Because the kinetics of MNPCEs reflects the process of erythropoiesis, the current results regarding the time points of appearance of radiation-induced MNPCEs provide the first information on the prolongation of one of the terminal stages of erythrocyte formation in bank vole specimens, namely the stage of maturation of PCEs from erythroblasts. Moreover, the observed time-course data, as well as the low-background frequencies of MNPCEs and characteristic level of PCEs response to radiation, showed similarities between the two model species: bank vole (this study) and laboratory mice (literature data).

  6. Absence of activated murine leukaemia virus in X-irradiated CBA/H-T6Crc mice

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, H.C.; Tuffrey, M.; Wilson, L.; Barnes, R.D. (Medical Research Council, Harrow (UK). Clinical Research Centre)

    1981-04-01

    CBA/H-T6Crc mice, a substrain that does not normally express demonstrable levels of murine leukaemia virus (MuLV) and has a low natural incidence of leukaemia, were examined for evidence of virus activation at various times following X-irradiation. Although X-irradiation caused a high incidence of leukaemia, no ecotropic, xenotropic or recombinant MuLV was detected by in vitro co-cultivation of bone marrow, spleen and thymus cells from pre-leukaemic and leukaemic animals with selectively permissive cell lines followed by indirect immunofluorescence for MuLV group-specific (gs) antigen. These results therefore, are not consistent with the hypothesis that endogenous viruses are the universal aetiological agents of leukaemia.

  7. Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice

    Science.gov (United States)

    Xu, Guoshun; Wu, Hongying; Zhang, Junling; Li, Deguan; Wang, Yueying; Wang, Yingying; Zhang, Heng; Lu, Lu; Li, Chengcheng; Huang, Song; Xing, Yonghua; Zhou, Daohong; Meng, Aimin

    2016-01-01

    Exposure to ionizing radiation (IR) increases the production of reactive oxygen species (ROS) not only by the radiolysis of water but also through IR-induced perturbation of the cellular metabolism and disturbance of the balance of reduction/oxidation reactions. Our recent studies showed that the increased production of intracellular ROS induced by IR contributes to IR-induced late effects, particularly in the hematopoietic system, because inhibition of ROS production with an antioxidant after IR exposure can mitigate IR-induced long-term bone marrow (BM) injury. Metformin is a widely used drug for the treatment of type 2 diabetes. Metformin also has the ability to regulate cellular metabolism and ROS production by activating AMP-activated protein kinase. Therefore, we examined whether metformin can ameliorate IR-induced long-term BM injury in a total-body irradiation (TBI) mouse model. Our results showed that the administration of metformin significantly attenuated TBI-induced increases in ROS production and DNA damage and upregulation of NADPH oxidase 4 expression in BM hematopoietic stem cells (HSCs). These changes were associated with a significant increase in BM HSC frequency, a considerable improvement in in vitro and in vivo HSC function, and complete inhibition of upregulation of p16Ink4a in HSCs after TBI. These findings demonstrate that metformin can attenuate TBI-induced long-term BM injury at least in part by inhibiting the induction of chronic oxidative stress in HSCs and HSC senescence. Therefore, metformin has the potential to be used as a novel radioprotectant to ameliorate TBI-induced long-term BM injury. PMID:26086617

  8. Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A. [Academy of Sciences of the Czech Republic, Inst. of Biophysics, Brno (Czech Republic); Znojil, V.; Vacha, J. [Masaryk Univ., Medical Faculty, Brno (Czech Republic)

    1998-03-01

    The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of {sup 60}Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au) 43 refs.

  9. Total Body Irradiation using VMAT (RapidArc: A Planning Study of a novel treatment delivery method

    Directory of Open Access Journals (Sweden)

    Santam Chakraborty

    2015-01-01

    Full Text Available Purpose: To evaluate the feasibility of using volumetric modulated arc therapy (VMAT using RapidArc to deliver total body irradiation (TBI treatment. Methods: VMAT planning was performed a whole body computed tomography (CT data set using Rapid Arc. The planning target volumes included entire body trimmed to 3 mm below the skin. The organs at risk included the lungs and kidneys. A dose of 12 Gy in 10 fractions was prescribed to the target volume. The VMAT-TBI technique consisted of three isocentres and three overlapping arcs: the head and neck, the chest, and the pelvis. The plans were prescribed to ensure, at a minimum, 95% planning target volume dose coverage with the prescription dose (percentage of volume receiving dose of 12 Gy was 95% and maximum dose of 109.8%. Mean dose to lung was restricted at 8.6Gy. Results: The total body volume in the study was 15469cm3 and the PTV volume was 11322cm3. The mean dose to PTV was 104%. The homogeneity index was 0.09. Sparing of normal tissues with adequate coverage of skeletal bones was shown to be feasible with Rapid Arc. The study demonstrates that VMAT is feasible for TBI treatment. Unlike conventional TBI chest wall boost with electrons was not required. Conclusion: The technique for total body irradiation using RapidArc VMAT was found feasible and is undergoing further studies prior to clinical use.

  10. Citrulline as a Biomarker in the Non-human Primate Total- and Partial-body Irradiation Models: Correlation of Circulating Citrulline to Acute and Prolonged Gastrointestinal Injury.

    Science.gov (United States)

    Jones, Jace W; Bennett, Alexander; Carter, Claire L; Tudor, Gregory; Hankey, Kim G; Farese, Ann M; Booth, Catherine; MacVittie, Thomas J; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for acute and prolonged gastrointestinal injury via exposure to total- and partial-body irradiation (6 MV LINAC-derived photons; 0.80 Gy min) in nonhuman primate models was investigated. The irradiation exposure covered gastrointestinal injuries spanning lethal, mid-lethal, and sub-lethal doses. The acute gastrointestinal injury was assessed via measurement of plasma citrulline and small intestinal histopathology over the first 15 d following radiation exposure and included total-body irradiation at 13.0 Gy, 10.5 Gy, and 7.5 Gy and partial-body irradiation at 11.0 Gy with 5% bone marrow sparing. The dosing schemes of 7.5 Gy total-body irradiation and 11.0 Gy partial-body irradiation included time points out to day 60 and day 180, respectively, which allowed for correlation of plasma citrulline to prolonged gastrointestinal injury and survival. Plasma citrulline values were radiation-dependent for all radiation doses under consideration, with nadir values ranging from 63-80% lower than radiation-naïve NHP plasma. The nadir values were observed at day 5 to 7 post irradiation. Longitudinal plasma citrulline profiles demonstrated prolonged gastrointestinal injury resulting from acute high-dose irradiation had long lasting effects on enterocyte function. Moreover, plasma citrulline did not discriminate between total-body or partial-body irradiation over the first 15 d following irradiation and was not predictive of survival based on the radiation models considered herein.

  11. Effects of the physical form of the diet on food intake, growth, and body composition changes in mice.

    Science.gov (United States)

    Yan, Lin; Combs, Gerald F; DeMars, Lana C; Johnson, LuAnn K

    2011-07-01

    The present study investigated effects of the physical form of the diet on food intake, growth, and body composition in male C57BL/6 mice. Three-week-old mice were fed isocaloric diets (AIN93G or a modification containing 25% wheat) in powdered or pelleted form. In experiment 1, mice were assigned into 4 groups offered the AIN93G or the wheat-modified diet in powdered or pelleted form. In experiment 2, mice were pair-fed the powdered diets to the ad libitum level of food intake of those fed the pelleted form of the respective diets. Body weight, food intake, and fecal excretion were recorded, and body composition was assessed on mice 1 wk before termination of the experiment. Mice fed the powdered diets showed greater increases in body weight in 2 wk of feeding than did mice fed the pelleted diets. Compared with the pelleted diets, the powdered diets supported an approximately 85% increase in the fat-mass:body-mass ratio and a 2-fold increase in the abdominal-fat-weight:carcass-weight ratio. In addition, mice fed the powdered diet showed significantly greater plasma concentrations of insulin and leptin and significantly lower plasma adiponectin, compared with their pellet-fed counterparts. Food intake of mice fed the powdered diet was 11% greater for the AIN93G and 16% greater for the wheat diet compared with that of the respective pelleted diet. These results demonstrate that C57BL/6 mice responded to the physical form of these diets in terms of food intake, which affected their growth, body composition, and plasma concentrations of insulin and adipocytokines.

  12. 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....

  13. The use of Micronucleus Assay on Swiss-Webster Mice (Mus Musculus Bone Marrow for the Mutagenicity Test of γ-Irradiation

    Directory of Open Access Journals (Sweden)

    R. Sofyan

    2005-07-01

    Full Text Available Ionizing radiation is a potentially chromosomal damaging agent. The induction of chromosomal damage as well as the incidence of cell cycle disturbances may depend on the dose of irradiation. One of the indication of chromosomal damage is the formation of micronucleus (MN during the anaphase of mitosis. This study deals with the MN assay on femur bone marrow polychromatic erythrocyte (PCE cells of Swiss-Webster mice, for the mutagenicity test of g-irradiation. The study was conducted on five groups of mice (each group consist of five mice that were irradiated at the doses of 0; 0,2; 0,4; 0,6 and 0,8 Gy respectively. One day after irradiation, the mice were killed by cervical dislocation. Furthermore the femur bone marrow was taken, the cells were then prepared by smear technique onto slides followed by Giemsa staining. The MN in PCE cells or MNPCE were examined microscopically by the magnification of 1000 and counted for every 1000 cells in each mice. The results showed that the MNPCE frequencies on the treatment groups were significantly higher than that of the control (P< 0,05. Further evaluation indicated that the MNPCE frequencies increased with the increase of irradiation dose.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-09-01

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

  15. Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Kotzin, B.L.; Arndt, R.; Okada, S.; Ward, R.; Thach, A.B.; Strober, S.

    1986-05-01

    We used total lymphoid irradiation (TLI; total dose = 3400 rad) to treat the lupus-like renal disease of 6-mo-old female NZB/NZW mice. Similar to our past studies, this treatment resulted in a marked prolongation of survival, decrease in proteinuria, and decrease in serum anti-DNA antibodies compared with untreated littermate controls. Although there was no evidence of disease recurrence in TLI-treated mice until after 12 mo of age, the in vitro proliferative response to phytohemagglutinin by NZB/NZW spleen cells recovered within 6 wk such that responses were greater than control NZB/NZW animals. A similar recovery and overshoot after TLI were evident in the primary antibody response to the T cell-dependent antigen sheep red blood cells (SRBC). Both the total and IgG anti-SRBC antibody responses after TLI were greater than those of untreated NZB/NZW controls, and were comparable with those of untreated non-autoimmune mice. Despite this increased response to mitogens and antigens after TLI, we noted a decrease in spontaneous splenic IgG-secreting cells and a decrease in IgG but not IgM antinuclear antibody production. Nonspecific suppressor cells of the mixed leukocyte response were detectable in the spleens of NZB/NZW mice early after TLI. However, the disappearance of suppressor cells was not associated with recrudescence of disease activity. Furthermore, transfer of large numbers of spleen cells from TLI-treated NZB/NZW mice did not result in disease suppression in untreated age-matched recipients. In summary, treatment of NZB/NZW mice with TLI results in a prolonged remission in autoimmune disease, which is achieved in the absence of generalized immunosuppression.

  16. Hemi body irradiation: An economical way of palliation of pain in bone metastasis in advanced cancer

    Directory of Open Access Journals (Sweden)

    Santanu Pal

    2014-01-01

    Full Text Available Background: The primary aim of this prospective non-randomized study was to evaluate the effect of hemi-body irradiation (HBI on pain and quality of life in cancer patients with extensive bone metastases. The secondary aim was to evaluate side-effects and cost-effectiveness of the treatment. Materials and Methods: Between March 2008 and December 2010, a total of 23 (male = 14, female = 9, median age = 60 years diagnosed cases of metastatic cancer patients (prostate = 11, breast = 6, and lung = 6 received HBI, which was delivered as lower (n = 7 (dose = 8 Gy, upper (n = 8 (dose = 6 Gy, or sequential HBI (n = 8 with a Telecobalt unit (Theratron 780C. Among them, one lung cancer patient died at 2 months and one prostate cancer patient defaulted after the second follow-up. Thus, 21 patients (male = 13, female = 8, median age = 65 years (prostatic cancer = 10, breast cancer = 6, and lung cancer = 5 were followed up for a minimum of 6 months. Evaluations were performed before and at 2, 4, 8, 16, and 24 weeks after treatment. Pain evaluation was done by Visual Analogue Scale (VAS, Verbal Rating Scale (VRS, Percentage of Pain Relief (PRR, and Global Pain Score (GPS. Toxicity was assessed by CTC v-3 toxicity scores in the medical record. Assessment of oral morphine consumption was done before and after radiation using paired t-test, and correlation analysis was also done with decrease of morphine consumption and reduction of pain score using statistical analysis. Results: Response (control of pain was partial (PR in 67% and complete (CR in 22% of patients. For most patients, the pain control lasted throughout the follow-up period (6 months. From 66.66% patients requiring 13 or more Morphine (10 mg tablets per day prior to HBI, none of the patients required to consume 13 or more Morphine (10 mg tablets per day following HBI, which was correlated with significant reduction in various pain scores (P < 0.05. One way ANOVA with Dunnett′s Multiple Comparison

  17. Evaluation of the analgesic activity and safety of ketorolac in whole body fractionated gamma irradiated animals

    Directory of Open Access Journals (Sweden)

    Sara Aly

    2015-06-01

    Full Text Available This study was performed to evaluate the analgesic activity and the toxicity of ketorolac in normal and fractionated (1.5 Gy/day/4 days γ-irradiated animals. Determination of brain serotonin content and serum prostaglandin level were also undertaken. The analgesic activity was tested using formalin test, at three dose levels (15, 30 and 60 mg/kg after 1 and 7 days post radiation exposure. LD50 determinations and assessment of liver and kidney function tests were performed. Our results indicated marked analgesic effects on the early and late phases of nociception. Double treatment with ketorolac and irradiation increased brain serotonin content. The acute LD50 of ketorolac was decreased in irradiated animals as compared to the LD50 of normal animals. Double treatment with ketorolac and irradiation induced an elevation of gastric mucin content, urea and BUN levels on the 1st day post irradiation, whereas, albumin level was lowered and globulin level was elevated after 7 days post irradiation. Depending on this study the dose of ketorolac used for treating cancer patients addressed to radiotherapy should be reduced, however, this requires further clinical confirmation.

  18. The effects of p38 MAPK inhibition combined with G-CSF administration on the hematoimmune system in mice with irradiation injury.

    Directory of Open Access Journals (Sweden)

    Deguan Li

    Full Text Available The acute and residual (or long-term bone marrow (BM injury induced by ionizing radiation (IR is a major clinic concern for patients receiving conventional radiotherapy and victims accidentally exposed to a moderate-to-high dose of IR. In this study, we investigated the effects of the treatment with the p38 inhibitor SB203580 (SB and/or granulocyte colony-stimulating factor (G-CSF on the hematoimmune damage induced by IR in a mouse model. Specifically, C57BL/6 mice were exposed to a sublethal dose (6 Gy of total body irradiation (TBI and then treated with vehicle, G-CSF, SB, and G-CSF plus SB. G-CSF (1 µg/mouse was administrated to mice by intraperitoneal (ip injection twice a day for six successive days; SB (15 mg/kg by ip injection every other day for 10 days. It was found that the treatment with SB and/or G-CSF significantly enhanced the recovery of various peripheral blood cell counts and the number of BM mononuclear cells 10 and 30 days after the mice were exposed to TBI compared with vehicle treatment. Moreover, SB and/or G-CSF treatment also increased the clonogenic function of BM hematopoietic progenitor cells (HPCs and the frequency of BM lineage -Sca1+c-kit+ cells (LSK cells and short-term and long term hematopoietic stem cells (HSCs 30 days after TBI, in comparison with vehicle treated controls. However, the recovery of peripheral blood B cells and CD4+ and CD8+ T cells was not significantly affected by SB and/or G-CSF treatment. These results suggest that the treatment with SB and/or G-CSF can reduce IR-induced BM injury probably in part via promoting HSC and HPC regeneration.

