WorldWideScience

Sample records for low-dose radiation-induced protective

  1. Low dose irradiation and antioxidants protect against high dose radiation induced lymphoma in mice

    International Nuclear Information System (INIS)

    Ionizing radiation-induced tumor induction in thymus and its suppression by pre-exposure to low dose irradiation has been investigated in Swiss albino mice in our laboratory. These studies showed that a single dose of whole body gamma irradiation (3 Gy) induced thymic lymphoma (TL) after 3-4 months followed by shortening of the life span of tumor bearing animals. These findings have been extended to detailed investigations on the mechanisms of radiation-induced occurrence of tumor and its modification by antioxidants and low dose exposures prior to tumor causing radiation dose. The induced tumor has been found to exhibit sensitivity to therapeutic doses of gamma radiation and concentration dependent anti-tumor drug, doxorubicin. Moreover, transplanted tumor growth was found significantly reduced by exposure to fractionated doses of radiation. Studies have further confirmed that pre-exposure of animals to low doses of radiation significantly suppressed the growth of the transplanted tumor. In addition, tumor cells exposed to 1 cGy of radiation and transplanted to mice showed 30% reduction in the incidence of tumor. The development of TL was found associated with the enlargement of spleen and induction of anaemia. Recent results have shown that whole body exposure of animals to sub-lethal doses (1-5 Gy) resulted in dose-dependent increase in reactive oxygen species (ROS) level in thymocytes from irradiated animals. In vitro studies on thymocytes of irradiated mice showeies on thymocytes of irradiated mice showed increased percent apoptosis, as measured by annexin V fluorescence method, which was inhibited by antioxidants such as vit E and curcumin. More recent results have shown that radiation induced tumor induction was dependent on the age of animal at the time of irradiation. The younger age irradiation showed greater sensitivity to tumor induction. In addition, radiation mediated tumor induction was found gender dependent. This brief review presents a highlight of involvement of ? radiation generated ROS in cell/membrane oxidative damage and the role of cellular apoptosis in the mechanism of radiation-induced lymphoma tumor in mice. (author)

  2. Protective Effects of Prunus armeniaca L (Apricot on Low Dose Radiation-Induced Kidney Damage in Rats

    Directory of Open Access Journals (Sweden)

    Meltem KURUS

    2014-05-01

    Full Text Available OBJECTIVE: This experimental study was designed to evaluate radiation-induced kidney damage and the protective effect of apricot against it using histological parameters. MATERIAL and METHODS: Rats were divided into 6 groups each containing 10 Sprague Dawley rats as follows: Regc: Rats on a regular diet (control diet for 28 weeks; control group. Regx: Rats on a regular diet for 28 weeks, XRE on last day of eighth week. Aprc: Rats on an apricot diet for 28 weeks; control for no XRE. Aprx: Rats on an apricot diet for 28 weeks, XRE on last day of eighth week. Reg+Aprc: Rats on a regular diet for 8 weeks, followed by an apricot diet for the following 20 weeks; control. Reg + Aprx: Rats on a regular diet for 8 weeks, XRE on last day of eighth week, followed by an apricot diet for 20 weeks. RESULTS: The kidneys of the control groups showed normal kidney histology, whereas Regx group showed major histopathological changes, such as glomerular collapse, hemorrhage, interstitial fibrosis and inflammatory infiltrates. The Aprx and Reg+Aprx groups showed smaller amounts of degeneration. CONCLUSION: In conclusion, we suggest that agents with antioxidant properties such as apricot may have a positive effect in the treatment of renal diseases.

  3. Radiation-induced stress effects following low dose exposure

    International Nuclear Information System (INIS)

    Complete text of publication follows. Recent advances in our understanding of effects of radiation on living cells suggest that fundamentally different mechanisms are operating at low doses compared with high doses. Also, acute low doses appear to involve different response mechanisms compared with chronic low doses. Both genomic instability and so called 'bystander effects' show many similarities with well known cellular responses to oxidative stress. These predominate following low dose exposures and are maximally expressed at doses as low as 5mGy. At the biological level this is not surprising. Chemical toxicity has been known for many years to show these patterns of dose response. Cell signaling and coordinated stress mechanisms appear to dominate acute low dose exposure to chemicals. Adaptation to chemical exposures is also well documented although mechanisms of adaptive responses are less clear. In the radiation field adaptive responses also become important when low doses are protracted or fractionated. Recent data from our group concerning bystander effects following multiple low dose exposures suggest that adaptive responses can be induced in cells which only receive signals from irradiated neighbours. We have data showing delayed and bystander effects in humans, rodents 3 fish species and in prawns following in vitro and/or in vivo irradiation of haematopoietic tissues and, from the aquatic groups, gill and skin/fin tissue. Bystander signals induced by radiatissue. Bystander signals induced by radiation can be communicated from fish to fish in vivo and are detectable as early as the eyed egg stage, i.e. as soon as tissue starts to develop. Using proteomic approaches we have determined that the bystander and the direct irradiation proteomes are different. The former show significant upregulation of 5 proteins with anti-oxidant, regenerative and restorative functions while the direct radiation proteome has 2 upregulated proteins both involved in proliferation. These data have implications for environmental radiation protection of human and non-human species alike and suggest a highly conserved mechanism of stress response. Simple extrapolations from high to low dose exposure may need to be re evaluated. This presentation will discuss our knowledge about these low dose radiobiological effects in both human and non-human biota.

  4. Low dose radiation induced bystander effect and its mechanism

    International Nuclear Information System (INIS)

    Objective: To investigate whether the supernatant (the conditioned fluid) of myeloid cells suspension after low dose radiation (6 cGy) in vitro could result in hormesis on the normal or radiation damage cells and its mechanism. Methods: Mice myeloid cell suspension was irradiated by 0, 2 and 5 Gy, respectively, and cultured in vitro. MTT method was used to measure the reproductive activity of cells. Cytochrome C reduction method was used to determine the concentration of O2-, the immunohistochemical method to test the protein expression of c-fos. Results: Co-cultured with the conditioned fluid, the reproductive activity of the myeloid cells after high dose irradiation (P2- and the protein expression of c-fos were enhanced (P2- and the protein expression of c-fos. (authors)

  5. Non-Problematic Risks from Low-Dose Radiation-Induced DNA Damage Clusters

    OpenAIRE

    Hayes, Daniel P.

    2008-01-01

    Radiation-induced DNA damage clusters have been proposed and are usually considered to pose the threat of serious biological damage. This has been attributed to DNA repair debilitation or cessation arising from the complexity of cluster damage. It will be shown here, contrary to both previous suggestions and perceived wisdom, that radiation induced damage clusters contribute to non-problematic risks in the low-dose, low-LET regime. The very complexity of cluster damage which inhibits and/or c...

  6. Low-dose radiation induces drosophila innate immunity through toll pathway activation

    International Nuclear Information System (INIS)

    Numerous studies report that exposing certain organisms to low-dose radiation induces beneficial effects on lifespan, tumorigenesis, and immunity. By analyzing survival after bacterial infection and antimicrobial peptide gene expression in irradiated flies, we demonstrate that low-dose irradiation of Drosophila enhances innate immunity. Low-dose irradiation of flies significantly increased resistance against gram-positive and gram-negative bacterial infections, as well as expression of several antimicrobial peptide genes. Additionally, low-dose irradiation also resulted in a specific increase in expression of key proteins of the Toll signaling pathway and phosphorylated forms of p38 and N-terminal kinase (JNK). These results indicate that innate immunity is activated after low-dose irradiation through Toll signaling pathway in Drosophila. (author)

  7. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

    Science.gov (United States)

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

  8. DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

    Science.gov (United States)

    A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

  9. The relevance of radiation induced bystander effects for low dose radiation carcinogenic risk

    International Nuclear Information System (INIS)

    Full text: Where epidemiology studies lack the ability to prescribe radiation doses, customise sample sizes and replicate findings, radiobiology experiments provide greater flexibility to control experimental conditions. This control simplifies the process of answering questions concerning carcinogenic risk after low dose radiation exposures. However, the flexibility requires critical evaluation of radiobiology findings to ensure that the right questions are being asked, the experimental conditions are relevant to human exposure scenarios and that the data are cautiously interpreted in the context of the experimental model. In particular, low dose radiobiology phenomena such as adaptive responses, genomic instability and bystander effects need to be investigated thoroughly, with continual reference to the way these phenomena might occur in the real world. Low dose radiation induced bystander effects are of interest since their occurrence in vivo could complicate the shape of the radiation dose-response curve in the low dose range for a number of biological endpoints with subsequent effects on radiation-induced cancer risk. Conversely, radiation-induced abscopal effects implicate biological consequences of radiation exposure outside irradiated volumes, and complicate the notion of effective dose calculations. Achieving a consensus on the boundaries that distinguish the radiobiology phenomena of bystander and abscopal effects will aid progress towards understanding theill aid progress towards understanding their relevance to in vivo radiation exposures. A proposed framework for discussing bystander effects and abscopal effects in their appropriate context will be outlined, with a discussion on the future investigation of radiation-induced bystander effects. Such frameworks can assist the integration of results from experimental radiobiology to risk evaluation and management practice. This research was funded by the Low Dose Radiation Research Program, BioI. and Environ. Research, US Dept. of Energy, Grant DE-FG02-05ER64I 04.

  10. Radiation Induced Bystander Effects in Mice Given Low Doses of Radiation in Vivo

    OpenAIRE

    Singh, Harleen; Saroya, Rohin; Smith, Richard; Mantha, Rebecca; Guindon, Lynda; Mitchel, Ron E. J.; Seymour, Colin; Mothersill, Carmel

    2010-01-01

    The bystander effect phenomenon has challenged the traditional framework for assessing radiation damage by showing radiation induced changes in cells which have not been directly targeted, but are neighbors to or receive medium from directly hit cells. Our group performed a range of single and serial low dose irradiations on two genetically distinct strains of mice. Bladder explants established from these mice were incubated in culture medium, which was used to measure death responses i...

  11. Using Drosophila Larval Imaginal Discs to Study Low-Dose Radiation-Induced Cell Cycle Arrest

    OpenAIRE

    Yan, Shian-jang; Li, Willis X.

    2011-01-01

    Under genotoxic stress, activation of cell cycle checkpoint responses leads to cell cycle arrest, which allows cells to repair DNA damage before continuing to cycle. Drosophila larval epithelial sacs, called imaginal discs, are an excellent in vivo model system for studying radiation-induced cell cycle arrest. Larval imaginal discs go into cell cycle arrest after being subjected to low-dose irradiation, are subject to easy genetic manipulation, are not crucial for survival of the organism, an...

  12. Reduction of radiation-induced apoptosis by the previous radiation exposure at low dose rates

    International Nuclear Information System (INIS)

    The previous exposure of cells to low dose radiation (PE) reduces their responses to subsequent several Gy radiation exposure: the so-called adaptive response to radiation. This paper describes the mechanism of the reduction in PE of p53 signal transduction and of p53-dependent radiation-induced apoptosis in cultured cells and in the whole mouse body. DNA damage by radiation induces p53 protein, through which expression of genes are controlled: p53 signal transduction. The low dose radiation is <0.2 Gy in cells or 0.1-0.5 Gy in the mouse, of which effect is not accumulated but becomes ineffective even after continuous irradiation. PE induces the DNA repair mechanisms and thereby may reduce DNA damage by the subsequent radiation. Studies concerning phosphorylation around p53 are in progress with DNA-PK deleted mice (Scid mice). There is possibly a biological response to the low dose radiation differing from that to high dose radiation. (K.H.)

  13. Modification of low dose radiation induced radioresistance by 2-deoxy-D-glucose in Saccharomyces cerevisiae: mechanistic aspects.

    Science.gov (United States)

    Bala, Madhu; Goel, Harish C

    2007-07-01

    Use of 2-deoxy-D-glucose (2-DG) in combination with radiotherapy to radio-sensitize the tumor tissue is undergoing clinical trials. The present study was designed to investigate the effect of 2-DG on radiation induced radioresistance (RIR) in normal cells. The sub-lethal radiation dose to the normal cells at the periphery of target tumor tissue is likely to induce radioresistance and protect the cells from lethal radiation dose. 2-DG, since, enters both normal and tumor cells, this study have clinical relevance. A diploid respiratory proficient strain D7 of S. cerevisiae was chosen as the model system. In comparison to non-pre-irradiated cultures, the cultures that were pre-exposed to low doses of UVC (254 nm) or (60)Co-gamma-radiation, then maintained in phosphate buffer (pH 6.0, 67 mM), containing 10 mM glucose (PBG), for 2-5 h, showed 18-35% higher survivors (CFUs) after subsequent exposure to corresponding radiation at lethal doses suggesting the radiation induced radioresistance (RIR). The RIR, in the absence of 2-DG, was associated with reduced mutagenesis, decreased DNA damage, and enhanced recombinogenesis. Presence of 2-DG in PBG countered the low dose induced increase in survivors and protection to DNA damage. It also increased mutagenesis, altered the recombinogenesis and the expression of rad50 gene. The changes differed quantitatively with the type of radiation and the absorbed dose. These results, since, imply the side effects of 2-DG, it is suggested that new approaches are needed to minimize the retention of 2-DG in normal cells at the time of radiation exposure. PMID:17587773

  14. Modification of low dose radiation induced radioresistance by 2-deoxy-D-glucose in Saccharomyces cerevisiae. Mechanistic aspects

    International Nuclear Information System (INIS)

    Use of 2-deoxy-D-glucose (2-DG) in combination with radiotherapy to radio-sensitize the tumor tissue is undergoing clinical trials. The present study was designed to investigate the effect of 2-DG on radiation induced radioresistance (RIR) in normal cells. The sub-lethal radiation dose to the normal cells at the periphery of target tumor tissue is likely to induce radioresistance and protect the cells from lethal radiation dose. 2-DG, since, enters both normal and tumor cells, this study have clinical relevance. A diploid respiratory proficient strain D7 of S. cerevisiae was chosen as the model system. In comparison to non-pre-irradiated cultures, the cultures that were pre-exposed to low doses of UVC (254 nm) or 60Co-gamma-radiation, then maintained in phosphate buffer (pH 6.0, 67 mM), containing 10 mM glucose (PBG), for 2-5 h, showed 18-35% higher survivors (CFUs) after subsequent exposure to corresponding radiation at lethal doses suggesting the radiation induced radioresistance (RIR). The RIR, in the absence of 2-DG, was associated with reduced mutagenesis, decreased DNA damage, and enhanced recombinogenesis. Presence of 2-DG in PBG countered the low dose induced increase in survivors and protection to DNA damage. It also increased mutagenesis, altered the recombinogenesis and the expression of rad50 gene. The changes differed quantitatively with the type of radiation and the absorbed dose. These results, since, imply the side effects of 2-DG, it is sug imply the side effects of 2-DG, it is suggested that new approaches are needed to minimize the retention of 2-DG in normal cells at the time of radiation exposure. (author)

  15. Radiation induced bystander effects: Implications for low dose radiation risk assessment

    Science.gov (United States)

    Zhou, H.; Suzuki, M.; Randers-Pehrson, G.; Waldren, C.; Hei, T.

    Current model used in radiation risk assessment is based on the dogma that the DNA of the nucleus is the main target for radiation-induced genotoxicity and, as fewer cells are directly damaged at low doses, the deleterious effects of radiation proportionally decline. Using a precision microbeam to target an exact fraction of cells in a population and irradiated their nuclei with exactly one alpha particle each, we found that the frequencies of induced mutations and chromosomal changes in populations where some known fractions of nuclei were hit are consistent with non- hit cells contributing significantly to the response. In fact, irradiation of 10% of a mammalian cell population with a single alpha particle per cell results in a mutant yield similar to that observed when all of the cells in the population are irradiated. This effect was significantly eliminated in cells pretreated with gap junction inhibitor or in cells carrying a dominant negative connexin 43 vector. The data imply that the relevant target for radiation mutagenesis is larger than an individual cell and suggest a need to reconsider the validity of the linear extrapolation in making risk estimate for low dose radiation exposure.

  16. Low dose radiation induced protein and its effect on expression of CD25 molecule in lymphocytes

    International Nuclear Information System (INIS)

    Objective: To find the substantial basis for effects of low dose radiation, on development, extraction, and the biogical activity of the low-dose radiation-induced proteins, and the effects of LDR induced proteins on CD25 molecule expression of human lymphocytes. Methods: 1. Healthy Kumning male mice exposed to radiation of 226Ra ?-rays at 5, 10 and 15 cGy respectively. The mice were killed 2 hours after exposure, the spleen cells were broken with ultrasonic energy and then ultra-centrifugalized at low temperature (4 degree C). The LDR-induced proteins were obtained in the supernatant solution. Then the changes of CD25 molecule was measured by flow cytometry (FCM) with immunofluorescence technique, which was used to reflect the effect of LDR induced proteins on CD25 molecule expression of human lymphocytes. Results: LDR induced proteins were obtained from spleen cells in mice exposed to 5-15 cGy whole body radiation. Conclusion: The expression of CD25 molecule of lymphocytes was increased significantly after use of LDR induced proteins. LDR induced proteins can enhance expression of CD25 molecule of lymphocytes slightly

  17. Radiation-induced bystander effects induce radio-adaptive response by low-dose radiation

    International Nuclear Information System (INIS)

    When normal human fibroblast cells (MRC-5) received a priming irradiation of 3-20 mGy 4 h prior to irradiation with 1000 mGy, the number of DNA double-stranded breaks (DSBs) decreased significantly to 18.2-18.7 per cell compared with 21 per cell when there was no priming irradiation. This result indicates that a priming irradiation of 3-20 mGy induces a radio-adaptive response in MRC-5. The authors' previous study had indicated that DSBs induced by <20 mGy are due to a radiation-induced bystander effect. These findings suggest that radiation-induced bystander effects might contribute to induction of the radio-adaptive response. To test this hypothesis, MRC-5 were suspended in lindane, an inhibitor of radiation-induced bystander effects, which was added to the medium for the priming irradiation of 3-20 mGy. Lindane inhibited the protective effect of priming irradiation on DSBs caused by subsequent irradiation with 1000 mGy. Thus, radiation-induced bystander effects may play a role in radio-adaptive responses. (authors)

  18. Pre-irradiation with a low dose-rate depressed radiation-induced apoptosis in BALB/c mice spleens

    International Nuclear Information System (INIS)

    We aim to elucidate the effects of pre-irradiation to the whole-body with a low dose-rate on the acute radiation-induced apoptosis in the spleens of BALB/c mice. We found significant suppression of apoptosis induced by challenging irradiation at 2.0 Gy (1 Gy/min) immediately after chronic irradiation at 1.5 Gy with a low dose-rate (0.001 Gy/min). These findings suggest that chronic pre-irradiation with a low dose-rate induces some kind of radical detoxification systems and/or repair mechanisms against DNA damage which induces apoptosis. (author)

  19. A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

    Energy Technology Data Exchange (ETDEWEB)

    Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

    2013-05-15

    The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a ??Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

  20. Low dose radiation induced protein and its experimental and ophthalmic clinical research

    International Nuclear Information System (INIS)

    The protective effects of low dose radiation (LDR) induced protein on cellular impairments caused by some harmful chemical and physical factors were studied. Male Kunming mice were irradiated with LDR, then the spleen cells of the mice were broken with ultrasonic energy and then ultracentrifugalized. The supernatant solution contained with LDR induced protein. The newly emerging protein was detected by gel filtration and its molecular weight was determined by gel electrophoresis. The content of newly emerging protein (LDR induced protein) was determined by Lowry's method. The method of isotope incorporation was used to observe the biological activity and its influence factors, the protective effects of LDR induced protein on the cells impaired by irradiating with ultraviolet (UV), high doses of 60Co ?-rays and exposed to heat respectively, and the stimulative effects of LDR induced protein on human peripheral blood lymphocytes. Newly emerging protein has been observed in the experiment. The molecular weight of the protein is in the region 76.9 KD+- - 110.0 KD+-, the yield of the protein was 613.33 +- 213.42 ?g per 3 x 107 spleen cells. DPM values (isotope were incorporated) of normal and injured mice spleen cells increased significantly after stimulating with the solution contained LDR induced protein. It is concluded that LDR induced protein could be obtained from mice spleen cells exposed to 5 - 15 cGy radiation for 2 - 16 h. The protein had biological activity and was able to stimulate the transformation of the spleen cells in vitro. It had obvious protective effects on some impaired cells caused by high dose radiation, UV radiation, heat and so on. It also had stimulative effects on the transformation of peripheral blood T and B lymphocytes of healthy individual and patients with eye diseases. It indicates that LDR induced protein increased immune function of human

  1. Low Doses of Gamma-Radiation Induce Nonlinear Dose Responses in Mammalian and Plant Cells

    OpenAIRE

    Zaichkina, S. I.; Rozanova, O. M.; Aptikaeva, G. F.; Achmadieva, A. Ch; Klokov, D. Y.

    2004-01-01

    The percentage of cells with chromosome aberrations or micronuclei induced by low doses of acute (dose rate of 47 cGy/min) or chronic (dose rate of 0.01 cGy/min) gamma-irradiation was studied in vitro in Chinese hamster fibroblasts, human lymphocytes, and Vicia faba seeds and seedlings. The sensitivity of the indicated biological entities to low doses was greater than expected based on linear extrapolation from higher doses. The dose-response curves for cytogenetic damage that were obtained w...

  2. Mechanisms of Low Dose Radiation-induced T helper Cell Function

    Energy Technology Data Exchange (ETDEWEB)

    Gridley, Daila S.

    2008-10-31

    Exposure to radiation above levels normally encountered on Earth can occur during wartime, accidents such as those at Three Mile Island and Chernobyl, and detonation of dirty bombs by terrorists. Relatively high levels of radiation exposure can also occur in certain occupations (low-level waste sites, nuclear power plants, nuclear medicine facilities, airline industry, and space agencies). Depression or dysfunction of the highly radiosensitive cells of the immune system can lead to serious consequences, including increased risk for infections, cancer, hypersensitivity reactions, poor wound healing, and other pathologies. The focus of this research was on the T helper (Th) subset of lymphocytes that secrete cytokines (proteins), and thus control many actions and interactions of other cell types that make up what is collectively known as the immune system. The Department of Energy (DOE) Low Dose Radiation Program is concerned with mechanisms altered by exposure to high energy photons (x- and gamma-rays), protons and electrons. This study compared, for the first time, the low-dose effects of two of these radiation forms, photons and protons, on the response of Th cells, as well as other cell types with which they communicate. The research provided insights regarding gene expression patterns and capacity to secrete potent immunostimulatory and immunosuppressive cytokines, some of which are implicated in pathophysiological processes. Furthermore, the photon versus proton comparison was important not only to healthy individuals who may be exposed, but also to patients undergoing radiotherapy, since many medical centers in the United States, as well as worldwide, are now building proton accelerators. The overall hypothesis of this study was that whole-body exposure to low-dose photons (gamma-rays) will alter CD4+ Th cell function. We further proposed that exposure to low-dose proton radiation will induce a different pattern of gene and functional changes compared to photons. Over the course of this research, tissues other than spleens were archived and with funding obtained from other sources, including the Department of Radiation Medicine at the Loma Linda University Medical Center, some additional assays were performed. Furthermore, groups of additional mice were included that were pre-exposed to low-dose photons before irradiating with acute photons, protons, and simulated solar particle event (SPE) protons. Hence, the original support together with the additional funding for our research led to generation of much valuable information that was originally not anticipated. Some of the data has already resulted in published articles, manuscripts in review, and a number of presentations at scientific conferences and workshops. Difficulties in reliable and reproducible quantification of secreted cytokines using multi-plex technology delayed completion of this study for a period of time. However, final analyses of the remaining data are currently being performed and should result in additional publications and presentations in the near future. Some of the most notable conclusions, thus far, are briefly summarized below: - Distribution of leukocytes were dependent upon cell type, radiation quality, body compartment analyzed, and time after exposure. Low-dose protons tended to have less effect on numbers of major leukocyte populations and T cell subsets compared to low-dose photons. - The patterns of gene and cytokine expression in CD4+ T cells after protracted low-dose irradiation were significantly modified and highly dependent upon the total dose and time after exposure. - Patterns of gene and cytokine expression differed substantially among groups exposed to low-dose photons versus low-dose protons; differences were also noted among groups exposed to much higher doses of photons, protons, and simulated SPE protons. - Some measurements indicated that exposure to low-dose photon radiation, especially 0.01 Gy, significantly normalized at least some adverse effects of simulated SPE protons, thereby suggesting that this l

  3. Possible expressions of radiation-induced genomic instability, bystander effects or low-dose hypersensitivity in cancer epidemiology

    International Nuclear Information System (INIS)

    Recent publications on the integration of radiobiological effects in the two-step clonal expansion (TSCE) model of carcinogenesis and applications to radioepidemiological data are reviewed and updated. First, a model version with radiation-induced genomic instability was shown to be a possible explanation for the age dependence of the radiation-induced cancer mortality in the Techa River Cohort. Second, it is demonstrated that inclusion of a bystander effect with a dose threshold allows an improved description of the lung cancer mortality risk for the Mayak workers cohort due to incorporation of plutonium. The threshold for the annual lung dose is estimated to 12 (90%CI: 4; 14) mGy/year. This threshold applies to the initiation of preneoplastic cells and to hyperplastic growth. There is, however, no evidence for a threshold for the effects of gamma radiation. Third, models with radiation-induced cell inactivation tend to predict lower cancer risks among the atomic bomb survivors with exposure at young age than conventionally used empirical models. Also, risks after exposures with doses in the order of 100 mGy are predicted to be higher in models with low-dose hypersensitivity than in models with conventional cell survival curves. In the reviewed literature, models of carcinogenesis tend to describe radioepidemiological data better than conventionally used empirical models.

  4. Does occupational exposure to low-dose ionizing radiation induce cell membrane damage?

    Directory of Open Access Journals (Sweden)

    ?urovi? Branka 1

    2004-01-01

    Full Text Available BACKGROUND: Chronic exposure to low-dose radiation doses could be much more harmful than high, short-term doses because of lipid peroxidation initiated by free radicals. The cell membranes and cellular organelles are the main targets for free radicals attack. Peroxidation of cell membrane increases with decreasing dose rate (Petkau effect. The aim of this study was to establish if chronic occupational exposure to low-dose ionizing radiation could induce cell membrane damage. METHODS: Our investigation comprised 77 medical workers: 44 occupationally exposed to ionizing radiation (E, divided in two subgroups-exposed to x-rays (Ex or gamma rays (En, and 33 controls (C. Informed consent and questionnaire containing dietary, habits, medical factors and exposure history were taken. Groups were matched in gender, age, dietary habits, alcohol consumption, smoking habit, and specific exposure time. Radiation dose accumulated by occupationally exposed over years was calculated on the basis of individual TL-dose records. Besides regular biochemical and cytogenetic tests, lipid peroxidation index, expressed as malondyaldehyde production was performed. RESULTS: Significantly higher lipid peroxidation index was found in workers occupationally exposed to low-dose of ionizing radiation (p>0.000028, which is correlated with age, smoking habit, and significantly correlated with doses. After blood samples in vitro irradiation by 2 Gy of gamma-radiation malondyaldehyde production significantly increased in each group, but were not significantly different between groups. CONCLUSION: Lipid peroxidation index could be considered as triage parameter for further cytogenetic studies in workers chronically exposed to low-dose radiation.

  5. Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process.

    Science.gov (United States)

    Alessio, Nicola; Del Gaudio, Stefania; Capasso, Stefania; Di Bernardo, Giovanni; Cappabianca, Salvatore; Cipollaro, Marilena; Peluso, Gianfranco; Galderisi, Umberto

    2015-04-10

    Low doses of radiation may have profound effects on cellular function. Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites.We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body's homeostasis.The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal. We also showed that low radiation affected the autophagic flux. We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence.An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells. This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination). PMID:25544750

  6. 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.