  19. A study on the changing of the irradiated mice salivary glands and it's influence to the pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Funahara, Takayuki; Nasu, Masanori; Furumoto, Keiichi (Nippon Dental Univ., Tokyo (Japan))

    1991-02-01

    X-ray irradiation (10 Gy) was given to the salivary gland in mice. Protein and glycoprotein syntheses in the salivary glands and pancreas were examined by using {sup 3}H-leucine and {sup 14}C-acetylglucosamine as tracers. Quantitative analysis of serum amylase and histochemical examination were also conducted. Uptake of {sup 3}H-leucine was low in the parotid, submandibular, and sublingual glands 3 and 7 days after irradiation, which were close to those in the non-irradiated group 21 days after irradiation. Uptake of {sup 14}C-acetylglucosamine in the parotid, submandibular, and sublingual glands varied with time, which was similar to that of {sup 3}H-leucine uptake. The uptake of both {sup 14}C-acetylglucosamine and {sup 3}H-leucine in the pancreas, as opposed to that in the salivary glands, varied with time, with the highest levels on Days 3 and 7, respectively. Serum amylase level, determined by the maltopentaose method, was 5,341+-772 mU/ml in the non-irradiated group. On Day 3, it was 6,706+-583 mU/ml. This was slightly higher than the level in the non-irradiated group on Days 7 and 21, with no statistically significant difference. Hematoxylin-eosin staining revealed hypertrophy of the glandular cells on Day 3, atrophy of the glandular cells on Day 7, and irregular cell arrangement on Day 21 for the parotid gland; and atrophied granular ampulla on Day 3, and hypertrophy on Day 7 for the submandibular gland. No marked changes were observed in either the sublingual gland or pancreas. Ninhydrin staining revealed a decreased stainability in the submandibular gland on Day 3; and an increased stainability in the pancreas on Day 7. In conclusion, protein and glycoprotein syntheses in the salivary glands after X-ray irradiation of 10 Gy decreased on Days 3 and 7, respectively. This seemed to be associated with compensatory function of the pancreas. (N.K.).

  20. Transition pattern and mechanism of B-lymphocyte precursors in regenerated mouse bone marrow after subtotal body irradiation.

    Directory of Open Access Journals (Sweden)

    Deping Han

    Full Text Available Little is known about the effects of ionizing radiation on the transition and the related signal transduction of progenitor B cells in the bone marrow. Thus, using an NIH Swiss mouse model, we explored the impact of ionizing radiation on the early stage of B-cell development via an examination of the transition of CLP to pro-B to pre-B cells within bone marrow as a function of radiation doses and times. Our results showed that while the total number of bone marrow lymphoid cells at different stages were greatly reduced by subtotal body irradiation (sub-TBI, the surviving cells continued to transition from common lymphoid progenitors to pro-B and then to pre-B in a reproducible temporal pattern. The rearrangement of the immunoglobulin heavy chain increased significantly 1-2 weeks after irradiation, but no change occurred after 3-4 weeks. The rearrangement of the immunoglobulin light chain decreased significantly 1-2 weeks after sub-TBI but increased dramatically after 3-4 weeks. In addition, several key transcription factors and signaling pathways were involved in B-precursor transitions after sub-TBI. The data indicate that week 2 after irradiation is a critical time for the transition from pro-B cells to pre-B cells, reflecting that the functional processes for different B-cell stages are well preserved even after high-dose irradiation.

  1. Gamma-irradiated influenza A virus provides adjuvant activity to a co-administered poorly immunogenic SFV vaccine in mice.

    Directory of Open Access Journals (Sweden)

    Rachelle eBabb

    2014-06-01

    Full Text Available Many currently available inactivated vaccines require 'adjuvants' to maximise the protective immune responses generated against the antigens of interest. Recent studies in mice with gamma-irradiated influenza A virus (γ-FLU have shown its superior efficacy compared to other forms of inactivated FLU vaccines and its ability to induce both potent type-I interferon (IFN-I responses and the IFN-I associated partial lymphocyte activation. Commonly, IFN-I responses induced by adjuvants, combined in vaccine preparations, have been shown to effectively enhance the immunogenicity of the antigens of interest. Therefore, we investigated the potential adjuvant activity of γ-FLU and the possible effect on antibody responses against co-administrated antigens, using gamma-irradiated Semliki Forest Virus (γ-SFV as the experimental vaccine in mice. Our data show that co-vaccination with γ-FLU and γ-SFV resulted in enhanced SFV-specific antibody responses in terms of increased titres by 6 fold and greater neutralisation efficacy, when compared to vaccination with γ-SFV alone. This study provides promising evidence related to the possible use of γ-FLU as an adjuvant to poorly immunogenic vaccines without compromising the vaccine efficacy of γ-FLU.

  2. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice.

    Directory of Open Access Journals (Sweden)

    Renata M Martinez

    Full Text Available Naringenin (NGN exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid (ABTS and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10. Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2, and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation.

  3. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice.

    Science.gov (United States)

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Silva, Thais C C; Caviglione, Carla V; Bottura, Carolina; Fonseca, Maria J V; Vicentini, Fabiana T M C; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2016-01-01

    Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation.

  4. In vivo mutagenicity studies in rats mice and Chinese hamsters fed irradiated foodstuffs - chicken, fish, dates, pulses, mangoes and cocoa beans

    Energy Technology Data Exchange (ETDEWEB)

    Renner, H.W.

    1982-11-01

    Three in vivo genetic toxicity tests were performed in rats, mice and Chinese hamsters to detect possible mutagenic effects of irradiated chicken, dried dates, fish, cocoa beans, pulses and mangoes. The tests employed were the micronucleus test and sister-chromatid exchange (SCE) test for irradiated and unirradiated samples of all foodstuffs listed, and the spermatogonia test, (including SCE technique) in mice for irradiated and unirradiated chicken, fish and dates only. In the case of cocoa beans, the mutagenicity tests were performed on an additional test group fed beans fumigated with ethylene oxide. The different mammalian species used for the various experiments are given below. None of the tests provided any evidence of mutagenicity induced by irradiation in any of the foodstuffs studied. Moreover, these tests are currently considered to be the most sensitive in vivo mutagenicity tests in mammals.

  5. Dystrophic changes in extraocular muscles after gamma irradiation in mdx:utrophin(+/-) mice.

    Science.gov (United States)

    McDonald, Abby A; Kunz, Matthew D; McLoon, Linda K

    2014-01-01

    Extraocular muscles (EOM) have a strikingly different disease profile than limb skeletal muscles. It has long been known that they are spared in Duchenne (DMD) and other forms of muscular dystrophy. Despite many studies, the cause for this sparing is not understood. We have proposed that differences in myogenic precursor cell properties in EOM maintain normal morphology over the lifetime of individuals with DMD due to either greater proliferative potential or greater resistance to injury. This hypothesis was tested by exposing wild type and mdx:utrophin(+/-) (het) mouse EOM and limb skeletal muscles to 18 Gy gamma irradiation, a dose known to inhibit satellite cell proliferation in limb muscles. As expected, over time het limb skeletal muscles displayed reduced central nucleation mirrored by a reduction in Pax7-positive cells, demonstrating a significant loss in regenerative potential. In contrast, in the first month post-irradiation in the het EOM, myofiber cross-sectional areas first decreased, then increased, but ultimately returned to normal compared to non-irradiated het EOM. Central nucleation significantly increased in the first post-irradiation month, resembling the dystrophic limb phenotype. This correlated with decreased EECD34 stem cells and a concomitant increase and subsequent return to normalcy of both Pax7 and Pitx2-positive cell density. By two months, normal het EOM morphology returned. It appears that irradiation disrupts the normal method of EOM remodeling, which react paradoxically to produce increased numbers of myogenic precursor cells. This suggests that the EOM contain myogenic precursor cell types resistant to 18 Gy gamma irradiation, allowing return to normal morphology 2 months post-irradiation. This supports our hypothesis that ongoing proliferation of specialized regenerative populations in the het EOM actively maintains normal EOM morphology in DMD. Ongoing studies are working to define the differences in the myogenic precursor cells

  6. Long-term results of total body irradiation in adults with acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Marnitz, Simone; Zich, Alexander; Budach, Volker; Jahn, Ulrich; Neumann, Oliver [Charite University Medicine, Department of Radiation Oncology, Berlin (Germany); Martus, Peter [University Tuebingen, Institute of Clinical Epidemiology and Applied Biostatistics, Tuebingen (Germany); Arnold, Renate [Charite University Medicine, Campus CVK, Department of Hematology and Oncology, Bone Marrow Transplant Unit, Berlin (Germany)

    2014-05-15

    The aim of this chart review of adult patients treated for acute lymphoblastic leukemia (ALL) with total body irradiation (TBI) was to evaluate early and late toxicity and long-term outcome. A total of 110 adult patients (34 ± 12 years) with ALL underwent TBI (6 fractions of 2 Gy for a total of 12 Gy) as a part of the treatment regimen before transplantation. Treatment-related toxicity, mortality, and hematologic outcome are reported. Mean follow-up was 70 months. The 2- and 5-year leukemia-free survival rates were 78 and 72 %, respectively. In all, 29 % (32/110) patients suffered from medullary recurrence after a median time of 7 months. Gender was the only statistically significant prognostic factor in terms of overall survival in favor of female patients. Treatment-related mortality and overall survival after 2 and 5 years were 16 and 22 %, and 60 and 52.7 %, respectively. The most frequent late reaction wascGVHD of the skin (n = 33, 30 %). In addition, 15.5 % (17/110 patients) suffered pulmonary symptoms, and 6 patients developed lung fibrosis. Eyes were frequently affected by the radiation (31/110 = 28 %); 12 of 110 patients (11 %) presented with symptoms from osteoporosis, 5 of 110 patients (4.5 %) developed hypothyreosis and 2 patients diabetes mellitus. Of the male patients, 11 % reported erectile dysfunction or loss of libido, while 2 of 36 women reported menopausal syndrome at the mean time of 28 months after treatment with requirement for substitution. No women became pregnant after treatment. No acute or late cardiac toxicities were documented in our patients. No secondary malignancies were documented. Although hematologic outcome was in the upper range of that reported in the literature, treatment-related mortality (TRM) and medullary recurrences remain a challenge. Sophisticated radiation techniques allow for decreasing toxicity to certain organs and/or dose escalation to the bone marrow in highly selected patients in order to improve therapeutic

  7. SU-E-T-540: Volumetric Modulated Total Body Irradiation Using a Rotational Lazy Susan-Like Immobilization System

    Energy Technology Data Exchange (ETDEWEB)

    Gu, X; Hrycushko, B; Lee, H; Lamphier, R; Jiang, S; Abdulrahman, R; Timmerman, R [UT Southwestern Medical Center, Dallas, TX (United States)

    2014-06-01

    Purpose: Traditional extended SSD total body irradiation (TBI) techniques can be problematic in terms of patient comfort and/or dose uniformity. This work aims to develop a comfortable TBI technique that achieves a uniform dose distribution to the total body while reducing the dose to organs at risk for complications. Methods: To maximize patient comfort, a lazy Susan-like couch top immobilization system which rotates about a pivot point was developed. During CT simulation, a patient is immobilized by a Vac-Lok bag within the body frame. The patient is scanned head-first and then feet-first following 180° rotation of the frame. The two scans are imported into the Pinnacle treatment planning system and concatenated to give a full-body CT dataset. Treatment planning matches multiple isocenter volumetric modulated arc (VMAT) fields of the upper body and multiple isocenter parallel-opposed fields of the lower body. VMAT fields of the torso are optimized to satisfy lung dose constraints while achieving a therapeutic dose to the torso. The multiple isocenter VMAT fields are delivered with an indexed couch, followed by body frame rotation about the pivot point to treat the lower body isocenters. The treatment workflow was simulated with a Rando phantom, and the plan was mapped to a solid water slab phantom for point- and film-dose measurements at multiple locations. Results: The treatment plan of 12Gy over 8 fractions achieved 80.2% coverage of the total body volume within ±10% of the prescription dose. The mean lung dose was 8.1 Gy. All ion chamber measurements were within ±1.7% compared to the calculated point doses. All relative film dosimetry showed at least a 98.0% gamma passing rate using a 3mm/3% passing criteria. Conclusion: The proposed patient comfort-oriented TBI technique provides for a uniform dose distribution within the total body while reducing the dose to the lungs.

  8. Effects of the Physical Form of the Diet on Food Intake, Growth, and Body Composition Changes in Mice

    OpenAIRE

    Yan, Lin; Combs, Gerald F.; Lana C DeMars; LuAnn K. Johnson

    2011-01-01

    The present study investigated effects of the physical form of the diet on food intake, growth, and body composition in male C57BL/6 mice. Three-week-old mice were fed isocaloric diets (AIN93G or a modification containing 25% wheat) in powdered or pelleted form. In experiment 1, mice were assigned into 4 groups offered the AIN93G or the wheat-modified diet in powdered or pelleted form. In experiment 2, mice were pair-fed the powdered diets to the ad libitum level of food intake of those fed t...

  9. A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.

    Directory of Open Access Journals (Sweden)

    Michelle R Newman

    Full Text Available The low dose radioadaptive response has been shown to be protective against high doses of radiation as well as aging-induced genomic instability. We hypothesised that a single whole-body exposure of low dose radiation would induce a radioadaptive response thereby reducing or abrogating aging-related changes in repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation, serial peripheral blood sampling was performed and differences in Long Interspersed Nucleic Element 1 (L1, B1 and Intracisternal-A-Particle (IAP repeat element methylation between samples were assessed using high resolution melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation- or aging-related changes in the methylation of peripheral blood, spleen or liver L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues of cohorts of untreated aging mice showed that the 17-19 month age group exhibited higher repeat element methylation than younger or older mice, with no overall decline in methylation detected with age. This is the first temporal analysis of the effect of low dose radiation on repeat element methylation in mouse peripheral blood and the first to examine the long term effect of this dose on repeat element methylation in a radiosensitive tissue (spleen and a tissue fundamental to the aging process (liver. Our data indicate that the methylation of murine DNA repeat elements can fluctuate with age, but unlike human studies, do not demonstrate an overall aging-related decline. Furthermore, our results indicate that a low dose of ionising radiation does not induce detectable changes to murine repeat element DNA methylation in the tissues and at the time-points examined in this study. This radiation dose is relevant to human diagnostic radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose radiation, does not cause significant short or long term changes to repeat element or global DNA

  10. The effect of pentoxifylline on early and late radiation injury following fractionated irradiation in C3H mice

    Energy Technology Data Exchange (ETDEWEB)

    Dion, M.W.; Hussey, D.H.; Osborne, J.W.

    1989-07-01

    An experiment was performed to test the effectiveness of pentoxifylline in reducing late radiation injury. One hundred and four C3H mice were randomized into eight groups of 13 mice each, and the right hind limbs were irradiated with 4000, 5000, 6000, or 7000 cGy in ten fractions. Each group was treated with once daily injections of either pentoxifylline or saline for 30+ weeks. An additional ten mice received daily injections of pentoxifylline or saline, but no irradiation. The pentoxifylline animals demonstrated significantly less late injury than the saline treated animals. The most obvious differences were observed in the 5000 and 6000 cGy groups. There were seven radiation related deaths in the saline treated control groups, but only one radiation related death in the pentoxifylline treated groups. Whereas 42% (20/48) of the saline treated animals had a late injury score of 3.0 or greater, only 8% (4/51) of the pentoxifylline treated animals had a late skin score as high as 3.0. Pentoxifylline had no effect on the acute radiation injury scores. The drug was well tolerated with no toxic effects noted. Pentoxifylline is a methyl xanthine derivative that is used to treat vascular occlusive disease in humans. It improves perfusion through small capillaries by improving the deformability of red blood cells, inhibiting platelet aggregation, and stimulating the release of prostacyclin. This study shows that the prophylactic administration of pentoxifylline can modify late radiation induced injury in the mouse extremity. It may have value in the prevention or treatment of late radiation induced injury in humans, and it could be a useful tool to help define the mechanisms of late radiation injury in specific organs.

  11. Neonatal and maternal body burdens of hexachlorobenzene (HCB) in mice: gestational exposure and lactational transfer

    Energy Technology Data Exchange (ETDEWEB)

    Courtney, K.D.; Andrews, J.E.