  7. Radiation-induced bystander effects and adaptive responses--the Yin and Yang of low dose radiobiology?

    Science.gov (United States)

    Mothersill, Carmel; Seymour, Colin

    2004-12-01

    Our current knowledge of the mechanisms underlying the induction of bystander effects by low doses of high or low LET ionizing radiation is reviewed. The question of what actually constitutes a protective effect is discussed in the context of adaptive (often referred to as hormetic or protective) responses. Finally the review considers critically, how bystander effects may be related to observed adaptive responses or other seemingly protective effects of low doses exposures. Bystander effects induce responses at the tissue level, which are similar to generalized stress responses. Most of the work involving low LET radiation exposure discussed in the existing literature measures a death response. Since many cell populations carry damaged cells without being exposed to radiation (so-called "background damage"), it is possible that low doses exposures cause removal of cells carrying potentially problematic lesions, prior to exposure to radiation. This mechanism could lead to the production of "U-shaped" or hormetic dose-response curves. The level of adverse, adaptive or apparently beneficial response will be related to the background damage carried by the original cell population, the level of organization at which damage or harm are scored and the precise definition of "harm". This model may be important when attempting to predict the consequences of mixed exposures involving low doses of radiation and other environmental stressors. PMID:15530545

  8. Radiation-induced bystander effects and adaptive responses--the Yin and Yang of low dose radiobiology?

    International Nuclear Information System (INIS)

    Our current knowledge of the mechanisms underlying the induction of bystander effects by low doses of high or low LET ionizing radiation is reviewed. The question of what actually constitutes a protective effect is discussed in the context of adaptive (often referred to as hormetic or protective) responses. Finally the review considers critically, how bystander effects may be related to observed adaptive responses or other seemingly protective effects of low doses exposures. Bystander effects induce responses at the tissue level, which are similar to generalized stress responses. Most of the work involving low LET radiation exposure discussed in the existing literature measures a death response. Since many cell populations carry damaged cells without being exposed to radiation (so-called 'background damage'), it is possible that low doses exposures cause removal of cells carrying potentially problematic lesions, prior to exposure to radiation. This mechanism could lead to the production of 'U-shaped' or hormetic dose-response curves. The level of adverse, adaptive or apparently beneficial response will be related to the background damage carried by the original cell population, the level of organization at which damage or harm are scored and the precise definition of 'harm'. This model may be important when attempting to predict the consequences of mixed exposures involving low doses of radiation and other environmental stressorsors

  9. Radiation induced bystander effects: mechanisms and implication for low dose radiation risk assessment

    International Nuclear Information System (INIS)

    Using a precision microbeam to target an exact fraction of cells in a population and irradiated their nuclei with exactly one alpha particle each, we found that the frequencies of induced mutations and chromosomal changes in populations where some known fractions of nuclei were hit are consistent with non-hit cells contributing significantly to the response. In fact, irradiation of 10% of a mammalian cell population with a single alpha particle per cell results in a mutant yield similar to that observed when all of the cells in the population are irradiated. Although the bystander observations have been well established, the underlying mechanism(s) remain largely unknown. There are indications that multiple pathways are involved in the bystander phenomenon and different cell types respond differently to the bystander signaling. In confluent monolayers, there is evident that gap junctional communication is crucial in mediating the bystander effect whereas reactive oxygen and reactive nitrogen species have been implicated as the mediating molecules in sub-confluent cultures. Although p53 is not necessary for the expression of bystander effect, there is evident that repair deficient cells may express a higher bystander response. Using cDNA microarrays, a number of cellular signaling genes have been shown to be differentially expressed among bystander cells. The functional roles of these genes in the bystander effect will be discussed. The bystander observations imply thassed. The bystander observations imply that the relevant target for various radiobiological endpoints is larger than an individual cell and suggest a need to reconsider the validity of the linear extrapolation in making risk estimate for low dose radiation exposure. (Work supported by NIH grants CA 49062 and CA-RR11623)

  10. Risks of low-dose radiation induced carcinogenesis. Uncertainties following the UNSCEAR report, 1988

    International Nuclear Information System (INIS)

    The uncertainties remained after the publication of UNSCEAR report in 1988 are analyzed and a number of new investigations which can give a useful information are generalized. Risk coefficients presented in the UNSCEAR report are based only on the latest data on Hiroshima and Nagasaki: disregarding the results of the recent examinations of irradiated patients. There are 3 reasons explaining the increase of the risk coefficient as compared to the previous assessment: a) change in dose-effect ratio due to the revision of monitoring system; b) prediction models; c) increase of investigation time. Epidemiological investigations of patients result in a smaller risk coefficients. A hasty revision of the currently applicable dose limits in the radiation protection which has no scientific basis, will inevitably trigger unreasonable discussions. It is recommended to aim the radiation protection at reducing the effect of radon in premises and medical examination exposure doses as well as at decreasing genotoxic chemical risk

  11. Apoptosis is signalled early by low doses of ionising radiation in a radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Highlights: ? Molecular mechanisms involved in the production of a radiation induced bystander effect are not well known. ? We investigate gene expression changes in apoptotic genes in both direct and bystander responses. ? We demonstrate initiation of the apoptotic cascade in a bystander response. ? Lower doses reveal a specific but differential response related to apoptosis compared to higher doses. - Abstract: It is known that ionising radiation (IR) induces a complex signalling apoptotic cascade post-exposure to low doses ultimately to remove damaged cells from a population, specifically via the intrinsic pathway. Therefore, it was hypothesised that bystander reporter cells may initiate a similar apoptotic response if exposed to low doses of IR (0.05 Gy and 0.5 Gy) and compared to directly irradiated cells. Key apoptotic genes were selected according to their role in the apoptotic cascade; tumour suppressor gene TP53, pro-apoptotic Bax and anti-apoptotic Bcl2, pro-apoptotic JNK and anti-apoptotic ERK, initiator caspase 2 and 9 and effector caspase 3, 6 and 7. The data generated consolidated the role of apoptosis following direct IR exposure for all doses and time points as pro-apoptotic genes such as Bax and JNK as well as initiator caspase 7 and effector caspase 3 and 9 were up-regulated. However, the gene expression profile for the bystander response was quite different and more complex in comparison to the direct response. The 0.05 Gy dose point had a more significant apoptosis gene expression profile compared to the 0.5 Gy dose point and genes were not always expressed within 1 h but were sometimes expressed 24 h later. The bystander data clearly demonstrates initiation of the apoptotic cascade by the up-regulation of TP53, Bax, Bcl-2, initiator caspase 2 and effector caspase 6. The effector caspases 3 and 7 of the bystander samples demonstrated down-regulation in their gene expression levels at 0.05 Gy and 0.5 Gy at both time points therefore not fully executing the apoptotic pathway. Extensive analysis of the mean-fold gene expression changes of bystander data demonstrated that the apoptosis is initiated in the up-regulation of pro-apoptotic and initiator genes but may not very well be executed to final stages of cell death due to down-regulation of effector genes

  12. The Dose Window for Radiation-Induced Protective Adaptive Responses

    OpenAIRE

    Mitchel, Ronald E. J.

    2009-01-01

    Adaptive responses to low doses of low LET radiation occur in all organisms thus far examined, from single cell lower eukaryotes to mammals. These responses reduce the deleterious consequences of DNA damaging events, including radiation-induced or spontaneous cancer and non-cancer diseases in mice. The adaptive response in mammalian cells and mammals operates within a certain window that can be defined by upper and lower dose thresholds, typically between about 1 and 100 mGy for a single low ...

  13. Low dose radiation adaptive protection to control neurodegenerative diseases.

    Science.gov (United States)

    Doss, Mohan

    2014-05-01

    Concerns have been expressed recently regarding the observed increased DNA damage from activities such as thinking and exercise. Such concerns have arisen from an incomplete accounting of the full effects of the increased oxidative damage. When the effects of the induced adaptive protective responses such as increased antioxidants and DNA repair enzymes are taken into consideration, there would be less endogenous DNA damage during the subsequent period of enhanced defenses, resulting in improved health from the thinking and exercise activities. Low dose radiation (LDR), which causes oxidative stress and increased DNA damage, upregulates adaptive protection systems that may decrease diseases in an analogous manner. Though there are ongoing debates regarding LDR's carcinogenicity, with two recent advisory committee reports coming to opposite conclusions, data published since the time of the reports have overwhelmingly ruled out its carcinogenicity, paving the way for consideration of its potential use for disease reduction. LDR adaptive protection is a promising approach to control neurodegenerative diseases, for which there are no methods of prevention or cure. Preparation of a compelling ethics case would pave the way for LDR clinical studies and progress in dealing with neurodegenerative diseases. PMID:24910585

  14. Enhancement of radiation-induced apoptosis by preirradiation with low-dose X-rays in human leukemia MOLT-4 cells

    International Nuclear Information System (INIS)

    The effects of low-dose preirradiation on the process of radiation-induced cell death were investigated in human leukemic MOLT-4 cells. By 0.2 Gy of X-rays given 12 h prior to a challenge dose of 5 Gy, the process of apoptosis was accelerated. The acceleration was associated with a certain increase in caspase 3 activity, a disruption of the mitochondrial transmembrane potential, and an accumulation of p53 proteins. This finding is in contrast to the radiation adaptive responses in which a small dose of preirradiation would induce certain radiation resistance and decrease the cell death after irradiation with higher doses. (author)

  15. Halofuginone Mediated Protection against Radiation-Induced Leg Contracture

    OpenAIRE

    Ishii, Hisanari; Choudhuri, Rajani; Mathias, Askale; Sowers, Anastasia L.; Flanders, Kathleen C.; Cook, John A.; Mitchell, James B.

    2009-01-01

    Fibrosis of normal tissues often accompanies radiation treatment of cancer. Activation of the transforming growth factor-? (TGF-?) signaling pathway is thought to play a major role in radiation-induced fibrosis and has prompted the development and assessment of low molecular weight inhibitors of the pathway. Previous studies with halofuginone have shown it to inhibit TGF-? signaling in vitro and protect mice from radiation-induced leg contraction (a model for soft tissue fibrosis). The cur...

  16. Cloning of low dose radiation induced gene RIG1 by RACE based on non-cloned cDNA library

    International Nuclear Information System (INIS)

    Objective: To obtain full-length cDNA of radiation induced new gene RIG1 based on its EST fragment. Methods: Based on non-cloned cDNA library, enhanced nested RACE PCR and biotin-avidin labelled probe for magnetic bead purification was used to obtain full-length cDNA of RIG1. Results: About 1 kb of 3' end of RIG1 gene was successfully cloned by this set of methods and cloning of RIG1 5' end is proceeding well. Conclusion: The result is consistent with the design of experiment. This set of protocol is useful for cloning of full-length gene based on EST fragment

  17. Mitigating effects of L-selenomethionine on low-dose iron ion radiation-induced changes in gene expression associated with cellular stress.

    Science.gov (United States)

    Nuth, Manunya; Kennedy, Ann R

    2013-07-01

    Ionizing radiation associated with highly energetic and charged heavy (HZE) particles poses a danger to astronauts during space travel. The aim of the present study was to evaluate the patterns of gene expression associated with cellular exposure to low-dose iron ion irradiation, in the presence and absence of L-selenomethionine (SeM). Human thyroid epithelial cells (HTori-3) were exposed to low-dose iron ion (1 GeV/n) irradiation at 10 or 20 cGy with or without SeM pretreatment. The cells were harvested 6 and 16 h post-irradiation and analyzed by the Affymetrix U133Av2 gene chip arrays. Genes exhibiting a 1.5-fold expression cut-off and 5% false discovery rate (FDR) were considered statistically significant and subsequently analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) for pathway analysis. Representative genes were further validated by real-time RT-PCR. Even at low doses of radiation from iron ions, global genome profiling of the irradiated cells revealed the upregulation of genes associated with the activation of stress-related signaling pathways (ubiquitin-mediated proteolysis, p53 signaling, cell cycle and apoptosis), which occurred in a dose-dependent manner. A 24-h pretreatment with SeM was shown to reduce the radiation effects by mitigating stress-related signaling pathways and downregulating certain genes associated with cell adhesion. The mechanism by which SeM prevents radiation-induced transformation in vitro may involve the suppression of the expression of genes associated with stress-related signaling and certain cell adhesion events. PMID:23946774

  18. Apoptosis is signalled early by low doses of ionising radiation in a radiation-induced bystander effect.

    Science.gov (United States)

    Furlong, Hayley; Mothersill, Carmel; Lyng, Fiona M; Howe, Orla

    2013-01-01

    It is known that ionising radiation (IR) induces a complex signalling apoptotic cascade post-exposure to low doses ultimately to remove damaged cells from a population, specifically via the intrinsic pathway. Therefore, it was hypothesised that bystander reporter cells may initiate a similar apoptotic response if exposed to low doses of IR (0.05Gy and 0.5Gy) and compared to directly irradiated cells. Key apoptotic genes were selected according to their role in the apoptotic cascade; tumour suppressor gene TP53, pro-apoptotic Bax and anti-apoptotic Bcl2, pro-apoptotic JNK and anti-apoptotic ERK, initiator caspase 2 and 9 and effector caspase 3, 6 and 7. The data generated consolidated the role of apoptosis following direct IR exposure for all doses and time points as pro-apoptotic genes such as Bax and JNK as well as initiator caspase 7 and effector caspase 3 and 9 were up-regulated. However, the gene expression profile for the bystander response was quite different and more complex in comparison to the direct response. The 0.05Gy dose point had a more significant apoptosis gene expression profile compared to the 0.5Gy dose point and genes were not always expressed within 1h but were sometimes expressed 24h later. The bystander data clearly demonstrates initiation of the apoptotic cascade by the up-regulation of TP53, Bax, Bcl-2, initiator caspase 2 and effector caspase 6. The effector caspases 3 and 7 of the bystander samples demonstrated down-regulation in their gene expression levels at 0.05Gy and 0.5Gy at both time points therefore not fully executing the apoptotic pathway. Extensive analysis of the mean-fold gene expression changes of bystander data demonstrated that the apoptosis is initiated in the up-regulation of pro-apoptotic and initiator genes but may not very well be executed to final stages of cell death due to down-regulation of effector genes. PMID:23454491

  19. Low dose/low fluence ionizing radiation-induced biological effects: The role of intercellular communication and oxidative metabolism

    Science.gov (United States)

    Azzam, Edouard

    Mechanistic investigations have been considered critical to understanding the health risks of exposure to ionizing radiation. To gain greater insight in the biological effects of exposure to low dose/low fluence space radiations with different linear energy transfer (LET) properties, we examined short and long-term biological responses to energetic protons and high charge (Z) and high energy (E) ions (HZE particles) in human cells maintained in culture and in targeted and non-targeted tissues of irradiated rodents. Particular focus of the studies has been on mod-ulation of gene expression, proliferative capacity, induction of DNA damage and perturbations in oxidative metabolism. Exposure to mean doses of 1000 MeV/nucleon iron ions, by which a small to moderate proportion of cells in an exposed population is targeted through the nucleus by an HZE particle, induced stressful effects in the irradiated and non-irradiated cells in the population. Direct intercellular communication via gap-junctions was a primary mediator of the propagation of stressful effects from irradiated to non-irradiated cells. Compromised prolif-erative capacity, elevated level of DNA damage and oxidative stress evaluated by measurements of protein carbonylation, lipid peroxidation and activity of metabolic enzymes persisted in the progeny of irradiated and non-irradiated cells. In contrast, progeny of cells exposed to high or low doses from 150-1000 MeV protons retained the ability to form colonies and harbored similar levels of micronuclei, a surrogate form of DNA damage, as control, which correlated with normal reactive oxygen species (ROS) levels. Importantly, a significant increase in the spontaneous neoplastic transformation frequency was observed in progeny of bystander mouse embryo fibroblasts (MEFs) co-cultured with MEFs irradiated with energetic iron ions but not protons. Of particular significance, stressful effects were detected in non-targeted tissues of rats that received partial body irradiation, 20 months earlier, from low mean doses of HZE particles. These effects were associated with disruption of mitochondrial function in the non-irradiated tissues and in modulation of immune cell populations. Collectively, our data support the concept that the response of the organism to high LET radiations involves irradiated and non-irradiated cells/tissues and is associated with changes in several physiological functions. Supported by the US National Aeronautics and Space Administration

  20. Radiation-induced developmental anomalies in mammalian embryos by low doses and interaction with drugs, stress and genetic factors

    International Nuclear Information System (INIS)

    The effect of low doses of radiation with different LET (140kV X-rays, negative pions and 15MeV electrons), as well as the interaction with drugs, genetic and stress factors, has been studied in rat and mouse embryos. Pregnant mice of two different strains (F/A and NMRI) and rats (Sprague-Dawley) were irradiated at day 8 or 9 of gestation. Four to five days after irradiation (with and without additional treatment) the foetuses were observed macro- and microscopically for developmental anomalies such as post-implantation loss, growth retardation, eye defects, exencephaly, cleft palate, and limb defects. In both mice strains it was found that a radiation dose as low as 1rad results in a significant increase in the rates of abnormal foetuses. Irradiation with peak pions (high LET) was more effective than 140kV X-rays or 15MeV electrons (RBE 1.4). Application of iodoacetamide and tetracyclines (Reverin, Ledermycin) before irradiation with X-rays led to a significant sensitization of radiation effects. The most impressive synergistic effect was shown with lucanthone (Miracil D) where the radiation damage after 50rads was multiplied almost fourfold. With smaller radiation doses the injection of lucanthone led to various degrees of sensitization depending on both the mouse strain (genetic factors) and dosage used. Besides chemical substances, a short time restraint of pregnant females represents a stress situation which was teratogenic in mice, and may enhance radiation and ic in mice, and may enhance radiation and chemically induced developmental anomalies. Combinations of modifying factors with different radiation might deserve further attention. (author)

  1. Exposure to low-dose (56)Fe-ion radiation induces long-term epigenetic alterations in mouse bone marrow hematopoietic progenitor and stem cells.

    Science.gov (United States)

    Miousse, Isabelle R; Shao, Lijian; Chang, Jianhui; Feng, Wei; Wang, Yingying; Allen, Antio R; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Zhou, Daohong; Koturbash, Igor

    2014-07-01

    There is an increasing need to better understand the long-term health effects of high-linear energy transfer (LET) radiation due to exposure during space missions, as well as its increasing use in clinical treatments. Previous studies have indicated that exposure to (56)Fe heavy ions increases the incidence of acute myeloid leukemia (AML) in mice but the underlying molecular mechanisms remain elusive. Epigenetic alterations play a role in radiation-induced genomic instability and the initiation and progression of AML. In this study, we assessed the effects of low-dose (56)Fe-ion irradiation on epigenetic alterations in bone marrow mononuclear cells (BM-MNCs) and hematopoietic progenitor and stem cells (HPSCs). Exposure to (56)Fe ions (600 MeV, 0.1, 0.2 and 0.4 Gy) resulted in significant epigenetic alterations involving methylation of DNA, the DNA methylation machinery and expression of repetitive elements. Four weeks after irradiation, these changes were primarily confined to HPSCs and were exhibited as dose-dependent hypermethylation of LINE1 and SINE B1 repetitive elements [4.2-fold increase in LINE1 (P exposure to 0.4 Gy; n = 5]. Epigenetic alterations were persistent and detectable for at least 22 weeks after exposure, when significant loss of global DNA hypomethylation (1.9-fold, P exposure to 0.4 Gy. In contrast, exposure to (56)Fe ions did not result in accumulation of increased production of reactive oxygen species (ROS) and DNA damage, exhibited as DNA strand breaks. Furthermore, no significant alterations in cellular senescence and apoptosis were detected in HPSCs after exposure to (56)Fe-ion radiation. These findings suggest that epigenetic reprogramming is possibly involved in the development of radiation-induced genomic instability and thus, may have a causative role in the development of AML. PMID:24960414

  2. Radiation-induced bystander effects in the Atlantic salmon (salmo salar L.) following mixed exposure to copper and aluminum combined with low-dose gamma radiation.

    Science.gov (United States)

    Mothersill, Carmel; Smith, Richard W; Heier, Lene Srlie; Teien, Hans-Christian; Lind, Ole Christian; Land, Ole Christian; Seymour, Colin B; Oughton, Deborah; Salbu, Brit

    2014-03-01

    Very little is known about the combined effects of low doses of heavy metals and radiation. However, such "multiple stressor" exposure is the reality in the environment. In the work reported in this paper, fish were exposed to cobalt 60 gamma irradiation with or without copper or aluminum in the water. Doses of radiation ranged from 4 to 75 mGy delivered over 48 or 6 h. Copper doses ranged from 10 to 80 ?g/L for the same time period. The aluminum dose was 250 ?g/L. Gills and skin were removed from the fish after exposure and explanted in tissue culture flasks for investigation of bystander effects of the exposures using a stress signal reporter assay, which has been demonstrated to be a sensitive indicator of homeostatic perturbations in cells. The results show complex synergistic interactions of radiation and copper. Gills on the whole produce more toxic bystander signals than skin, but the additivity scores show highly variable results which depend on dose and time of exposure. The impacts of low doses of copper and low doses of radiation are greater than additive, medium levels of copper alone have a similar level of effect of bystander signal toxicity to the low dose. The addition of radiation stress, however, produces clear protective effects in the reporters treated with skin-derived medium. Gill-derived medium from the same fish did not show protective effects. Radiation exposure in the presence of 80 ?g/L led to highly variable results, which due to animal variation were not significantly different from the effect of copper alone. The results are stressor type, stressor concentration and time dependent. Clearly co-exposure to radiation and heavy metals does not always lead to simple additive effects. PMID:24352529

  3. Low Dose Radiation Adaptive Protection to Control Neurodegenerative Diseases

    OpenAIRE

    Doss, Mohan

    2013-01-01

    Concerns have been expressed recently regarding the observed increased DNA damage from activities such as thinking and exercise. Such concerns have arisen from an incomplete accounting of the full effects of the increased oxidative damage. When the effects of the induced adaptive protective responses such as increased antioxidants and DNA repair enzymes are taken into consideration, there would be less endogenous DNA damage during the subsequent period of enhanced defenses, resulting in impro...

  4. A functional genomics approach using radiation-induced changes in gene expression to study low dose radiation effects in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Fornace, Jr, A J

    2007-03-03

    Abstract for final report for project entitled ??A functional genomics approach using radiation-induced changes in gene expression to study low dose radiation effects in vitro and in vivo? which has been supported by the DOE Low Dose Radiation Research Program for approximately 7 years. This project has encompassed two sequential awards, ER62683 and then ER63308, in the Gene Response Section in the Center for Cancer Research at the National Cancer Institute. The project was temporarily suspended during the relocation of the Principal Investigator??s laboratory to the Dept. of Genetics and Complex Diseases at Harvard School of Public Health at the end of 2004. Remaining support for the final year was transferred to this new site later in 2005 and was assigned the DOE Award Number ER64065. The major aims of this project have been 1) to characterize changes in gene expression in response to low-dose radiation responses; this includes responses in human cells lines, peripheral blood lymphocytes (PBL), and in vivo after human or murine exposures, as well as the effect of dose-rate on gene responses; 2) to characterize changes in gene expression that may be involved in bystander effects, such as may be mediated by cytokines and other intercellular signaling proteins; and 3) to characterize responses in transgenic mouse models with relevance to genomic stability. A variety of approaches have been used to study transcriptional events including microarray hybridization, quantitative single-probe hybridization which was developed in this laboratory, quantitative RT-PCR, and promoter microarray analysis using genomic regulatory motifs. Considering the frequent responsiveness of genes encoding cytokines and related signaling proteins that can affect cellular metabolism, initial efforts were initiated to study radiation responses at the metabolomic level and to correlate with radiation-responsive gene expression. Productivity includes twenty-four published and in press manuscripts, as well as a U.S. patent. There are several additional publications that will be submitted in 2007 that were supported in part by this program. These future publications include one manuscript on in vivo expression profiling analysis in mouse models, one manuscript on radiation responses in human cell lines, at least one on development of stress signatures in human cells, and three manuscripts on radiation metabolomics.

  5. Protection against Radiation Induced Performance Decrement in Mice

    Directory of Open Access Journals (Sweden)

    S. K. Mukherjee

    1997-04-01

    Full Text Available Recognising that there is lack of information on the effects of low-level ionizing radiations and the modifying role of radioprotectors, an attempt has been made in this study to explore the relationship between impairment of spatial learning and low level of radiation exposure. A radial arm maze was utilised to evaluate radiation-induced behavioural alterations and performance decrement in mice. Immediately after whole body exposure to gamma radiation (absorbed dose, I Gy significant perturbations in the learned behaviour of the animals were observed. The regular control movement became irregular and the food consumption time was reduced appreciably (40 %. Recovery took place in four days. If diltiazem (7 mg/kg b.w., a Ca/sup 2+/ channel blocker and a radioprotector, was administered i.p. 20-30 min prior to irradiation, radiation-induced behavioural abnormalities were reduced. Mechanisms underlying protection by diltiazem against radiation-induced performance decrement observed in the present study need to be investigated.

  6. Inducible HSP70 Protects Radiation-Induced Salivary Gland Damage

    International Nuclear Information System (INIS)

    Irradiation (IR) delivered to the head and neck is a common treatment for malignancies. Salivary glands in the irradiation field are severely damaged, and consequently this resulted in marked salivary hypofunction. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that inducible heat shock protein 70 (HSP70i) induced radioresistance in vitro. Moreover, HSP70i localized to salivary glands by gene transfer has great potential for the treatment of salivary gland. Herein, we investigated whether HSP70 can use as radio protective molecules for radiation-induced salivary gland damage in vivo

  7. Radiation protection and environment day the low doses in everyday life

    International Nuclear Information System (INIS)

    The consequences of low doses exposures are difficult to explore and the studies give often place to controversies. According to the are, differences exist in the methodological approaches. It results from it a confusion on the acceptable levels of exposure, even on the definition of low dose. This day organised by the sections 'non ionizing and research and health of the French society of radiation protection (S.F.R.P.), will be a meeting between professionals of different disciplines, to compare the approaches used for the ionizing and non ionizing radiations as well as the chemical and microbiological agents. It will allow to share the knowledge and the abilities and to progress on methodologies adapted to the evaluation and the management of risks in relation with low doses. (N.C.)

  8. Low-Dose-Radiation Stimulated Natural Chemical and Biological Protection Against Lung Cancer

    OpenAIRE

    Scott, B. R.

    2008-01-01

    Research is being conducted world-wide related to chemoprevention of future lung cancer among smokers. The fact that low doses and dose rates of some sparsely ionizing forms of radiation (e.g., x rays, gamma rays, and beta radiation) stimulate transient natural chemical and biological protection against cancer in high-risk individuals is little known. The cancer preventative properties relate to radiation adaptive response (radiation hormesis) and involve stimulated protective biological sign...

  9. HSP25 Protects Radiation-Induced Salivary Gland Damage

    International Nuclear Information System (INIS)

    Irradiation (IR) is a central treatment modality administered for head and neck malignancies. A significant consequence of this IR treatment is irreversible damage to salivary gland in the IR field. While the exact mechanism of salivary gland damage remains enigmatic, fluid secreting acinar cells are lost, and saliva output is dramatically reduced. Previously we have reported that heat shock protein 25 (HSP25) induced radioresistance in vitro. HSP25 interferes negatively with apoptosis through several pathways which involve its direct interaction with cytochrome c, protein kinase c delta or Akt. And localized gene transfer to salivary glands has great potential for the treatment of salivary gland. Herein, we investigated whether HSP25 can use as radio protective molecules for radiation-induced salivary gland damage in vivo

  10. Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

    International Nuclear Information System (INIS)

    In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

  11. Hydrogen Protects Mice from Radiation Induced Thymic Lymphoma in BALB/c Mice

    OpenAIRE

    Luqian Zhao, Chuanfeng Zhou

    2011-01-01

    Ionizing radiation (IR) is a well-known carcinogen, however the mechanism of radiation induced thymic lymphoma is not well known. Moreover, an easy and effective method to protect mice from radiation induced thymic lymphoma is still unknown. Hydrogen, or H2, is seldom regarded as an important agent in medical usage, especially as a therapeutic gas. Here in this study, we found that H2 protects mice from radiation induced thymic lymphoma in BALB/c mice.

  12. Commentary: Ethical Issues of Current Health-Protection Policies on Low-Dose Ionizing Radiation

    OpenAIRE

    Socol, Yehoshua; Dobrzyn?ski, Ludwik; Doss, Mohan; Feinendegen, Ludwig E.; Janiak, Marek K.; Miller, Mark L.; Sanders, Charles L.; Scott, Bobby R.; Ulsh, Brant; Vaiserman, Alexander

    2013-01-01

    The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based on the assumption that every radiation dose increment constitutes increased cancer risk for humans. The risk is hypothesized to increase linearly as the total dose increases. While this model is the basis for radiation safety regulations, its scientific validity has been questioned and debated for many decades. The recent memorandum of the International Commission on Radiological Protection admits that the LNT-m...

  13. Low-dose propranolol for the protection of the left ventricle from ischaemic damage.

    OpenAIRE

    Brown, A. H.; Krause, B. L.; Morritt, G. M.

    1981-01-01

    Global myocardial ischaemia improves intracardiac operating conditions but damages the myocardium. Propranolol should reduce this damage but may impair postoperative myocardial contractility. An assessment of its protective effect during 90 minutes of normothermic ischaemia in canine hearts has been made. The early and late changes of contractility caused by low-dose propranolol were also recorded. A comparison of cardiac isovolumic contractile force, velocity, and compliance was made in thre...