    1985-04-01

    Hexachlorobenzene (HCB), a ubiquitous lipophilic pollutant, was readily transferred in the milk of lactating dams to their suckling neonates. Pregnant CD-1 mice were treated during gestation, and the body burdens of HCB in the neonates and the dams were determined during lactation. Also, neonates from dams treated with HCB during gestation were cross-fostered at birth to dams treated with corn oil during gestation. The body burdens of HCB were greater in the neonates exposed to HCB by lactational transfer than the neonates exposed only by gestational transfer. In many tissues, the concentration of HCB in the pups from full litter was similar to that in pups from litters reduced to two pups per litter. Lactational transfer of HCB from the dams to the pups was a major route of excretion in that 95% of HCB was depleted during 20 days of lactation. HCB depletion was similar in dams with whole litters, and those with litters reduced to two pups.

  12. Subchronic and mild social defeat stress accelerates food intake and body weight gain with polydipsia-like features in mice.

    Science.gov (United States)

    Goto, Tatsuhiko; Kubota, Yoshifumi; Tanaka, Yuki; Iio, Wataru; Moriya, Naoko; Toyoda, Atsushi

    2014-08-15

    Development and characterization of animal models of depression are essential for fully understanding the pathogenesis of depression in humans. We made and analyzed a mouse model exhibiting social deficit and hyperphagia-like behavior using a subchronic and mild social defeat stress (sCSDS) paradigm. The body weight, food and water intake of mice were monitored during a test period, and their behaviors and serum components were analyzed at two stages: immediately after the sCSDS period and 1 month after the sCSDS. The body weight and food intake of defeated mice were significantly higher than control mice at the sCSDS period, and these differences were sustained until 1 month after the sCSDS, whereas the water intake of defeated mice was significantly higher than control mice for the period of sCSDS only. Behavioral analyses revealed that the defeated mice exhibit significant social aversion to unfamiliar mice in a social interaction test and a trend of anxiety-like behavior in an elevated-plus maze test. Possibly due to polydipsia-like symptoms, defeated mice had significantly lower levels of albumin and blood urea nitrogen than control mice immediately after the sCSDS period but not at 1 month after sCSDS. The present study revealed that our sCSDS mice keep much more water in their body than control mice. This study reports the first step toward an understanding of the mechanisms of stress-induced overhydration, over-eating and resultant weight gain.

  13. The magnitude and kinetics of delayed-type hypersensitivity responses in mice vaccinated with irradiated cercariae of Schistoma mansoni

    Energy Technology Data Exchange (ETDEWEB)

    Ratcliffe, E.C.; Wilson, R.A. (York Univ. (United Kingdom). Dept. of Biology)

    1991-08-01

    A footpad assay was used to measure the DTH of mice to soluble worm antigens (SWAP), and to living day 7 lung schistosomula, following vaccination and challenge infections with Schistosoma mansoni. DTH to SWAP was first observed on day 10, and reached its maximum on day 17 post-vaccination. Treatment of mice with anti-CD4 antibody on the 3 days prior to footpad challenge completely abrogated this response. Reactivity to living parasites was of a slower order than that to SWAP; it also peaked earlier, on day 10 post-vaccination. By day 35, responsiveness to both sets of antigens had declined almost to control levels. There was no correlation between the level of DTH to living schistosomula, at any time, and the degree of resistance subsequently developed. Percutaneous challenge of vaccinated mice was followed by a resurgence of reactivity to SWAP. This secondary response occurred more rapidly than the primary response, peaking on day 7 post-challenge, and was of a similar magnitude. We were unable to detect a similar recall of DTH to living schistosomula, possibly because the assay was insufficiently sensitive. We conclude that the intensity and kinetics of DTH responsiveness are crucial features of the irradiated vaccine model, and suggest that further investigation of cell-mediated immune reaction, particularly those occuring in the lungs, is vital to a better understanding of events underlying the development and expression of immunity. (author).

  14. Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

    Energy Technology Data Exchange (ETDEWEB)

    Hiniker, Susan M. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Agarwal, Rajni [Section of Stem Cell Transplantation, Department of Pediatrics, Stanford University, Stanford, California (United States); Modlin, Leslie A. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gray, Christine C. [Division of Child and Adolescent Psychiatry, Department of Psychiatry, Stanford University, Stanford, California (United States); Harris, Jeremy P.; Million, Lynn [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Kiamanesh, Eileen F. [Cancer Clinical Trials Office, Stanford Cancer Institute, Stanford University, Stanford, California (United States); Donaldson, Sarah S., E-mail: sarah2@stanford.edu [Department of Radiation Oncology, Stanford University, Stanford, California (United States)

    2014-05-01

    Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

  15. Combined total body X-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Halberg, F.E.; Fu, K.K.; Weaver, K.A.; Zackheim, H.S.; Epstein, E.H. Jr.; Wintroub, B.U.

    1989-08-01

    Twelve consecutive patients with advanced stage mycosis fungoides (MF) were treated with combined total body X ray irradiation (TBI) and total skin electron beam radiotherapy (EBRT). Six had generalized plaque disease and dermatopathic nodes, three had tumor stage disease and node biopsy positive for mycosis fungoides, and three had erythroderma/Sezary syndrome. The treatment regimen consisted of split course total body X ray irradiation, given in twice weekly 15 cGy fractions to 75 cGy, then total skin electron beam radiation therapy given in once weekly 400 cGy fractions to a total dose of 2400 cGy. Underdosed areas and areas of greatest initial involvement were boosted 400 cGy twice weekly for an additional 1200 cGy. This was followed by a second course of total body X ray irradiation, to a total dose of 150 cGy. The total skin electron beam radiotherapy technique is a modification of an established six position EBRT technique for mycosis fungoides. Measurements to characterize the beam with and without a lexan scattering plate, demonstrated that the combination of no-plate beams produced better dose uniformity with a much higher dose rate. This improved technique is particularly advantageous for elderly and/or frail patients. Nine (75%) of the 12 patients achieved complete response (CR). The other three had significant improvement with greater than 80% clearing of their disease and resolution of symptoms. All six patients with generalized plaque disease achieved complete response and remained free of disease from 2 to 16 months. Two of three node positive patients also achieved complete response; one, with massive biopsy-documented mycosis fungoides nodal disease and deep open tumors, remained relapse-free over 2 years. Only one of the three patients with erythroderma/Sezary syndrome achieved a complete response, which was short lived.

  16. New method of investigation of urine microflora in mice after irradiation

    Directory of Open Access Journals (Sweden)

    Ivanov A.A.

    2013-12-01

    nated with one drop of urine, placed on surface Endo media, incubate in thermostat (37°C in during 1-2 days and numbers of positive crops (Esch. coli, Proteus, Enterococcus, were indicated. It was shown that after irradiation the numbers of positive probes increased. The test displayed that the method is easy, economic and demonstrative.

  17. Extended lifespan, reduced body size and leg skeletal muscle mass, and decreased mitochondrial function in clk-1 transgenic mice.

    Science.gov (United States)

    Takahashi, Kazuhide; Noda, Yoshihiro; Ohsawa, Ikuroh; Shirasawa, Takuji; Takahashi, Mayumi

    2014-10-01

    Mutational inactivation of clk-1, which encodes an enzyme necessary for the biosynthesis of coenzyme Q (CoQ), extends the lifespan of Caenorhabditis elegans. However, whether mammalian clk-1 regulates the lifespan of mice is not known because clk-1-deficiencies are embryonic lethal. Here, we investigated the lifespan of clk-1 transgenic mice (Tg96/I), which were rescued from embryonic lethality via the transgenic expression of mouse clk-1. Tg96/I mice lived longer and had smaller bodies than wild-type mice, but Tg96/I mice had CoQ levels equivalent to wild-type mice. The small-sized Tg96/I mice exhibited reduced whole-body oxygen consumption (VO2) during the dark period, and lean leg skeletal muscles with reduced mitochondrial VO2 and ATP content compared with wild-type mice. These findings indicate a close relationship between lifespan extension and decreased mitochondrial function, which was induced by the transgenic expression of clk-1, in leg skeletal muscles that exhibit high metabolic activity.

  18. Multiple Irradiation Capsule Experiment (MICE)-3B Irradiation Test of Space Fuel Specimens in the Advanced Test Reactor (ATR) - Close Out Documentation for Naval Reactors (NR) Information

    Energy Technology Data Exchange (ETDEWEB)

    M. Chen; CM Regan; D. Noe

    2006-01-09

    Few data exist for UO{sub 2} or UN within the notional design space for the Prometheus-1 reactor (low fission rate, high temperature, long duration). As such, basic testing is required to validate predictions (and in some cases determine) performance aspects of these fuels. Therefore, the MICE-3B test of UO{sub 2} pellets was designed to provide data on gas release, unrestrained swelling, and restrained swelling at the upper range of fission rates expected for a space reactor. These data would be compared with model predictions and used to determine adequacy of a space reactor design basis relative to fission gas release and swelling of UO{sub 2} fuel and to assess potential pellet-clad interactions. A primary goal of an irradiation test for UN fuel was to assess performance issues currently associated with this fuel type such as gas release, swelling and transient performance. Information learned from this effort may have enabled use of UN fuel for future applications.

  19. Skin Inqjuries Reduce Survival and Modulate Corticosterone, C-Reactive Protein, Complement Component 3, IgM, and Prostaglandin E2 after Whole-Body Reactor-Produced Mixed Field (n + γ-Photons Irradiation

    Directory of Open Access Journals (Sweden)

    Juliann G. Kiang

    2013-01-01

    Full Text Available Skin injuries such as wounds or burns following whole-body γ-irradiation (radiation combined injury (RCI increase mortality more than whole-body γ-irradiation alone. Wound-induced decreases in survival after irradiation are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to systemic bacterial infection. Among these factors, radiation-induced increases in interleukin-6 (IL-6 concentrations in serum were amplified by skin wound trauma. Herein, the IL-6-induced stress proteins including C-reactive protein (CRP, complement 3 (C3, immunoglobulin M (IgM, and prostaglandin E2 (PGE2 were evaluated after skin injuries given following a mixed radiation environment that might be found after a nuclear incident. In this report, mice received 3 Gy of reactor-produced mixed field (n+γ-photons radiations at 0.38 Gy/min followed by nonlethal skin wounding or burning. Both wounds and burns reduced survival and increased CRP, C3, and PGE2 in serum after radiation. Decreased IgM production along with an early rise in corticosterone followed by a subsequent decrease was noted for each RCI situation. These results suggest that RCI-induced alterations of corticosterone, CRP, C3, IgM, and PGE2 cause homeostatic imbalance and may contribute to reduced survival. Agents inhibiting these responses may prove to be therapeutic for RCI and improve related survival.

  20. Assessing Cardiac Injury in Mice With Dual Energy-MicroCT, 4D-MicroCT, and MicroSPECT Imaging After Partial Heart Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang-Lung; Min, Hooney [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Befera, Nicholas; Clark, Darin; Qi, Yi [Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States); Das, Shiva [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Johnson, G. Allan; Badea, Cristian T. [Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States); Kirsch, David G., E-mail: david.kirsch@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina (United States)

    2014-03-01

    Purpose: To develop a mouse model of cardiac injury after partial heart irradiation (PHI) and to test whether dual energy (DE)-microCT and 4-dimensional (4D)-microCT can be used to assess cardiac injury after PHI to complement myocardial perfusion imaging using micro-single photon emission computed tomography (SPECT). Methods and Materials: To study cardiac injury from tangent field irradiation in mice, we used a small-field biological irradiator to deliver a single dose of 12 Gy x-rays to approximately one-third of the left ventricle (LV) of Tie2Cre; p53{sup FL/+} and Tie2Cre; p53{sup FL/−} mice, where 1 or both alleles of p53 are deleted in endothelial cells. Four and 8 weeks after irradiation, mice were injected with gold and iodinated nanoparticle-based contrast agents, and imaged with DE-microCT and 4D-microCT to evaluate myocardial vascular permeability and cardiac function, respectively. Additionally, the same mice were imaged with microSPECT to assess myocardial perfusion. Results: After PHI with tangent fields, DE-microCT scans showed a time-dependent increase in accumulation of gold nanoparticles (AuNp) in the myocardium of Tie2Cre; p53{sup FL/−} mice. In Tie2Cre; p53{sup FL/−} mice, extravasation of AuNp was observed within the irradiated LV, whereas in the myocardium of Tie2Cre; p53{sup FL/+} mice, AuNp were restricted to blood vessels. In addition, data from DE-microCT and microSPECT showed a linear correlation (R{sup 2} = 0.97) between the fraction of the LV that accumulated AuNp and the fraction of LV with a perfusion defect. Furthermore, 4D-microCT scans demonstrated that PHI caused a markedly decreased ejection fraction, and higher end-diastolic and end-systolic volumes, to develop in Tie2Cre; p53{sup FL/−} mice, which were associated with compensatory cardiac hypertrophy of the heart that was not irradiated. Conclusions: Our results show that DE-microCT and 4D-microCT with nanoparticle-based contrast agents are novel imaging approaches

  1. Effect of antihistamines, disodium cromoglycate (DSCG) or methysergide on post-irradiation cerebral blood flow and mean systemic arterial blood pressure in primates after 25 Gy, whole-body, gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cockerham, L.G.; Forcino, C.D. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)

    1995-06-01

    Exposure to ionizing radiation causes hypotension, cerebral ischemia and release of histamine (HA) and serotonin (5-HT). To investigate the relationship among these responses, rhesus monkeys (Macaca mulatta) received physiological saline (i.v.), disodium cromoglycate (DSCG), antihistamines (AH, mepyramine and cimetidine), or methysergide (METH), then were given 25 Gy whole-body irradiation. Monkeys receiving DSCG, AH or METH had higher post-irradiation mean arterial blood pressure (MBP) than saline-treated controls. Compared to levels in controls, post-irradiation hippocampal blood flow (rCBF) levels were higher in monkeys receiving DSCG, AH or METH. Treatment with the 5-HT{sub 2} receptor antagonist methysergide was the most effective in maintaining both rCBF and MBP after irradiation. Results support the hypothesis that the irradiation-induced cerebral ischemia and, to some extent, the hypotension is mediated by serotonin through 5-HT{sub 2} receptor sites. (author) 72 refs.

  2. Presence of. gamma. G and. beta. 1C globulins in renal glomeruli of aging and neonatally x-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Guttman, P.H.; Wuepper, K.D.; Fudenberg, H.H.

    1967-01-01

    A renal lesion in rodents, termed progressive intercapillary glomerulosclerosis (IGS), is characterized by gradual increase in the thickness of the mesangium due to cell proliferation, clustering, and pleomorphism of the mesangial cells, accumulation of PAS-positive mesangial matrix and progressive increase in the thickness of capillary basement membranes. Electron microscopy reveals deposits of electron-dense material in kidneys with IGS suggestive of plasma proteins in the mesangial matrix and in the basement membranes. IGS appears early in life and progresses with age. Whole body irradiation or direct irradiation of the kidneys causes acceleration of the glomerular lesion. A latent period precedes the onset of demonstrable histologic changes following x-ray; this latent period is of shorter duration in animals irradiated late in life. In previous studies, the possible role of an immune mechanism in the pathogenesis of IGS was suggested by the following observations: (1) the progressive course of the disease after a latent period following a single exposure to x-ray; (2) the similarity of the lesions to those seen in experimental immune disease of the kidney in rodents; (3) the presence of electron-dense material suggesting plasma protein deposits in the basement membranes and matrix; and (4) the potentiating effect of neonatal thymectomy on the course of radiation-induced IGS.

  3. Clone-forming activity of embryonal stem hemopoietic cells after transplantation to newborn or adult sublethally irradiated mice.

    Science.gov (United States)

    Drize, N I; Chertkov, I L

    2000-07-01

    Hemopoietic activity of stem hemopoietic cells from the liver of embryos was studied at different terms of intrauterine development. The fate of individual clones of hemopoietic cells marked by human adenosine deaminase gene was followed up in sublethally irradiated or newborn recipients. The efficiency of marker gene incorporation in primitive stem hemopoietic cells from the liver of 12-, 13-, and 17-day embryos was not high. Gene transfer was performed without cell prestimulation to division, and hence, these data show that primitive stem cells proliferate even in 17-day embryos. Cells from embryonal liver in all terms maintain hemopoiesis both in newborn and adult microenvironment, hemopoiesis being realized according to the clonal succession model, i. e. in the some way after transplantation of the bone marrow from adult mice.