  14. Low concentration of exogenous carbon monoxide protects mammalian cells against proliferation induced by radiation-induced bystander effect.

    Science.gov (United States)

    Tong, Liping; Yu, K N; Bao, Lingzhi; Wu, Wenqing; Wang, Hongzhi; Han, Wei

    2014-01-01

    Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after ?-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor ?1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy. PMID:24333162

  15. Protecting effects specifically from low doses of ionizing radiation to mammalian cells challenge the concept of linearity

    International Nuclear Information System (INIS)

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced changes in intracellular signaling that induce mechanisms of DNA damage control different from those operating at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. The aim of this paper is to demonstrate that by use of microdosimetric concepts, the energy deposited in cell mass can be related to the occurrence of cellular responses, both damaging and defensive

  16. Protecting effects specifically from low doses of ionizing radiation to mammalian cells challenge the concept of linearity

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.; Bond, V.P. [Washington State Univ., Richland, WA (United States); Sondhaus, C.A. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Radiology and Radiation Control Office; Altman, K.I. [Univ. of Rochester Medical Center, NY (United States). Dept. of Biochemistry and Biophysics

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced changes in intracellular signaling that induce mechanisms of DNA damage control different from those operating at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. The aim of this paper is to demonstrate that by use of microdosimetric concepts, the energy deposited in cell mass can be related to the occurrence of cellular responses, both damaging and defensive.

  17. Low doses of ionizing radiation incurred at low dose rates

    International Nuclear Information System (INIS)

    This paper is a draft report by a Task Group of the International Nuclear Societies Council. It addresses the scientific information available on the biological effects of low radiation doses and dose rates, defined for the purpose of the report as total doses less than 10 mSv, received at high rates in single events, or dose rates less than 20 mSv per year, received continuously. It is concluded that there is no scientific evidence which supports the hypothesis that radiation causes an increase in the incidences of cancers or hereditary effects in humans at low doses. For radiation protection purposes, the International Commission on Radiological Protection recommends the assumption that the risk of radiation induced cancer is proportional to the dose without a threshold. However, at low doses and low dose rates, the available evidence indicates either that there is no significant risk or that there may be benefits from exposure. For all purposes other than scientific research, the Task Group therefore recommends the assumption (on the current basis of information) that there is no significant biological effect from low doses of radiation. There is a range of views amongst members of the Task Group on several matters, particularly the bio-positive effects of low radiation doses. However, there is complete agreement that the possibility and significance of bio-positive effects from radiation exposure of humans need to be accepted and investigated without prejudiceted and investigated without prejudice

  18. A Low-Dose Electron Diffraction Assay for Protection of Protein Structure against Damage from Drying

    Science.gov (United States)

    Massover, William H.

    2004-04-01

    A new assay using low-dose electron diffraction to measure the protection of protein structure against damage from drying is described. When thin single crystals of catalase are dried within water alone, low-dose electron diffraction yields no Bragg spots. Drying within an experimental aqueous solution that permits detection of diffraction spots thereby indicates a positive result, and the extent of these Bragg reflections into the high angle range gives a quantitative measure of the degree of protection. Bragg spots out to 3.7 3.9 [Angstrom capital A, ring] are recorded for drying within 100 mM solutions of the known structure-preserving sugars, sucrose, tannin, and trehalose. The ability of trehalose to maintain native protein structure during drying starts between 10 and 25 mM, and changes only slightly at concentrations above this threshold; with drying in 150-mM trehalose, catalase crystals yield diffraction spots out to 3.7 [Angstrom capital A, ring]. Drying within the organic nonsugar polymer polyvinylpyrrolidone gives Bragg spots to 4.0 [Angstrom capital A, ring]. This new assay should be useful to measure the unexamined structure-preserving capabilities of modified sugars, other nonsugars, and mixtures to identify which protective matrix maintains native protein structure to the greatest extent during drying; electron crystallography using that optimal matrix should yield protein structure at improved levels of high resolution.

  19. Low Dose Radiation-Induced Genome and Epigenome Instability Symposium and Epigenetic Mechanisms, DNA Repair, and Chromatin Symposium at the EMS 2008 Annual Meeting - October 2008

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F; Kovalchuk, Olga; Dolinoy, Dana C; Dubrova, Yuri E; Coleman, Matthew A; Schr, Primo; Pogribny, Igor; Hendzel, Michael

    2010-02-19

    The Low Dose Radiation Symposium thoughtfully addressed ionizing radiation non-mutational but transmissable alterations in surviving cells. Deregulation of epigenetic processes has been strongly implicated in carcinogenesis, and there is increasing realization that a significant fraction of non-targeted and adaptive mechanisms in response to ionizing radiation are likely to be epigenetic in nature. Much remains to be learned about how chromatin and epigenetic regulators affect responses to low doses of radiation, and how low dose radiation impacts other epigenetic processes. The Epigenetic Mechanisms Symposium focused on on epigenetic mechanisms and their interplay with DNA repair and chromatin changes. Addressing the fact that the most well understood mediators of epigenetic regulation are histone modifications and DNA methylation. Low levels of radiation can lead to changes in the methylation status of certain gene promoters and the expression of DNA methyltransferases, However, epigenetic regulation can also involve changes in higher order chromosome structure.

  20. Linearity at low doses - fact or fiction?

    International Nuclear Information System (INIS)

    This article briefly reviews the effect of low dose irradiation on radiation-induced chromosome aberrations in human lymphocytes. Attempts with this system to follow the dose-effect relationship to doses below about 10 or 20 mGy of x-rays have been unsuccessful. The implications of such lymphocyte studies for radiological protection purposes where cancer is the end-point of importance are discussed. (author)

  1. Mitigating effects of L-selenomethionine on low-dose iron ion radiation-induced changes in gene expression associated with cellular stress

    OpenAIRE

    NUTH, MANUNYA; KENNEDY, ANN R.

    2013-01-01

    Ionizing radiation associated with highly energetic and charged heavy (HZE) particles poses a danger to astronauts during space travel. The aim of the present study was to evaluate the patterns of gene expression associated with cellular exposure to low-dose iron ion irradiation, in the presence and absence of L-selenomethionine (SeM). Human thyroid epithelial cells (HTori-3) were exposed to low-dose iron ion (1 GeV/n) irradiation at 10 or 20 cGy with or without SeM pretreatment. The cells we...

  2. Low concentration of exogenous carbon monoxide protects mammalian cells against proliferation induced by radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Liping [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Bao, Lingzhi; Wu, Wenqing; Wang, Hongzhi [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Han, Wei, E-mail: hanw@hfcas.cn [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China)

    2014-01-15

    Highlights: We show the possibility of modulate proliferation induced by radiation-induced bystander effect with low concentration carbon monoxide. Carbon monoxide inhibited proliferation via modulating the transforming growth factor ?1 (TGF-?1)/nitric oxide (NO) signaling pathway. Exogenous carbon monoxide has potential application in clinical radiotherapy. - Abstract: Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after ?-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor ?1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy.

  3. Low concentration of exogenous carbon monoxide protects mammalian cells against proliferation induced by radiation-induced bystander effect

    International Nuclear Information System (INIS)

    Highlights: We show the possibility of modulate proliferation induced by radiation-induced bystander effect with low concentration carbon monoxide. Carbon monoxide inhibited proliferation via modulating the transforming growth factor ?1 (TGF-?1)/nitric oxide (NO) signaling pathway. Exogenous carbon monoxide has potential application in clinical radiotherapy. - Abstract: Radiation-induced bystander effect (RIBE) has been proposed to have tight relationship with the irradiation-caused secondary cancers beyond the irradiation-treated area after radiotherapy. Our previous studies demonstrated a protective effect of low concentration carbon monoxide (CO) on the genotoxicity of RIBE after ?-particle irradiation. In the present work, a significant inhibitory effect of low-dose exogenous CO, generated by tricarbonyldichlororuthenium (II) dimer [CO-releasing molecule (CORM-2)], on both RIBE-induced proliferation and chromosome aberration was observed. Further studies on the mechanism revealed that the transforming growth factor ?1/nitric oxide (NO) signaling pathway, which mediated RIBE signaling transduction, could be modulated by CO involved in the protective effects. Considering the potential of exogenous CO in clinical applications and its protective effect on RIBE, the present work aims to provide a foundation for potential application of CO in radiotherapy

  4. How low-dose research initiative will have 'major implications' for radiological protection

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2014-02-15

    An initiative to bring together all the scientific research on exposure to low and very low doses of ionising radiation will improve the global radiological protection system and could have major implications for dealing with the rehabilitation of areas affected by the March 2011 Fukushima-Daiichi nuclear accident, the head of the initiative has said. Jacques Repussard, director-general of the French Institut de Radioprotection et de Suerete Nucleaire (IRSN) and president of Melodi (Multidisciplinary European Low Dose Initiative), told NucNet that science has not yet provided all the answers that governments need to respond to concerns about low doses of radiation. (orig.)

  5. Low Dose and Low Dose Rate Radiation Effects and Models. Summary of National Council on Radiation Protection and Measurements NCRP Forty Fourth Annual Meeting (14-15 April 2008 in Bethesda, Maryland, USA

    International Nuclear Information System (INIS)

    This paper summarizes the highlights of presentations at the 44th Annual National Council on Radiation Protection and Measurements (NCRP) Annual Meeting, primary conclusions drawn by the speakers, and future activities of NCRP in analysing the biological and potential human health effects of exposure to low doses of ionizing radiation. A related subject discussed by speakers at the meeting was the effect of the rate of delivery of radiation doses (i.e., dose rate). The goal of the 2008 NCRP Annual Meeting was to bring these subjects into the perspective of currently available data and models of the biological responses and human health impacts of exposure to low doses of radiation. Views of the public and the role of growing knowledge of low dose radiation effects on regulatory decision making were also discussed. Future plans by the NCRP to continue its analysis of biological and human health effects of low dose and low dose rate ionizing radiation are described. (author)

  6. Low-dose ionizing radiation induces direct activation of natural killer cells and provides a novel approach for adoptive cellular immunotherapy.

    Science.gov (United States)

    Yang, Guozi; Kong, Qingyu; Wang, Guanjun; Jin, Haofan; Zhou, Lei; Yu, Dehai; Niu, Chao; Han, Wei; Li, Wei; Cui, Jiuwei

    2014-12-01

    Recent evidence indicates that limited availability and cytotoxicity have restricted the development of natural killer (NK) cells in adoptive cellular immunotherapy (ACI). While it has been reported that low-dose ionizing radiation (LDIR) could enhance the immune response in animal studies, the influence of LDIR at the cellular level has been less well defined. In this study, the authors aim to investigate the direct effects of LDIR on NK cells and the potential mechanism, and explore the application of activation and expansion of NK cells by LDIR in ACI. The authors found that expansion and cytotoxicity of NK cells were markedly augmented by LDIR. The levels of IFN-? and TNF-? in the supernatants of cultured NK cells were significantly increased after LDIR. Additionally, the effect of the P38 inhibitor (SB203580) significantly decreased the expanded NK cell cytotoxicity, cytokine levels, and expression levels of FasL and perforin. These findings indicate that LDIR induces a direct expansion and activation of NK cells through possibly the P38-MAPK pathway, which provides a potential mechanism for stimulation of NK cells by LDIR and a novel but simplified approach for ACI. PMID:25402754

  7. Protective and Therapeutic Role of Low Dose Gamma Radiation on Streptozotocin Induced Diabetes in Rats

    International Nuclear Information System (INIS)

    Diabetes mellitus is a multi-factorial disease which is characterized by vascular and renal complication. This study was initiated to investigate the protective and the therapeutic effect of low dose of gamma radiation (LDR) on diabetic complications. A total of 30 adult male rats were divided into 5 groups: Group I: served as control and injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group II: rats became diabetic via intraperitoneal injection with 60 mg/kg streptozotocin (STZ) dissolved in 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group III irradiated rats (IRR): submitted to fractionated dose of whole body gamma rays; 0.25 Gy for 2 consecutive days (whole dose 0.5 Gy), group IV diabetic irradiated rats (STZ + IRR): rats became diabetic as group II then four weeks after diabetes induction (day 28), rats were submitted to 2 fractions of whole body gamma rays as in group III, and group V irradiated diabetic rats (IRR + STZ): rats were injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer then submitted to whole body gamma rays; 0.25 Gy for 2 consecutive days then one hour after the last IRR dose, rats were made diabetic as group II. In pre and post-irradiation of STZ rats, significant changes were observed in serum lipid profiles, hepatic and cardiac serum enzymes. Significant decrease in hepatic and cardiac malondialdehyde (MDA) and total nitrate/nitrite (NO(x)) levels, and significant increase in superoxide dismutase (SOicant increase in superoxide dismutase (SOD) and glutathione (GSH) levels were observed as compared to diabetic group. The study suggests that LDR may provide useful protective and therapeutic option in the reversal of oxidative stress induced in diabetic rats

  8. Low-dose atorvastatin, losartan, and particularly their combination, provide cardiovascular protection in isolated rat heart and aorta.

    Science.gov (United States)

    Lunder, Mojca; Ziberna, Lovro; Jani?, Miodrag; Jerin, Ale; Skitek, Milan; Sabovi?, Mio; Drevenek, Gorazd

    2013-03-01

    Statins and angiotensin receptor blockers at therapeutic doses have beneficial cardiovascular effects, which can be applied for cardiovascular protection. We explored whether low doses of atorvastatin, losartan, and particularly their combination, possess important pleiotropic vasodilatory effects. Wistar rats were treated daily with low-dose atorvastatin (2 mg/kg, n = 15), low-dose losartan (5 mg/kg, n = 15), their combination (n = 15), or saline (n = 15). After 4, 6, or 8 weeks the animals were anesthetized, blood samples taken, and their hearts and thoracic aortas isolated. Two kinds of experiments were performed: the measurement of coronary flow rate after ischemia/reperfusion myocardial injury and endothelium-dependent relaxation of thoracic aorta. In both models, maximal vasodilation activity was obtained in rats treated for 6 weeks. In the ischemia/reperfusion myocardial injury model, coronary flow increased (atorvastatin or losartan 1.9-fold, P < 0.01; combination 2.4-fold, P < 0.001) compared with controls. In the thoracic aorta model, endothelium-dependent relaxation significantly increased only in the combination group compared with the control group (up to 1.4-fold; P < 0.01). Simultaneously, we detected increased anti-inflammatory activity and increased nitric oxide concentration, but no changes in lipids and blood pressure. In a rat model we showed important vasodilatory activity of low-dose atorvastatin, losartan, and particularly their combination. The effects of the low-dose combination were accompanied by, and probably at least partly achieved by, anti-inflammatory and nitric oxide pathways. Overall, these results could be valuable for the development of new vascular protective strategies focusing on a low-dose regimen of statins and sartans, and particularly their combination. PMID:22610592

  9. Anti-apoptotic peptides protect against radiation-induced cell death

    International Nuclear Information System (INIS)

    The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues

  10. Protective Effect of Curcumin on ? - radiation Induced Chromosome Aberrations in Human Blood Lymphocytes

    International Nuclear Information System (INIS)

    The present work is aimed at evaluating the radioprotective effect of curcumin on ? radiation induced genetic toxicity. The DNA damage was analyzed by the frequencies of chromosome aberrations assay. Human lymphocytes were treated in vitro with 5.0 ?g/ml of curcumin for 30 min at 37 degree C then exposed to 1, 2 and 4 Gy gamma-radiation. The lymphocytes which were pre-treated with curcumin exhibited a significant decrease in the frequency of chromosome aberration at 1 and 2 Gy radiation-induced chromosome damage as compared with the irradiated cells which did not receive the curcumin pretreatment. Thus, pretreatment with curcumin gives protection to lymphocytes against ?-radiation induced chromosome aberration at certain doses. (author)

  11. Expression of the Ku70 subunit (XRCC6) and protection from low dose ionizing radiation during zebrafish embryogenesis

    OpenAIRE

    Bladen, Catherine L.; Navarre, Sammy; Dynan, William S.; Kozlowski, David J.

    2007-01-01

    The Ku70 protein, a product of the XRCC6 gene, is a component of the nonhomologous end-joining (NHEJ) pathway of DNA repair, which protects cells from the effects of radiation-induced DNA damage. Although the spatial expression of Ku70 during vertebrate embryogenesis has not been described, DNA repair proteins are generally considered to be housekeeping genes, which are required for radioprotection in all cells. Here, we report the cloning and characterization of the zebrafish Ku70 orth...

  12. Protective Effect of Low Dose Gamma Irradiation against Oxidative Damage in Rats Administrated with Ferric- Nitrilotriacetate

    International Nuclear Information System (INIS)

    Many studies have demonstrated the beneficial adaptive response of low dose gamma-irradiation. Low dose gamma-irradiation (LDR) might be effective for the prevention of various reactive oxygen species-related diseases. Ferric nitrilotriacetate (Fe-NTA) is a strong oxidant, which generates highly reactive hydroxyl radical and causes injuries of various organs including the kidney and liver. This study was designed to investigate the ability of low dose gamma-irradiation to restrain Fe-NT A induced oxidative stress. Sprague Dawley male albino rats were subjected to low dose gamma-irradiation (50 cGy). Animals were challenged with Fe-NT A (9 mg Fe/kg body weight, intraperitoneally). Results showed that Fe-NTA enhances lipid peroxidation (LPx) accompanied with reduction in glutathione (GSH) content, antioxidant enzymes, viz., glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and phase-U metabolizing enzyme glutathione-S-transferase (GST). Fe-NTA also enhances the concentration of blood urea nitrogen (BUN) and serum creatinine as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) activities. Exposure to low dose gamma- irradiation (3 h after Fe-NTA administration) resulted in a significant decrease in LPx, BUN, serum creatinine contents as well as ALT, AST and GGT enzyme activities. GSH content; GST and antioxidant enzymes were also recovered to significant levees were also recovered to significant level. Thus, our data suggest that exposure to LDR might be a useful antioxidant mediator to suppress the Fe-NTA induced-oxidative damage in rats

  13. Liv.52 protection against radiation induced lesions in mammalian liver

    International Nuclear Information System (INIS)

    The effect of Liv.52 on mammalian liver was studied after whole body exposure to 5.5 Gy of cobalt-60 gamma radiation. It was found that the drug protected the organ against radation-induced changes. The protective effect was manifested in the form of early recovery as indicated by the absence of pathological changes like cytoplasmic degranulation, loss of nuclei from many cells and abnormal architecture at 10 days and restoration of normal structure by 4 weeks. Liv.52 may neutralize the peroxides formed from water molecules after irradiation which are toxic and cause the damage to the organ. Thus it seems the drug may act as a detoxicating agent. (author)

  14. Pharmacologic approaches to protection against radiation-induced lethality and other damage.

    OpenAIRE

    Weiss, J. F.

    1997-01-01

    Studies on mechanisms of radioprotection are leading to a more rational use of protectors for different applications. In considering the feasibility of radioprotectors that act through various mechanisms, it is necessary to distinguish the application needed, e.g., protection against accidental external or internal exposures, acute high-dose radiation injury or low doses over a long period, high-LET radiation exposures during space flight, and protection of normal tissues of cancer patients w...

  15. A model for low dose effects of low-LET radiation delivered at high dose rates

    OpenAIRE

    Scho?llnberger, H.; Stewart, R. D.; Mitchel, R. E. J.

    2006-01-01

    In vitro studies show that protective tumour-reducing effects occur for low dose rates (mGy per minute). To account for these phenomena, we have previously developed stochastic and deterministic multi-stage cancer models that include radiation-induced adaptations in DNA repair processes and radical scavenging. Here, these models are extended to account for the induction of radioprotective mechanisms for low doses of low LET radiation delivered at high dose rates. Cellular adaptations in DNA r...

  16. Health effect of low dose/low dose rate radiation

    International Nuclear Information System (INIS)

    The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned lly conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose radiation effects may affect the concept of human carcinogenic process. (T.T.)

  17. Protection of human cells from the effect of cadmium chloride pre-treated by vitamins, interferon and low dose ?-irradiation

    International Nuclear Information System (INIS)

    Protective properties of interferon, vitamins in comparison with low-dose irradiation were considered. Results of induction of DNA breaks and their resynthesis in human cells treated with cadmium chloride under formation of adaptive response and in case of preliminary treatment with vitamins and interferon. It was shown that pretreatment of cells by combination of retinol and ascorbic acid resulted in complete repair of DNA injuries, induced by cadmium chloride. The presented data permitted to recommend combination of A and C vitamins fro protection of man exposed to the effect of heavy metal salts and cadmium compound in particular

  18. Protective effect of tanshinone IIA against radiation-induced ototoxicity in HEI-OC1 cells.

    Science.gov (United States)

    DU, Shasha; Yao, Qiwei; Tan, Peixin; Xie, Guozhu; Ren, Chen; Sun, Quanquan; Zhang, Xiao; Zheng, Rong; Yang, Kaijun; Yuan, Yawei; Yuan, Quan

    2013-10-01

    Radiotherapy is a highly efficient treatment method for nasopharyngeal carcinoma that is often accompanied by significant ototoxic side-effects. The inner ear hair cells are particularly prone to serious injury following radiotherapy. Tanshinone IIA is a transcription factor inhibitor that is extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge. The present study investigated the effects of tanshinone IIA treatment on radiation-induced toxicity in the HEI-OC1 hair cell line. Using an MTT assay and flow cytometry, the radiation-induced weakening of the cells was observed to be alleviated when the cells were pre-treated with tanshinone IIA. Radiation exposure promoted p65/nuclear factor (NF)-?B nuclear translocation and activated the p53/p21 pathway, two processes which play a significant role in radiation-induced cell apoptosis. However, pre-treatment of the cells with tanshinone IIA inhibited p65/NF-?B nuclear translocation and p53/p21 pathway activation. These results demonstrate that tanshinone IIA is capable of protecting cochlear cells from radiation-induced injury through the suppression of p65/NF-?B nuclear translocation and the p53/p21 signaling pathway. PMID:24137434

  19. Regulation Of Nf=kb And Mnsod In Low Dose Radiation Induced Adaptive Protection Of Mouse And Human Skin Cells

    Energy Technology Data Exchange (ETDEWEB)

    Jian Li

    2012-11-07

    A sampling of publications resulting from this grant is provided. One is on the subject of NF-κB-Mediated HER2 Overexpression in Radiation-Adaptive Resistance. Another is on NF-κB-mediated adaptive resistance to ionizing radiation.

  20. Radiation-induced bystander effects: are they relevant for radiation protection of non-human biota?

    International Nuclear Information System (INIS)

    This paper reviews our current knowledge of the mechanisms underlying the induction of bystander effects by low dose low LET ionizing radiation and discusses how they may be related to observed adaptive responses, low dose hyper-sensitivities or other effects of low dose exposures which are not correlated with dose in a simple relationship. Bystander effects appear to be the result of a generalized stress response in tissues or cells. They occur widely in many classes, including Crustacea, Molluscs, Pisces and Mammals and have been demonstrated following in vivo exposure to irradiation.. The signals may be produced by all exposed cells but the response appears to require a quoram to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but is p53 independent. Whilst a death response might appear to be adverse, it is also possible that it could, at these low doses, be protective and remove damaged cells from the population. Since many cell populations carry damaged cells without being exposed to radiation (so called 'background damage'), it is possible that low doses exposures could cause removal of cells damaged by agents other than the test dose of radiation. This mechanism would lead to the production of 'U-shaped' dose response curves often observed in toxicology and radiobiology where a non-linear protective dose response precedes a linear or curvil dose response precedes a linear or curvilinear high dose response. In this scenario, the level of 'adaptive' or beneficial response will be related to the background damage carried by the cell population. This model may be important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors. (authors)

  1. Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents

    International Nuclear Information System (INIS)

    Purpose: To evaluate the protective effects of antioxidant agents against space radiation-induced oxidative stress in cultured human epithelial cells. Methods and Materials: The effects of selected concentrations of N-acetylcysteine, ascorbic acid, sodium ascorbate, co-enzyme Q10, ?-lipoic acid, L-selenomethionine, and vitamin E succinate on radiation-induced oxidative stress were evaluated in MCF10 human breast epithelial cells exposed to radiation with X-rays, ?-rays, protons, or high mass, high atomic number, and high energy particles using a dichlorofluorescein assay. Results: The results demonstrated that these antioxidants are effective in protecting against radiation-induced oxidative stress and complete or nearly complete protection was achieved by treating the cells with a combination of these agents before and during the radiation exposure. Conclusion: The combination of antioxidants evaluated in this study is likely be a promising countermeasure for protection against space radiation-induced adverse biologic effects

  2. Protective effect of DNA-spermidine (DA-51) against radiation-induced leukopenia

    International Nuclear Information System (INIS)

    DNA-spermidine (DA-51), which has been originally developed by Dr. Sekiguchi et al. as a protective agent against radiation-induced leukopenia, was submitted to clinical trial by the double blind test. The protective effect against radiation-induced leukopenia and side effect of DA-51 were compared with those of Inosine, selected as a control agent, on breast cancer cases receiving prophylactic irradiation. Daily dose of 2700 mg of DA-51 and 1800 mg of Inosine were administered orally during 5 week a period of irradiation. The differences between the white blood cell counts, the thrombocyte counts and the percentages of lymphocytes in the DA-51 and the Inosine treated groups were assessed at 1, 3 and 5 weeks by x2 and T tests, and the following results are obtained: No significant difference in white blood cell or thrombocyte counts was demonstrated at 1, 3 or 5 weeks between the two groups. The only significant difference noted was in the percentage of lymphocyte at 5 weeks, and the thrombocyte counts at 3 weeks. DNA-spermidine is considered to be an effective drug against radiation-induced leukopenia, comparable to Inosine and without noticeable side effects. (Evans, J.)