  4. Clinical efficacy of blue light full body irradiation as treatment option for severe atopic dermatitis.

    Directory of Open Access Journals (Sweden)

    Detlef Becker

    Full Text Available BACKGROUND: Therapy of atopic dermatitis (AD relies on immunosuppression and/or UV irradiation. Here, we assessed clinical efficacy and histopathological alterations induced by blue light-treatment of AD within an observational, non-interventional study. METHODOLOGY/PRINCIPAL FINDINGS: 36 patients with severe, chronic AD resisting long term disease control with local corticosteroids were included. Treatment consisted of one cycle of 5 consecutive blue light-irradiations (28.9 J/cm(2. Patients were instructed to ask for treatment upon disease exacerbation despite interval therapy with topical corticosteroids. The majority of patients noted first improvements after 2-3 cycles. The EASI score was improved by 41% and 54% after 3 and 6 months, respectively (p≤0.005, and p≤0.002. Significant improvement of pruritus, sleep and life quality was noted especially after 6 months. Also, frequency and intensity of disease exacerbations and the usage of topical corticosteroids was reduced. Finally, immunohistochemistry of skin biopsies obtained at baseline and after 5 and 15 days revealed that, unlike UV light, blue light-treatment did not induce Langerhans cell or T cell depletion from skin. CONCLUSIONS/SIGNIFICANCE: Blue light-irradiation may represent a suitable treatment option for AD providing long term control of disease. Future studies with larger patient cohorts within a randomized, placebo-controlled clinical trial are required to confirm this observation.

  5. Citrulline as a Biomarker in the Murine Total-Body Irradiation Model: Correlation of Circulating and Tissue Citrulline to Small Intestine Epithelial Histopathology.

    Science.gov (United States)

    Jones, Jace W; Tudor, Gregory; Li, Fei; Tong, Yan; Katz, Barry; Farese, Ann M; MacVittie, Thomas J; Booth, Catherine; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for gastrointestinal acute radiation syndrome via exposure to total-body irradiation in a murine model was investigated. The radiation exposure covered lethal, mid-lethal, and sub-lethal gastrointestinal acute radiation syndrome. Plasma citrulline profiles were generated over the first 6 d following total-body irradiation exposure of 6-15 Gy. In addition, plasma citrulline was comprehensively evaluated in the context of matching small intestine citrulline and histopathology. Higher plasma citrulline was significantly associated with lower irradiation doses over the first 6 d following the irradiation insult. Furthermore, higher plasma citrulline was significantly associated with higher crypt survival. The correlation of the plasma citrulline to crypt survival was more robust for higher irradiation doses and for later time points. The data suggested plasma citrulline was most informative for reflecting gastrointestinal injury resulting from exposure to 9-15 Gy total-body irradiation covering time-points 2-5 d post the irradiation insult.

  6. Identification of Protein Markers in Intestine and Brain of Irradiated Mice by Proteomic Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Young Bin; Pyun, Bo Jeong; Lee, Hae June; Jeon, Sang Rok; Lee, Yun Sil [Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2010-04-15

    Several bioassays such as cytogenetics, mutations, cell survival, clonogenicity, and celltransformation, have been used for decades to aid in the assessment of health risk following exposure to radiation. However, the currently available assays do not directly reveal molecular mechanisms involved in response to radiationmaking the estimation of long tern health risks uncertain. Consequently, there are increasing efforts in developing more sensitive and rapid molecular methodologiesboth at the genomic and proteomic levels for the identification of biomarkers of exposure to radiation. Our data have shown that PGK1 was specifically upregulated in irradiated mouse intestine and TA1 was down-regulated in irradiated mouse brains without their alterations in other tissues. Based on these data, we suggest that TA1 and PGK1 might be candidates for tissue specific biomarkers of IR exposure.

  7. Irradiation induces different inflammatory and thrombotic responses in carotid arteries of wildtype C57BL/6J and atherosclerosis-prone ApoE(-/-) mice

    NARCIS (Netherlands)

    Hoving, S.; Heeneman, S.; Gijbels, M.J.J.; Te Poele, J.A.; Visser, N.; Cleutjens, J.; Russell, N.S.; Daemen, M.J.; Stewart, F.A.

    2012-01-01

    BACKGROUND AND PURPOSE: We have previously shown that irradiation to the carotid arteries of hypercholesterolemic ApoE(-/-) mice accelerated the development of macrophage-rich, inflammatory atherosclerotic lesions. We now investigated the mechanism underlying the development of radiation-induced ath

  8. The effect of fast created inbreeding on litter size and body weights in mice

    Directory of Open Access Journals (Sweden)

    Meuwissen Theo

    2005-09-01

    Full Text Available Abstract This study was designed to reveal any differences in effects of fast created versus total inbreeding on reproduction and body weights in mice. A line selected for large litter size for 124 generations (H and a control line (K maintained without selection for the same number of generations were crossed (HK and used as a basis for the experiment. Within the HK cross, full sib, cousin or random mating were practised for two generations in order to create new inbreeding (IBF at a fast rate. In the first generation of systematic mating, old inbreeding was regenerated in addition to creation of new inbreeding from the mating design giving total inbreeding (IBT. The number of pups born alive (NBA and body weights of the animals were then analysed by a model including both IBT and IBF. The IBT of the dam was in the present study found to reduce the mean NBA with -0.48 (± 0.22 (p F was -0.42 (± 0.27. For the trait NBA per female mated, the effect of IBT was estimated to be -0.45 (± 0.29 per 10% increase in the inbreeding coefficient and the effect of IBF was -0.90 (± 0.37 (p F of the dam could be found on sex-ratio and body weights at three and six weeks of age in a population already adjusted for IBT.

  9. Optimizing the Microscopy Time Schedule for Chromosomal Dosimetry of High-dose and Partial-body Irradiations

    Science.gov (United States)

    Vinnikov, Volodymyr A.

    2017-01-01

    The methodology of cytogenetic triage can be improved by optimizing a schedule of microscopy for different exposure scenarios. Chromosome aberrations were quantified by microscopy in human blood lymphocytes irradiated in vitro to ~2, 4, and 12 Gy acute 60Co γ-rays mixed with the unirradiated blood simulating 10%, 50%, 90%, and 100% exposure and in along with a sample from a homogeneous exposure to ~20 Gy. Biodosimetry workload was statistically modeled assuming that 0.5, 1, 5, or 25 h was available for scoring one case or for analysis of up to 1000 cells or 100 dicentrics plus centric rings by one operator. A strong negative correlation was established between the rates of aberration acquisition and cell recording. Calculations showed that the workload of 1 case per operator per·day (5 h of scoring by microscopy) allows dose estimates with high accuracy for either 90%–100% irradiations of 2 Gy or 50%–90% irradiations of 4–12 Gy; lethal homogeneous (100%) exposures of 12 and 20 Gy can be evaluated with just 1 h of microscopy. Triage analysis of 0.5 h scoring per case results in the minimum tolerable accuracy only for partial- and total-body exposure of 4–20 Gy. Time-related efficacy of conventional biodosimetry depends primarily on the aberration yield in the sample, which is dependent on the radiation dose and its distribution in the patient's body. An optimized schedule of microscopy scoring should be developed for different exposure scenarios in each laboratory to increase their preparedness to radiological emergencies. PMID:28250910

  10. Survival of irradiated recipient mice after transplantation of bone marrow from young, old and "early aging" mice.

    Science.gov (United States)

    Guest, Ian; Ilic, Zoran; Scrable, Heidi; Sell, Stewart

    2015-12-01

    Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-old p53+/m donor cells compared to recipients of 8 week-old wild-type (WT) donor cells (70 weeks) or of recipients of 16-18 weeks-old donor cells from either p53+/m or WT mice. There is shorter survival in recipients of older versus younger WT donor bone marrow, but the difference is only significant when comparing 8 and 18 week-old donors. In the p44-based model, short term survival/engraftment is significantly reduced in recipients of 11 month-old p44 donor cells compared to 4 week-old p44 or wild type donor cells of either age; mid-life survival at 40 weeks is also significantly less in recipients of p44 cells. BMDSCs are readily detectable within recipient bone marrow, lymph node, intestinal villi and liver sinusoids, but not in epithelial derived cells. These results indicate that recipients of young BMDSCs may survive longer than recipients of old bone marrow, but the difference is marginal at best.

  11. Detection of Inter-chromosomal Stable Aberrations by Multiple Fluorescence In Situ Hybridization (mFISH) and Spectral Karyotyping (SKY) in Irradiated Mice.

    Science.gov (United States)

    Pathak, Rupak; Koturbash, Igor; Hauer-Jensen, Martin

    2017-01-11

    Ionizing radiation (IR) induces numerous stable and unstable chromosomal aberrations. Unstable aberrations, where chromosome morphology is substantially compromised, can easily be identified by conventional chromosome staining techniques. However, detection of stable aberrations, which involve exchange or translocation of genetic materials without considerable modification in the chromosome morphology, requires sophisticated chromosome painting techniques that rely on in situ hybridization of fluorescently labeled DNA probes, a chromosome painting technique popularly known as fluorescence in situ hybridization (FISH). FISH probes can be specific for whole chromosome/s or precise sub-region on chromosome/s. The method not only allows visualization of stable aberrations, but it can also allow detection of the chromosome/s or specific DNA sequence/s involved in a particular aberration formation. A variety of chromosome painting techniques are available in cytogenetics; here two highly sensitive methods, multiple fluorescence in situ hybridization (mFISH) and spectral karyotyping (SKY), are discussed to identify inter-chromosomal stable aberrations that form in the bone marrow cells of mice after exposure to total body irradiation. Although both techniques rely on fluorescent labeled DNA probes, the method of detection and the process of image acquisition of the fluorescent signals are different. These two techniques have been used in various research areas, such as radiation biology, cancer cytogenetics, retrospective radiation biodosimetry, clinical cytogenetics, evolutionary cytogenetics, and comparative cytogenetics.

  12. Effects of 0.075 Gy x-ray irradiation on the expression of IL-10 and IL-12 in mice

    Science.gov (United States)

    Liu, Xiao-Dong; Ma, Shu-Mei; Liu, Shu-Zheng

    2003-07-01

    The objective was to observe the effects of 0.075 Gy low dose radiation (LDR) on the synthesis of IL-10 in splenocytes and the secretion of IL-12 by peritoneal macrophages. Kunming mice were selected and randomly grouped. Northern blot and flow cytometry were adopted to detect the changes of IL-10 at mRNA and protein levels, respectively. Northern blot and ELISA were used, respectively, to examine the changes of IL-12 p35/p40 mRNA and IL-12 p70 protein levels. IL-10 mRNA decreased significantly in splenocytes, while both IL-12 p35 and p40 subunit mRNA levels in macrophages increased after whole body irradiation (WBI) with 0.075 Gy x-rays. Meanwhile, IL-10 synthesis in splenocytes decreased beginning from 4 h after exposure and remaining at a lower level up to 48 h, and IL-12 secretion by macrophages was found to take the opposite direction, i.e. increase significantly. In conclusion, WBI with 0.075 Gy x-rays may suppress IL-10 both at the mRNA level and protein level and stimulate IL-12 expression simultaneously, which might contribute to a shift of the immune response in favour of Th1 differentiation.

  13. Effect of carnitine, acetyl-, and propionylcarnitine supplementation on the body carnitine pool, skeletal muscle composition, and physical performance in mice

    OpenAIRE

    Morand, Réjane; Bouitbir, Jamal; Felser, Andrea; Hench, Jürgen; Handschin, Christoph; Frank, Stephan; Krähenbühl, Stephan

    2014-01-01

    Pharmacokinetics and effects on skeletal muscle and physical performance of oral acetylcarnitine and propionylcarnitine are not well characterized. We therefore investigated the influence of oral acetylcarnitine, propionylcarnitine, and carnitine on body carnitine homeostasis, energy metabolism, and physical performance in mice and compared the findings to non-supplemented control animals.; Mice were supplemented orally with 2 mmol/kg/day carnitine, acetylcarnitine, or propionylcarnitine for ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-10-01

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

  15. Evaluation of sex specificity on oxidative stress induced in lungs of mice irradiated by 12C6+ions

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The aim of this work is to identify if there is sex specificity on 12C+ ion-induced oxidative damage in mouse lung at different time points.Kun-Ming mice were divided into two groups,each composed of six males and six females:control group and irradiation group with a single acute dose of 4 Gy.Animals were sacrificed at 2,4 and 12 h respectively,there lungs were removed immediately,and the oxidative stress-related biomarkers were measured by Diagnostic Reagent Kits.The results showed that the relative activities of superoxide dismutasc(4 h),catalase(2 h)and Se-dependent glutathione peroxidase(12 h)have significant changes(P<0.05)between male groups and female groups,suggesting that the lungs of male mice are more sensitive to counteracting the oxidative challenge.Moreover,higher levels of malondiadehyde and lower contents of glutathione were also found in males,indicating that oxidative stress induced by 12C6+ ion is pronounced in the lungs of males.We thought that these sex-responded differences may be attributed to the influence of sex hormones.

  16. Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice

    Science.gov (United States)

    Patwardhan, Sachin V.; Bloch, Sharon R.; Achilefu, Samuel; Culver, Joseph P.

    2005-04-01

    We present a fast scanning fluorescence optical tomography system for imaging the kinetics of probe distributions through out the whole body of small animals. Configured in a plane parallel geometry, the system scans a source laser using a galvanometer mirror pair (τswitch~1ms) over flexible source patterns, and detects excitation and emission light using a high frame rate low noise, 5 MHz electron multiplied charge-coupled device (EMCCD) camera. Phantom studies were used to evaluate resolution, linearity, and sensitivity. Time dependent (δt=2.2 min.) in vivo imaging of mice was performed following injections of a fluorescing probe (indocyanine green). The capability to detect differences in probe delivery route was demonstrated by comparing an intravenous injection, versus an injection into a fat pocket (retro orbital injection). Feasibility of imaging the distribution of tumor-targeted molecular probes was demonstrated by imaging a breast tumor-specific near infrared polypeptide in MDA MB 361 tumor bearing nude mice. A tomography scan, at 24 hour post injection, revealed preferential uptake in the tumor relative to surrounding tissue.

  17. Thrombospondin 2-null mice display an altered brain foreign body response to polyvinyl alcohol sponge implants

    Energy Technology Data Exchange (ETDEWEB)

    Tian Weiming; Kyriakides, Themis R, E-mail: themis.kyriakides@yale.ed [Vascular Biology and Therapeutics Program, Departments of Pathology and Biomedical Engineering, Yale University, New Haven, CT 06519 (United States)

    2009-02-15

    Thrombospondin (TSP)-2 is a matricellular protein that participates in the processes of tissue repair and the foreign body response. In addition, TSP2 has been shown to influence synaptogenesis and recovery of the brain following stroke. In the present study we investigated the response following the implantation of polyvinyl alcohol (PVA) sponges in the brain. PVA sponges were implanted into the brain cortex of wild type and TSP2-null mice for a period of 4 and 8 weeks and the response was analyzed by histochemistry and quantitative immunohistochemistry. TSP2 expression was detected in the interstices of the sponge and co-localized with the extracellular matrix and astrocytes. PVA sponge invasion in TSP2-null mice was characterized by dense deposition of extracellular matrix and increased invasion of reactive astrocytes and macrophages/microglia. Furthermore, the angiogenic response was elevated and the detection of mouse serum albumin (MSA) in the brain cortex indicated excessive vessel leakage, suggesting that TSP2 plays a role in the repair/maintenance of the blood brain barrier. Finally, immunostaining demonstrated an increase in the levels of matrix metalloproteinase (MMP)-2 and MMP-9. Taken together, our observations support a role for TSP2 as critical determinant of the brain response to biomaterials.