  3. Protective effect of triphala on radiation induced acute intestinal mucosal damage in Sprague Dawley rats.

    Science.gov (United States)

    Yoon, Won Sup; Kim, Chul Yong; Yang, Dae Sik; Park, Young Je; Park, Won; Ahn, Yong Chan; Kim, Seok-Hyung; Kwon, Ghee Young

    2012-03-01

    Aim of the study was to determine protective effect of triphala on radiation-induced rectal mucosal damage. Male Sprague Dawley rats (30) were divided into 5 groups. Rats in group A were sham irradiated and rats in group B underwent only irradiation. Rats in group C were administered triphala 1 g/kg/day orally for 5 consecutive days before irradiation. Rats in group D and E were administered triphala 1 and 1.5 g/kg/day orally for 10 consecutive days, respectively. Rectal mucosal damage was induced by a single fraction of 12.5Gy gamma irradiation (Ir-192) on 5th day. All the rats were autopsied on 11th day and histological changes in surface epithelium, glands, and lamina propria were assessed. Proctitis showed significant improvement in surface epithelium (P triphala improved radiation-induced damage of glands. PMID:22439434

  4. Protection against radiation induced oxidative stress by Syzygium cumini seed extract

    International Nuclear Information System (INIS)

    Chemical radiation protection is an important strategy to protect living beings against the deleterious effects of radiation. Earlier, the synthetic chemical substances, which could minimize the pathological changes in the living systems after exposure to ionizing radiation, were looked into. However, the practical applicability of these compounds remained limited owing to high toxicity at their optimum protective dose. Jambul (Syzygium cumini) is an evergreen tropical tree in the flowering plant family Myrtaceae, native to Bangladesh, India, Nepal, Pakistan and Indonesia. This tree species has been of interest to researchers because the chemical constituents such as gallic acid, ellagic acid, corilagin and related ellagitannins, 3,6-hexahydroxydiphenoyl-glucose and its isomer, 4,6-hexahydroxydiphenoyl glucose, 1-galloyl glucose, 3-galloyl glucose and quercetin is reported in the alcoholic extract of Jambul seeds. In the present study, the radioprotective effect of Syzygium cumini seed extract (SCE) was studied on radiation-induced deleterious alterations. Oral administration of such extract (25 mg/kg b. wt./day/animal) for 5 consecutive days, half an hr. before whole-body exposure to 6 Gy gamma radiation, enhanced the 30 days survival and also inhibited the radiogenic sickness, weight loss and life shortening. SCE ameliorated radiation induced depletion in glutathione (GSH) and antioxidant enzymes (SOD, CAT and GST) as well as elevation of lipid peroxidation (LPO) les elevation of lipid peroxidation (LPO) level in blood and liver of mice. The significant reduction in the yield of LPO demonstrates that Syzygium cumini seed protects the membranes against radiation-induced oxidative damage. These findings conclude that such seed extract provides significant radioprotection, and it may be potentially valuable in the prevention of injuries caused during planned and unplanned radiation exposure. (author)

  5. Alzheimer's Disease: Fatty Acids We Eat may be Linked to a Specific Protection via Low-dose Aspirin.

    Science.gov (United States)

    Pomponi, Massimo F L; Gambassi, Giovanni; Pomponi, Massimiliano; Masullo, Carlo

    2010-08-01

    It has been suggested that cognitive decline in aging is the consequence of a growing vulnerability to an asymptomatic state of neuroinflammation. Moreover, it is becoming more evident that inflammation occurs in the brain of Alzheimer's disease (AD) patients and that the classical mediators of inflammation, eicosanoids and cytokines, may contribute to the neurodegeneration. In agreement with this observation, aspirin (ASA) - a non-steroidal anti-inflammatory drug - may protect against AD and/or vascular dementia. However, both the time of prescription and the dose of ASA may be critical. A major indication for low-dose ASA is in combination with docosahexaenoic acid (DHA). DHA plays an essential role in neural function and its anti-inflammatory properties are associated with the well-known ability of this fatty acid to inhibit the production of various pro-inflammatory mediators, including eicosanoids and cytokines. Higher DHA intake is inversely correlated with relative risk of AD and DHA+ASA supplement may further decrease cognitive decline in healthy elderly adults. Although low-dose ASA may be insufficient for any anti-inflammatory action the concomitant presence of DHA favours a neuroprotective role for ASA. This depends on the allosteric effects of ASA on cyclooxygenase-2 and following production - from DHA - of specific lipid mediators (resolvins, protectins, and electrophilic oxo-derivatives). ASA and DHA might protect against AD, although controlled trials are warranted. PMID:22396856

  6. Alzheimers Disease: Fatty Acids We Eat may be Linked to a Specific Protection via Low-dose Aspirin

    Science.gov (United States)

    Pomponi, Massimo F. L.; Gambassi, Giovanni; Pomponi, Massimiliano; Masullo, Carlo

    2010-01-01

    It has been suggested that cognitive decline in aging is the consequence of a growing vulnerability to an asymptomatic state of neuroinflammation. Moreover, it is becoming more evident that inflammation occurs in the brain of Alzheimers disease (AD) patients and that the classical mediators of inflammation, eicosanoids and cytokines, may contribute to the neurodegeneration. In agreement with this observation, aspirin (ASA) - a non-steroidal anti-inflammatory drug - may protect against AD and/or vascular dementia. However, both the time of prescription and the dose of ASA may be critical. A major indication for low-dose ASA is in combination with docosahexaenoic acid (DHA). DHA plays an essential role in neural function and its anti-inflammatory properties are associated with the well-known ability of this fatty acid to inhibit the production of various pro-inflammatory mediators, including eicosanoids and cytokines. Higher DHA intake is inversely correlated with relative risk of AD and DHA+ASA supplement may further decrease cognitive decline in healthy elderly adults. Although low-dose ASA may be insufficient for any anti-inflammatory action the concomitant presence of DHA favours a neuroprotective role for ASA. This depends on the allosteric effects of ASA on cyclooxygenase-2 and following production - from DHA - of specific lipid mediators (resolvins, protectins, and electrophilic oxo-derivatives). ASA and DHA might protect against AD, although controlled trials are warranted. PMID:22396856

  7. Evaluation of Antioxidant Activity and ?-radiation Induced Oxidative Stress Protection of Aquilaria crassna Leaf Extract

    International Nuclear Information System (INIS)

    In Asia Aquilaria has long been used in many traditional medicines due to its enrichment inseveral active ingredients such as flavonoids, tannins, and cardiac glycosides. The objective of this work is to investigate and evaluate antioxidant and ?-radiation induced oxidative stress protection activities of the Aquilaria leaf extract. The leaf was extracted by Soxhlet extractor in which both the upper fraction (filtrate) and the lower fraction (precipitate) were kept separately for evaluation. In terms of antioxidant activity, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) was used in a free radical scavenging assay. The precipitate of 3.13, 6.25, 12.50, 25.00, 50.00 and 100 ?g/ml exhibited 17.70%, 33.52%, 45.80%, 60.49%, 76.30% and 85.71% DPPH inhibition, respectively. The filtrate at the same concentrations showed approximately 50% less inhibition than the precipitate. The extracts did not exhibit any cytotoxicity by MTT assay. However, the precipitate at 10, 20, 100 ?g/ml and the filtrate at 50, 100, 200 ?g/ ml could not protect human dermal fibroblast cells from irradiation damage when the cells were treated for 45 min or 24 h prior to exposure to gamma radiation at 0, 3 and 10 Gy. In conclusion, the Aquilaria leaf extract contained a potent antioxidant activity, but not ?-radiation induced oxidative stress protection activity.

  8. Protective effects of acemannan against radiation induced damage in Swiss albino mice

    International Nuclear Information System (INIS)

    Aloe vera is one of the well known medicinal plant and posses a large no. of beneficial bioactive components like Anthraquinone, C-glycosides, anthrones, emodin, acemannan etc. Acemannan (poly-acetylated mannose) is one of the active component present in aloe vera gel and has anticancerous and antimicrobial properties. It has also been reported to have wound healing properties and has role as immunomodulator. The objective of the present study was to evaluate protective efficacy of acemannan against radiation induced damage in in-vitro and in in-vivo using murine splenocytes and Swiss albino mice as a model system. In vitro studies were done using primary mouse splenocytes cultures and effect of radiation on cell proliferation, viability, ROS, DNA damage and apoptosis were studies using MTT, trypan blue, DCFDA, single cell gel electrophoresis and ladder assay respectively. For in-vivo studies mice were pretreated with different doses of drug for 7 days followed by irradiation (5 Gy). Twenty four hours post-irradiation mice was sacrificed to observe the activity of antioxidant enzymes and level of protein expression. Acemannan showed a significant induction of proliferation of splenocytes in radiation treated groups both in in-vitro and in in-vivo. Beside a decrease in radiation induced ROS and DNA damage was observed in in-vitro system. Acemannan treatment was able to reduce the radiation induced apoptosis by about 50% both in in-vitro and in in-vivo. In in-vivo acemannan helps in the restoration of the antioxidant enzyme level (catalase, SOD, DTD and GST) besides maintaining the proper redox status via GSH, in irradiated mice. In our studies a dose of 50 mg/kg body wt of acemannan showed the best protective effects. On the basis of the above results it could be concluded that acemannan may have radioprotective potential. (author)

  9. Experimental study of the protective effects of Zhongfei decoction on radiation-induced pneumonia in rats

    International Nuclear Information System (INIS)

    Objective: To investigate the protective effect and its possible mechanism of ZhongFei Decoction on radiation-induced pneumonia in rats. Methods: Single irradiation was given at two thorax of female Wistar rats with 30 Gy of 6 MV X irradiation. Sixty rats were randomly divided into the control group, radiation group, radiation plus DXM and ZhongFei Decoction plus radiation group. On days 14 and 28 after treatment, 5 rats of each group were sacrificed, and their lungs were harvested for measurement of the lung index, the difference of the histopathology change, the concentration of hydroxyproline (hyp), and expression of transforming growth factor-?1 in lungs were analyzed by HE stain, biochemical method and immunohistochemical method, respectively. Results: The pathological study showed marked lung injury in the radiation group while only slight hyperemia hemorrhage, exudation and thickness of alveolar walls in the lungs of ZhongFei Decoction plus radiation group, the concentration of hydroxyproline and expression of TGF-?1 in the radiation lungs increased compared with that in the control group and reduced in the ZhongFei Decoction plus radiation group compared with that in the radiation group. Conclusions: ZhongFei Decoction could have protective effects on the radiation-induced pneumonia and the mechanism of its may be related with down-regulating the expression of TGF-?1 in the irritated lung tissue. (authors)

  10. Radiation-induced bystander effects: Relevance for radiation protection of human and non-human biota

    International Nuclear Information System (INIS)

    In this paper our current knowledge of the mechanisms underlying the induction of bystander effects by low dose low LET ionizing radiation is reviewed in the context of relevance to radiation protection issues. The question of how bystander effects may be related to observed adaptive responses, systemic genomic instability or other effects of low doses exposures is also considered. Bystander effects appear to be the result of a generalized stress response in tissues or cells. The signals may be produced by all exposed cells, but the response may require additional system parameters to exist in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response. This can manifest as apoptotic cell death, terminal differentiation, reproductive cell death or necrosis. While a death response might appear to be adverse, the position is argued in this paper, that it can in fact be protective and remove damaged cells from the reproducing population. Since many cell populations carry damaged cells without being exposed to radiation (so-called 'background damage'), it is possible that low dose radiation exposures cause removal of cells damaged by agents other than the test dose of radiation. This mechanism would lead to the production of 'u- or n-shaped' dose response curves. In this scenario, the level of harmful or beneficial response will be related to the background damage carried by the cell population and damage carried by the cell population and the genetic program determining response to damage. This model--may be particularly important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors on biota. (author)

  11. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase ones risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low-LET radiation). Such phantom risks also may arise from risk assessments conducted for com

  12. Zinc and low-dose of cadmium protect sertoli cells against toxic-dose of cadmium: The role of metallothionein

    Directory of Open Access Journals (Sweden)

    Fatemeh Kheradmand

    2013-06-01

    Full Text Available Background: The impact of cadmium (Cd on male infertility may be related to the interaction with metal-binding proteins known as metallothioneins (Mts. Trace elements like zinc (Zn have protective effects on testicular damage induced by Cd. Objective: We determined the effect of Zn and low-dose Cd pre-treatment on the expression of Mt1 and Mt2 genes on testicular Sertoli cells. Materials and Methods: The cultured TM4 mouse sertoli cells were treated with 50 ?M ZnSO4 (Zn pre-treated group; ZnPG, 2 ?M CdCl2 (Cd pre-treated group; CdPG, or distilled water (DW pre-treated group; DWPG. After 18 hour, all of these groups were exposed to 100 ?M CdCl2 for different periods of time (1, 2, 3, and 6 hours. There was also a control group for all three groups, which was treated only with distilled water (without Cd or Zn pre-treatment. Cellular viability, Zn and Cd concentrations and gene expression were assessed by MTT, atomic absorption spectrometry and real time PCR methods, respectively. Results: The expression of Mt1 and Mt2 genes in ZnPG, CdPG, and DWPG was greater than the control group (p=0.02 and p=0.01, respectively. Cd concentrations in CdPG and DWPG were greater than the control group (p=0.00. Expression of both genes in ZnPG and CdPG increased after 3 hours of treatment and Cd concentration decreased simultaneously, which was more obvious in ZnPG. Conclusion: Zn and short term low-dose Cd pre-treatment might reduce the adverse effects of Cd by increasing expression of Mts genes in Sertoli cells. The protective effect of Zn was stronger than Cd.

  13. Protective effects of Korean red ginseng against radiation-induced apoptosis in human HaCaT keratinocytes

    International Nuclear Information System (INIS)

    Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways. (author)

  14. Chromosomal damage by low doses of radiation: protection by combination of dietary antioxidants

    International Nuclear Information System (INIS)

    Mice which were fed antioxidants, consisting of a combination of ?-carotene, ?tocopherol and ascorbic acid, or curcumin, ascorbic acid and chlorogenic acid are substantially protected against ?-ray induced micronuclei in polychromatic erythrocytes obtained from bone-marrow. In this context, the relevance of a more balanced intake of food material especially those with anti carcinogens/anti mutagenic principles for human health care needs no over-emphasis. (author). 9 refs., 1 tab., 1 fig

  15. Protective effect of zingerone, a dietary compound against radiation induced damage

    International Nuclear Information System (INIS)

    The radioprotective potential of phenolic alkanone, Zingerone (ZO) was investigated using human peripheral blood lymphocytes as well as Chinese hamster fibroblast (V79) cells growing in vitro and in vivo by using Swiss albino mice exposed to gamma radiation. In the in vivo studies, mice were administered with ZO (10-100 mg/kg b.wt), once daily for five consecutive days. One hour after the last administration of ZO on the fifth day, animals were whole body exposed to 10 Gy gamma radiations. The radioprotective potential was assessed using animal survival, haemopoietic stem cell survival (CFU) assay, mouse bone marrow micronucleus test, histological observations of intestinal and bone marrow damage. Effect of ZO pretreatment on radiation-induced changes in glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPx) levels was also analyzed. ZO treatment resulted increase in the LD50/30 by 1.8 Gy (dose reduction factor = 1.2). The number of spleen colonies after whole body irradiation of mice (4.5 or 7.5 Gy) was increased when ZO was administered 1 h prior to irradiation. The histological observations indicated a decline in the villus height and crypt number with an increase in goblet and dead cell population in the irradiated group, which was normalized by pretreatment with ZO. A significant (p < 0.001) reduction in micronucleated polychromatic, normochromatic erythrocytes, increased PCE/NCE ratio, increaserocytes, increased PCE/NCE ratio, increase in the GSH, GST, SOD, CAT and decreased LPx levels were observed in ZO by pretreated group when compared to the irradiated animals. Our in vitro and in vivo studies demonstrate the potential of ZO in mitigating radiation-induced cytotoxic, genotoxicity, apoptosis in cell culture and animal mortality, cytogenetic damage, intestinal and bone marrow protection in vivo. Radioprotective potential of ZO may be attributed to the inhibition radiation-induced decline in the endogenous antioxidant levels, scavenging of radiation-induced free radicals and by the suppression of lipid peroxidation as well as oxidative stress. (author)

  16. Protection by polaprezinc against radiation-induced apoptosis in rat jejunal crypt cells

    International Nuclear Information System (INIS)

    Polaprezinc, an anti-ulcer drug, is a chelate compound consisting of zinc and L-carnosine. Polaprezinc has been shown to prevent gastric mucosal injury. The anti ulcer effects of polaprezinc have been ascribed to its antioxidative property. The effect of polaprezinc on ionizing radiation-induced apoptosis was studied in the jejunal epithelial crypt cells of rats. Seven-to eight week-old Wistar rats, which were treated with 100 mg/kg of polaprezinc orally 1 h before irradiation or 2% carboxymethyl cellulose sodium in controls, were exposed to whole body X-ray irradiation at 2 Gy. The number of apoptotic cells per jejunum crypt was counted in haematoxylin and eosin stained sections at 0-6 h after irradiation. TdT-mediated dUTP-biotin nick end-labeling (TUNEL) positive cells and immunopositive cells for active caspase-3 per crypt were also counted. Accumulation of p53, p21WAF1/CIP1 and Bax expression in the jejunum after irradiation were examined by Western blot analyses. Polaprezinc treatment given prior to radiation resulted in a significant reduction in numbers of apoptotic cells, TUNEL positive cells and active caspase-3 immunopositive cells in jejunal crypt cells. Polaprezinc treatment resulted in decreases of p53 accumulation, p21WAF1/CIP1 and Bax expression after irradiation. Polaprezinc has a protective effect against ionizing radiation induced apoptosis in rat jejunal crypt cells. (author)

  17. Protection by polaprezinc against radiation-induced apoptosis in rat jejunal crypt cells.

    Science.gov (United States)

    Matsuu-Matsuyama, Mutsumi; Shichijo, Kazuko; Okaichi, Kumio; Nakayama, Toshiyuki; Nakashima, Masahiro; Uemura, Takashi; Niino, Daisuke; Sekine, Ichiro

    2008-07-01

    Polaprezinc, an anti-ulcer drug, is a chelate compound consisting of zinc and L-carnosine. Polaprezinc has been shown to prevent gastric mucosal injury. The anti ulcer effects of polaprezinc have been ascribed to its antioxidative property. The effect of polaprezinc on ionizing radiation-induced apoptosis was studied in the jejunal epithelial crypt cells of rats. Seven-to eight week-old Wistar rats, which were treated with 100 mg/kg of polaprezinc orally 1h before irradiation or 2% carboxymethyl cellulose sodium in controls, were exposed to whole body X-ray irradiation at 2 Gy. The number of apoptotic cells per jejunum crypt was counted in haematoxylin and eosin stained sections at 0-6 h after irradiation. TUNEL positive cells and immunopositive cells for active caspase-3 per crypt were also counted. Accumulation of p53, p21(WAF1/CIP1) and Bax expression in the jejunum after irradiation were examined by Western blot analyses. Polaprezinc treatment given prior to radiation resulted in a significant reduction in numbers of apoptotic cells, TUNEL positive cells and active caspase-3 immunopositive cells in jejunal crypt cells. Polaprezinc treatment resulted in decreases of p53 accumulation, p21(WAF1/CIP1) and Bax expression after irradiation. Polaprezinc has a protective effect against ionizing radiation induced apoptosis in rat jejunal crypt cells. PMID:18413982

  18. Punica granatum peel extract protects against ionizing radiation-induced enteritis and leukocyte apoptosis in rats

    International Nuclear Information System (INIS)

    Radiation-induced enteritis is a well-recognized sequel of therapeutic irradiation. Therefore we examined the radioprotective properties of Punica granatum peel extract (PPE) on the oxidative damage in the ileum. Rats were exposed to a single whole-body X-ray irradiation of 800 cGy. Irradiated rats were pretreated orally with saline or PPE (50 mg/kg/day) for 10 days before irradiation and the following 10 days, while control rats received saline or PPE but no irradiation. Then plasma and ileum samples were obtained. Irradiation caused a decrease in glutathione and total antioxidant capacity, which was accompanied by increases in malondialdehyde levels, myeloperoxidase activity, collagen content of the tissue with a concomitant increase 8-hydroxy-2'-deoxyguanosine (an index of oxidative DNA damage). Similarly, pro-inflammatory cytokines (TNF-?, IL-1? and IL-6) and lactate dehydrogenase were elevated in irradiated groups as compared to control. PPE treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Furthermore, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in irradiated animals, while PPE reversed these effects. PPE supplementation reduced oxidative damage in the ileal tissues, probably by a mechanism that is associated with the decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms. Adjuvant therapy of PPE may have a pos. Adjuvant therapy of PPE may have a potential to support a successful radiotherapy by protecting against radiation-induced enteritis. (author)

  19. Protective capacity of Rosemary extract against radiation induced hepatic injury in mice

    International Nuclear Information System (INIS)

    This study was carried out to observe the radioprotective effects of Rosemarinus officinalis leaves extract (ROE) against radiation-induced histopathological alterations in liver of mice. Materials and Methods: Adult Swiss albino mice were exposed to 6 Gy gamma radiation in the presence (experimental) or absence (control) of ROE to study the qualitative and quantitative alterations in the liver. Results: Normal hepatocyte counts were found to be declined up to day 10th post-irradiation in both the groups but thereafter such cells increased reaching to near normal level at the last autopsy interval, only in experimental group. Contrary, frequency of abnormal hepatocytes increased up to day 10th after irradiation in both the groups. Bi nucleate hepatic cells showed a biphasic mode of elevation after irradiation, first at 12 hours and second on day 10th in control group; whereas in experimental group, the elevation was comparatively less marked and even the second peak was not evident. Irradiation of animals resulted in an elevation in lipid peroxidation (L Px) and a significant decrease in glutathione (GSH) concentration in liver as well as in blood. Conversely, experimental group showed a significant decline in LPx and an elevation in GSH concentration. Conclusion: These results indicate that Rosemarinus officinalis leaves extract (ROE) is able to protect the liver of Swiss albino mice against radiation induced histopathol-ogical alteraadiation induced histopathol-ogical alterations

  20. Protective effect of triphala on radiation induced acute intestinal mucosal damage in Sprague Dawley rats

    International Nuclear Information System (INIS)

    Aim of the study was to determine protective effect of triphala on radiation-induced rectal mucosal damage. Male Sprague Dawley rats (30) were divided into 5 groups. Rats in group A were sham irradiated and rats in group B underwent only irradiation. Rats in group C were administered triphala 1g/kg/day orally for 5 consecutive days before irradiation. Rats in group D and E were administered triphala 1 and 1.5 g/kg/day orally for 10 consecutive days, respectively. Rectal mucosal damage was induced by a single fraction of 12.5Gy gamma irradiation (192Ir) on 5th day. All the rats were autopsied on 11th day and histological changes in surface epithelium, glands, and lamina propria were assessed. Proctitis showed significant improvement in surface epithelium (P<0.024), glands (P<0.000) and lamina propria (P<0.002) in group E compared to group B. Rats in group E showed significantly less change in glands (P<0.000) compared to rats in group D. All histological variables (surface epithelium, P<0.001; glands, P<0.000; lamina propria, P<0.003) compared to rats in group C. In a Tukey-b test, group E had a significantly recovered grade for glands (P<0.000) compared to groups B, C and D. Results of the present study showed that high-dose triphala improved radiation-induced damage of glands. (author)

  1. Protective role of garlic against gamma radiation induced histological and histochemical changes in rat liver

    International Nuclear Information System (INIS)

    The present work was planned to evaluate the radioprotective effect of garlic (Allium sativum) against the hazardous action of gamma radiation on liver of rat one and ten days post-exposure. Garlic was orally administered (100 mg/ kg body wt) to rats daily for two weeks before exposure to single dose whole body gamma-irradiation (5Gy). The results showed that exposure of rats to gamma- irradiation caused massive portal infiltration with inflammatory cells, dilatation of blood sinusoids, an increase in the number of Kupffer cells, vacuolation of some hepatocytes as well as pyknosis and karyolysis of hepatic nuclei in the liver tissue. Histochemical examination of liver one day post- irradiation illustrated weak to moderate glycogen particles. While, on ten days post-irradiation, a strong activity for glycogen was detected. The disturbance in carbohydrate metabolism is closely related to the radiation induced histological damage in the liver tissue. Administration of garlic for 2 weeks pre-irradiation reduced the radiation induced histopathological changes and showed marked protection against the tissue damaging effect of radiation. It could be concluded that treatment of rats with garlic before exposure to gamma-irradiation offered a noticeable radioprotective effect of the studied organ

  2. Protective effect of esculentoside A on radiation-induced dermatitis and fibrosis

    International Nuclear Information System (INIS)

    Purpose: To investigate the effect of esculentoside A (EsA) on radiation-induced cutaneous and fibrovascular toxicity and its possible molecular mechanisms, both in vivo and in vitro. Methods and Materials: Mice received drug intervention 18 hours before 30 Gy to the right hind leg. Alterations in several cytokines expressed in skin tissue 2 days after irradiation were determined by ELISA. Early skin toxicity was evaluated 3 to 4 weeks after irradiation by skin scoring, and both tissue contraction and expression of TGF-?1 were determined for soft-tissue fibrosis 3 months after irradiation. In vitro, the effect of EsA on radiation-induced nitric oxide (NO) and cytokine production in different cell types was measured by application of 2, 4, and 8 Gy. Results: In vivo, EsA reduced levels of IL-1?, MCP-1, VEGF, and TGF-?1 in cutaneous tissue and reduced soft-tissue toxicity. In vitro, EsA inhibited the IL-1? ordinarily produced after 4 Gy in A431 cells. In Raw264.7 cells, EsA reduced levels of IL-1?, IL-1?, and NO production costimulated by radiation and lipopolysaccharide (LPS). In L-929 cells, EsA inhibited VEGF, TNF, and MCP-1 production at 2, 4, and 8 Gy. Conclusions: Esculentoside A protects soft tissues against radiation toxicity through inhibiting the production of several proinflammatory cytokines and inflammatory mediators in epithelial cells, macrophages, fibroblasts, and skin tissue

  3. Protective Effect of Carica papaya Linn Against gamma-Radiation-Induced Tissue Damage in Rats

    International Nuclear Information System (INIS)

    The present study was designed to determine the possible protective effects of the Carica papaya fruit aqueous extract (CP) against ?-radiation induced oxidative stress, biochemical and hematological alterations in male albino rats. Papaya (250 mg/Kg BW /day) was given to male albino rats, via gavages for 6 days prior exposure to the 1st radiation fraction and the treatment was continued for 14 days after the 1st irradiation fraction till the end of the experiment (4 Gy / week up to 8 Gy total doses). The samples were taken from the blood and some organs, liver and kidney for the biochemical analysis. In the irradiated group, there were a significant decrease in RBCs, WBCs count and Hb content. Dramatic increments in the serum indices of liver (aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin) and kidney (urea, uric acid and creatinine) functions were also recorded depicting a liver and kidney impairment state. Also, a significant increase in thiobarbituric acid reactive substances (TBARS) content and Xanthine oxidase (XO) activity in parallel to a significant decrease in the activity of xanthine dehydrogenase accompanied by a significant decrease in reduced glutathione content (GSH), superoxide dismutase (SOD), catalase (CAT) activities were recorded in both liver and kidney tissues compared to control group. Treatment with CP (250 mg/kg) was found to offer significant protection against gamma-radiation induced toxicity in the tissues, which was evident by the improved status of most of the parameters investigated. These results suggest that CP could increase the antioxidant defense systems in the liver and kidney of irradiated animals, and may protect from adverse effects of whole body radiation

  4. Sesamol protects human embryonic kidney cells from radiation induced cell death: a potential radioprotective agent

    International Nuclear Information System (INIS)

    Radioprotectors are agents which reduce the radiation effects on cell when applied prior to exposure of radiation. In our earlier studies, we have demonstrated that sesamol protected DNA (plasmid and calf thymus) and V79 cells from radiation induced cell death and the effect was higher (DMF=2) in comparison to melatonin (DMF=1.3). This prompted us to study, sesamol mediated radioprotection in detail to understand the mechanism of action. We have chosen human embryonic kidney (HEK) cells to understand the mechanism of radioprotection. The HEK cells were treated with sesamol before exposure of g rays (60Co teletherapy, Bhabhatron II) in the radiation dose range 0-7 Gy for clonogenic survival. Toxicity, antioxidant enzyme activity other biochemical assays were performed. Flow cytometric analysis (FACS Calibre, BD, USA) was used to determine the apoptotic population and mitochondrial membrane potential (Rh 123, JC-1). ROS was determined using DCFHDA. Cell cycle analysis, caspase 3 activity and cytochrome C were also measured. Results suggested that sesamol protected HEK cells from cell death. The dose modifying factor for sesamol was 1.3, whereas the alpha protection factor was 2. Sesamol inhibited radiation induced cell cycle arrest in G2/M phase; ROS generation and depolarization of mitochondrial membrane potential and caspase-3 activity. Sesamol inhibited damage of critical cellular components (protein, lipids, membrane and amino acid) and maintained the redane and amino acid) and maintained the redox status of cells. The results will be helpful in understanding the mechanistic aspects and development of sesamol based radioprotector. (author)

  5. Biology responses to low dose radiation

    International Nuclear Information System (INIS)

    Biology responses to low dose radiation is the most important problem of medical radiation and radiation protection. The especial mechanism of low dose or low dose rate induced cell responses, has been found independent with linear no-threshold model. This article emphasize to introduce low dose or low dose rate induced biology responses of adaptive response, by-effect, super-sensitivity and genomic instability. (authors)

  6. Low-dose recombinant properdin provides substantial protection against Streptococcus pneumoniae and Neisseria meningitidis infection.