  18. Impact of Orexin-A Treatment on Food Intake, Energy Metabolism and Body Weight in Mice

    Science.gov (United States)

    Blais, Anne; Drouin, Gaëtan; Chaumontet, Catherine; Voisin, Thierry; Couvelard, Anne; Even, Patrick Christian; Couvineau, Alain

    2017-01-01

    Orexin-A and -B are hypothalamic neuropeptides of 33 and 28-amino acids, which regulate many homeostatic systems including sleep/wakefulness states, energy balance, energy homeostasis, reward seeking and drug addiction. Orexin-A treatment was also shown to reduce tumor development in xenografted nude mice and is thus a potential treatment for carcinogenesis. The aim of this work was to explore in healthy mice the consequences on energy expenditure components of an orexin-A treatment at a dose previously shown to be efficient to reduce tumor development. Physiological approaches were used to evaluate the effect of orexin-A on food intake pattern, energy metabolism body weight and body adiposity. Modulation of the expression of brain neuropeptides and receptors including NPY, POMC, AgRP, cocaine- and amphetamine related transcript (CART), corticotropin-releasing hormone (CRH) and prepro-orexin (HCRT), and Y2 and Y5 neuropeptide Y, MC4 (melanocortin), OX1 and OX2 orexin receptors (Y2R, Y5R, MC4R, OX1R and OX2R, respectively) was also explored. Our results show that orexin-A treatment does not significantly affect the components of energy expenditure, and glucose metabolism but reduces intraperitoneal fat deposit, adiposity and the expression of several brain neuropeptide receptors suggesting that peripheral orexin-A was able to reach the central nervous system. These findings establish that orexin-A treatment which is known for its activity as an inducer of tumor cell death, do have minor parallel consequence on energy homeostasis control. PMID:28085909

  19. Prenatal irradiation and spatial memory in mice: investigation of critical period

    Energy Technology Data Exchange (ETDEWEB)

    Sienkiewicz, Z.J.; Saunders, R.D.; Butland, B.K. (National Radiological Protection Board, Chilton (United Kingdom))

    1992-08-01

    Pregnant CD1 mice were exposed on various gestational or postnatal days to 1 Gy of 250 kV X-rays. Ten adult, male offspring from each exposure condition were tested in a radial arm maze. Compared to sham-exposed control mice, acquisition of spatial information was unimpaired in animals exposed on gestational days 13 or 15, or on postnatal day 10, but animals exposed on gestational day 18 or postnatal day 1 showed sustained deficits in acquisition. These results appear consistent with the known time-course for the proliferation and migration of the dentate granule cells of the hippocampus in the mouse, and are discussed in relation to the dependence on hippocampal integrity of the acquisition and use of spatial information. The results suggest that comparable deficits in mental function might be expected in humans similarly exposed to ionizing radiation during periods of proliferation and migration of the dentate granule cells. (author).

  20. Hepatic entrapment of esterified cholesterol drives continual expansion of whole body sterol pool in lysosomal acid lipase-deficient mice.

    Science.gov (United States)

    Aqul, Amal; Lopez, Adam M; Posey, Kenneth S; Taylor, Anna M; Repa, Joyce J; Burns, Dennis K; Turley, Stephen D

    2014-10-15

    Cholesteryl ester storage disease (CESD) results from loss-of-function mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL). Hepatomegaly and deposition of esterified cholesterol (EC) in multiple organs ensue. The present studies quantitated rates of synthesis, absorption, and disposition of cholesterol, and whole body cholesterol pool size in a mouse model of CESD. In 50-day-old lal(-/-) and matching lal(+/+) mice fed a low-cholesterol diet, whole animal cholesterol content equalled 210 and 50 mg, respectively, indicating that since birth the lal(-/-) mice sequestered cholesterol at an average rate of 3.2 mg·day(-1)·animal(-1). The proportion of the body sterol pool contained in the liver of the lal(-/-) mice was 64 vs. 6.3% in their lal(+/+) controls. EC concentrations in the liver, spleen, small intestine, and lungs of the lal(-/-) mice were elevated 100-, 35-, 15-, and 6-fold, respectively. In the lal(-/-) mice, whole liver cholesterol synthesis increased 10.2-fold, resulting in a 3.2-fold greater rate of whole animal sterol synthesis compared with their lal(+/+) controls. The rate of cholesterol synthesis in the lal(-/-) mice exceeded that in the lal(+/+) controls by 3.7 mg·day(-1)·animal(-1). Fractional cholesterol absorption and fecal bile acid excretion were unchanged in the lal(-/-) mice, but their rate of neutral sterol excretion was 59% higher than in their lal(+/+) controls. Thus, in this model, the continual expansion of the body sterol pool is driven by the synthesis of excess cholesterol, primarily in the liver. Despite the severity of their disease, the median life span of the lal(-/-) mice was 355 days.

  1. Coevolution of telomerase activity and body mass in mammals: from mice to beavers.

    Science.gov (United States)

    Gorbunova, Vera; Seluanov, Andrei

    2009-01-01

    Telomerase is repressed in the majority of human somatic tissues. As a result human somatic cells undergo replicative senescence, which plays an important role in suppressing tumorigenesis, and at the same time contributes to the process of aging. Repression of somatic telomerase activity is not a universal phenomenon among mammals. Mice, for example, express telomerase in somatic tissues, and mouse cells are immortal when cultured at physiological oxygen concentration. What is the status of telomerase in other animals, beyond human and laboratory mouse, and why do some species evolve repression of telomerase activity while others do not? Here we discuss the data on telomere biology in various mammalian species, and a recent study of telomerase activity in a large collection of wild rodent species, which showed that telomerase activity coevolves with body mass, but not lifespan. Large rodents repress telomerase activity, while small rodents maintain high levels of telomerase activity in somatic cells. We discuss a model that large body mass presents an increased cancer risk, which drives the evolution of telomerase suppression and replicative senescence.

  2. Total-body irradiation and host reconstitution with stored autologous marrow: an experimental model for the induction of allogeneic unresponsiveness in large mammals. [Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Rapaport, F.T.; Bachvaroff, R.J.; Dicke, K.; Santos, G.

    1979-03-01

    These results point to the capacity of suprelethal total-body irradiation and autologous bone marrow replacement to produce in the host a time-dependent privileged phase of immunologic reactivity during which exposure to alloantigens is more likely to produce unresponsiveness, rather than sensitization. The mechanisms implicated in the mediation of this phenomenon are not clear. Regardless of hypothetical interpretations, however, the current growing interest in total-body irradiation and autologous bone marrow replacement in clinical medicine, and the ease with which this approach appears to produce allogenic unresponsiveness in large mammals, raise the possibility that this method may constitute a highly promising approach to the facilitation of survival of vital transplanted organs in man. This possibility is further supported by the long-term record of the world's longest surviving renal allograft recipient, whose preoperative preparation consisted of total-body irradiation 24 hr before a kidney transplant.

  3. Acute effects of whole body gamma irradiation on exocrine pancreatic secretion in the pig; Effets aigus d'une irradiation corps entier sur la secretion pancreatique exocrine chez le porc

    Energy Technology Data Exchange (ETDEWEB)

    Monti, P.; Scanff, P.; Joubert, C.; Vergnet, M.; Grison, S.; Griffiths, N. [Institut de Radioprotection et de Surete Nucleaire (IRSN), DPRH/SRBE, 92 - Fontenay aux Roses (France)

    2004-06-01

    Reports on radiation damage to the pancreas deal essentially with long-term morphological changes with few data on pancreatic exocrine function. The aim of this work was to study the acute effects of whole body irradiation on volume and enzyme activities in the pancreatic juice. A whole body gamma irradiation (6 Gy) was investigated in pigs with continuous sampling of pancreatic juice before and after exposure via an indwelling catheter in the pancreatic duct. For each sample collected, total protein concentration and enzyme activities of trypsin, chymotrypsin, elastase, lipase and amylase were determined. Pancreatic juice volume was monitored during all periods of collection. The volume of pancreatic juice secreted daily decreased one day after irradiation and remained lower than the control values over the experimental period. Total proteins secreted in the pancreatic juice and total activities of pancreatic enzymes were reduced similarly. On the other hand, only specific activities of elastase and lipase were affected by irradiation. Whole body gamma irradiation resulted in a rapid and marked decrease of exocrine pancreatic secretion, in terms of volume as well as secreted enzymes. This may contribute in part to the intestinal manifestations of the acute and/or late radiation syndrome. (author)

  4. Persistent induction of somatic reversions of the pink-eyed unstable mutation in F1 mice born to fathers irradiated at the spermatozoa stage.

    Science.gov (United States)

    Shiraishi, Kazunori; Shimura, Tsutomu; Taga, Masataka; Uematsu, Norio; Gondo, Yoichi; Ohtaki, Megu; Kominami, Ryo; Niwa, Ohtsura

    2002-06-01

    Untargeted mutation and delayed mutation are features of radiation-induced genomic instability and have been studied extensively in tissue culture cells. The mouse pink-eyed unstable (p(un)) mutation is due to an intragenic duplication of the pink-eyed dilution locus and frequently reverts back to the wild type in germ cells as well as in somatic cells. The reversion event can be detected in the retinal pigment epithelium as a cluster of pigmented cells (eye spot). We have investigated the reversion p(um) in F1 mice born to irradiated males. Spermatogonia-stage irradiation did not affect the frequency of the reversion in F1 mice. However, 6 Gy irradiation at the spermatozoa stage resulted in an approximately twofold increase in the number of eye spots in the retinal pigment epithelium of F1 mice. Somatic reversion occurred for the paternally derived p(un) alleles. In addition, the reversion also occurred for the maternally derived, unirradiated p(un) alleles at a frequency equal to that for the paternally derived allele. Detailed analyses of the number of pigmented cells per eye spot indicated that the frequency of reversion was persistently elevated during the proliferation cycle of the cells in the retinal pigment epithelium when the male parents were irradiated at the spermatozoa stage. The present study demonstrates the presence of a long-lasting memory of DNA damage and the persistent up-regulation of recombinogenic activity in the retinal pigment epithelium of the developing fetus.

  5. TH-C-12A-04: Dosimetric Evaluation of a Modulated Arc Technique for Total Body Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tsiamas, P; Czerminska, M; Makrigiorgos, G; Karen, M; Zygmanski, P [Brigham and Women' s Hospital/ Dana-Farber Institute/ Harvard Medical School, Boston, MA (United States)

    2014-06-15

    Purpose: A simplified Total Body Irradiation (TBI) was developed to work with minimal requirements in a compact linac room without custom motorized TBI couch. Results were compared to our existing fixed-gantry double 4 MV linac TBI system with prone patient and simultaneous AP/PA irradiation. Methods: Modulated arc irradiates patient positioned in prone/supine positions along the craniocaudal axis. A simplified inverse planning method developed to optimize dose rate as a function of gantry angle for various patient sizes without the need of graphical 3D treatment planning system. This method can be easily adapted and used with minimal resources. Fixed maximum field size (40×40 cm2) is used to decrease radiation delivery time. Dose rate as a function of gantry angle is optimized to result in uniform dose inside rectangular phantoms of various sizes and a custom VMAT DICOM plans were generated using a DICOM editor tool. Monte Carlo simulations, film and ionization chamber dosimetry for various setups were used to derive and test an extended SSD beam model based on PDD/OAR profiles for Varian 6EX/ TX. Measurements were obtained using solid water phantoms. Dose rate modulation function was determined for various size patients (100cm − 200cm). Depending on the size of the patient arc range varied from 100° to 120°. Results: A PDD/OAR based beam model for modulated arc TBI therapy was developed. Lateral dose profiles produced were similar to profiles of our existing TBI facility. Calculated delivery time and full arc depended on the size of the patient (∼8min/ 100° − 10min/ 120°, 100 cGy). Dose heterogeneity varied by about ±5% − ±10% depending on the patient size and distance to the surface (buildup region). Conclusion: TBI using simplified modulated arc along craniocaudal axis of different size patients positioned on the floor can be achieved without graphical / inverse 3D planning.

  6. SU-E-T-600: In Vivo Dosimetry for Total Body and Total Marrow Irradiations with Optically Stimulated Luminescence Dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Niedbala, M; Save, C [The Ottawa Hospital Cancer Ctr., Ottawa, ON (Canada); Cygler, J [The Ottawa Hospital Cancer Ctr., Ottawa, ON (Canada); University of Ottawa (Canada); Carleton University (Canada)

    2014-06-01

    Purpose: To evaluate the feasibility of using optically stimulated luminescence dosimeters (OSLDs) for in-vivo dosimetry of patients undergoing Total Body and Total Marrow Irradiations (TBI and TMI). Methods: TBI treatments of 12 Gy were delivered in 6 BID fractions with the patient on a moving couch under a static 10 MV beam (Synergy, Elekta). TMI treatments of 18 Gy in 9 BID fractions were planned and delivered using a 6 MV TomoTherapy unit (Accuray). To provide a uniform dose to the entire patient length, the treatment was split into 2 adjacent fields junctioned in the thigh region. Our standard clinical practice involves in vivo dosimetry with MOSFETs for each TBI fraction and TLDs for at least one fraction of the TMI treatment for dose verification. In this study we also used OSLDs. Individual calibration coefficients were obtained for the OSLDs based on irradiations in a solid water phantom to the dose of 50 cGy from Elekta Synergy 10 MV (TBI) and 6 MV (TMI) beams. Calibration coefficients were calculated based on the OSLDs readings taken 2 hrs post-irradiation. For in vivo dosimetry OSLDs were placed alongside MOSFETs for TBI patients and in approximately the same locations as the TLDs for TMI patients. OSLDs were read 2 hours post treatment and compared to the MOSFET and TLD results. Results: OSLD measured doses agreed within 5% with MOSFET and TLD results, with the exception of the junction region in the TMI patient due to very high dose gradient and difficulty of precise and reproducible detector placement. Conclusion: OSLDs are useful for in vivo dosimetry of TBI and TMI patients. The quick post-treatment readout is an advantage over TLDs, allowing the results to be obtained between BID fractions, while wireless detectors are advantageous over MOSFETs for treatments involving a moving couch.

  7. Poster — Thur Eve — 38: Feasibility of a Table-Top Total Body Irradiation Technique using Robotic Couch Motion

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Erika; Otto, Karl; Hoppe, Richard; Hsu, Annie; Loo, Billy; Million, Lynn; Xing, Lei; Fahimian, Benjamin [Department of Radiation Oncology, Stanford University (United States)

    2014-08-15

    Purpose: To develop and test the feasibility of a table-top implementation for total body irradiation (TBI) via robotic couch motion and coordinated monitor unit modulation on a standard C-arm linac geometry. Methods: To allow for collision free delivery and to maximize the effective field size, the couch was rotated to 270° IEC and dropped to 150 cm from the vertical radiation source. The robotic delivery was programmed using the TrueBeam STx Developer Mode using custom XML scripting. To assess the dosimetry of a sliding 30×20 cm{sup 2} field, irradiation on a solid water phantom of varying thickness was analyzed using EDR2 radiographic film and OSLDs. Beam modulation was achieved by dividing the couch path into multiple segments of varying dose rates and couch speeds in order to deliver 120 cGy to the midline. Results: The programmed irradiation in conjunction with coordinated couch motion was successfully delivered on a TrueBeam linac. When no beam modulation was employed, the dose difference between two different phantom sections was 17.0%. With simple beam modulation via changing dose rates and couch speeds, the desired prescription dose can be achieved at the centre of each phantom section within 1.9%. However, dose deviation at the junction was 9.2% due to the nonphysical change in the phantom thickness. Conclusions: The feasibility of robotic table-top TBI on a C-arm linac geometry was experimentally demonstrated. To achieve a more uniform dose distribution, inverse-planning allowing for a combination of dose rate modulation, jaw tracking and MLC motion is under investigation.

  8. Effect of whole body proton or gamma irradiation on genetic damage and hematological variables

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Ji-Young; Ahn, Ji-Yeon; Yi, Jae Youn; Kang, Chang-Mo; Yun, Yeon-Sook; Song, Jie-Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-05-15

    For the purpose of cancer therapy or spaceflight with mission or simple trip, a considerable concern about the absorbed amount of radiation and its deleterious effect on physiological system, if any, has been increased. Many efforts have been dedicated to estimate the risk, however, there is very little known about the spectrum of radiations during the flight through arctic zone as well as the effects of low-dose radiation. Here, we aimed to evaluate the effect of proton or gamma-irradiation at a recommended dose limit of occupational (20mGy per year) and the standardized radio-therapeutic fraction dose (2Gy) on gastro-intestinal damages, peripheral hematology, and the frequency of micronuclei formation.

  9. Teratology, survival, and reversal learning after fetal irradiation of mice by 2450-MHz microwave energy

    Energy Technology Data Exchange (ETDEWEB)

    Chernovetz, M.E. (Univ. of Tulsa, OK); Justesen, D.R.; King, N.W.; Wagner, J.E.

    1975-12-01

    Eighty primigravid mice of the C3H-HeJ strain were subjected to 2450-MHz sinusoidally modulated microwave radiation or to sham radiation (with or without an accompanying injection of 5 mg of cortisone as a teratological marker) on the 11th, 12th, 13th or 14th day of gestation. The radiation treatment consisted of a single intense dosing of microwave energy (38 mW/g for 600 sec = 22.8 J/g) in a multi-mode cavity. On the 19th day of gestation fetuses were taken via Caesarean section and were observed for gross structural abnormalities. While radiation of dams failed reliably to increase the incidence of fetal mortality or morbidity above that of controls, the dams treated with cortisone gave birth to reliably greater numbers of stillborn and deformed fetuses. During their 14th day of gestation 60 primigravid mice received the radiation or sham-radiation treatment, half with and half without the accompanying injection of cortisone. A virtually complete failure to survive to weaning characterized the pups born of the sham-radiated cortisone-treated group of dams, but the incidence of cortisone-induced mortality was reliably reduced in pups whose dams were also radiated by microwave energy. No differences in maze performances were observed in the mice as a function of their placement in the control or the radiation condition, but offspring of cortisone-treated, radiated dams made reliably more errors. Careful measurement of elevations of colonic temperatures of radiated dams shortly after treatment with cortisone revealed an averaged ..delta..T that is close to that observed in a comparably radiated volume of water of equivalent mass. If the finding has generality beyond the gravid mouse--if, that is, cortisone effectively and reversibly renders the mammal ectothermic--an important advance in biological dosimetry of non-ionizing radiation may be at hand.

  10. Analysis of changes in intestinal microflora of irradiated mice. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mal' tsev, V.N.; Pinegin, B.V.; Korshunov, V.M.

    1977-01-01

    In experiments on 3 groups of CBA mice exposed to doses of 900, 600 and 300 R ..gamma..-rays, it was demonstrated that the integral severity of post-radiation microflora in the intestine can be determined by means of information index h, which takes into consideration all changes occurring in different representatives of the intestinal microflora. Differential analysis of the mechanisms of radioinduced changes in microflora indicates that it is based on a decrease in lactobacilli and increase in enterococcus, proteus, colibacillus and yeast in the small intestine, with increase in colibacillus, clostridia, proteus and enterococcus in the large intestine.

  11. Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

    Energy Technology Data Exchange (ETDEWEB)

    Sakaguchi, N.; Sakaguchi, S. (Stanford Univ. School of Medicine, CA (United States) Scripps Research Institute, La Jolla, CA (United States) PRESTO, JRDC, Institute of Phical and Chemical Research, Tsukuba, Ibaraki (Japan)); Miyai, K. (Univ. of California, San Diego, LA Jolla, CA (United States))

    1992-11-01

    Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.

  12. The Lack of Cytotoxic Effect and Radioadaptive Response in Splenocytes of Mice Exposed to Low Level Internal β-Particle Irradiation through Tritiated Drinking Water in Vivo

    Directory of Open Access Journals (Sweden)

    Matthew Flegal

    2013-12-01

    Full Text Available Health effects of tritium, a β-emitter and a by-product of the nuclear industry, is a subject of significant controversy. This mouse in vivo study was undertaken to monitor biological effects of low level tritium exposure. Mice were exposed to tritiated drinking water (HTO at 10 KBq/L, 1 MBq/L and 20 MBq/L concentrations for one month. The treatment did not result in a significant increase of apoptosis in splenocytes. To examine if this low level tritium exposure alters radiosensitivity, the extracted splenocytes were challenged in vitro with 2 Gy γ-radiation, and apoptotic responses at 1 and 24 h were measured. No alterations in the radiosensitivity were detected in cells from mice exposed to tritium compared to sham-treated mice. In contrast, low dose γ-irradiation at 20 or 100 mGy, resulted in a significant increase in resistance to apoptotic cell death after 2 Gy irradiation; an indication of the radioadaptive response. Overall, our data suggest that low concentrations of tritium given to mice as HTO in drinking water do not exert cytotoxic effect in splenocytes, nor do they change cellular sensitivity to additional high dose γ-radiation. The latter may be considered as the lack of a radioadaptive response, typically observed after low dose γ-irradiation.

  13. Regeneration of the epidermis and basement membrane of the planarian Dugesia japonica after total-body x irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hori, I.

    1979-03-01

    Fresh-water planarians were studied to examine effects of x rays on regeneration of the epidermis and basement membrane. During early stages of regeneration, free rhabdite-forming cells were associated with the wound epidermis and recruited it. In later stages, however, a gradual degeneration occurred in the epidermis and cells undergoing epithelization decreased in number. Eventually epidermal cells on the wound surface appeared necrotic as evidenced by pyknotic nuclei and vacuolized dense cytoplasm. The entire basement membrane could not be reconstituted in any stage after wounding though its precursor-like material was secreted in the interspace between epidermis and parenchyma. Morphological changes in extracellular products and in the cells surrounding the products suggest that epidermal cells which have covered the wound surface synthesize precursors of the basement membrane. Possible factors of a characteristic perturbation in epithelization and basement membrane formation after total-body irradiation are discussed.

  14. High-dose total body irradiation and myeloablative conditioning before allogeneic hematopoietic cell transplantation: time to rethink?

    Science.gov (United States)

    Mohty, Mohamad; Malard, Florent; Savani, Bipin N

    2015-04-01

    Over the last decade, the care of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has significantly improved, leading to a decrease in deaths related to allo-HCT as well as improved long-term survival. However, for many patients, long-term survivorship is associated with a substantial burden of chronic morbidities. Indeed, malignant and nonmalignant late complications after allo-HCT are numerous and usually multifactorial, with all organs and tissues a potential target. In many cases, these long-term side effects are associated with the use of high-dose total body irradiation, myeloablative conditioning regimens, and the onset of chronic graft-versus-host disease. It appears to be essential to change the natural history of these late effects. This requires the introduction of improved conditioning regimens and the development of lifelong monitoring controls, patient counseling, and preventative treatment measures. This approach will allow us to pursue our efforts to improve patient outcome.

  15. Effect of low-level laser therapy on irradiated parotid glands—study in mice

    Science.gov (United States)

    Acauan, Monique Dossena; Gomes, Ana Paula Neutziling; Braga-Filho, Aroldo; de Figueiredo, Maria Antonia Zancanaro; Cherubini, Karen; Salum, Fernanda Gonçalves

    2015-10-01

    The objective of this study was to evaluate the effect of low-level laser therapy (LLLT) on radiotherapy-induced morphological changes and caspase-3 immunodetection in parotids of mice. Forty-one Swiss mice were divided into control, radiotherapy, 2- and 4-J laser groups. The experimental groups were exposed to ionizing radiation in a single session of 10 Gy. In the laser groups, a GaAlAs laser (830 nm, 100 mW, 0.028 cm2, 3.57 W/cm2) was used on the region corresponding to the parotid glands, with 2-J energy (20 s, 71 J/cm2) or 4 J (40 s, 135 J/cm2) per point. LLLT was performed immediately before and 24 h after radiotherapy. One point was applied in each parotid gland. The animals were euthanized 48 h or 7 days after radiotherapy and parotid glands were dissected for morphological analysis and immunodetection of caspase-3. There was no significant difference between groups in the immunodetection of caspase-3, but the laser groups had a lower percentage compared to the radiotherapy group. LLLT promoted the preservation of acinar structure, reduced the occurrence of vacuolation, and stimulated parotid gland vascularization. Of the two LLLT protocols, the one using 4 J of energy showed better results.

  16. Effect of low-level laser therapy on irradiated parotid glands--study in mice.

    Science.gov (United States)

    Acauan, Monique Dossena; Gomes, Ana Paula Neutziling; Braga-Filho, Aroldo; de Figueiredo, Maria Antonia Zancanaro; Cherubini, Karen; Salum, Fernanda Gonçalves

    2015-10-01

    The objective of this study was to evaluate the effect of low-level laser therapy (LLLT) on radiotherapy-induced morphological changes and caspase-3 immunodetection in parotids of mice. Forty-one Swiss mice were divided into control, radiotherapy, 2- and 4-J laser groups. The experimental groups were exposed to ionizing radiation in a single session of 10 Gy. In the laser groups, a GaAlAs laser (830 nm, 100 mW, 0.028  cm2, 3.57  W/cm2) was used on the region corresponding to the parotid glands, with 2-J energy (20 s, 71  J/cm2) or 4 J (40 s, 135  J/cm2) per point. LLLT was performed immediately before and 24 h after radiotherapy. One point was applied in each parotid gland. The animals were euthanized 48 h or 7 days after radiotherapy and parotid glands were dissected for morphological analysis and immunodetection of caspase-3. There was no significant difference between groups in the immunodetection of caspase-3, but the laser groups had a lower percentage compared to the radiotherapy group. LLLT promoted the preservation of acinar structure, reduced the occurrence of vacuolation, and stimulated parotid gland vascularization. Of the two LLLT protocols, the one using 4 J of energy showed better results.

  17. Comparative seric TGF({beta}1, {beta}2) levels and platelets count response in total body irradiated baboons; Evolution comparee des taux seriques des TGF ({beta}1, {beta}2) et de la numeration plaquettaire chez le babouin irradie globalement

    Energy Technology Data Exchange (ETDEWEB)

    Mestries, J.C.; Veyret, J.; Agay, D.; Van Uye, A.; Caterini, R.; Herodin, F.; Mathieu, J.; Chancerelle, Y.

    1994-12-31

    Total body irradiation associated or not with r-hIL-6 treatment a relation between TGF-{beta}1 and TGF-{beta}2 blood levels and platelets count. During radio-induced thrombocytopenia, by decreasing its ability to inhibit proliferation of stem cells and megakaryocytopoiesis, the TGF-{beta} falling induced a favorable condition for hematopoietic recovery. (author). 5 refs.

  18. DNA repair and damage pathway related cancer suppressor genes in low-dose-rate irradiated AKR/J an IR mice

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Hyun Soon; Bong, Jin Jong; Kang, Yumi; Choi, Moo Hyun; Lee, Hae Un; Yoo, Jae Young; Choi, Seung Jin; Kim, Hee Sun [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd, Gyeongju (Korea, Republic of); Lee, Kyung Mi [Global Research Lab, BAERI Institute, Dept. of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

    2012-11-15

    It has been reported that low-dose-rate radiation stimulates the immune response, prolongs life span and inhibits carcinogenesis. The high dose-rate radiation influences the expression of DNA repair and damage-related genes. In contrast, DNA repair and damage signaling triggered by low-dose-rate irradiation remain unclear. In the present study, we investigated the differential expression of DNA repair and damage pathway related genes in the thymus of AKR/J and ICR mice after 100th day low-dose-rate irradiation. Our findings demonstrated that low-dose-rate γ -radiation suppressed tumorigenesis.

  19. Quantitative lipidomics reveals age-dependent perturbations of whole-body lipid metabolism in ACBP deficient mice.

    Science.gov (United States)

    Gallego, Sandra F; Sprenger, Richard R; Neess, Ditte; Pauling, Josch K; Færgeman, Nils J; Ejsing, Christer S

    2017-02-01

    The acyl-CoA binding protein (ACBP) plays a key role in chaperoning long-chain acyl-CoAs into lipid metabolic processes and acts as an important regulatory hub in mammalian physiology. This is highlighted by the recent finding that mice devoid of ACBP suffer from a compromised epidermal barrier and delayed weaning, the physiological process where newborns transit from a fat-based milk diet to a carbohydrate-rich diet. To gain insights into how ACBP impinges on weaning and the concomitant remodeling of whole-body lipid metabolism we performed a comparative lipidomics analysis charting the absolute abundance of 613 lipid molecules in liver, muscle and plasma from weaning and adult Acbp knockout and wild type mice. Our results reveal that ACBP deficiency affects primarily lipid metabolism of liver and plasma during weaning. Specifically, we show that ACBP deficient mice have elevated levels of hepatic cholesteryl esters, and that lipids featuring an 18:1 fatty acid moiety are increased in Acbp depleted mice across all tissues investigated. Our results also show that the perturbation of systemic lipid metabolism in Acbp knockout mice is transient and becomes normalized and similar to that of wild type as mice grow older. These findings demonstrate that ACBP serves crucial functions in maintaining lipid metabolic homeostasis in mice during weaning.

  20. Protective effects of polysaccharides of tricholoma matsutake on the anti-oxide system of irradiated mice%松茸多糖对受照小鼠抗氧化系统的保护作用

    Institute of Scientific and Technical Information of China (English)

    王宏芳; 李雪静; 徐坤; 浦昀; 李娟

    2011-01-01

    目的 探讨松茸多糖(PTM)对辐射损伤小鼠血清抗氧化系统的保护作用.方法 150只健康雄性ICR小鼠随机分为5组,正常对照组、辐射对照组和高、中、低3个剂量PTM组,每组30只.正常对照组和辐射对照组给予生理盐水灌胃,3个剂量PTM组给予不同剂量PTM灌胃,每天1次,连续7d;第8天给予辐射对照组和PTM组动物全身一次性照射,总剂量2.0Gy,检测小鼠照射后第1、5、14天的血清中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷光肝肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量的变化.结果 与辐射对照组比较,PTM组小鼠血清中SOD、CAT、GSH-Px活性明显升高,MDA含量明显降低(P<0.05或P<0.01).结论 松茸多糖对辐射损伤小鼠的血清抗氧化系统有显著保护作用.%Objective To observe the protective effects of polysaccharides of tricholoma matsutake (PTM) on the anti-oxide system in the serum of X-ray irradiated mice. Methods A total of 150 healthy male ICR mice were divided equally into five groups by random. In the first seven days, the mice in normal control group (NC) and irradiation control group (IC) were treated with 0.9% sodium chloride solution by gastric lavage while the mice in PTM groups were treated with three different doses of PTM (1 200 mg/kg, 800 mg/kg and 400 mg/kg) by gastric lavage. On the 8th day, mice in all groups except NC group were irradiated once all over the body with 2.0 Gy X-rays. The activities of superoxide dismuease (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in the serum of mice were measured on the 1st, 5th, and 14th day after irradiation. Results The activities of SOD, CAT and GSH-Px in PTM groups were much higher than those in IC group. The content of MDA was much lower in PTM groups than in IC group during the experiment days (P<0.05 or P<0.01). Conclusion Polysaccharides of tricholoma matsutake exhibit significant protective

  1. Dose-dependence of the time of appearance of lung damage in mice given thoracic irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Collis, C.H.; Steel, G.G. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

    1982-09-01

    Male CBA mice were given X-radiation to the thorax in the range 7 to 23 Gy and their response was quantified by measuring ventilation rate and carbon monoxide uptake at intervals up to 2 years thereafter; their survival was also documented. The two functional end-points were similarly sensitive indicators of lung damage. Radiation damage was not observed below 10 Gy. As radiation dose was raised above this level there was a rapid shortening of the time to the appearance of damage and subsequent death. At a dose of 15 Gy the median survival time was 14 weeks but raising the dose above this level only slightly reduced the survival time. The way in which the time of survival after lung damage depends on dose is an important characteristic of the development of radiation-induced lung damage which should be considered when examining factors that may influence the development of radiation-induced lung damage.

  2. Capric Acid Reduces Body Weight in C57BL/6J Mice Fed a High Fat Diet

    Institute of Scientific and Technical Information of China (English)

    Ying-hua LIU; Yong ZHANG; Qing XU; Xin-sheng ZHANG; Jin WANG; Xiao-ming YU; Xue-yan YANG; Chang-yong XUE

    2014-01-01

    Objective To compare the body weight reducing effect of two medium-chain fatty acids (MCFA), capric acid and caprylic acid, and the potential underlying mechanisms in C57BL/6J mice fed a high fat diet.Methods Obese C57BL/6J mice were developed on a high-fat diet containing 2% caprylic acid (C8:0), 2% capric acid (C10:0), or 2% oleic acid (C18:1). Body weight and diet intake were monitored twice a week. After 8 weeks of feeding, body fat composition and the protein or mRNA expression of lipolysis-related genes in the white adipose tissue (WAT) were analyzed.Results In the capric acid group, significant reductions were observed in body weight gain, Lee's index, BMI, and epididymal adipose tissue weight, while increased levels of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), cyclic adenosine monophosphate (cAMP) and beta 3 adrenergic receptor (β3-AR) were found in the adipose tissue, compared to the oleic acid group. No significant differences in these parameters were found between caprylic acid and oleic acid groups.Conclusion Capric acid, but not caprylic acid, is effective in reducing body weight in obese C57BL/6J mice,possibly due to up-regulation of β3-AR, ATGL, and HSL in WAT.