    Science.gov (United States)

    Ali, Youssif Mohammed; Hayat, Azam; Saeed, Bayad Mawlood; Haleem, Kashif S; Alshamrani, Saleh; Kenawy, Hany I; Ferreira, Viviana P; Saggu, Gurpanna; Buchberger, Anna; Lachmann, Peter J; Sim, Robert B; Goundis, Dimitrios; Andrew, Peter W; Lynch, Nicholas J; Schwaeble, Wilhelm J

    2014-04-01

    Modern medicine has established three central antimicrobial therapeutic concepts: vaccination, antibiotics, and, recently, the use of active immunotherapy to enhance the immune response toward specific pathogens. The efficacy of vaccination and antibiotics is limited by the emergence of new pathogen strains and the increased incidence of antibiotic resistance. To date, immunotherapy development has focused mainly on cytokines. Here we report the successful therapeutic application of a complement component, a recombinant form of properdin (Pn), with significantly higher activity than native properdin, which promotes complement activation via the alternative pathway, affording protection against N. menigitidis and S. pneumoniae. In a mouse model of infection, we challenged C57BL/6 WT mice with N. menigitidis B-MC58 6 h after i.p. administration of Pn (100 g/mouse) or buffer alone. Twelve hours later, all control mice showed clear symptoms of infectious disease while the Pn treated group looked healthy. After 16 hours, all control mice developed sepsis and had to be culled, while only 10% of Pn treated mice presented with sepsis and recoverable levels of live Meningococci. In a parallel experiment, mice were challenged intranasally with a lethal dose of S. pneumoniae D39. Mice that received a single i.p. dose of Pn at the time of infection showed no signs of bacteremia at 12 h postinfection and had prolonged survival times compared with the saline-treated control group (P < 0.0001). Our findings show a significant therapeutic benefit of Pn administration and suggest that its antimicrobial activity could open new avenues for fighting infections caused by multidrug-resistant neisserial or streptococcal strains. PMID:24706855

  7. Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

    Science.gov (United States)

    Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

    2015-05-25

    The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent ?-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on ?-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against ?-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy. PMID:25824410

  8. Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice

    Science.gov (United States)

    Lee, Wan; Son, Yeonghoon; Jang, Hyosun; Bae, Min Ji; Kim, Jungki; Kang, Dongil

    2015-01-01

    Purpose Pelvic irradiation for the treatment of cancer can affect normal cells, such as the rapidly proliferating spermatogenic cells of the testis, leading to infertility, a common post-irradiation problem. The present study investigated the radioprotective effect of rolipram, a specific phosphodiesterase type-IV inhibitor known to increase the expression and phosphorylation of the cyclic adenosine monophosphate response element-binding protein (CREB), a key factor for spermatogenesis, with the testicular system against pelvic irradiation. Materials and Methods Male C57BL/6 mice were treated with pelvic irradiation (2 Gy) and rolipram, alone or in combination, and were sacrificed at 12 hours and 35 days after irradiation. Results Rolipram protected germ cells from radiation-induced apoptosis at 12 hours after irradiation and significantly increased testis weight compared with irradiation controls at 35 days. Rolipram also ameliorated radiation-induced testicular morphological changes, such as changes in seminiferous tubular diameter and epithelial height. Additionally, seminiferous tubule repopulation and stem cell survival indices were higher in the rolipram-treated group than in the radiation group. Moreover, rolipram treatment counteracted the radiation-mediated decrease in the sperm count and mobility in the epididymis. Conclusions These protective effects of rolipram treatment prior to irradiation may be mediated by the increase in pCREB levels at 12 hours post-irradiation and the attenuated decrease in pCREB levels in the testis at 35 days post-irradiation in the rolipram-treated group. These findings suggest that activation of CREB signaling by rolipram treatment ameliorates the detrimental effects of acute irradiation on testicular dysfunction and the related male reproductive functions in mice. PMID:25927059

  9. Possible Radio-Protective Efficiency of Bee-Pollen against Radiation Induced Cardiotoxicity in Male Rats

    International Nuclear Information System (INIS)

    The Present study was designed to evaluate the possible radio-protective effect of Bee-Pollen (B.P.) against radiation-induced cardiotoxicity. B.P. was orally administrated to rats in a concentration of 2 mg/ kg body wt/ day for 7 days before as well as during exposure to fractionated doses of gamma-radiation (1 Gy 3 times week for a period of 2 weeks to attain a cumulative dose of 6 Gy). The protective effect of B.P. was monitored by assessment of activities of lactate dehydrogenase (LDH), aspartate transaminase (AST) and creatin phosphatase (CPK) in serum and superoxide dismutase activity (SOD), glutathione peroxidase activity (GSHPX) and reduced glutathione (GSH) and concentrations of malonaldehyde (MDA) and nitric oxide (NO) were determined in heart tissues.In addition, certain metals (Fe, Cu, Zn and Ca) were also measured in serum, selenium (Se) was detected in heart tissues.Results revealed that when B.P. was given before as well as during irradiation, it ameliorated the increases in serum enzyme activities (LDH, AST and CPK), decreases in the cardiac antioxidants, an increase in MDA and NO concentrations and metals disturbances in irradiated rats. The present results demonstrated that B.P. has antioxidant properties and could exert radio-protective effect. These, might be related to its balanced nutritional antioxidant components

  10. The Protective Role of Septilin Against Gamma Radiation-Induced Testicular Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Omaima Soliman Eissa* and Nehal Aly Moustafa

    2007-06-01

    Full Text Available Backgrounds: This study deals with evaluation of the histological and some histochemical alterations in rat testes induced by whole body gamma irradiation as well as evaluation of the protective effect of septilin (a herbal preparation against these effects. Results : The obtained results indicated that doses of (3 Gy and 6 Gy gamma radiation have testicular toxic effects in rats. The histological lesions observed in the testes varied between vacuolation, swelling, pyknosis and even necrosis in some spermatogenic cells as well as significant depletion in the number of spermatogonia, primary spermatocytes, secondary spermatocytes and spermatids. The histochemical observations revealed diminution in the polysaccharides content and increase in the collagen fibres in the testis of irradiated animals. These effects were mostly perceptive with the high dose of the radiation than with the lower one. Treatment with septilin (a herbal preparation for one week followed by gamma radiation proved that septilin has a protective effect against gamma radiation-induced toxic effects in the testes of rats; where most of the histological and histochemical changes observed due to irradiation were minimized to a large extent; however there was no complete protection. Conclusion: Thus, this study concluded that gamma-irradiation exerts toxic effects in the testes of rats and pre-treatment with septilin inhibits these toxic effects, which in turn advocate using such herbal extract as a radioprotector.

  11. The Possible Mechanisms Involved in the Protection Strategies against Radiation-Induced Cellular Damage by Carnitines

    Directory of Open Access Journals (Sweden)

    Ashraf Virmani

    2015-02-01

    Full Text Available There is constant low level background radiation from the cosmos but in certain situation the body may be subjected to increased acute or chronic exposure from other sources. This occurs in situations such as radiation accidents, medical use and could possibly occur in military/terrorist incident. Dependent on the type, strength of the actual source, degree of exposure and type of radiation different strategies may be employed to reduce damage to the body tissues. A number of pharmacological agents such as peroxisome proliferator-activated receptor (PPAR gamma agonists, diltiazem, amifostine and palifermin as well as antioxidants and metabolic compounds have been shown to be effective in preventing and also in reducing the long-term damage of the exposure of the living cells to radiation. The major drawback of synthetic (pharmacological compounds has been that they are highly toxic at the optimum protective dose. Studies have shown that various endogenously found compounds such as L-carnitine, and its derivative acetyl-L-carnitine, are able to protect tissues and organs against various forms of toxic insult including radiation damage. The radiation-induced chronic injury may also be counteracted by other metabolic compounds with amine groups and antioxidant properties similar to the carnitines such as cysteine, 3,3-diindolylmethane (DIM and N-acetylcysteine. This review discuses the radioprotective compounds as well as the potential mechanism of cellular protection against radiation by carnitines and other compounds.

  12. Possible Protective Role of Carnosine against gamma-Radiation-Induced Cardiac Dysfunction in Mice

    International Nuclear Information System (INIS)

    Oxidative Stress with subsequent production of reactive oxygen species (ROS) has been postulated as one of the mechanisms of cardiac toxicity. Carnosine (?-alanyl-L-histidine) a biological antioxidant, is a relatively non-toxic dipeptide which possesses many functions (antiglycator, scavenger of ions of zinc and copper, toxic aldehydes and protein carbonyls) that are likely to suppress oxidative stress. The aim of the present work is to investigate the possible protective effects of carnosine on gamma-radiation-induced cardiac damage in mice. Carnosine was supplemented daily to mice (50 mg/ Kg body wt), by gavage, 10 days before whole body gamma-irradiation at a dose of 5 Gy (applied as a shot dose). The results obtained showed that whole body gamma-irradiation of mice produced biochemical alteration in levels of serum glucose and lipid profile fractions. Furthermore, some markers of cardiac injury enzymes as serum lactate dehydrogenase (LDH), creatin phosphokinase (CPK) and aspartate transaminase (AST) activities showed significant increases associated with alteration in the antioxidant status of cardiac tissues. Significant increases of lipid peroxidation end product malonaldehyde (MDA) and protein carbonyl levels, xanthine oxidase (XO) activity along with reduction in the activity of cardiac antioxidant enzymes; glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were observed. Carnosine-treatment prior irradiation has attenuated the cardioior irradiation has attenuated the cardiotoxic effects of radiation obvious by reduction in the levels of MDA and protein carbonyl and XO activity, rescued the depletion of endogenous antioxidant enzymes and diminished the increases of cardiac injury markers. It could be postulated that carnosine as a multi-functional dietary supplement could exert a modulator role in the radiation-induced cardiac damage and serum biochemical changes through its antioxidant properties

  13. Protective Role of Clove Against Radiation-Induced Oxidative Stress in Rats

    International Nuclear Information System (INIS)

    Antioxidants in food play an important role in preventing the generation of reactive oxygen species (ROS). Clove is widely used in Egypt as a spice which is a potent scavenger of a variety of free radicals. Clove (Syzygium aromaticum, Eugenia aromaticum or Eugenia caryophyllata) is the aromatic dried flower buds of a tree in the family Myrtaceae. The aim of this study was to investigate the radioprotective effect of cloves against oxidative stress and tissue injury, in animals, induced by gamma irradiation. Rats were subjected to two doses of gamma radiation (2 and 4 Gy). Four weeks before irradiation animals received cloves in basal diets. In liver and serum of irradiated animals, thiobarbituric acid reactive substances (TBARS) showed a significant increase associated to a marked decrease in glutathione (GSH) and catalase (CAT). The level of total lipids, cholesterol, triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) showed significant increase in the serum of irradiated rats. On the other hand, the level of high density lipoprotein-cholesterol (HDL-C), total protein, albumin and total globulins showed significant decrease. Rats fed on a basal diet containing cloves during a period of 4 weeks before irradiation showed significant improvement in the oxidant/antioxidant status denoted by a significant reduction in TBARS level associated with signiction in TBARS level associated with significant increase in GSH and CAT. Moreover, the radiation-induced changes in lipids, proteins and enzyme activities were significantly ameliorated. It could be concluded that cloves possibly protect against radiation-induced oxidative stress and tissue damage

  14. Evidence for radiation-induced Bystander effects and relevance to radiotherapy and to radiation protection

    International Nuclear Information System (INIS)

    Full text: There are two major arms of radiation science in which Bystander effects (ByEff) could be of practical importance: radiotherapy and risk assessment. Basic biological principles, including dose-response relationships that have become dogma in the context of targeted effects of IR must now be reconsidered. The direct effects of radiation and the bystander components had to be reinvestigated to show the difference between them. It may be necessary to introduce a factor for ByEff's when calculating dose to both normal tissues and tumor. Presumably the relative effects on normal or tumor tissues could be different and that difference may not be always predictable. In relation to radiation protection, the existence of RIByEff's raises important questions for the way radiation dose is measured and modeled. The biological effect of exposure to low-doses radiation is likely to vary between individuals and between organs in one the same individual. Further studies on non-targeted effects should contribute to the establishment of adequate environmental and occupational radiation protection standards. This lecture looks at the history, the current data and controversies that are now beginning to resolve the questions concerning the mechanisms underlying the induction and transmission of ByEff. Especially, effects on radiotherapy and radiation protection are discussed

  15. Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

    International Nuclear Information System (INIS)

    The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations

  16. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

    OpenAIRE

    Olga Loseva; Emman Shubbar; Siamak Haghdoost; Bastiaan Evers; Thomas Helleday; Mats Harms-Ringdahl

    2014-01-01

    The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR) exposure (5 or 15 mGy/h) of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after c...

  17. The low-dose atorvastatin and valsartan combination effectively protects the arterial wall from atherogenic diet-induced impairment in the guinea pig.

    Science.gov (United States)

    Jani?, Miodrag; Lunder, Mojca; Zupan, Janja; ?erne, Darko; Marc, Janja; Drevenek, Gorazd; abovi?, Mio

    2014-11-15

    New preventive strategies for atherosclerosis are needed. In this study, we tested whether a new therapeutic approach consisting of low-dose treatment with a statin and sartan combination could prevent atherogenic diet-induced impairment of the arterial wall in guinea pigs. Twenty-five Dunkin-Hartley guinea pigs were randomly assigned to five experimental groups: 1) normal diet; 2) atherogenic diet (AD); 3) AD + a low-dose atorvastatin and valsartan combination (5mg/kg/day and 2.4mg/kg/day, respectively); 4) AD + low-dose atorvastatin (5mg/kg/day); 5) AD + low-dose valsartan (2.4mg/kg/day). After 8 weeks of treatment, the animals were killed, blood samples collected and thoracic and abdominal aortas isolated. The atherogenic diet significantly impaired maximal thoracic aorta endothelium-dependent relaxation by 40.1% relative to the normal diet. The low-dose combination, compared to the separate drugs, completely preserved thoracic aorta endothelium-dependent relaxation at the level of the group receiving normal diet. This substantial effect was associated with a significant change in the expression of NOS3 (R=0.93; P=0.0002) and IL1b (R=-0.79; P=0.003) genes. In addition, treatment with the low-dose combination or the separate drugs also prevented atherosclerotic plaque formation. We found that treatment with the low-dose atorvastatin and valsartan combination has the capability to completely protect the arterial wall from atherogenic diet-induced damage in the guinea pig model. Further studies evaluating this new therapeutic approach are desirable. PMID:25261034

  18. Propionyl-L-carnitine as a potential protective agent against radiation-induced cardiotoxicity

    International Nuclear Information System (INIS)

    In this study, propiony-L-carnitine (PLC); a natural short-chain derivative of L-carnitine, has been tested as a potential protective agent against radiation-induced cardio-toxicity. Cardiotoxicity was assessed in the homo-genate of the heart by measuring the plasma levels of creatine phosphokinase (CPK), lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST), as well as malon-dialdehyde (MDA), glutathione content (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), adenosine triphosphate (ATP) and nitric oxide (NO) production, whole body gamma-irradiation (2 and 6Gy ) of rats significantly increased CPK, LDH, AST,MDA, and NO and significantly decreased GSH,GSH-PX, SOD and ATP. Daily administration (one week) of PLC before whole body irradiation caused significant recovery for the serum enzyme CPK, LDH, AST and MDA, GSH, GSH-PX, SOD, ATP and NO levels in cardiac tissue. The protective effect PLC was attributed to it's antioxidant properties. Radiation therapy, likewise, is a valuable method of treatment for a variety of intrathoracic neoplasms. During radiotherapy of thoracic tumorus, the heart is often included in the primary treatment volume and chronic impairment of myocadial function occurs (cilliers and lochner, 1993; benderitter et al., 1995). Irradiation causes numerous changes in different metabolic reactions within the cardiac cells with major adverse undersirable effects that involve cardiotoxicityoxicity

  19. Protective effect of Nardostachys jatamansi on radiation induced anxiety and oxidative stress in mice

    International Nuclear Information System (INIS)

    Nardostachys jatamansi (family Valerianaceae), an indigenous medicinal plant induces in organism a state of resistance against stress. It helps to promote physical and mental health augment resistance of the body against disease and has shown potent antioxidant activity. To study the anxiolytic and protective effect of 100 mg of ethanolic extract of Nardostachys jatamansi was studied on the mice exposed to 6 Gy Electron beam radiation (EBR). The animals were treated with 100 mg of Nardostachys jatamansi extract (NJE) for 15 days before radiation exposure. The anxiety status of animals observed once for every 3 days during experiment period. The level of lipid peroxidation and glutathione (GSH) was estimated 15 days after irradiation. The irradiation of animals resulted in an elevation in anxiety, lipid peroxidation and reduction in GSH. Treatment of mice with NJE before irradiation caused a significant depletion in anxiety, lipid peroxidation followed by significant elevation in GSH. Our results indicate that the protective activity of NJE on radiation induced anxiety and oxidative stress may be due to free radical scavenging and increased antioxidant level in mice. (author)

  20. Nardostachys Jatamansi root extract protects of radiation induced glycogen depletion in Albino Wistar rats

    International Nuclear Information System (INIS)

    Exposure to ionizing radiation cause variety of pathological processes in irradiated cells. The killing action of ionizing radiation is mainly mediated through the free radicals generated from the radiolysis of cellular water. In the present study, protective effects of Nardostachys Jatamansi root extract (NJE) on radiation induced depletion of glycogen in rats exposed to 3 Gy whole body electron beam irradiation (EBR) was investigated. EBR was performed at Microtron centre, Mangalore University. Treatment of rats with NJE at a dosage of 100, 200 and 400 mg/kg bw respectively once daily for 15 days before, after and both before and after irradiation was done. The liver, kidney and muscle was separated and used for the estimation of total glycogen content using standard procedures and also for the histochemical localization of glycogen by PAS staining method. The data was analyzed by paired t test and Kruskal Wallis test. P<0.05 was the level of significance. The irradiated rats exhibited significant decline (p=0.000) in the level of total glycogen content in the tissues of liver, kidney and muscle whereas, a nonsignificant variation was recorded in rats treated with NJE. This study indicated that treatment with NJE both before and after irradiation for 15 consecutive days provided significant protection against irradiation induced depletion of glycogen. (author)

  1. Radiological protection optimization derived from radiation induced lesions in interventional cardiology finding

    International Nuclear Information System (INIS)

    Interventional Cardiology is one of the specialties in which patients are submitted to the greatest radiation doses with x ray systems used for diagnostic purposes and then, it is also a specialty of high occupational radiation risk. In the last years, several cases of radiation induced lesions produced on patients derived of new complex interventional procedures have been described. As consequence, different rules for avoiding this kind of incidents have been recommended by International Organisations and regulatory Bodies. Nevertheless it has been devoted relatively few attention to the evaluation of the occupational risks that inevitably are also high in these facilities. In this work, some cases of radioinduced skin lesions produced on patients submitted to cardiac ablation procedures are described. Radiological protection considerations of interest for the regulatory Bodies are made, that permit to minimize the probability of these incidents, in what to the X-rays equipment is referred as well as to the operation procedures and level of radiation protection training of the medical specialists. (author)

  2. Radiation protection and environment day the low doses in everyday life; Radioprotection et environnement les faibles doses dans la vie quotidienne

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    The consequences of low doses exposures are difficult to explore and the studies give often place to controversies. According to the are, differences exist in the methodological approaches. It results from it a confusion on the acceptable levels of exposure, even on the definition of low dose. This day organised by the sections 'non ionizing and research and health of the French society of radiation protection (S.F.R.P.), will be a meeting between professionals of different disciplines, to compare the approaches used for the ionizing and non ionizing radiations as well as the chemical and microbiological agents. It will allow to share the knowledge and the abilities and to progress on methodologies adapted to the evaluation and the management of risks in relation with low doses. (N.C.)

  3. Protective effect of an extract of Phyllanthus amarus against radiation-induced damage in mice

    International Nuclear Information System (INIS)

    The radioprotective effect of an extract of the plant Phyllanthus amarus (P. amarus) was investigated in adult BALB/c mice. P. amarus extract (750 mg/kg b.wt and 250 mg/kg b.wt) was administered orally to mice for five days prior to whole body radiation (6 Gy) and for one month after radiation. The animals were sacrificed on days 3, 9, 12, and 30 after radiation. P. amarus significantly increased the total white blood cell (W.B.C) count, bone marrow cellularity, and ?-esterase activity as compared to untreated radiation-exposed animals. P. amarus treatment also increased the activity of various antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPX), and glutathione reductase (GR), both in blood and tissue, which were reduced by radiation treatment. There was also a significant increase in the glutathione (GSH) levels of blood and tissue. Lipid peroxidation levels, which were increased after radiation, were significantly reduced by P. amarus treatment, both in serum and liver. The results collectively indicate that P. amarus extract could increase the antioxidant defense mechanism in mice and there by protect the animals from radiation-induced cellular damage. (author)

  4. Protection against radiation induced testicular damage in Swiss albino mice by mentha piperita (Linn)

    International Nuclear Information System (INIS)

    Mentha piperita linn or peppermint (Family - Labiatae) is aromatic and has stimulant and carminative properties. The protective effects of mentha piperita (Linn) extract against radiation induced damage in testis of Swiss albino mice have been studied. Animals (Male Swiss albino mice) were given leaf extract of M. piperita orally (1 g kg-1 day-1) for three consecutive days prior to radiation exposure (8 Gy gamma radiation). Mice were autopsied at 1, 3, 7, 14 and 30 days of post-irradiation to evaluate the radiomodulatory effect in terms of histological alterations, lipid peroxidation, acid and alkaline phosphatases levels in testis. There was significantly less degree of damage to testis tissue architecture and various cell populations including spermatogonia, spermatids and Leydig cells. Significant decreases in the LPO and acid phosphatase level and increase in level of alkaline phosphatase were observed in testis. The methanolic extract of M. piperita showed high amount of phenolic content, flavonoids content and flavonol. Leaf extract of M. piperita has significant radioprotective effect and the amount of phenolic compounds, flavonoids and flavonol content of extract of M. piperita may be held responsible for its radioprotective effect. (author)

  5. Rhubarb extract has a protective role against radiation-induced brain injury and neuronal cell apoptosis.

    Science.gov (United States)

    Lu, Kui; Zhang, Cheng; Wu, Wenjun; Zhou, Min; Tang, Yamei; Peng, Ying

    2015-08-01

    Oxidative stress caused by ionizing radiation is involved in neuronal damage in a number of disorders, including trauma, stroke, Alzheimer's disease and amyotrophic lateral sclerosis. Ionizing radiation can lead to the formation of free radicals, which cause neuronal apoptosis and have important roles in the development of some types of chronic brain disease. The present study evaluated the effects of varying concentrations (2, 5 and 10g/ml) of ethanolic rhubarb extract on the neuronal damage caused by irradiation in primary neuronal cultures obtained from the cortices of rat embryos aged 20days. Brain damage was induced with a single dose of ??irradiation that induced DNA fragmentation, increased lactate dehydrogenase release in neuronal cells and acted as a trigger for microglial cell proliferation. Treatment with rhubarb extract significantly decreased radiation?induced lactate dehydrogenase release and DNA fragmentation, which are important in the process of cell apoptosis. The rhubarb extract exhibited dose?dependent inhibition of lactate dehydrogenase release and neuronal cell apoptosis that were induced by the administration of ionizing radiation. The effect of a 10g/ml dose of rhubarb extract on the generation of reactive oxygen species (ROS) induced by radiation was also investigated. This dose led to significant inhibition of ROS generation. In conclusion, the present study showed a protective role of rhubarb extract against irradiation?induced apoptotic neuronal cell death and ROS generation. PMID:25936269

  6. Radiation-induced late brain injury and the protective effect of traditional Chinese medicine

    International Nuclear Information System (INIS)

    Objective: To investigate whether radiation-induced late injury of the brain can be ameliorated by traditional Chinese Medicine through blocking the primary events. Methods: This trial included five animal groups: sham irradiation, irradiation only, and three treatment groups. The whole brain of BALB/C mouse was irradiated with 22 Gy by using a 6 MV linear accelerator. Step down method was used to evaluate the study and memory abilities. Mouse weight was also recorded every week before and after irradiation. On D90, all mice alive were euthanized and Glee's silver dye method and Bielschousky silver dye method were used to detect the senile plaque and the neurofibrillary tangle. One-Way ANOVA was used to evaluate the differences among the groups in the various aspects of study and memory abilities as well as quality of life. Kaplan-Meier was used to evaluate the survival. Log-rank was used to detect the differences among the survival groups. Results: 1. There was no significant difference in survival among the treatment groups, even though Salvia Miltiorrhiza (SM) was able to improve the quality of life. As to the cognition function, it was shown that whole brain radiation would make a severe cognition damage with the learning and memorizing ability of the irradiated mice being worse than those of the sham irradiation group. The Traditional Chinese Medicine Salvia Miltiorrhiza possesses the role of a protective agent against cognition function damage induced by irradiagnition function damage induced by irradiation. 2. Glee's silver dye and Bielschousky silver dye show much more senile plaque and the neurofibrillary tangle in brain tissue of R group and R + 654-2 group than those in the R + SM group. Conclusions: Salvia Miltiorrhiza is able to protect the mouse from cognition function damage induced by irradiation and improve the quality of life by ameliorating the primary events, though it does not improve the survival

  7. Radiation-induced biochemical changes in blood cells and BAL fluid of the people, affected by low dose of irradiation during the Chernobyl accident, discovered by the electron spin resonance method

    International Nuclear Information System (INIS)

    It was shown that the samples of BAL, blood plasma and leucocyte concetrates of Chernobyl liquidators have been radical products registered by ESR technique, the concentrations of these products being dependent on the length of work of the liquidators at the 4-th Energy Unit of Chernobyl atomic power station. It was shown that these parametric centers are radiation-induced and have melanin-containing nature. The malanin-containing free radical products were not discovered in the patients with pulmonary diseases who did not take part in the liquidation of Chernobyl catastrophe consequences. The changes of content of the plasma proteins (transferring and ceruloplasmin) and blood components in the tests of the patients with pulmonary diseases and Chernobyl liquidators had the opposite directed dynamics

  8. The new knowledge on human response to low doses of radiation: the crisis of the prevailing conception in radiation protection

    International Nuclear Information System (INIS)

    Recent statistical data on human response to low-dose radiation are discussed. The probability of lungs cancer among the USA population is decreasing with radon content growth in the buildings, even at the levels, where in intervention is envisaged. Thus, the conception assuming that any radiation is dangerous, is rejected. The summarized statistical data on the nuclear facilities in the USA, Great Britain and Canada show that the death rate from cancer among the personnel is lower than by control. Leucosises are the only exclusion, but their cases are rare. Thus, the existing dose limits prove to be safe enough. 36 refs., 1 fig., 1 tab

  9. Radiation induced deactivation, post deactivation of horse radish peroxidase, glucose oxidase and the protective effect

    International Nuclear Information System (INIS)

    In order to check the fact if the radiation induced post deactivation are possessed by all the enzymes, the radiation effects of horse radish peroxidase (HRP) and glucose oxidase (GOD) were investigated. It was found that in dilute aqueous solution the irradiated HRP has the post deactivation also. The effects of absorbed dose, initial HRP concentration in solution, atmosphere, temperature and additives (three kinds of complex agents: EDTA, CDTA and D) on the post deactivation of HRP were investigated. The regularity of post deactivation of HRP is similar with the catalase. Oxygen in enzyme samples is necessary for the post deactivation. 5 x 10-3 mol/l of the three additives could control the phenomenon efficiently. Of course, the radiation deactivation of HRP was given as well. In the case of GOD the post deactivation was not found, although it's radiation deactivation is serious. It means that the radiation induced post deactivation is not a common phenomenon for all enzymes

  10. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    OpenAIRE

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-vinasco, Liliana; Bittman, Robert; Chen, Chin Tu

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components...

  11. Protective effect of tanshinone IIA against radiation-induced ototoxicity in HEI-OC1 cells

    OpenAIRE

    Du, Shasha; Yao, Qiwei; TAN, PEIXIN; Xie, Guozhu; REN, CHEN; SUN, QUANQUAN; Zhang, Xiao; Zheng, Rong; YANG, KAIJUN; YUAN, YAWEI; Yuan, Quan

    2013-01-01

    Radiotherapy is a highly efficient treatment method for nasopharyngeal carcinoma that is often accompanied by significant ototoxic side-effects. The inner ear hair cells are particularly prone to serious injury following radiotherapy. Tanshinone IIA is a transcription factor inhibitor that is extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge. The present study investigated the effects of tanshinone IIA treatment on radiation-induced toxicity in the HEI-OC1 hair cell li...