  3. Effects of combination of antibiotic-resistant bifidobacteria and corresponding antibiotics on survival of irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Korshunov, V.M.; Pinegin, B.V.; Ivanova, N.P.; Mal' tsev, V.N.

    1982-05-01

    Broad-spectrum antibiotics are used to treat intestinal dysbacteriosis of diverse etiology, including postradiation dysbacteriosis. Antibiotic therapy is instrumental in decontaminating the intestine. In addition to pathogenic microorganisms, there is disappearance of lactobacilli and bifidobacteria which perform several important and useful functions. For this reason, in addition to antibiotics, bifidobacterial preparations are used to restore the microbial cenosis and administration thereof is started after antibiotics are discontinued. There are some flaws to deferred administration of bifidobacteria, since the process of colonization of the intestine with commercial bifidobacterial preparations is rather lengthy, and there is slow elevation of bididobacterium level in the intestinal tract, whereas exogenous recontamination of the intestine by conditionally pathogenic bacteria is possible after antibiotic therapy is discontinued. On the other hand, use of antibiotics alone could, in turn, be the cause of intestinal dysbacteriosis. Our objective was to eliminate intestinal dysbacteriosis in irradiated animals by means of combining antibiotics and preparations of bifidobacteria resistant to these antibiotics, and thus prolong the life of these animals.

  4. [Features of behavioral reactions of chronically irradiated mice in the raised crosswise labyrinth with various genetically determined radiosensitivity and possibilities of their modification by the fungal biopolymer complex].

    Science.gov (United States)

    Seniuk, O F; Gorovoĭ, L F; Kovalev, V A; Palamar, L A; Krul', N I; Zhidkov, A V; Chemerskiĭ, G F; Kireev, S I; Khatuntseva, I V

    2013-01-01

    Structural elements of the central nervous system--neurons, along with the higher neuroendocrine structures and the hypothalamus centres, show high sensitivity to a chronic action of low doses of ionizing radiation (IR) in view of their extreme enrichment by phospholipids and intensive supply by oxygen, creating favorable conditions for the development of oxidizing stress. Stressful influences cause negative emotions in the behaviour of animals manifested as fear or uneasiness. The study represents the results of comparative research into the behavioral reactions characterized by uneasiness in the Balb/c and C57bl/6 mice exposed to a chronic irradiation at low doses. The chitin-melanin-glucan complex from fungi Fomes fomentarius (ChMG) was approved as an adaptive agent. It has been shown that under identical conditions, deposition levels of radionuclides 137Cs and 90Sr are raised in mice with IR hypersensitivity--line Balb/c, in comparison with less radio sensitive mice--line C57bl/6. Simultaneously, Balb/c mice were observed to exhibit the signs of a more anxious behaviour in the new environment. Chronic external and internal radiation exposure to rare ionizing radiation at low doses promotes strengthening of anxiety and phobic reactions in mice with IR hypersensitivity. The use of ChMG in animals neutralized the increase in anxiety and phobic reactions after a prolonged irradiation, thus indicating the presence in ChMG of the anxiolitic activity along with the above mentioned powerful radiosorbent, antioxidant, gene protective and immunomodulatory properties.

  5. SEM analysis of body hairs and whiskers of heterozygous tortoiseshell (Moto/+) female mice (Mus musculus).

    OpenAIRE

    Sheedlo, H J; Beck, M L

    1982-01-01

    Back hairs of +/+ and Moto/+ female Mus musculus generally exhibited identical form when examined by SEM. However, the hair shafts of Moto/+ female mice were beaded in appearance (monilethrix), twisted (pili torti) or exhibited a rough nodular appearance. Also, some hairs of Moto/+ female mice which were devoid of pigment appeared enlarged and bitubular. The whiskers of +/+ and Moto/+ female mice were identical in form. The hair abnormalities of Moto/+ female mice resulted from a copper defic...

  6. Belgian class II nuclear facilities such as irradiators and accelerators. Regulatory Body attention points and operating experience feedback

    Energy Technology Data Exchange (ETDEWEB)

    Minne, Etienne; Peters, Christelle; Mommaert, Chantal; Kennes, Christian; Cortenbosch, Geert; Schmitz, Frederic; Haesendonck, Michel van [Bel V, Brussels (Belgium); Carlier, Pascal; Schrayen, Virginie; Wertelaers, An [Federal Agency for Nuclear Control, Brussels (Belgium)

    2016-11-15

    The aim of this paper is to present the Regulatory Body attention points and the operating experience feedback from Belgian ''class IIA'' facilities such as industrial and research irradiators, bulk radionuclides producers and conditioners. Reinforcement of the nuclear safety and radiation protection has been promoted by the Federal Agency for Nuclear Control (FANC) since 2009. This paper is clearly a continuation of the former paper [1] presenting the evolution in the regulatory framework relative to the creation of Bel V, the subsidiary of the FANC, and to the new ''class IIA'' covering heavy installations such as those mentioned above. Some lessons learnt are extracted from the operating experience feedback based on the events declared to the authorities. Even though a real willingness to meet the new safety requirements is observed among the ''class IIA'' licensees, promoting the safety culture, the nuclear safety and radiation protection remains an endless challenge for the Regulatory Body.

  7. Radioprotective Effect of rmIL-12 on Mice Irradiated by γ-Ray%白介素12对辐射损伤小鼠的防护作用

    Institute of Scientific and Technical Information of China (English)

    王利; 翟瑞仁; 逄朝霞; 张超; 余长林

    2013-01-01

    The aim of this study was to investigate the radioprotecfive effect of recombinant murine intefleukin 12 (rmIL-12) on mice irradiated by γ-ray.Fifty-six BALB/c mice were totally irradiated by 6.0 Gy of 60Co γ-ray and randomly divided into irradiation control group,rmIL-12 treated group and recombinant murine thrombopoietin (rmTPO) treated group.The 5 and 20 μg/kg of rmIL-12 were administrated intraperitoneally at 24 h before irradiation respectively (low and high dose rmIL-12 treated group),15 μg/kg of rmTPO was administrated subcutaneously at 30 min and 24 h following irradiation in rmTPO treated group.The general conditions of mice were observed twice a day,the changes in body weight and peripheral blood cell counts were examined once every three days,bone marrow cells were collected to perform colony cultivation at day 14 and 28 after irradiation.The results showed that the general conditions of mice in rmIL-12 treated group were better than those in irradiation control group.Compared with the irradiation control group,5 and 20 μg/kg rmIL-12 treatment significantly promoted platelet recovery,resulting in less profound nadirs (15.9% vs 8.1%,18.2% vs 8.1%,P<0.01) and rapid recovery to normal levels ((*)11 days vs 14 days).WBC count recovery rate in rmIL-12 treated group was faster than that in the irradiation control group.The WBC and platelet count recovery rate in 5 μg/kg rmIL-12 treated group were as fast as that in the rmTPO treated group,both of which were slower than that in 20 μg/kg rmIL-12 treated group (P > 0.05).Semi-solid bone marrow cell culture also demonstrated that rmIL-12 could stimulate bone marrow cells to form more CFU-Mix than those in the irradiation control group in vitro at day 14 and 28 after irradiation(P <0.01).There was no significant difference between rmIL-12 and rmTPO treated groups (P >0.05),CFU-GM counts in 5 μg/kg rmIL-12 treated group and rmTPO treated group at day 28 after irradiation were higher than

  8. Suppression of unprimed T and B cells in antibody responses by irradiation-resistant and plastic-adherent suppressor cells in Toxoplasma gondii-infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Y.; Kobayashi, A.

    1983-04-01

    In the acute phase of Toxoplasma infection, the function of both helper T and B cells was suppressed in primary antibody responses to dinitrophenol (DNP)-conjugated protein antigens. During the course of infection, the suppressive effect on T cells seems to continue longer than that on B cells, since suppression in responses to sheep erythrocytes, a T-dependent antigen, persisted longer than those to DNP-Ficoll, a T-independent antigen. Plastic-adherent cells from the spleens of Toxoplasma-infected and X-irradiated (400 rads) mice had strong suppressor activity in primary anti-sheep erythrocyte antibody responses of normal mouse spleen cells in vitro. These data suggest that the activation of irradiation-resistant and plastic-adherent suppressor cells causes the suppression of both T and B cells in Toxoplasma-infected mice.

  9. Ly-1 B cells and disease activity in (New Zealand black x New Zealand white)F1 mice. Effect of total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Farinas, M.C.; Stall, A.M.; Solovera, J.J.; Tarlinton, D.M.; Herzenberg, L.A.; Strober, S. (Stanford Univ. School of Medicine, CA (USA))

    1990-04-01

    The treatment of female (New Zealand black x New Zealand white)F1 mice with total lymphoid irradiation resulted in a prolonged remission of autoimmune disease activity. Total lymphoid irradiation-treated mice also showed a marked reduction of Ly-1 B cells, which lasted up to 3 months. The subsequent return of Ly-1 B cells to preirradiation levels was not associated with a simultaneous return of disease when measured by parameters such as IgG anti-DNA antibodies and spontaneous secretion of IgG by splenic cells. In cell sorting experiments, most of the cells spontaneously secreting IgG were found within the Ly-1- (CD5-) splenic B cell population.

  10. Ultrastructure and Light Microscope Analysis of Intact Skin after a Varying Number of Low Level Laser Irradiations in Mice

    Directory of Open Access Journals (Sweden)

    Mamie Mizusaki Iyomasa

    2014-01-01

    Full Text Available Low level laser therapy (LLLT has been used to relieve pain, inflammation, and wound healing processes. Thus, the skin is overexposed to laser and this effect is not completely understood. This study analyzed the effects of the number of laser applications (three, six, and 10 on the intact skin of the masseteric region in mice of strain HRS/J. The animals (n=30 were equally divided into control (0 J/cm2 and irradiated (20 J/cm2, and each of these groups was further equally divided according to the number of laser applications (three, six, and 10 and underwent LLLT on alternate days. Samples were analyzed by light microscopy and transmission electron microscope (TEM. The animals receiving applications exhibited open channels more dilated between the keratinocytes and photobiomodulation effect on endothelial cells and fibroblasts by TEM. Under the light microscope after 10 laser applications, the type I collagen decreased (P<0.05 compared to the three and six applications. Under these experimental conditions, all numbers of applications provided photobiomodulatory effect on the epidermis and dermis, without damage. More studies are needed to standardize the energy density and number of applications recommended for laser therapy to have a better cost-benefit ratio associated with treatment.

  11. Quercetin decreases high-fat diet induced body weight gain and accumulation of hepatic and circulating lipids in mice.

    Science.gov (United States)

    Hoek-van den Hil, E F; van Schothorst, E M; van der Stelt, I; Swarts, H J M; Venema, D; Sailer, M; Vervoort, J J M; Hollman, P C H; Rietjens, I M C M; Keijer, J

    2014-09-01

    Dietary flavonoids may protect against cardiovascular diseases (CVD). Increased circulating lipid levels and hepatic lipid accumulation are known risk factors for CVD. The aim of this study was to investigate the effects and underlying molecular mechanisms of the flavonoid quercetin on hepatic lipid metabolism in mice with high-fat diet induced body weight gain and hepatic lipid accumulation. Adult male mice received a 40 energy% high-fat diet without or with supplementation of 0.33 % (w/w) quercetin for 12 weeks. Body weight gain was 29 % lower in quercetin fed mice (p lipid accumulation to 29 % of the amount present in the control mice (p lipid profiling revealed that the supplementation significantly lowered serum lipid levels. Global gene expression profiling of liver showed that cytochrome P450 2b (Cyp2b) genes, key target genes of the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3), were downregulated. Quercetin decreased high-fat diet induced body weight gain, hepatic lipid accumulation and serum lipid levels. This was accompanied by regulation of cytochrome P450 2b genes in liver, which are possibly under transcriptional control of CAR. The quercetin effects are likely dependent on the fat content of the diet.

  12. Differential body weight and feeding responses to high-fat diets in rats and mice lacking cholecystokinin 1 receptors.

    Science.gov (United States)

    Bi, Sheng; Chen, Jie; Behles, R Ryan; Hyun, Jayson; Kopin, Alan S; Moran, Timothy H

    2007-07-01

    Prior data demonstrated differential roles for cholecystokinin (CCK)1 receptors in maintaining energy balance in rats and mice. CCK1 receptor deficiency results in hyperphagia and obesity of Otsuka Long-Evans Tokushima Fatty (OLETF) rats but not in mice. To ascertain the role of CCK1 receptors in high-fat-diet (HFD)-induced obesity, we compared alterations in food intake, body weight, fat mass, plasma glucose, and leptin levels, and patterns of hypothalamic gene expression in OLETF rats and mice lacking CCK1 receptors in response to a 10-wk exposure to HFD. Compared with Long-Evans Tokushima Otsuka (LETO) control rats, OLETF rats on HFD had sustained overconsumption over the 10-wk period. High fat feeding resulted in greater increases in body weight and plasma leptin levels in OLETF than in LETO rats. In situ hybridization determinations revealed that, while HFD reduced neuropeptide Y (NPY) mRNA expression in both the arcuate nucleus (Arc) and the dorsomedial hypothalamus (DMH) of LETO rats, HFD resulted in decreased NPY expression in the Arc but not in the DMH of OLETF rats. In contrast to these results in OLETF rats, HFD increased food intake and induced obesity to an equal degree in both wild-type and CCK1 receptor(-/-) mice. NPY gene expression was decreased in the Arc in response to HFD, but was not detectable in the DMH in both wild-type and CCK1 receptor(-/-) mice. Together, these data provide further evidence for differential roles of CCK1 receptors in the controls of food intake and body weight in rats and mice.

  13. TDRD5 is required for retrotransposon silencing, chromatoid body assembly, and spermiogenesis in mice.

    Science.gov (United States)

    Yabuta, Yukihiro; Ohta, Hiroshi; Abe, Takaya; Kurimoto, Kazuki; Chuma, Shinichiro; Saitou, Mitinori

    2011-03-01

    The Tudor domain-containing proteins (TDRDs) are an evolutionarily conserved family of proteins involved in germ cell development. We show here that in mice, TDRD5 is a novel component of the intermitochondrial cements (IMCs) and the chromatoid bodies (CBs), which are cytoplasmic ribonucleoprotein granules involved in RNA processing for spermatogenesis. Tdrd5-deficient males are sterile because of spermiogenic arrest at the round spermatid stage, with occasional failure in meiotic prophase. Without TDRD5, IMCs and CBs are disorganized, with mislocalization of their key components, including TDRD1/6/7/9 and MIWI/MILI/MIWI2. In addition, Tdrd5-deficient germ cells fail to repress LINE-1 retrotransposons with DNA-demethylated promoters. Cyclic adenosine monophosphate response element modulator (CREM) and TRF2, key transcription factors for spermiogenesis, are expressed in Tdrd5-deficient round spermatids, but their targets, including Prm1/Prm2/Tnp1, are severely down-regulated, which indicates the importance of IMC/CB-mediated regulation for postmeiotic gene expression. Strikingly, Tdrd5-deficient round spermatids injected into oocytes contribute to fertile offspring, demonstrating that acquisition of a functional haploid genome may be uncoupled from TDRD5 function.

  14. Thermal conditions influence changes in body temperature induced by intragastric administration of capsaicin in mice.

    Science.gov (United States)

    Mori, Noriyuki; Urata, Tomomi; Fukuwatari, Tsutomu

    2016-08-01

    Capsaicin has been reported to have unique thermoregulatory actions. However, changes in core temperature after the administration of capsaicin are a controversial point. Therefore, we investigated the effects of environmental thermal conditions on changes in body temperature caused by capsaicin in mice. We showed that intragastric administration of 10 and 15 mg/kg capsaicin increased tail temperature and decreased colonic temperatures in the core temperature (CT)-constant and CT-decreasing conditions. In the CT-increasing condition, 15 mg/kg capsaicin increased tail temperature and decreased colonic temperature. However, 10 mg/kg capsaicin increased colonic temperature. Furthermore, the amount of increase in tail temperature was greater in the CT-decreasing condition and lower in the CT-increasing condition, compared with that of the CT-constant condition. These findings suggest that the changes in core temperature were affected by the environmental thermal conditions and that preliminary thermoregulation state might be more important than the constancy of temperature to evaluate the effects of heat diffusion and thermogensis.