  12. Chemical protection of mice against radiation-induced sickness and mortality by 2-mercaptopropionylglycine

    International Nuclear Information System (INIS)

    Adult female Swiss albino mice were exposed to a whole body exposure of 10 Gy gamma radiation in the presence and absence of MPG. Radiation- induced sickness, body weight loss and mortality were recorded. The results indicate that the time of onset of radiation sickness was delayed in the drug-treated group. Prior administration of the drug helped in reducing the body weight loss and delayed the mortality by two days. (author)

  13. New risk estimates at low doses

    International Nuclear Information System (INIS)

    The age of molecular radiation epidemiology may be at hand. The techniques are available to establish with the degree of precision required to determine whether agent-specific mutations can be identified consistently. A concerted effort to examine radiation-induced changes in as many relevant genes as possible appears to be justified. Cancers in those exposed to low doses of ionizing radiation should be chosen for the investigation. Parallel studies of radiation-induced cancers in experimental animals would not only complement the human studies, but perhaps reveal approaches to extrapolation of risk estimates across species. A caveat should be added to this optimistic view of what molecular studies might contribute to the knotty problem of risk estimates at low doses. The suggestions are made by one with no expertise in the field of molecular biology

  14. Possible Protective Effect of Aqueous Extract of Moringa oleifera Lam. on Gamma Radiation Induced-Oxidative Stress in Rats

    International Nuclear Information System (INIS)

    Medicinal herbs are used in indigenous system of medicine for various diseases. Moringa oleifera (M. oleifera) has a high medicinal value which has been recognized. The present study was designed to evaluate the protective effect of aqueous extract of M. oleifera leaves against whole body gamma radiation-induced toxicity in rats. Rats received orally by gavage the aqueous extract of M. oleifera leaves 300 mg/Kg body weight/day for 40 days and rats subjected to whole body gamma-irradiation at a dose of 5 Gy delivered as single exposure dose at day 35 of M. oleifera treatment rats and sacrificed at 5th day after irradiation. The results obtained showed that exposure to gamma radiation provoked a significant increase in serum gamma-glutamyl transpeptidase (?-GT), alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP), glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (vLDL-C) level. While high density lipoprotein cholesterol (HDL-C) and insulin level showed a significant decrease. Moreover a significant decrease of glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT) activities associated to a significant increase of thiobarbituric acid reactive substances (TBARS) were recorded in blood and liver of rats. Treatment with M. oleifera significantly reduced the radiation-induced serum and liver biochemical disorders which wasciated with a significant amelioration in antioxidant status in both liver and serum. The results indicated that M. oleifera might protect from radiation induced damage due to its ability to scavenge free radicals

  15. Influence of substances offering protection against radiation-induced delayed damage to the liver of the mouse

    International Nuclear Information System (INIS)

    The influence of various radiation protection substances, among them cystamine, WR 638, WR 2721 and polymer-bound WR 2721, on the formation of liver tumours was investigated on a histological basis in long-term experiments in male mice following wholebody irradiation at the 2.5 Gy dose level, in the 7 Gy to 8 Gy dose range and at the 15 Gy level as well as following irradiation of the liver region alone with a dose of 5 Gy. Tumours in the liver region were observed to develop no earlier than 170 days after exposure. With the exception of a dextrane (WR 2721) conjugate/amine, there were no indications whatsoever that radiation protection substances may prevent the occurrence of radiation-induced liver tumours or reduce the tumour rate. The available body of evidence appears to suggest that liver tumours largely are primary changes. The radiation-induced hepatic tumours found in the mice studied showed great histological resemblance to those caused in man by toxic substances or the influences of thorotrast. The mechanisms underlying the formation of liver tumours are discussed in detail. (orig./MG)

  16. Protective effects of L-selenomethionine on space radiation induced changes in gene expression.

    Science.gov (United States)

    Stewart, J; Ko, Y-H; Kennedy, A R

    2007-06-01

    Ionizing radiation can produce adverse biological effects in astronauts during space travel. Of particular concern are the types of radiation from highly energetic, heavy, charged particles known as HZE particles. The aims of our studies are to characterize HZE particle radiation induced biological effects and evaluate the effects of L-selenomethionine (SeM) on these adverse biological effects. In this study, microarray technology was used to measure HZE radiation induced changes in gene expression, as well as to evaluate modulation of these changes by SeM. Human thyroid epithelial cells (HTori-3) were irradiated (1 GeV/n iron ions) in the presence or in the absence of 5 microM SeM. At 6 h post-irradiation, all cells were harvested for RNA isolation. Gene Chip U133Av2 from Affymetrix was used for the analysis of gene expression, and ANOVA and EASE were used for a determination of the genes and biological processes whose differential expression is statistically significant. Results of this microarray study indicate that exposure to small doses of radiation from HZE particles, 10 and 20 cGy from iron ions, induces statistically significant differential expression of 196 and 610 genes, respectively. In the presence of SeM, differential expression of 77 out of 196 genes (exposure to 10 cGy) and 336 out of 610 genes (exposure to 20 cGy) is abolished. In the presence or in the absence of SeM, radiation from HZE particles induces differential expression of genes whose products have roles in the induction of G1/S arrest during the mitotic cell cycle, as well as heat shock proteins. Some of the genes, whose expressions were affected by radiation from HZE particles and were unchanged in irradiated cells treated with SeM, have been shown to have altered expression levels in cancer cells. The conclusions of this report are that radiation from HZE particles can induce differential expression of many genes, some of which are known to play roles in the same processes that have been shown to be activated in cells exposed to radiation from photons (like cell cycle arrest in G1/S), and that supplementation with SeM abolishes HZE particle-induced differential expression of many genes. Understanding the roles that these genes play in the radiation-induced transformation of cells may help to decipher the origins of radiation-induced cancer. PMID:17265150

  17. Bystander effects and biota: implications of radiation-induced bystander effects for protection of the environment from ionising radiation

    International Nuclear Information System (INIS)

    Bystander effects are now known to be induced by both high and low LET in a variety of cells in culture. They have been proven to occur in vivo in mice following 0.5Gy total body irradiation and in blood from humans being treated for cancer by radiotherapy. Effects have also been detected in fish, crustacea and molluscs. The important questions now are not whether bystander effects occur but why and what implications they have, if any, for radiation protection. Different species and different genetic backgrounds within a species produce different types of bystander effect, different organs also produce different effects. This paper will review the data in this field and will discuss likely implications for protection of man and non-human biota. In particular it will look at the potential long-term outcomes for different organisational levels, from cell to ecosystem, of bystander mechanisms. In view of new concerns about the effects of low level radiation on non-human biota, emphasis will be placed on considering how bystander effects might operate at chronic low doses versus acute accidental low doses. Problems of radiation interaction with chemicals, whether chemicals can also induce 'bystander effects' , and how regulators might handle these situations which occur all the time in real environments, will be presented for discussion. Finally the paper will discuss likely implications of these mechanisms for evolutionary biologyy

  18. Protection from radiation induced damages to biological system in mice exposed to whole body ?-radiation by phytophenol gallic acid

    International Nuclear Information System (INIS)

    Ionizing radiation can induce various deleterious effects on mammalian system. Radiation induced suppression of hematopoiesis and immune function has been considered to be one of the most life-threatening consequences of radiation exposure, and radiation-induced damages in vital cellular targets such as genomic DNA and membranes preventing the normal growth and proliferation of the cells are responsible for other deleterious consequences. The present study is aimed to evaluate radioprotecting ability of the natural polyphenol, gallic acid (3,4,5-trihydroxybenzoic acid, GA) in Swiss albino mice exposed to , whole body gamma radiation. Radiation induced damages in cellular DNA of different tissues were analyzed by alkaline comet assay; genotoxicity was assessed by micronucleus assay and chromosomal aberrations analysis. The bone marrow cellularity, WBC counts and spleen colony formation were also monitored in mice orally administered with GA prior to whole body ?-radiation exposure. Exposure of mice to whole body gamma-radiation resulted in the formation of micronuclei in blood reticulocytes and chromosomal aberrations in bone marrow cells. The oral administration of GA resulted in the inhibition of micronucleus formation, chromosomal aberrations, and also showed an enhancement in the rate of cellular DNA repair process in irradiated animals. There was a significant increase in bone marrow cellularity, WBC counts and endogenous spleen colony formation following GA admispleen colony formation following GA administration, in animals administered with GA and exposed to whole body gamma-radiation. The results from the study reveal the significant protection offered by phytopolyphenol gallic acid to mammalian system on radiation exposure. (author)

  19. Yeast DEL assay detects protection against radiation-induced cytotoxicity and genotoxicity: adaptation of a microtiter plate version.

    Science.gov (United States)

    Hafer, Kurt; Rivina, Yelena; Schiestl, Robert H

    2010-12-01

    The DEL assay in yeast detects DNA deletions that are inducible by many carcinogens. Here we use the colorimetric agent MTS to adapt the yeast DEL assay for microwell plate measurement of ionizing radiation-induced cell killing and DNA deletions. Using the microwell-based DEL assay, cell killing and genotoxic DNA deletions both increased with radiation dose between 0 and 2000 Gy. We used the microwell-based DEL assay to assess the effectiveness of varying concentrations of five different radioprotectors, N-acetyl-l-cysteine, l-ascorbic acid, DMSO, Tempol and Amifostine, and one radiosensitizer, 5-bromo-2-deoxyuridine. The microwell format of the DEL assay was able to successfully detect protection against and sensitization to both radiation-induced cytotoxicity and genotoxicity. Such radioprotection and sensitization detected by the microwell-based DEL assay was validated and compared with similar measurements made using the traditional agar-based assay format. The yeast DEL assay in microwell format is an effective tool for rapidly detecting chemical protectors and sensitizers to ionizing radiation and is automatable for chemical high-throughput screening purposes. PMID:21128795

  20. Functional analysis of molecular mechanisms of radiation induced apoptosis, that are not mediated by DNA damages

    International Nuclear Information System (INIS)

    The effects of low-dose irradiation pose new challenges on the radiation protection efforts. Enhanced cellular radiation sensitivity is displayed by disturbed cellular reactions and resulting damage like cell cycle arrest, DNA repair and apoptosis. Apoptosis serves as genetically determinate parameter for the individual radiation sensitivity. In the frame of the project the radiation-induced apoptosis was mechanistically investigated. Since ionizing radiation induced direct DNA damage and generates a reactive oxygen species, the main focus of the research was the differentiation and weighting of DNA damage mediated apoptosis and apoptosis caused by the reactive oxygen species (ROS).

  1. Protection from radiation-induced lung injury by MnTE-2-PyP in rats

    International Nuclear Information System (INIS)

    Objective: To determine the Manganese (III) Tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP), a superoxide dismutase (SOD) mimic, protective effect against oxidative damage and tolerance enhancement to radiation-induced lung injury in the rat model. Methods: Female 150-160 g Fisher-344 rats were randomized into a RT + MnTE-2-PyP group and a RT group. The anesthetized rats were administrated with a single dose of 28 Gy of 4 MV photon to their right lung with MnTE-2-PyP (6 mg/kg) given intraperitoneally 15-30 min before irradiation in the former group. The breathing rate and plasma TGF-?1 level were assessed every two weeks after radiation. Once dyspnea appeared, the animals with severe respiratory distress were euthanized. Otherwise, they were sacrificed 6 months after irradiation. The irradiated lungs were revolved and processed for definitive analysis, including hydroxyproline content, immunohistochemical assay, histopathology and fibrosis scores. Results: The disparity of breathing frequency showed an ability of MnTE-2-PyP to reduce the severity of radiation-induced lung injury with evidently postponed and alleviated dyspnea in the RT+ MnTE-2-PyP group by 30% (P<0.01). Three rats died of respiratory distress with seven rats developed pleural effusion in the RT only group, while only one in the RT + MnTE-2-PyP group did so. There were significant reduction of the TGF-?1 level [(3.100.50) ng/ml vs (1.340.63) ng/ml; t=2.41, P=0.029)] and hydroxyproline co=2.41, P=0.029)] and hydroxyproline content per gram of dry and wet lung in the RT + MnTE-2-PyP group compared with those in the RT alone group. The histopathological comparison also revealed the protective effect of MnTE-2-PyP. The lung fibrosis score was significantly lower in rats with MnTE-2-PyP administered (3.600.15 vs 5.820.34, P<0.05). TGF-?1 expression was also markedly reduced in RT+MnTE-2-PyP group, whereas intense immunoreactivity was found in the RT alone group. Conclusions: MnTE-2-PyP, a kind of novel SOD mimic demonstrating a significant protective effect from radiation-induced lung injury, may be a potential radio-protector

  2. Health effects of low-dose radiation: Molecular, cellular, and biosystem response

    International Nuclear Information System (INIS)

    Since the fifties, the prime concern of radiation protection has been protecting DNA from damage. UNSCEAR initiated a focus on biosystem response to damage with its 1994 report, ''Adaptive Responses to Radiation of Cells and Organisms''. The DNA damage-control biosystem is physiologically operative on both metabolic and radiation induced damage, both effected predominantly by free radicals. These adaptive responses are suppressed by high-dose and stimulated by low dose radiation. Increased biosystem efficiently reduces the number of mutations that accumulate during a lifetime and decrease DNA damage-control with resultant aging and malignancy. Several statistically significant epidemiologic studies have shown risk decrements of cancer mortality and mortality from all causes in populations exposed to low-dose radiation. Further biologic and epidemiologic research is needed to establish a valid threshold below which risk decrements occur. (author)

  3. Protective effects of Punica Granatum (L) and synthetic ellagic acid on radiation induced biochemical alterations in Swiss albino mice

    International Nuclear Information System (INIS)

    Ionizing radiations produce deleterious effects in the living organisms and the rapid technological advancement has increased human exposure to ionizing radiations enormously. Radiotherapy, which is a chief modality to treat cancer, faces a major drawback because it produces severe side effects developed due to damage to normal tissue by reactive oxygen species (ROS). Recent studies have indicated that some commonly used medicinal plants may be good sources of potent but non-toxic radioprotectors. The pomegranate, Punica granatum L., an ancient, mystical, and highly distinctive fruit, is the predominant member of the Punicaceae family. It is used in several systems of medicine for a variety of ailments. The objective of the present study was to investigate the protective effects of ethanolic extracts of pomegranate whole fruit (EPWF) and seeds (EPS) and Synthetic Ellagic acid (EA) against Electron beam radiation(EBR) induced biochemical alterations in Swiss albino mice. The extracts and synthetic compound were assessed for its radical scavenging property by DPPH radical scavenging and Ferric Reducing Antioxidant Power assays. The animals were exposed to sub-lethal dose (6 Gy) of Electron Beam Radiation and then treated with 200 mg/kg body wt. of pomegranate extracts and synthetic ellagic acid for 15 consecutive days. The biochemical estimations were carried out in the liver homogenate of the sacrificed animals. Radiation induced depletion in the level of reduced glutathione and total antioxidant capacity were prevented significantly by EPWF, EPS and EA administration. Also there was significant reduction in the levels of membrane lipid peroxidation in the treated groups compared to irradiated control. The findings of our study indicate the protective efficacy of pomegranate extracts and synthetic ellagic acid on radiation induced biochemical changes in mice may be due to its free radical scavenging and increased antioxidant levels. (author)

  4. Protective effect of selenium on malignant transformation of rat lung fibroblasts in vitro radiation-induced by alpha particles

    International Nuclear Information System (INIS)

    The protective effect of selenium (Se) on malignant transformation of adult Wistar rat lung fibroblasts (WAL-F1) radiation-induced by plutonium-238 alpha particles were described. The 238Pu alpha particles source consisted of a stainless-steel dish with 9 x 109 Bq of 238Pu had been electroplated evenly across its surface. Absorbed dose rate was 1.10 Gy/min, the thickness of monolayer cells was 8 ?m, and distance between the cell and source was 0.75 cm. The samples were divided into four groups: (a) control group, the cells have no any treatment, (b) selenium group, the concentration of Se in culture medium was 0.05 mmol/mL, (c) irradiation group, the cells were irradiated by alpha particles at dose of 0.5 Gy and (d) protection group, 0.05 mmol/mL of Se was added in culture medium at 30 min before exposure of the cells to alpha particles at dose of 0.5 Gy. The morphology of cells, proliferative ability, chromosome karyology, Con A agglutination, ability to form colonies in semisolid agar media and carcinogens in immunosuppressed animals was observed after irradiation of cells. The results show that when Se was added in culture medium 30 min before exposure of cells to alpha particles, it appears manifest protective effect and the mean efficiencies of protection was 73.5%

  5. Low dose rate proton irradiation of quartz crystal resonators

    International Nuclear Information System (INIS)

    Quartz crystal resonators were systematically irradiated with 65 MeV protons to characterize low dose rate radiation-induced degradation. Results indicate: (1) test samples that exhibit large frequency shifts during testing tend to show large frequency shifts prior to irradiation, or during off-irradiation periods; (2) for radiation-sensitive samples, short-term effects seem to decrease after each irradiation on/off cycle (moreover, those devices in which radiation effects do not decrease after a few cycles are not very sensitive); (3) the fabrication process may be an important determinant of susceptibility to low dose radiation-induced degradation; and (4) total-dose effects may be sublinear

  6. Radiation Leukemogenesis at Low Dose Rates

    Energy Technology Data Exchange (ETDEWEB)

    Weil, Michael; Ullrich, Robert

    2013-09-25

    The major goals of this program were to study the efficacy of low dose rate radiation exposures for the induction of acute myeloid leukemia (AML) and to characterize the leukemias that are caused by radiation exposures at low dose rate. An irradiator facility was designed and constructed that allows large numbers of mice to be irradiated at low dose rates for protracted periods (up to their life span). To the best of our knowledge this facility is unique in the US and it was subsequently used to study radioprotectors being developed for radiological defense (PLoS One. 7(3), e33044, 2012) and is currently being used to study the role of genetic background in susceptibility to radiation-induced lung cancer. One result of the irradiation was expected; low dose rate exposures are ineffective in inducing AML. However, another result was completely unexpected; the irradiated mice had a very high incidence of hepatocellular carcinoma (HCC), approximately 50%. It was unexpected because acute exposures are ineffective in increasing HCC incidence above background. This is a potential important finding for setting exposure limits because it supports the concept of an 'inverse dose rate effect' for some tumor types. That is, for the development of some tumor types low dose rate exposures carry greater risks than acute exposures.

  7. Protective mechanism of p53 against radiation-induced teratological lesions

    International Nuclear Information System (INIS)

    The functional loss of p53, called as the guardian of the genome, frequently results in the carcinogenic and teratogenic tendency of cells and fetuses, respectively, and this paper describes the role of p53 from the latter point of view. Many developmental abnormalities are known to be yielded in p53 knockout mice (p53 -/-). Recipient mice which were transplanted with fertilized ovum of p53 (+/+), (+/-) or (-/-) gene, were irradiated by 2 Gy of X-ray at stages of pre-nidation and organogenesis and occurrence of surface malformation was investigated before delivery. Results showed that p53 suppressed the radiation-induced malformation. The dose rate effect revealed by irradiation of X-ray with a large or small dose rate is attributable to repair of produced DNA strand breaks. Authors' investigation for the effect using the above recipient mice shows the role of p53-dependent apoptosis in suppressing the malformation. Despite these facts, it would be difficult to understand the mechanism of malformation by the role of p53 alone.(K.H.)

  8. Alzheimers Disease: Fatty Acids We Eat may be Linked to a Specific Protection via Low-dose Aspirin

    OpenAIRE

    Pomponi, Massimo F. L.; Gambassi, Giovanni; Pomponi, Massimiliano; Masullo, Carlo

    2010-01-01

    It has been suggested that cognitive decline in aging is the consequence of a growing vulnerability to an asymptomatic state of neuroinflammation. Moreover, it is becoming more evident that inflammation occurs in the brain of Alzheimers disease (AD) patients and that the classical mediators of inflammation, eicosanoids and cytokines, may contribute to the neurodegeneration. In agreement with this observation, aspirin (ASA) - a non-steroidal anti-inflammatory drug - may protect against AD a...

  9. -cell specific overexpression of suppressor of cytokine signalling-3 does not protect against multiple low dose streptozotocin induced type 1 diabetes in mice

    DEFF Research Database (Denmark)

    Brjesson, A; Rnn, S G

    2011-01-01

    We investigated the impact of -cell specific overexpression of suppressor of cytokine signalling-3 (SOCS-3) on the development of multiple low dose streptozotocin (MLDSTZ) induced Type 1 diabetes and the possible mechanisms involved. MLDSTZ treatment was administered to RIP-SOCS-3 transgenic and wild-type (wt) mice and progression of hyperglycemia monitored. Isolated islets from both strains were exposed to human IL-1 (25U/ml) or a combination of human IL-1 (25U/ml) and murine IFN- (1000U/ml) for 24h or 48h and we investigated the expression of IL-1 receptor antagonist (IL-1Ra) mRNA in islet cells and secretion of IL-1Ra into culture medium. MLDSTZ treatment caused gradual hyperglycemia both in the wt mice and in the transgenic mice with the latter tending to be more sensitive. In vitro experiments on wt and transgenic islets did not reveal any differences in sensitivity to damaging effects of STZ. Exposure of wt islets to IL-1 or IL-1+IFN- seemed to lead to a failing IL-1Ra response from SOCS-3 transgenic islets. It could be that an increased expression of a possible protective molecule against -cell destruction may lead to a dampered response of another putative protective molecule. This may have counteracted a protective effect against MLDSTZ in SOCS-3 transgenic mice.

  10. Protective effect of apigenin on radiation-induced chromosomal damage in human lymphocytes

    Science.gov (United States)

    Rithidech, Kanokporn Noy; Tungjai, Montree; Whorton, Elbert B.

    2005-01-01

    The potential use of flavonoids as a radioprotector is of increasing interest because of their high antioxidant activity and abundance in the diet. The aim of this study is to examine genotoxic and radioprotective effects of one of the most common flavonoids, apigenin, on radiation-induced chromosome aberrations in human lymphocytes. The cytokinesis-block micronucleus (CBMN) assay was used to evaluate such effects of apigenin. Blood samples were collected from two non-smoking healthy male volunteers who had no history of previous exposure to other clastogenic agents. Isolated lymphocytes were cultured. There were two tubes per concentration for all treatments. To evaluate the genotoxicity of apigenin, cells were first treated with different concentrations of apigenin (0, 2.5, 5, 10 and 25 microg/mL) at 24 h after culture initiation, followed by cytochalasin-B (Cyt-B) treatment (3 microg/mL) and cell harvest at 44 and 72 h, respectively. Secondly, to investigate the radioprotective effect, cell cultures were exposed to different concentrations of apigenin as described above for 30 min before being irradiated to 2 Gy of 137Cs gamma rays (at a dose rate of 0.75 Gy/min). In all instances, the frequency of MN was scored in binucleated (BN) cells. The nuclear proliferation index also was calculated. We did not detect an increase in the frequency of MN in non-irradiated human lymphocyte cultures treated with 2.5, 5.0 or 10 microg/mL apigenin; although, we did observe an increase in cultures treated with 25 microg/mL apigenin (the highest concentration of apigenin used in our study). We also observed a significant increase in the frequency of MN in irradiated cells overall; however, the frequency was decreased as the concentration of apigenin increased, suggesting a radioprotective effect. These findings provide a basis for additional studies to help clarify the potential use and benefit of apigenin as a radioprotector.

  11. Evidence of existence of low dose radiation induced tumor immunity

    International Nuclear Information System (INIS)

    Lymphocytes infiltrating into tumor tissues from a patient with Stage III hypopharyngeal squamous cell carcinoma were analyzed by the biotin-avidin-horseradish peroxidase method using monoclonal antibodies. Lymphocytes after delivering 4 Gy in 2 fractions showed significant infiltration surrounding cancer cells compared with pre-irradiation, most of which were composed of anti-Leu-1 positive lymphocytes (T lymphocytes). The majority of lymphocyte subsets were anti-Leu-3a + 3b positive lymphocytes (helper/inducer T lymphocytes); the minority were anti-Leu-2a positive lymphocytes (cytotoxic/suppresor T lymphocytes) and anti-Leu M3 positive lymphocytes (B lymphocytes). In addition, human leukocyte antigen-DR positive tumor cells and their interstitial cells were remarkably observed. There was no anti-Leu M3 positive cells (macrophages) or anti-Leu-IIb positive lymphocytes (natural killer cells). An analysis for surgical specimens after delivering 30 Gy revealed no evidence for the presence of viable cancer cells. The findings have important implications for radiation therapy in cancer patients. (Namekawa, K.)

  12. The Possible Protective Role of Foeniculum vulgare Mill. Against Radiation-Induced Certain Biochemical Changes in Albino Rats

    International Nuclear Information System (INIS)

    This study was conducted to evaluate the modulating efficacy of prolonged oral administration of Foeniculum vulgare Mill. essential oil (FEO) against gamma irradiation-induced biochemical changes in male rats. Essential oil of Foeniculum vulgare Mill. was orally administrated at dose level of 250 mg/kg body wt/day for 21 days before irradiation and 7 days post exposure (6.5 Gy single dose). Rats exposed to ionizing radiation exhibited a potential elevation of serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities, bilirubin, urea and creatinine levels, lipid abnormalities, and an increase in tissue lipid peroxidation (LPO) and metallothioneins (MTs). On the other hand, noticeable drop in liver and kidney glutathione content and serum total protein, albumin and testosterone levels were recorded. Tissue organs displayed some changes in trace element concentrations, which may be due to the radiation ability to induce oxidative stress. The data obtained from rats treated with fennel oil before and after whole body gamma irradiation revealed significant modulation in the biochemical tested parameters and profound improvement in the activity of antioxidant status, glutathione and metallothioneins. The treatment of irradiated rats with fennel oil also appeared to be effective in minimizing the radiation-induced increase in lipid peroxidation as well as changes in essential trace elements in some tissue organs. In addition to its containing many chemical antioxidant constituents such as polyphenols, fennel was found to contain detectable concentrations of essential trace elements (Zn, Cu, Fe, Se, Mg, Mn and Ca) which may be involved in multiple biological processes as constituents of enzymes system including superoxide dismutase (Cu, Zn, Mn, SODs), oxide reductase, glutathione (GSP, GSH, GST), metallothionein MTs, etc. Overall, it could be concluded that Foeniculum vulgare Mill. essential oil exerts beneficial protective role against radiation-induced deleterious biochemical effects related to many organ functions and deteriorated antioxidant defense system.

  13. Protective Role of L- Carnitine and Zinc against ?-Radiation induced Cardiac and testicular Disorders in Albino Rats

    International Nuclear Information System (INIS)

    L-Carnitine is a dipeptide amino acid necessary for fat metabolism, it provides energy by transporting long-chain fatty acids to mitochondria to act as a fuel and it is considered a powerful antioxidant. In addition, zinc is an essential mineral which helps to increase the secretion of male sex hormones and raises the sperm count, so its combination with L-carnitine is useful for the fertility process. The present study aims to evaluate the potency of L-carnitine and zinc as radio- protective and curative agent pre and after exposure to ?-radiation through biochemical, histological, morphological abnormalities of sperms and DNA damage in the sperms induced by ?-irradiation by comet assay. Animals received L-carnitine (LC) and zinc (Zn) orally at the dose 9.45 mg/100 gm body wt./day for successive 20 days and then exposed to whole body gamma radiation at the dose 4 Gy (1 Gy for 4 days, day after day) on the 7th day from treatment with antioxidant. Histological examinations of heart and testis tissues showed that administration of LC and Zn have attenuated radiation induced damage and improved tissues architecture. Moreover, the observed amelioration in the tissues was accompanied by a remarkable decrease of their lipid peroxide levels (malondialdehyde (MDA)), together with an increase in glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) activities. Hormonal determinations of serum testosterone (T), follicular stimulating hormone (FSH) and luteinine (LH) which carried out for fertility assessment showed that whole body ?-irradiation of rats induced significant decrease in serum testosterone while FSH and LH were significantly increased as compared with control group. On the other hand, irradiation caused significant elevation in the total number of abnormal head, and / or tail of sperms in comparison to the control rats. The comet assay showed that exposure to ?-radiation induced DNA damage of sperms (tail moment values).

  14. Studies of ionising radiation induced bystander effects in 3D artificial tissue system and applications for radiation protection

    International Nuclear Information System (INIS)

    The universality of the target theory of radiation-induced effects is challenged by observations on non-targeted effects such as bystander effects. Essential features of non-targeted effects are that they do not require direct nuclear exposure by radiation and they are particularly significant at low doses. This new evidence suggests a need for a new paradigm in radiation biology. The new paradigm should cover both the classical (targeted) and the non-targeted effects. The bystander effect cannot be comprehensively explained on the basis of a single cell reaction. It is well known that an organism is composed of different cell types that interact as functional units in a way to maintain normal tissue function. Therefore the radiation response is not simply the sum of cellular responses as assumed in classical radiobiology, predominantly from studies using cell cultures. Experimental models, which maintain tissue-like intercellular cell signalling and 3D structure, are essential for proper understanding of the bystander effect. Our work relates to experimentation with novel 3D artificial human tissue systems available from MatTek Corporation (Boston, USA). Air-liquid interface culture technique is used to grow artificial tissues, which allow to model conditions present in vivo. The Gray Cancer Institute (Northwood, UK) charged particle microbeam was used to irradiate tissue samples in a known pattern with a known number of 3He2+ particles or protons. After irradiation, the tissues models were incubated for 3 days, fixed in 10 % NBF, paraffin embedded and then sliced into 5 ?m histological sections located at varying distances from the plane of the irradiated cells. We studied in situ apoptosis and markers of differentiation. Significantly elevated bystander induced apoptosis was observed with 3'-OH DNA end-labelling based technique in 3D artificial tissue systems. Our results also suggested an importance of proliferation and differentiation status for bystander effect induction. A single 2 ?m location on tissue section was pre-irradiated with 1-10 3He2+ particles (5 MeV; LET 75 keV/?m) using microbeam system. Even although only a single region of the tissue section was targeted, thousands of additional cells were found to undergo bystander induced differentiation. This resulted in an overall increase in the fraction of differentiated cells for approximately 10-15 %, which are much greater than that observed for the induction of damage (not more than 1-2 % of apoptotic cells). Our theory is that the main functions of bystander effect are to decrease the risk of transformation in a multi cultural organism exposed to radiation by removing a group of potentially damaged cells via apoptosis and increased differentiation. (author)

  15. Subthreshold UV radiation-induced peroxide formation in cultured corneal epithelial cells: the protective effects of lactoferrin

    Energy Technology Data Exchange (ETDEWEB)

    Shimmura, Shigeto; Suematsu, Makoto; Shimoyama, Masaru; Oguchi, Yoshihisa; Ishimura, Yuzuru [Keio Univ., Tokyo (Japan). School of Medicine; Tsubota, Kazuo [Tokyo Dental Coll. (Japan)

    1996-11-01

    Acute exposure to suprathreshold ultraviolet B radiation (UV-B) is known to cause photokeratitis resulting from the necrosis and shedding of corneal epithelial cells. However, the corneal effects of low dose UV-B in the environmental range is less clear. In this study, subthreshold UV-B was demonstrated to cause non-necrotic peroxide formation in cultured corneal epithelial cells, which was attenuated by the major tear protein lactoferrin. Intracellular oxidative insults and cell viability of rabbit corneal epithelial cells (RCEC) were assessed by dual-color digital microfluorography using carboxydichlorofluorescin (CDCFH) diacetate bis (acetoxymethyl) ester, a hydroperoxide-sensitive fluoroprobe, and propidium iodode (PI) respectively. The magnitude of UV-induced oxidative insults was calibrated by concentrations of exogenously applied H{sub 2}O{sub 2} which evoke compatible levels of CDCFH oxidation. Exposure of RCEC to low-dose UV-B (2.0 mJ cm{sup -2} at 313 nm, 10.0 mJ cm{sup -2} total UV-B) caused intracellular oxidative changes which were equivalent to those elicited by 240 {mu}M hydrogen peroxide under the conditions of the study. The changes were dose dependent, non-necrotic, and were partially inhibited by lactoferrin ( 1 mg ml{sup -1}) but not by iron-saturated lactoferrin. Pretreatment with deferoxamine (2 m{Mu}) or catalase (100 U ml{sup -1}) also attenuated the UV-induced oxidative stress. The results indicate that UV-B comparable to solar irradiation levels causes significant intracellular peroxide formation in corneal epithelial cells, and that lactoferrin in tears may have a physiological role in protecting the corneal epithelium from solar UV irradiation. (Author).

  16. Subthreshold UV radiation-induced peroxide formation in cultured corneal epithelial cells: the protective effects of lactoferrin

    International Nuclear Information System (INIS)

    Acute exposure to suprathreshold ultraviolet B radiation (UV-B) is known to cause photokeratitis resulting from the necrosis and shedding of corneal epithelial cells. However, the corneal effects of low dose UV-B in the environmental range is less clear. In this study, subthreshold UV-B was demonstrated to cause non-necrotic peroxide formation in cultured corneal epithelial cells, which was attenuated by the major tear protein lactoferrin. Intracellular oxidative insults and cell viability of rabbit corneal epithelial cells (RCEC) were assessed by dual-color digital microfluorography using carboxydichlorofluorescin (CDCFH) diacetate bis (acetoxymethyl) ester, a hydroperoxide-sensitive fluoroprobe, and propidium iodode (PI) respectively. The magnitude of UV-induced oxidative insults was calibrated by concentrations of exogenously applied H2O2 which evoke compatible levels of CDCFH oxidation. Exposure of RCEC to low-dose UV-B (2.0 mJ cm-2 at 313 nm, 10.0 mJ cm-2 total UV-B) caused intracellular oxidative changes which were equivalent to those elicited by 240 ?M hydrogen peroxide under the conditions of the study. The changes were dose dependent, non-necrotic, and were partially inhibited by lactoferrin ( 1 mg ml-1) but not by iron-saturated lactoferrin. Pretreatment with deferoxamine (2 m?) or catalase (100 U ml-1) also attenuated the UV-induced oxidative stress. The results indicate that UV-B comparablThe results indicate that UV-B comparable to solar irradiation levels causes significant intracellular peroxide formation in corneal epithelial cells, and that lactoferrin in tears may have a physiological role in protecting the corneal epithelium from solar UV irradiation. (Author)

  17. Low dose irradiation and biological defense mechanisms

    International Nuclear Information System (INIS)

    It has been generally accepted in the context of radiation protection that ionizing radiation has some adverse effect even at low doses. However, epidemiological studies of human populations cannot definitively show its existence or absence. Furthermore, recent studies of populations living in areas of different background radiation levels reported some decrease in adverse health effects at high background levels. Genetic studies of atomic bomb survivors failed to produce statistically significant findings on the mutagenic effects of ionizing radiation. A British study however, suggests that a father's exposure to low dose radiation on the job may increase his children's risk of leukemia. On the other hand, many experimental studies have raised the possibility that low doses of ionizing radiation may not be harmful or may even produce stimulating or adaptive responses. The term 'hormesis' has come to be used to describe these phenomena produced by low doses of ionizing radiation when they were beneficial for the organisms studied. At the end of the International Conference on Low Dose Irradiation one conclusion appeared to be justified: radiation produces an adaptive response, though it is not universally detected yet. The conference failed to obtain any consensus on risk assessment at low doses, but raised many problems to be dealt with by future studies. The editors therefore believe that the Proceedings will be useful for all scientists and people concerned with rall scientists and people concerned with radiation protection and the biological effects of low-dose irradiation

  18. Effects of Radiation at Low Doses, Introduction

    Science.gov (United States)

    Wilson, Richard

    1996-05-01

    In 1924 the physicist Jeffery Crowther first proposed a model of carcinogenesis that showed linearity at low doses.(J.A. Crowther, Proc. R. Soc. Lond. B. Sci. 96, 207-211 (1924).) Since 1928, the International Commission on Radiological Protection (ICRP) advised that for prudent public protection it is wise to assume linearity and that no amount of radiation should be accepted without expectation of benefit. In the last 50 years a public belief has developed that this cautious approach is based upon scientific data. However, the direct epidemiological data are mostly from studies at high doses. The number of persons that are necessary to find a small effect at low doses is very large and the effect of bioassays can be considerable. The extrapolation to low doses is usually based on indirect data. This session will discuss three main collections of data that directly address cancers that might be caused by radiation at low doses.

  19. In vitro protective effect of atorvastatin against ionizing radiation induced genotoxicity in human lymphocytes.

    Science.gov (United States)

    Hosseinimehr, S J; Izakmehri, M; Ghasemi, A

    2015-01-01

    Atorvastatin (AT) is widely used as a medication for treatment of hypercholesterolemia. Recent studies showed that AT enhanced cell toxicity induced by ionizing radiation in cancerous cells. In this study, the radioprotective effect of AT was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with AT at different concentrations (0.05, 0.1, 1, or 10 ?M) for two hours. The whole blood was exposed to X-ray at dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. AT exhibited a significant decreasing in the frequency of micronuclei in human lymphocytes exposed to ionizing radiation, as compared to with similarly irradiated lymphocytes without AT treatment. The maximum protection and higher decreasing in frequency of micronuclei was observed at 10 ?M of AT (68% decrease), providing maximal protection against ionizing radiation. This data is promising for protection human normal cells from the genetic damage induced by ionizing irradiation. PMID:25817349

  20. Nonlinear Response for Neoplastic Transformation Following Low Doses of Low Let Radiation

    OpenAIRE

    Redpath, J. Leslie

    2005-01-01

    There are now several independent studies that indicate that the dose-response for the endpoint of radiation-induced neoplastic transformation in vitro is non-linear for low linear energy transfer (LET) radiation. At low doses (

  1. The prophylactic and protective effects of egg yolk immunoglobulin against Escherichia coli on radiation-induced enteritis in rats

    International Nuclear Information System (INIS)

    Objective: To observe the prophylactic and protective effects of egg yolk immunoglobulin (IgY) against Escherichia coli on radiation-induced enteritis in rats. Methods: Thirty rats were randomly divided into three groups: normal control group (group A), radiation control group (group B) and IgY treatment group (group C). The rats of groups B and C were subjected to whole abdominal irradiation of 1000 cGy. Feeding IgY began since the day before irradiation in group C. Four days later, all the rats were killed and the intestinal bacteria translocation, the concentration of endotoxin in blood, and pathological changes of intestinal mucosa were measured or observed. Results: Bacteria translocation was not found in group A, but evident in group B (96.7%), and much lighter in group C(13.3%) than in group B. The concentration of endotoxin in blood was very low in group A (0.001 EU/ml) and very high in group B (0.829 EU/ml), but it was much lower in group C(0.249 EU/ml) than in group B. The villus edema, infiltration of inflammatory cells in mucosa and epithelial desquamation were found in group B, but these pathological changes were much milder in group C and not found at all in group A. Conclusion: Whole abdomen irradiation will evidently cause enteritis in rats, and followed by bacteria translocation and endotoxemia; IgY against Escherichia coli can diminish these changes

  2. Triphala, an ayurvedic rasayana drug, protects mice against radiation-induced lethality by free-radical scavenging.

    Science.gov (United States)

    Jagetia, Ganesh Chandra; Malagi, Krishna J; Baliga, Manjeshwar Shrinath; Venkatesh, Ponemone; Veruva, Rosi Reddy

    2004-12-01

    The effects of 10 mg/kg of triphala extract (TE) was studied on radiation-induced sickness and mortality in mice exposed to 7-12 Gray (Gy) of gamma-irradiation. Treatment of mice with triphala once daily for 5 consecutive days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug double distilled water treated irradiated controls (DDW). Triphala provided protection against both gastrointestinal and hemopoetic death. However, animals of both the TE + irradiation and DDW + irradiation groups did not survive up to 30 days post-irradiation beyond 11 Gy irradiation. The LD50/30 was found to be 8.6 Gy for the DDW + irradiation group and 9.9 Gy for TE + irradiation group. The administration of triphala resulted in an increase in the radiation tolerance by 1.4 Gy, and the dose reduction factor was found to be 1.15. To understand the mechanism of action of triphala, the free radical scavenging activity of the drug was evaluated. Triphala was found to scavenge (.)OH, O(2) (.) 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) diammonium salt (ABTS)(.+) and NO(.) radicals in a dose dependent manner. PMID:15673991

  3. The protective effect of fermented milk kefir on radiation-induced apoptosis in colonic crypt cells of rats

    International Nuclear Information System (INIS)

    To evaluate the effect of fermented milk kefir on X-ray-induced apoptosis in the colon of rats, we examined the apoptotic index, the mean number of apoptotic cells detected by H and E staining per crypt in the colon, in control rats and kefir-pretreated rats drinking kefir for 12 days before irradiation. Apoptotic cells were confirmed by TUNEL staining, and active caspase-3 expression was studied by immunohistochemistry. The cell position of apoptotic cells and active caspase-3 positive cells were examined. The apoptotic index of kefir-treated rats was significantly (p<0.05) decreased 2 h after 1 Gy irradiation in comparison with control rats at crypt cell positions 1-3, 5-7, 13, and 15. Active caspase-3 expression in the kefir-treated rats was also significantly (p<0.05) reduced in comparison with control rats 2 h after 1 Gy irradiation at crypt cell positions 1-4, 13, and 15. This study indicated that kefir protects colonic crypt cells against radiation-induced apoptosis, which was most pronounced in the stem cell region of the crypt. The antiapoptotic effect of fermented milk kefir was due to the inhibition of caspase-3 activation. (author)

  4. Protective effects of silybin and analogues against X-ray radiation-induced damage.

    Science.gov (United States)

    Fu, Haiying; Lin, Mingzhang; Katsumura, Yosuke; Yokoya, Akinari; Hata, Kuniki; Muroya, Yusa; Fujii, Kentaro; Shikazono, Naoya

    2010-07-01

    Silybin (SLB) and similar analogues, namely, hesperetin (HESP), naringenin (NAN) and naringin (NAR), are believed to be active constituents of natural flavonoids that have been reported as chemopreventive agents for certain cancers. Moreover, SLB and analogues have been determined to fast repair DNA bases from oxidative damage by pulse radiolysis techniques. The present study was designed to evaluate the protective effects of SLB and analogues on soft X-ray-induced damage to plasmid DNA in vitro. The DNA damage was determined by agarose gel electrophoresis. SLB and analogues were found to protect DNA from radiation damage at micromolar concentrations. Among the compounds tested, HESP and SLB were the most effective in preventing X-ray-induced formation of DNA single-strand breaks (SSB). A comparison of these results with other experiments showed that the ability of SLB and analogues to inhibit DNA damage in vitro correlated with the ability of the compounds to scavenge free radicals. Our work revealed that natural flavonoids, SLB and analogues may be used as potent radioprotectors against radiation damage. PMID:20705588

  5. Protective effect of atorvastatin on radiation-induced endothelial cell injury

    International Nuclear Information System (INIS)

    Objective: To explore the protective effect of atorvastatin on irradiated endothelium and the thrombomodulin (TM) expression. Methods: Cultured human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC) were treated by atorvastatin at the final concentration of 10 ?mol/ml for 10 min, and then irradiated with 2 and 25 Gy. Cell cycles status and TM expression were quantitatively measured by flow cytometry 24 hours after irradiation. Protein C activation in endothelial cells was also assessod. Results: After administration with atorvastatin for 24 h, the TM expression increased by 77%, 59% and 61% in normal control group, 2 Gy group and 25 Gy group, respectively (t=27.395, 26.420, 58.065; P=0.000). The protein C levels decreased by 23% and 34% compared with the normal group post-irradiation to 2 and 25 Gy, but increased by 79% and 76% compared with the irradiated control group after administration with atorvastatin. The rates of cell apoptosis decreased by 6% and 16% in 2 Gy and 25 Gy groups, respectively after administration with atorvastatin for 24 h (t=4.178, 17.863; P=0.000). Conclusions: Atorva statin can protect endothelia cell from irradiation-induced apeptosis by increasing TM expression and protein C activation. (authors)

  6. Radiation-induced inhibition of splenocyte locomotion and its protection by C. parvum

    International Nuclear Information System (INIS)

    Normal C57/BL mice were stimulated by intraperitoneal (ip) injection of Corynebacterium parvum (CP) prior to sublethal whole-body or local (leg) irradiation. At different times after irradiation, spleens were removed and the direct leukocyte migration assay carried out in comparison with unirradiated controls. CP causes enlarged spleens with white pulp depleted of germinal centers, and red pulp increased due to nucleated cell proliferation. X irradiation causes depletion both in white and red pulp, and a reduction in splenocyte locomotion ability. Reduction in splenocyte locomotion due to whole-body irradiation was significantly less in CP-treated than in control mice. A factor of 1.5 to 3.3 for protection of migration by CP was obtained, depending upon timing between CP stimulation, whole-body irradiation, and migration assay. The largest protection factor 1 day postirradiation was observed when migration was 7 to 14 days post-CP treatment. It is postulated that nonspecific immune adjuvant stimulation of the reticuloendothelial system by CP induces greater repopulation of the radiation-depleted spleen by leukocytes having migration capability. These findings may have relevance to the clinical use of local radiation therapy combined with CP stimulation of host immune response

  7. Radiation-induced inhibition of splenocyte locomotion and its protection by C. parvum

    Energy Technology Data Exchange (ETDEWEB)

    Isac, M.; Schechter, M.; Likhite, V.; Rotman, M.; Sall, S.; Moroson, H.

    1978-05-01

    Normal C57/BL mice were stimulated by intraperitoneal (ip) injection of Corynebacterium parvum (CP) prior to sublethal whole-body or local (leg) irradiation. At different times after irradiation, spleens were removed and the direct leukocyte migration assay carried out in comparison with unirradiated controls. CP causes enlarged spleens with white pulp depleted of germinal centers, and red pulp increased due to nucleated cell proliferation. X irradiation causes depletion both in white and red pulp, and a reduction in splenocyte locomotion ability. Reduction in splenocyte locomotion due to whole-body irradiation was significantly less in CP-treated than in control mice. A factor of 1.5 to 3.3 for protection of migration by CP was obtained, depending upon timing between CP stimulation, whole-body irradiation, and migration assay. The largest protection factor 1 day postirradiation was observed when migration was 7 to 14 days post-CP treatment. It is postulated that nonspecific immune adjuvant stimulation of the reticuloendothelial system by CP induces greater repopulation of the radiation-depleted spleen by leukocytes having migration capability. These findings may have relevance to the clinical use of local radiation therapy combined with CP stimulation of host immune response.

  8. Involvement of peroxiredoxin I in protecting cells from radiation-induced death

    International Nuclear Information System (INIS)

    Peroxiredoxin I (Prx-I), a key member of the peroxiredoxin family, reduces peroxides and equivalents through the thioredoxin system. Our previous work has shown that expression of Prx-I in mammalian cells increases following ionizing radiation (IR), indicating, that Prx-I actively responds to IR-induced reactive oxygen species (ROS) and suggesting that Prx-I plays an important role in protecting cells from IR-induced death. To test this hypothesis, we suppressed the expression of Prx-I in SW480 cells by RNA interference. Our results show that IR induces the expression of Prx-I in SW480 cells in a dose- and time-dependent manner. The recombinant siRNA vector targeting Prx-I dramatically reduced the expression of Prx-I in SW480 cells. When Prx-I was knocked down in SW480 cells, the cells exhibited a decreased growth rate, a reduced antioxidant capability following IR and became more sensitive to IR-induced apoptosis. Together, our results demonstrate that Prx-I plays an important role in protecting cells from IR-induced cell death, which might be through scavenging IR-induced ROS in the cells. (author)

  9. Low-dose radiation

    International Nuclear Information System (INIS)

    The potential dangers of low level ionizing radiation are of concern to United States health officials, and there is mounting public anxiety. The near disaster at Three Mile Island near Harrisburg underlined this public concern. There is controversy among scientists who are unable to give clear definitions of the risks of exposure to low doses. The U.S. Department of Health, Education and Welfare is to embark on long-term health studies of plant workers, pregnant women and their offspring, and a sample of the general population in the area around Three Mile Island. The exposed population is sufficiently large to provide the required reliable estimates of the long term hazards of low dose irradiation. (U.K.)

  10. Protective effects of extracts of Vernonia amygdalina, Hibiscus sabdariffa and vitamin C against radiation-induced liver damage in rats

    International Nuclear Information System (INIS)

    The radioprotective efficacy of methanolic extracts of leaves of Vernonia amygdalina (VA) and Hibiscus sabdariffa (HS), and vitamin C (VIT C) against gamma radiation (4 Gy) induced liver damage was studied in male Wistar albino rats. VIT C was administered at a dose of 250 mg/kg body weight, while VA and HS were administered at doses; 200, 400 and 800-mg/kg body weight, orally for 4 weeks prior to radiation and 5 weeks after irradiation. The rats were sacrificed at 24 hours and 5 weeks after irradiation. Treatment with VIT C and VA (800 mg/kg) significantly (p<0.05) decreased the gamma radiation-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at 24 hours after irradiation, whereas, HS (400 mg/kg) significantly (p<0.05) decreased the serum ALT activity only. Similarly, treatment with VIT C and VA (800 mg/kg) significantly (p<0.05) decreased the serum conjugated bilirubin levels by 56% and 29%, respectively at 24 hours. Furthermore, VIT C, VA and HS significantly (p<0.05) decreased the levels of serum lipid peroxidation (LPO) and increased the hepatic superoxide dismutase (SOD) activities at 24 hours. Treatment for 5 weeks after irradiation with VIT C, VA and HS significantly (p<0.05) decreased the levels of unconjugated bilirubin, while VIT C and VA alone decreased the levels of conjugated bilirubin. Furthermore, treatment with VA (400 and 800 mg/kg) decreased the serum ALT activities by 25% and 34%, respectivelALT activities by 25% and 34%, respectively, at 5 weeks after irradiation. Similarly, alkaline phosphatase and lipid peroxidation (LPO) levels were significantly (p<0.05) attenuated following treatment with VIT C and VA (400 and 800 mg/kg) at 5 weeks after irradiation. In addition, treatment with VIT C, VA (800 mg/kg) and HS (400 and 800 mg/kg) significantly (p<0.05) elevated the levels of reduced glutathione (GSH) by 61%, 56%, 41% and 44%, respectively, at 5 weeks. Similar elevation of antioxidant enzymes; SOD, glutathione-s-transferase and catalase were obtained in animals treated with VIT C and extracts at 5 weeks. Taken together, the results suggest that the extracts of VA and HS, and VIT C could increase the antioxidant defense systems and may probably protect animals from radiation-induced liver damage. (author)

  11. Ciliary derived neurotrophic factor protects oligodendrocytes against radiation induced damage in vitro by a mechanism independent of a proliferative effect

    International Nuclear Information System (INIS)

    Purpose/Objective: Radiation-induced damage to the central nervous system in the from of myelopathy is a dose-limiting complication in the treatment of tumors situated in or close to the spinal cord. The target cell for this damage is not definitively identified, but demyelination due to oligodendrocyte damage is strongly implicated. Multiple neurotrophic factors have recently been identified which demonstrate a survival effect on oligodendrocytes. We investigated the effect of Ciliary Derived Neurotrophic Factor (CNTF), Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) on the radiosensitivity of oligodendrocytes in vitro to determine if this may ameliorate radiation damage, as a model for reducing myelopathy in vivo. Materials and Methods: Mature oligodendrocytes were cultured from the cortex of newborn Sprague-Dawley white rats and maintained on poly-d-lysine plates. The experimental arm was exposed to CNTF (0.01-100ng/ml), NGF (100ng/ml) or NT-3 (20ng/ml) for 24 hours prior to radiation, and control and experimental arms radiated using a cobalt 60 irradiator at a dose rate of .87 Gy/min with doses from 2 Gy to 10 Gy. Oligodendrocytes were identified using an O4 antibody, assessed for viability at 5 days using an MTT assay and counted using a phase contrast microscope. Combination studies of CNTF and NT-3 were also performed. BrdU studies were performed to determine if the various neurotrophins induced proliferation, with BrdU added for the 24 hour period prior toBrdU added for the 24 hour period prior to radiation only, for the 5 day period following radiation only, or for both periods combined. Results: The proportion of mature oligodendrocytes surviving 5 days after irradiation was not significantly increased by NGF, and was only modestly increased by NT-3. However, CNTF significantly increased the surviving proportion at all doses The addition of NT-3 to CNTF did not further increase the proportion of oligodendrocytes surviving. CNTF dose escalation studies confirmed 20ng/ml as an optimal dose. BrdU studies showed that CNTF did not function as a mitogen when added to the mature oligodendrocyte cultures. Following radiation, cells incorporating BrdU appeared to be non-viable. Conclusion: CNTF appeared to protect mature oligodendrocytes from irradiation by a mechanism other than proliferation. Our in vitro studies suggest that CNTF might have the potential for preventing or alleviating radiation induced myelopathy

  12. Low doses - great trouble

    International Nuclear Information System (INIS)

    Presents a critical review of scientifically groundless data on the special hazards of low-dose exposure caused by the Chernobyl accident published in Russia, Belarus and Ukraine. Demonstrates that these publications are at variance with the world experience gained by radiobiology and radiation medicine, for they exaggerate the contribution of the radiation factor to development of psychosomatic disorders and overstate the expected stochastic consequences. All this results in inadequate measures aimed at alleviation of the medical consequences of the accident

  13. Sunscreen protection against ultraviolet radiation-induced pyrimidine dimers in mouse epidermal DNA

    International Nuclear Information System (INIS)

    Solar ultraviolet radiation (UVR) induces a number of pathologic conditions of mammalian skin including erythema, oedema, hyperplasia, sunburn cell formation and skin cancer. Consequently, UVR-induced DNA damage has been implicated as one of the photochemical events that results in the formation of these pathological changes. The ability of sunscreens to protect against UVR-induced DNA damage has not been well characterized especially with UVA (320-400 nm) wavelengths and UVA absorbers. In this paper we present results of a study aimed at determining the efficacy of two sunscreens at preventing the induction of pyrmidine dimers in basal cell DNA of mice exposed to solar-simulated UVR (SSUV) wavelengths (290-400 nm) or to UVA (320-400 nm). (author)

  14. Protection by rosemary leaves extract against radiation-induced hepatic injuries

    International Nuclear Information System (INIS)

    The development of effective non-toxic radioprotective agents is of considerable interest in the improvement of radio therapy of cancer and protection against unplanned exposures. The synthetic drugs developed in post-world war II have had serious constrains in clinical application due to their toxicity at the optimal protective dose level. Search for non toxic protectors from natural sources have indicated that some of the commonly used medicinal plants and the polyherbal formulation could prove to be valuable sources of the clinically used radioprotector as their ratio of effective dose to toxic dose is very high. A worldwide hunt is on for the development of non-toxic/less toxic radioprotectors. Keeping this view, the present study has been undertaken to find out the possible radioprotective potential of the Rosemarinus officinalis extract (ROE) in the liver of Swiss albino mice as its leaves have various medicinal properties like analgesic, anti-epileptic, antioxidant, hepatoprotactive and anti-cancer etc. Adult male Swiss albino mice, 6-8 weeks old with an average weight of 233 gms, were selected from an inbred colony and divided into two groups carrying equal number of animals in each. First group was orally administered DDW with the dose of 1000 mg/kg.b.wt/day for 5 consecutive days, while the second group received ROE with the dose of 1000 mg/kg.b.wt/day for 5 consecutive days. On 5th day, after half an hr. of the last administration of DDW or ROE, both the t administration of DDW or ROE, both the groups were exposed to single dose of 9 Gy of gamma radiation. All the animals were monitored regularly from the day of treatment till their autopsy time or survival with respect to food and water intake, body weight change, sickness, general activity, mobility, fur and skin lesions and other visible abnormalities, if any. These animals from both the groups were autopsied at 12 hrs., 24 hrs., 3, 5, 10, 20 and 30 days post-irradiation and their liver were removed, weighed, and after routine processing, slides were prepared for the evaluation of quantitative variations in normal, abnormal and binucleated hepatocytes. Some part of liver was used for the study of biochemical parameters viz, lipid peroxidation (LPx) and glutathione (GSH)

  15. Protective Effect of Anthocyanins from Lingonberry on Radiation-induced Damages

    Directory of Open Access Journals (Sweden)

    Shuang-Qi Tian

    2012-12-01

    Full Text Available There is a growing concern about the serious harm of radioactive materials, which are widely used in energy production, scientific research, medicine, industry and other areas. In recent years, owing to the great side effects of anti-radiation drugs, research on the radiation protectants has gradually expanded from the previous chemicals to the use of natural anti-radiation drugs and functional foods. Some reports have confirmed that anthocyanins are good antioxidants, which can effectively eliminate free radicals, but studies on the immunoregulatory and anti-radiation effects of anthocyanins from lingonberry (ALB are less reported. In this experiment, mice were given orally once daily for 14 consecutive days before exposure to 6 Gy of gamma-radiation and were sacrificed on the 7th day post-irradiation. The results showed that the selected dose of extract did not lead to acute toxicity in mice; while groups given anthocyanins orally were significantly better than radiation control group according to blood analysis; pretreatment of anthocyanins significantly (p < 0.05 enhanced the thymus and spleen indices and spleen cell survival compared to the irradiation control group. Pretreatment with anthocyanins before irradiation significantly reduced the numbers of micronuclei (MN in bone marrow polychromatic erythrocytes (PCEs. These findings indicate that anthocyanins have immunostimulatory potential against immunosuppression induced by the radiation.

  16. Ambient ultraviolet radiation induces protective responses in soybean but does not attenuate indirect defense

    International Nuclear Information System (INIS)

    We investigated the effects of ambient ultraviolet (UV) radiation on (i) the performance and chemistry of soybean plants, (ii) the performance of Spodoptera frugiperda and (iii) the foraging behavior of the herbivore's natural enemy Cotesia marginiventris which exploits herbivore-induced plant volatiles (VOC) for host location. The accumulation of protective phenolics was faster in plants receiving ambient UV than in controls exposed to sun light lacking UV. Accordingly, isorhamnetin- and quercetin-based flavonoids were increased in UV exposed plants. No UV effects were found on the performance and feeding behavior of S. frugiperda. Herbivore-damaged plants emitted the same VOC when grown under ambient or attenuated UV for 5, 10 or 30 days. Consequently, C. marginiventris was attracted but did not discriminate between exposed and unexposed soybeans. In summary, ambient UV radiation affected soybean morphology and physiology but did not destabilize interactions between trophic levels. - Ambient ultraviolet radiation does not alter induced VOC emission in soybean and thus host location of the parasitoid Cotesia marginiventris remains effective

  17. Ambient ultraviolet radiation induces protective responses in soybean but does not attenuate indirect defense

    Energy Technology Data Exchange (ETDEWEB)

    Winter, Thorsten R. [Department of Botany II, Julius-von-Sachs Institute for Biosciences, University of Wuerzburg, Julius-von-Sachs-Platz 3, 97082 Wuerzburg (Germany); Rostas, Michael [Department of Botany II, Julius-von-Sachs Institute for Biosciences, University of Wuerzburg, Julius-von-Sachs-Platz 3, 97082 Wuerzburg (Germany)], E-mail: rostas@botanik.uni-wuerzburg.de

    2008-09-15

    We investigated the effects of ambient ultraviolet (UV) radiation on (i) the performance and chemistry of soybean plants, (ii) the performance of Spodoptera frugiperda and (iii) the foraging behavior of the herbivore's natural enemy Cotesia marginiventris which exploits herbivore-induced plant volatiles (VOC) for host location. The accumulation of protective phenolics was faster in plants receiving ambient UV than in controls exposed to sun light lacking UV. Accordingly, isorhamnetin- and quercetin-based flavonoids were increased in UV exposed plants. No UV effects were found on the performance and feeding behavior of S. frugiperda. Herbivore-damaged plants emitted the same VOC when grown under ambient or attenuated UV for 5, 10 or 30 days. Consequently, C. marginiventris was attracted but did not discriminate between exposed and unexposed soybeans. In summary, ambient UV radiation affected soybean morphology and physiology but did not destabilize interactions between trophic levels. - Ambient ultraviolet radiation does not alter induced VOC emission in soybean and thus host location of the parasitoid Cotesia marginiventris remains effective.