  15. Antigen localization and the induction of resistance in mice vaccinated with irradiated cercariae of Schistosoma mansoni

    Energy Technology Data Exchange (ETDEWEB)

    Mountford, A.P.; Coulson, P.S.; Wilson, R.A.

    1988-08-01

    The fate of /sup 75/Se-labelled parasites and their released pre-synthesized macromolecules has been followed in three murine infection models. Marked differences were found between the three models. The pattern of migration of normal schistosomula was similar to that previously reported. In addition we have described the transit of parasites through the lymph nodes draining the infection site. Significant quantities of released material were detected in the skin, draining lymph nodes, bloodstream and liver. The circulating material was of parasite origin, macromolecular, and hence potentially antigenic. In comparison to the normal infection, radiation-attenuated parasites (inducing a high level of resistance to challenge) persisted in the skin, draining lymph nodes and lungs, releasing a proportionally greater amount of material in the nodes. In mice exposed to attenuated parasites and treated with the compound RO11-3128 at 24 h (inducing a low level of resistance) there was an early death and rapid clearance of the parasites whilst still in the skin. This situation resulted in the highest levels of released material in the skin, bloodstream and liver, but negligible levels in the draining lymph nodes. We suggest that the persistence of radiation-attenuated parasites in the skin and draining lymph nodes, together with the prolonged release of antigen in the latter site, compared to the normal situation, are major factors in the induction of resistance.

  16. Identification of schistosoma mansoni antigens recognised by spleen cells of C57B1/6 mice immunized with ultraviolet-irradiated cercariae

    Energy Technology Data Exchange (ETDEWEB)

    Osman, A.; El Ridi, R. (Cairo Univ. (Egypt)); Guirguis, N. (VACSERA, El Agouza Cairo (Egypt). Biomedical Research Dept.); Dean, D.A. (U.S. Naval Medical Research Unit No. 3, Cairo (Egypt))

    1994-11-01

    Spleen cells of C57B1/6 mice immunized twice with Schistosoma mansoni cercariae attenuated by ultraviolet irradiation proliferated and produced interleukin-(I1)-2 and/or I1-4 in response to both soluble schistosomular and adult worm antigens of 72-68, 60-62, 50, 45, 29.5 and 28 kDa. All of these bands, except the 45 kDa, were also recognized by serum antibodies in Western blotting. (author).

  17. Effect of sesamol on the hematopoietic system damage in 4 Gy 137 Csγ-Ray irradiated mice%芝麻酚对4Gy137Csγ射线照射小鼠造血功能的影响

    Institute of Scientific and Technical Information of China (English)

    路璐; 李德冠; 张俊伶; 樊赛军; 孟爱民

    2014-01-01

    Objective To observe the effect of sesamol on the hematopoietic system in mice exposed to 4 Gy irradiation. Method Twenty C 57 BL/6 mice were randomly divided into control group, sesamol group, irradiated group and irradiated+sesamol group (n=5). Mice of control and sesamol group received sham irradiation, and the rest exposed to 4 Gy total body irradiation, dose rate 1.01 Gy/min. Mice in sesamol group and irradiated+sesamol group received a dose of 10 mg/kg sesamol administered by gavage every day for 7 days after irradiation exposure. Mice of other two groups were treated with vehicle solution. After 4 Gy irradiation 7 day, the peripheral bloods were collected. The levels of colony forming units-granulocyte-macrophage (CFU-GM) were detected. Results Compared to irradiation group, the level of WBC、cell count of BMNCs and CFU-GM significantly decreased in the irradiated mice, decreased in the irradiated mice (P<0.05). Compared to irradiation group, cell count of BMNCs and CFU-GM in the irradiated+sesamol group increased significantly (P<0.05). Conclusion Sesamol has a certain impact on the radiation-induced changes in hematopoietic system. The mechanism need to be further explored.%目的:探讨芝麻酚对小鼠造血功能辐射损伤的影响。方法取雌性C 57 BL/6小鼠20只,随机分为对照组、芝麻酚组、照射组和照射+芝麻酚组,每组5只。照射组和照射+芝麻酚组小鼠接受4 Gy 137 Csγ射线一次性全身照射。芝麻酚组和照射+芝麻酚组小鼠照射后2 h灌胃芝麻酚(10 mg/kg),连续给药7天,其余2组小鼠灌胃生理盐水。小鼠受照后7 d处死,取外周血进行血象测定,取骨髓细胞测定有核细胞数和集落形成能力。结果照射组与对照组比较,外周血白细胞、骨髓有核细胞数明显下降,粒单系集落形成单位(colony-forming unit-granulocyte/macrophage,CFU-GM)显著下降(P<0.05)。照射+芝麻酚组与照射组相比,骨髓有核细胞数

  18. The effect of local UVB skin irradiation on the rate of formazan deposition in the epidermis of hairless mice studied by means of a tetrazolium-reduction method.

    Science.gov (United States)

    Fosså, J; Iversen, O H; Thune, P O

    1980-01-01

    One-hundred-and-twenty hairless mice were irradiated with UVB (310 nm, exposure 60 mJ/cm2) on a limited area of the dorsal skin. At different time intervals after irradiation, the rate of endogenous dehydrogenase activity per mg dry epidermis was measured by the tetrazolium reduction method. The amount of formazan deposited remained normal for 18 h, and then increased, reaching a peak significantly higher than normal at 24 h, and thereafter returned to normal. At day 8 there was a new, probably significant peak. The reaction was followed for 14 days. It was concluded that UVB irradiation provokes a period of increased formazan deposition in the epidermis, similar to what has been observed after ionizing radiation and chemical carcinogens. The validity of the tetrazolium test for skin carcinogenic irritaments was thus also confirmed.

  19. Effect of Whole-Body X-Irradiation of the Synthesis of Individual Fatty Acids in Liver Slices from Normal and Fasted Rats

    DEFF Research Database (Denmark)

    Hansen, Heinz Johs. Max; Hansen, Lisbeth Grænge; Faber, M.

    1965-01-01

    (1) Using (2-14C) acetate and (1-14C) butyrate as precursors, rat-liver fatty acids were synthesized in vitro and assayed by paper chromatography. (2) Whole-body x-irradiation induced a change in the synthetic pattern of hepatic fatty acids towards a relatively enhanced synthesis of palmitic acid...

  20. Results of hematopoietic stem cell transplantation after treatment with different high-dose total-body irradiation regimens in five Dutch centers

    NARCIS (Netherlands)

    van Kempen-Harteveld, M. Loes; Brand, Ronald; Kal, Henk B.; Verdonck, Leo F.; Hofman, Pieter; Schattenberg, Anton V.; van der Maazen, Richard W.; Cornelissen, Jan J.; Eijkenboom, Wil M. H.; van der Lelie, Johannes P.; Oldenburger, Foppe; Barge, Renee M.; van Biezen, Anja; Vossen, Jaak M. J. J.; Noordijk, Evert M.; Struikmans, Henk

    2008-01-01

    Purpose: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. Methods and Materials: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia

  1. Results of hematopoietic stem cell transplantation after treatment with different high-dose total-body irradiation regimens in five Dutch centers.

    NARCIS (Netherlands)

    Kempen-Harteveld, ML van; Brand, R.; Kal, H.B.; Verdonck, L.F.; Hofman, P.; Schattenberg, A.V.M.B.; Maazen, R.W.M. van der; Cornelissen, J.J.L.M.; Eijkenboom, W.M.H.; Lelie, JP van der; Oldenburger, F.; Barge, R.M.; Biezen, A. van; Vossen, J.M.J.J.; Noordijk, E.M.; Struikmans, H.

    2008-01-01

    PURPOSE: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. METHODS AND MATERIALS: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia

  2. Early-response biomarkers for assessment of radiation exposure in a mouse total-body irradiation model.

    Science.gov (United States)

    Ossetrova, Natalia I; Condliffe, Donald P; Ney, Patrick H; Krasnopolsky, Katya; Hieber, Kevin P; Rahman, Arifur; Sandgren, David J

    2014-06-01

    Nuclear accidents or terrorist attacks could expose large numbers of people to ionizing radiation. Early biomarkers of radiation injury will be critical for triage, treatment, and follow-up of such individuals. The authors evaluated the utility of multiple blood biomarkers for early-response assessment of radiation exposure using a murine (CD2F1, males) total-body irradiation (TBI) model exposed to ⁶⁰Co γ rays (0.6 Gy min⁻¹) over a broad dose range (0-14 Gy) and timepoints (4 h-5 d). Results demonstrate: 1) dose-dependent changes in hematopoietic cytokines: Flt-3 ligand (Flt3L), interleukin 6 (IL-6), granulocyte colony stimulating factor (G-CSF), thrombopoietin (TPO), erythropoietin (EPO), and acute phase protein serum amyloid A (SAA); 2) dose-dependent changes in blood cell counts: lymphocytes, neutrophils, platelets, and ratio of neutrophils to lymphocytes; 3) protein results coupled with peripheral blood cell counts established very successful separation of groups irradiated to different doses; and 4) enhanced separation of dose was observed as the number of biomarkers increased. Results show that the dynamic changes in the levels of SAA, IL-6, G-CSF, and Flt3L reflect the time course and severity of acute radiation syndrome (ARS) and may function as prognostic indicators of ARS outcome. These results also demonstrate proof-in-concept that plasma proteins show promise as a complimentary approach to conventional biodosimetry for early assessment of radiation exposures and, coupled with peripheral blood cell counts, provide early diagnostic information to manage radiation casualty incidents effectively, closing a gap in capabilities to rapidly and effectively assess radiation exposure early, especially needed in case of a mass-casualty radiological incident.

  3. Stereotactic Body Radiation Therapy for Re-irradiation of Persistent or Recurrent Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Minatel, Emilio; Durofil, Elena [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Polesel, Jerry [Department of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Avanzo, Michele [Department of Medical Physics, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Baresic, Tania [Department of Nuclear Medicine, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Bearz, Alessandra [Department of Medical Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Del Conte, Alessandro [Department of Medical Oncology, Pordenone General Hospital, Aviano, Pordenone (Italy); Franchin, Giovanni; Gobitti, Carlo; Rumeileh, Imad Abu; Trovo, Mauro G. [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy)

    2014-04-01

    Purpose: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. Methods and Materials: The analysis was conducted in 17 patients with “in-field” recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. Results: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Conclusions: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern.

  4. The protective effects of resveratrol on irradiation induced oxidative damage in mice%白藜芦醇对小鼠辐射氧化损伤的保护性研究

    Institute of Scientific and Technical Information of China (English)

    李程程; 张恒; 吴红英; 王营营; 黄颂; 张珠博; 孟爱民

    2013-01-01

    Objective: To study the protective effects of resveratrol on irradiation induced damage in the mice and its probable mechanism . Methods : The mice received 6Gy total body irradiation . The SOD , Mn-SOD , and CAT activity in plasma , and the CAT in the BMMC were detected .Result :①The Mn-SOD activity in the Rev group was lower than that in the control group(P<0.05), the total SOD had slight variation ; Compared to the irradiated mouse, the total SOD activity in the Rev + IR group increased significantly (P<0 .05 ), suggesting that Rev could decrease Mn-SOD activity , but not the total SOD . ② Rev increased CAT in the plasma and BMMC (.P<0 .05), compared to the irradiated group , the CAT activity in the Rev + IR group increased significantly (P<0 .05 ) . Conclusion : Resveratrol has protective effects on the oxidative damage induced by irradiation exposure , and its mechanism is probably to promote the peroxidase activity .%目的:研究白藜芦醇(Rev)对辐射所致的小鼠氧化损伤的防护作用,探讨其可能作用机制.方法:使小鼠接受亚致死剂量(6Gy)的全身照射(TBI),制备辐射损伤模型.检测辐射损伤小鼠血浆中SOD,Mn-SOD和CAT的活性和骨髓单个核细胞中CAT的活性.结果:①在血浆中,单独给药组Mn-SOD水平低于对照组(P<0.05),总SOD变化不明显;照射给药组与照射组相比,总SOD水平显著上升(P<0.05),说明单独给予白藜芦醇后可以降低Mn-SOD水平,但对总SOD无影响.②骨髓单个核细胞和血浆中,单独给予白藜芦醇后可以显著提高CAT活性(P<0.05);照射给药组与照射组相比CAT活性明显提高(P<0.05).结论:白藜芦醇对由辐射引起的氧化应激损伤有保护作用,其机制可能与提高相应组织过氧化物酶活性有关.

  5. Total body irradiation (TBI) in pediatric patients. A single-center experience after 30 years of low-dose rate irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Linsenmeier, Claudia; Thoennessen, Daniel; Negretti, Laura; Streller, Tino; Luetolf, Urs Martin [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Bourquin, Jean-Pierre [University Children' s Hospital Zurich (Switzerland). Dept. of Hemato-Oncology; Oertel, Susanne [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Heidelberg Univ. (Germany). Dept. of Radiation Oncology

    2010-11-15

    To retrospectively analyze patient characteristics, treatment, and treatment outcome of pediatric patients with hematologic diseases treated with total body irradiation (TBI) between 1978 and 2006. 32 pediatric patients were referred to the Department of Radiation-Oncology at the University of Zurich for TBI. Records of regular follow-up of 28 patients were available for review. Patient characteristics as well as treatment outcome regarding local control and overall survival were assessed. A total of 18 patients suffered from acute lymphoblastic leukemia (ALL), 5 from acute and 2 from chronic myelogenous leukemia, 1 from non-Hodgkin lymphoma, and 2 from anaplastic anemia. The cohort consisted of 15 patients referred after first remission and 13 patients with relapsed leukemia. Mean follow-up was 34 months (2-196 months) with 15 patients alive at the time of last follow-up. Eight patients died of recurrent disease, 1 of graft vs. host reaction, 2 of sepsis, and 2 patients died of a secondary malignancy. The 5-year overall survival rate (OS) was 60%. Overall survival was significantly inferior in patients treated after relapse compared to those treated for newly diagnosed leukemia (24% versus 74%; p=0.004). At the time of last follow-up, 11 patients survived for more than 36 months following TBI. Late effects (RTOG {>=}3) were pneumonitis in 1 patient, chronic bronchitis in 1 patient, cardiomyopathy in 2 patients, severe cataractogenesis in 1 patient (48 months after TBI with 10 Gy in a single dose) and secondary malignancies in 2 patients (36 and 190 months after TBI). Growth disturbances were observed in all patients treated prepubertally. In 2 patients with identical twins treated at ages 2 and 7, a loss of 8% in final height of the treated twin was observed. As severe late sequelae after TBI, we observed 2 secondary malignancies in 11 patients who survived in excess of 36 months. However, long-term morbidity is moderate following treatment with the fractionated

  6. Quantitative lipidomics reveals age-dependent perturbations of whole-body lipid metabolism in ACBP deficient mice

    DEFF Research Database (Denmark)

    Gallego, Sandra F; Sprenger, Richard R; Neess, Ditte

    2017-01-01

    and delayed weaning, the physiological process where newborns transit from a fat-based milk diet to a carbohydrate-rich diet. To gain insights into how ACBP impinges on weaning and the concomitant remodeling of whole-body lipid metabolism we performed a comparative lipidomics analysis charting the absolute......The acyl-CoA binding protein (ACBP) plays a key role in chaperoning long-chain acyl-CoAs into lipid metabolic processes and acts as an important regulatory hub in mammalian physiology. This is highlighted by the recent finding that mice devoid of ACBP suffer from a compromised epidermal barrier...... abundance of 613 lipid molecules in liver, muscle and plasma from weaning and adult Acbp knockout and wild type mice. Our results reveal that ACBP deficiency affects primarily lipid metabolism of liver and plasma during weaning. Specifically, we show that ACBP deficient mice have elevated levels of hepatic...

  7. Quantitative lipidomics reveals age-dependent perturbations of whole-body lip