  18. SENSITIVITY TO RADIATION-INDUCED CANCER IN HEMOCHROMATOSIS

    Science.gov (United States)

    Determination of dose-response relationships for radiation-induced cancer in segments of the population with high susceptibility is critical for understanding the risks of low dose and low dose rates to humans. Clean-up levels for radionuclides will depend upon the fraction of t...

  19. TAT-Mediated Delivery of Tousled Protein to Salivary Glands Protects Against Radiation-Induced Hypofunction

    International Nuclear Information System (INIS)

    Purpose: Patients treated with radiotherapy for head-and-neck cancer invariably suffer its deleterious side effect, xerostomia. Salivary hypofunction ensuing from the irreversible destruction of glands is the most common and debilitating oral complication affecting patients undergoing regional radiotherapy. Given that the current management of xerostomia is palliative and ineffective, efforts are now directed toward preventive measures to preserve gland function. The human homolog of Tousled protein, TLK1B, facilitates chromatin remodeling at DNA repair sites and improves cell survival against ionizing radiation (IR). Therefore, we wanted to determine whether a direct transfer of TLK1B protein to rat salivary glands could protect against IR-induced salivary hypofunction. Methods: The cell-permeable TAT-TLK1B fusion protein was generated. Rat acinar cell line and rat salivary glands were pretreated with TAT peptide or TAT-TLK1B before IR. The acinar cell survival in vitro and salivary function in vivo were assessed after radiation. Results: We demonstrated that rat acinar cells transduced with TAT-TLK1B were more resistant to radiation (D0 = 4.13 1.0 Gy; ?/? = 0 Gy) compared with cells transduced with the TAT peptide (D0 = 4.91 1.0 Gy; ?/? = 20.2 Gy). Correspondingly, retroductal instillation of TAT-TLK1B in rat submandibular glands better preserved salivary flow after IR (89%) compared with animals pretreated with Opti-MEM or TAT peptidetreated with Opti-MEM or TAT peptide (31% and 39%, respectively; p < 0.01). Conclusions: The results demonstrate that a direct transfer of TLK1B protein to the salivary glands effectively attenuates radiation-mediated gland dysfunction. Prophylactic TLK1B-protein therapy could benefit patients undergoing radiotherapy for head-and-neck cancer.

  20. Protective Effect of Hawthorn (Crataegus Linn) against Radiation-Induced Damage in Rats

    International Nuclear Information System (INIS)

    Crataegus Linn., commonly known as Hawthorn, is one of the most widely used herbal heart tonic. The objective of this work is to investigate the radioprotective and antioxidant effect of hawthorn (H) extract against gamma irradiation induced biochemical disorders in rats .Twenty four animals were randomly divided into equal four groups as follows:- Group 1: control group rats Group 2: irradiated rats whole body exposed to 7Gy gamma-rays, Group 3: treated , rats in this group received freshly prepared Hawthorn(H) at dose (10mg/kg body wt/ day) by gavages for 28 consecutive days .Group4: rats received freshly Hawthorn for 7 consecutive days then exposed to 7Gy whole-body gamma irradiation and treated with Hawthorn for 21 consecutive days after irradiation . Exposure to gamma- irradiation induced a significant increase of aminotransferases (AST, ALT), and alkaline phosphatase (ALP) activities and total cholesterol (TC), triglycerides (TG) and Low density lipoprotein cholesterol (LDL-C) cotents. While, High density lipoprotein-cholesterol (HDL-C) cotent showed a decrease. Metabolic disorders were associated to significant increases in serum and liver thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) and marked reduction in glutathione (GSH) content and Catalase (CAT) and Superoxide dismutase (SOD) activities in blood and liver compared with controls. Administration of Hawthorn prior and after radiation exposure was found to offer protection against gamma irradiation induced oxidative stress in rats. Accordingly, it could be concluded that consumption of Hawthorn could modulate the oxidative stress caused by radiation exposure and that due to its antioxidant activity

  1. Low doses of ionizing radiation: Relationship between biological benefit and damage induction. A synopsis

    International Nuclear Information System (INIS)

    Absorption of ionizing radiation in biological tissue stochastically interacts with constituent atoms and molecules and always generates energy deposition (track) events accompanied by bursts of reactive oxygen species (ROS). These ROS are quite similar to those ROS that arise abundantly and constantly by normal oxidative metabolism. ROS effects from either source need attention when assessing radiation-induced alterations in biological structure and function. Endogenous ROS alone induce about 106 DNA oxyadducts per cell per day compared to about 5x10-3 total DNA damage per average cell per day from background radiation exposure (1 mGy per year). At this background level, the corresponding ratio of probabilities of endogenous versus radiogenic DNA double strand breaks (DSBs) per cell per day is about 103 with some 25-40 % of low-LET caused radiogenic DNA-DSBs being of the multi-damage-site type. Radiogenic DNA damage increases in proportion to absorbed dose over a certain dose range. By evolution, tissues possess physiological mechanisms of protection against an array of potentially toxic agents, externally from the environment and endogenously from metabolism, mainly against the abundantly and constantly produced ROS. Ad hoc protection operates at a level that is genetically determined. Following small to moderate perturbation of cell-tissue homeostasis by a toxic impact, adaptive responses develop with a delay and may last from hours to weeks, a delay and may last from hours to weeks, even months, and aim at protecting the system against renewed insults. Protective responses encompass defense by scavenging mechanisms, DNA repair, damage removal largely by apoptosis and immune responses, as well as changes in cell proliferation. Acute low-dose irradiation below about 0.2 Gy can not only disturb cell-tissue homeostasis but also initiate adaptived protection that appears with a delay of hours and may last from less than a day to months. The balance between damage production and adaptive protection favors damage at high doses but protection at low doses. This low-dose induced protection mainly functions against accumulation of DNA damage from endogenous sources, such as ROS. Bystander effects from high-dosed cells to non-irradiated neighboring cells appear to induce both damage and protection. With respect to oncogenesis, a model using microdosimetry and based on the above dual response pattern at low doses and dose rates is consistent with published non-linear epidemiological and experimental data and, thus, contradicts the linear-no-threshold dose-risk hypothesis for radiation induced cancer. The LNT hypothesis should be abandoned and be replaced by a hypothesis that is scientifically justified and causes less unreasonable fear and unnecessary expenditure. (author)

  2. Protective effect of treatment with low-dose gliclazide in a model of middle cerebral artery occlusion and reperfusion in rats.

    Science.gov (United States)

    Tan, Fang; Li, Hua; Ma, Mingyi; Yu, Yerong

    2014-04-29

    The aim of this study was to explore the expression of sulfonylurea receptor 1 (SUR1), the regulatory subunit of the NCCa-ATP channel, and to investigate the protective effects of gliclazide following middle cerebral artery occlusion (MCAO)/reperfusion in male Wistar rats. Adult rats underwent 2h of the left MCAO using the intraluminal thread technique before reperfusion. The core areas of the infarct at different reperfusion time points were examined for the mRNA level and protein expression of SUR1 using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting respectively. Gliclazide was administered intravenously into the right jugular vein for 12h simultaneously with the reperfusion. The number of apoptotic cells was determined using the TUNEL assay. The neurological functional deficits were evaluated using Bederson?s test, and the cerebral infarction volume was visualized with TTC staining. We found up-regulation of SUR1 mRNA and protein levels in ischemic infarct tissues after reperfusion following MCAO, and SUR1 mRNA and protein were maximally upregulated 8-12h after a 2-hour ischemia. The treatment with low-dose of gliclazide reduced the total number of TUNEL-positive cells, the neurological functional deficits and the brain infarct volume. These results suggest that the SUR1-regulated NCCa-ATP channel may be associated with MCAO/reperfusion injury and the infarct-reducing effects of intravenous treatment with gliclazide may be due, in part, to the blocked upregulation of SUR1 expression, the decreased infarct size and the reduced apoptosis in the ischemia-reperfusion brain. PMID:24602692

  3. Radiation-induced disruption of hippocampal redox homeostasis, neurogenesis and cognitive function: protective role of melatonin and its metabolites

    International Nuclear Information System (INIS)

    The sensitivity of neuronal tissues to ionizing radiation depends on the rate of differentiation and accompanying factors of the tissues as well as on the efficiency of the intrinsic antioxidative defense systems. Neurogenic area in the adult brain are reported be highly sensitive to ionizing radiation. While the pathogenesis of radiation induced cognitive impairment is not well understood, recent studies indicated that neuronal precursor cells in the hippocampus may be involved. The dentate gyrus of the hippocampus is unique in that it is one of two regions in the mammalian brain that continues to produce new neurons in adulthood. Moreover, brain is considered abnormally sensitive to oxidative damage and in fact early studies demonstrating the ease of peroxidation of brain membranes supported this notion. Brain is enriched in the more easily peroxidizable fatty acids, consumes an inordinate fraction (20%) of the total oxygen consumption for its relatively small weight (2%), and is not particularly enriched in antioxidant defenses. Our recent findings showed an inverse relationship between mice cognitive performance and cellular indicators of oxidative stress or redox status which was reported in the term glutathione homeostasis (GSH/GSSG), DNA damage, protein oxidation and lipid peroxidation. Radiation exposure severely impaired the hipocampal neurogenesis as measure in the terms of immunoreactivity of immature and proliferating neurons in dentate gyrus, the doublecoing neurons in dentate gyrus, the doublecortin (Dcx) and Ki-67 positive cells respectively. Our results showed a significant implication of hippocampus neurogenesis in cognitive functions and pre-treatment of melatonin and its metabolites significantly protected the neurogenic potential of brain and thereby the cognitive functions. (author)

  4. Second International MELODI Workshop on Low Dose Risk Research - Slides of the presentations

    International Nuclear Information System (INIS)

    The MELODI (Multidisciplinary European Low Dose Initiative) mission is to impulse low dose risk research in Europe through a strategic research agenda (SRA) and road-map of priorities. The last presentation is dedicated to the SRA and its preference research programs. The other presentations deal principally with the low-dose exposure in medical uses of ionizing radiations, radiosensitivity, radiation-induced cataracts, or epidemiology and radiobiology of cardiovascular disease. This document is composed of the slides of the presentations

  5. Radiation-induced acute brain injury and the protective effect of traditional Chinese medicine-salvia miltiorrhiza

    International Nuclear Information System (INIS)

    Objective: To understand the expression of acute brain injury induced by radiation and the protective effect of traditional Chinese Medicine in BALB/C mouse. Methods: The whole brain of BALB/C mouse was irradiated to a dose of 25 Gy using a 6 MV X linear accelerator. Ten hours later, the brain tissue and blood sample were taken. Thiobarbituric acid reaction was used to detect the malonaldehyde substitute for the lipid peroxide. Immunohistochemical method was used to detect the expression of ICAM-1 on D1, 2, 3, and 10 after having received radiation. One-Way ANOVA was used to evaluate the differences in the values of LPO in the brain tissue and plasma between the groups. The difference of expression of ICAM-1 between the groups was compared by ?2 method. Results: Two hundred and twelve female BALB/C mice were divided into five groups: Control group, Radiation alone group (R), R + dexamethasone group, R + 654-2 group and R + Salvia Miltiorrhiza group. The contents of LPO in the mouse brain tissue 10 hours after 25 Gy of whole brain irradiation were as follows (mean standard error): Control group (1975.594.2) nmol/g, Radiation alone group (R) (3417.3109.7) nmol/g, R + dexamethasone group (3113.6178.1) nmol/g, R + 654-2 group (3406.4159.1) nmol/g, R + Salvia Miltiorrhiza group (2981.5140.1) nmol/g. Salvia Miltiorrhiza significantly reduced the LPO increase induced by irradiation (P<0.05). There were no significant differences between the other grot differences between the other groups in the change of LPO in the plasma 10 hours after whole brain irradiation. The expression of ICAM-1 after whole brain irradiation was time-dependent . There was an increase of expression of ICAM-1 24 hours after irradiation, reaching the peak at 48 hours. Salvia Miltiorrhiza and dexamethasone strongly inhibited the expression of ICAM-1 when compared with radiation only, with the difference significant (P<0.01). Conclusions: The change of LPO content in the BALB/C mouse brain tissue and the increase in expression of ICAM-1 on the brain vascular endothelial cell can act as indexes of acute brain injury induced by radiation. Traditional Chinese medicine Salvia Miltiorrhiza has a protective effect on radiation-induced acute brain injury

  6. The effect of low dose ionizing radiation on homeostasis and functional integrity in an organotypic human skin model

    Energy Technology Data Exchange (ETDEWEB)

    von Neubeck, Claere; Geniza, Matthew; Kauer, Paula M.; Robinson, Joseph E.; Chrisler, William B.; Sowa, Marianne B.

    2015-05-01

    Outside the protection of earths atmosphere, astronauts are exposed to low doses of high linear energy transfer (LET) radiation. Future NASA plans for deep space missions or a permanent settlement on the moon are limited by the health risks associated with space radiation exposures. There is a paucity of direct epidemiological data for low dose exposures to space radiation-relevant high LET ions. Health risk models are used to estimate the risk for such exposures, though these models are based on high dose experiments. There is increasing evidence, however, that low and high dose exposures result in different signaling events at the molecular level, and may involve different response mechanisms. Further, despite their low abundance, high LET particles have been identified as the major contributor to health risk during manned space flight. The human skin is exposed in every external radiation scenario, making it an ideal epithelial tissue model in which to study radiation induced effects. Here, we exposed an in vitro three dimensional (3-D) human organotypic skin tissue model to low doses of high LET oxygen (O), silicon (Si) and iron (Fe) ions. We measured proliferation and differentiation profiles in the skin tissue and examined the integrity of the skins barrier function. We discuss the role of secondary particles in changing the proportion of cells receiving a radiation dose, emphasizing the possible impact on radiation-induced health issues in astronauts.

  7. Low-dose irradiation causes rapid alterations to the proteome of the human endothelial cell line EA.hy926.

    Science.gov (United States)

    Pluder, Franka; Barjaktarovic, Zarko; Azimzadeh, Omid; Mrtl, Simone; Krmer, Anne; Steininger, Sylvia; Sarioglu, Hakan; Leszczynski, Dariusz; Nylund, Reetta; Hakanen, Arvi; Sriharshan, Arundhathi; Atkinson, Michael J; Tapio, Soile

    2011-03-01

    High doses of ionising radiation damage the heart by an as yet unknown mechanism. A concern for radiological protection is the recent epidemiological data indicating that doses as low as 100-500 mGy may induce cardiac damage. The aim of this study was to identify potential molecular targets and/or mechanisms involved in the pathogenesis of low-dose radiation-induced cardiovascular disease. The vascular endothelium plays a pivotal role in the regulation of cardiac function and is therefore a potential target tissue. We report here that low-dose radiation induced rapid and time-dependent changes in the cytoplasmic proteome of the human endothelial cell line EA.hy926. The proteomes were investigated at 4 and 24 h after irradiation at two different dose rates (Co-60 gamma ray total dose 200 mGy; 20 mGy/min and 190 mGy/min) using 2D-DIGE technology. Differentially expressed proteins were identified, after in-gel trypsin digestion, by MALDI-TOF/TOF tandem mass spectrometry, and peptide mass fingerprint analyses. We identified 15 significantly differentially expressed proteins, of which 10 were up-regulated and 5 down-regulated, with more than 1.5-fold difference compared with unexposed cells. Pathways influenced by the low-dose exposures included the Ran and RhoA pathways, fatty acid metabolism and stress response. PMID:21104263

  8. Protective role of tea polyphenols in combination against radiation-induced haematopoietic and biochemical alterations in mice.

    Science.gov (United States)

    Hu, Yuan; Cao, Jing-Jing; Liu, Ping; Guo, Dai-Hong; Wang, Ya-Ping; Yin, Jian; Zhu, Ying; Rahman, Khalid

    2011-12-01

    The purpose of this study was to investigate the radioprotective effects of tea polyphenols (TPs) in various combinations against radiation-induced damage in mice. Mice were divided into different groups: non-irradiated control, irradiated control, amifostine (43.6?mg/kg, i.v. 30?min before irradiation; positive control) and various combinations of tea polyphenols in different doses. The radioprotective effect on the haematopoietic system, serum cytokines and endogenous antioxidant enzymes were studied. TP50, containing approximately 50% of (-)-epigallochatechin-3-gallate in addition to other catechins, showed the greatest radioprotective effect against radiation-induced changes in haematological parameters (red blood cell count, white blood cell count and haemoglobin), and maintained the spleen and thymus indices unchanged (spleen or thymus weight/body weight??1000). Tea polyphenols also significantly decreased radiation-induced lipid peroxidation (malondialdehyde levels), elevated endogenous antioxidant enzymes (superoxide dismutase) and reduced the serum cytokines which were elevated in radiation-induced toxicity. This evidence shows the potential of tea polyphenols, particularly in the combination found in TP50, as radioprotectors in mice, especially regarding recovery of the haematopoietic system, antioxidant potential activity and reduction of inflammatory cytokines. PMID:21452375

  9. Protective Effect of Hesperidin Against Gamma Radiation-Induced Oxidative Stress in Rats: Biochemical, Histopathological And Molecular Studies

    International Nuclear Information System (INIS)

    Hesperidin belongs to the class of flavonoids called flavonones which are abundant in citrus fruits and it is significantly contributed to the intracellular antioxidant defense system and has been reported to act as a powerful agent against superoxide, singlet oxygen and hydroxyl radicals. Hesperidin has also been reported to have membrane stabilizing properties as well as anti-inflammatory and anti-cancer properties. The aim of this study is to investigate the hepato protective and antioxidant effects of hesperidin, a naturally occurring citrus flavonoglycone, against gamma irradiation-induced oxidative damage in rat liver hepatocytes and DNA. The results showed that ionizing radiation-induced oxidative stress was evidenced by elevated levels of lipid peroxidation (MDA) and decrease in the levels of the antioxidants SOD, CAT and GSH in the liver. The data revealed elevation in liver enzymes (AST, ALT, ALP and GGT), increased of comet parameters (tailed %, tail length, % DNA in the tail and tail moment) as indication of DNA fragmentation of liver tissue and decrease in antioxidant GPx and SOD gene expression. The histopathological examination of liver tissues revealed increased tissue changes following the radiation exposure. Supplementation of hesperidin (100 mg/kg/day after day) by special gastric tube for one month before exposing rats to gamma irradiation of 10 Gy fractionated dose (2 Gy x 5 times) and to 8 Gy (single dose) induced significant amelioration and normalization in the levels of all studied parameters. The gamma irradiation-induced toxic effects were decreased by hesperidin administration before irradiation as observed by the restoration in the altered levels of the studied parameter. The pre-treatment with hesperidin can reduce lipid peroxidation (MDA) and increase SOD, CAT and GSH levels. Also, pre-treatment with hesperidin has ameliorated the liver enzymes (AST, ALT, ALP and GGT) and increased GPx and SOD gene expression in liver tissue. On the other hand, hesperidin could decrease DNA fragmentation in liver tissue by improving liver histopathological alterations in the rats administrated with hesperidin prior to gamma rays exposure. According to the results obtained, it could be concluded that hesperidin might provide potent antioxidant and radioprotective effects against liver hepatocellular and DNA damages induced by gamma radiation.

  10. Radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Apoptosis is an active process of gene-directed cellular self-destruction that can be induced in many cell types via numerous physiological and pathological stimuli. We found that interphasedeath of thymocytes is a typical apoptosis showing the characteristic features of apoptosis including cell shrinkage, chromatin condensation and DNA degradation. Moderate dose of radiation induces extensive apoptosis in rapidly proliferating cell population such as the epithelium of intestinal crypt. Recent reports indicate that the ultimate form of radiation-induced mitotic death in several cells is also apoptosis. One of the hallmarks of apoptosis is the enzymatic internucleosomal degradation of chromatin DNA. We identified an endonuclease responsible for the radiation-induced DNA degradation in rat thymocytes. The death-sparing effects of interrupting RNA and protein synthesis suggested a cell genetic program for apoptosis. Apoptosis of thymocytes initiated by DNA damage, such as radiation and radio mimetic substance, absolutely requires the protein of p53 cancer suppresser gene. The cell death induced by glucocorticoid, or aging, has no such requirement. Expression of oncogene bcl-2 rescues cells from the apoptosis. Massive apoptosis in radiosensitive cells induced by higher dose radiation may be fatal. It is suggested that selective apoptotic elimination of cells would play an important role for protection against carcinogenesis and malformation through removal of cells with unrepaired radiation-induced DNA damages. Data to evaluate the significance of apoptosis in the radiation risk are still poor. Further research should be done in order to clarify the roles of the cell death on the acute and late effects of irradiation. (author)

  11. Importance and present state of the research in radiation-induced bystander response

    International Nuclear Information System (INIS)

    Recently, accumulating evidences have reported non-targeted effects, which are not a direct effect of the initial damage produced in cellular DNA. Radiation-induced bystander responses (RIBR) are the most important non-targeted effect, which are defined as cellular responses which have not been directly induced by radiation but are induced in the neighborhood cells of the directly irradiated. Here the importance and current issues of RIBR in the low dose radiation risk assessment were reported through the summary of present topics of RIBR and microbeam probes of radiation responses. Non-targeted effects include adaptive responses, low dose hypersensitivity, genomic instability, gene expression, inverse dose rate effect and bystander responses, which have common features that saturate with increasing dose. The accumulating evidence of the results obtained using alpha-particles suggests that a linear extrapolation of risks from high to low doses would underestimate the risks at low doses. However, in the 2007 recommendations of the International Commission of Radiological Protection (ICRP), it has been concluded that knowledge of the roles of bystander cell signaling in the genesis of radiation-induced health effects is insufficiently well developed for radiological protection purposes. Now the study of RIBR is considered that one of the most important study to clear the mechanisms of the effect of low dose radiation. RIBR is mainly mediated by cell-to-cell communicatioinly mediated by cell-to-cell communication via gap-junction and/or secreted factors, i.e., Reactive oxygen species (ROS), cytokines and growth factors and NO radicals, and is transferred at least up to 7.5 mm away from targeted cells. RIBR contributes to the induction of radiation adaptive responses. To elucidate the mechanisms of RIBR many microbeam irradiation devices are in operation or underdeveloped. Our experimental, plans and the problems of the study of RIBR are also shown in this report. (author)

  12. Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

    Scientific Electronic Library Online (English)

    B.H., Bakkal; F.A., Gultekin; B., Guven; U.O., Turkcu; S., Bektas; M., Can.

    2013-09-27

    Full Text Available Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the [...] aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

  13. Protective Effects of Polysaccharides from Soybean Meal Against X-ray Radiation Induced Damage in Mouse Spleen Lymphocytes

    Directory of Open Access Journals (Sweden)

    Xin Yang

    2011-11-01

    Full Text Available The aim of this study was to investigate radioprotective effect of the polysaccharides from soybean meal (SMP against X-ray radiation-induced damage in mouse spleen lymphocytes. MTT and comet assay were performed to evaluate SMPs ability to prevent cell death and DNA damage induced by radiation. The results show that, X-ray radiation (30 KV, 10 mA, 8 min (4 Gy can significantly increase cell death and DNA fragmentation of mouse spleen lymphocytes. Pretreatment with SMP for 2 h before radiation could increase cell viability, moreover, the SMP can reduce X-ray radiation-induced DNA damage. The percentage of tail DNA and the tail moment of the SMP groups were significantly lower than those of the radiation alone group (p < 0.05. These results suggest SMP may be a good candidate as a radioprotective agent.

  14. Low doses effects and gamma radiations low dose rates

    International Nuclear Information System (INIS)

    This expose wishes for bringing some definitions and base facts relative to the problematics of low doses effects and low dose rates effects. It shows some already used methods and some actual experimental approaches by focusing on the effects of ionizing radiations with a low linear energy transfer. (N.C.)

  15. [Involvement of ATP in radiation-induced bystander effect as a signaling molecule].

    Science.gov (United States)

    Kojima, Shuji

    2014-01-01

    We previously reported that low doses (0.25-0.5 Gy) of ?-rays induce intracellular antioxidant, radioresistant, DNA damage repair, and so on. Meanwhile, we have recently reported that ATP is released from the cells exposed to low-dose ?-rays. Here, it was investigated whether or not ?-radiation-induced release of extracellular ATP contributes to various radiation effects, in paricular, focusing on the inductions of intracellular antioxidant and DNA damage repair. Irradiation with ?-rays or exogenously added ATP increased expression of intracellular antioxidants such as thioredoxin and the increases were blocked by pretreatment with an ecto-nucleotidase in both cases. Moreover, release of ATP and autocrine/paracrine positive feedback through P2Y receptors serve to amplify the cellular repair response to radiation-induced DNA damage. To sum up, it would be suggested that ATP signaling is important for the effective induction of radiation stress response, such as protection of the body from the radiation and DNA damage repair. In addition, the possibility that this signaling is involved in the radiation resistance of cancer cells and beneficial effect on the organism of low-dose radiation and radiation adaptive response, would be further suggested. PMID:24882651

  16. Paeoniflorin protects human EA.hy926 endothelial cells against gamma-radiation induced oxidative injury by activating the NF-E2-related factor 2/heme oxygenase-1 pathway.

    Science.gov (United States)

    Yu, Jing; Zhu, Xiaoyun; Qi, Xin; Che, Juanjuan; Cao, Bangwei

    2013-04-26

    Pulmonary endothelial cells have been demonstrated to have a critical role in the pathogenesis of radiation-induced lung injury. Our preliminary experiments indicated that paeoniflorin protected human EA.hy926 endothelial cells from radiation-induced oxidative injury. This study was designed to confirm the protective effect of paeoniflorin against radiation-induced endothelial cellular damage and to elucidate the underlying mechanisms. Preincubation of EA.hy926 cells with paeoniflorin before ?-radiation resulted in significant inhibition of apoptosis, a decrease in mitochondrial membrane potential and enhanced cell viability. In particular, we showed that paeoniflorin significantly reduced the formation of intracellular reactive oxygen species (ROS), the level of malondialdehyde (MDA) and lactate dehydrogenase (LDH) leakage, and enhanced production of the endogenous antioxidants, glutathione (GSH) and superoxide dismutase (SOD) in EA.hy926 cells. Treatment of these cells with paeoniflorin significantly induced HO-1 expression. Moreover, paeoniflorin promoted the nuclear translocation of nuclear factor erythroid 2 related factor-2 (Nrf-2). The paeoniflorin-induced HO-1 expression was abrogated by Nrf2 siRNA. Furthermore, inhibition of HO-1 with zinc protoporphyrin IX (ZNPP) significantly reversed the protective effect of paeoniflorin against radiation-induced damage in EA.hy926 cells. Our findings confirmed that paeoniflorin protected EA.hy926 cells against radiation-induced injury through the Nrf2/HO-1 pathway. PMID:23403272

  17. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    Satheesh Kumar P

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  18. Radiation-induced adaptive response in fish cell lines

    International Nuclear Information System (INIS)

    There is considerable interest at present in low-dose radiation effects in non-human species. In this study gamma radiation-induced adaptive response, a low-dose radiation effect, was examined in three fish cell lines, (CHSE-214 (Chinook salmon), RTG-2 (rainbow trout) and ZEB-2J (zebrafish)). Cell survival after exposure to direct radiation with or without a 0.1 Gy priming dose, was determined using the colony forming assay for each cell line. Additionally, the occurrence of a bystander effect was examined by measuring the effect of irradiated cell culture medium from the fish cell lines on unexposed reporter cells. A non-linear dose response was observed for all cell lines. ZEB-2J cells were very sensitive to low doses and a hyper-radiosensitive (HRS) response was observed for doses <0.5 Gy. A typical protective adaptive response was not detected in any of the three fish cell lines tested. Rather, it was found that pre-exposure of these cells to 0.1 Gy radiation sensitized the cells to subsequent high doses. In CHSE-214 cells, increased sensitivity to subsequent high doses of radiation was observed when the priming and challenge doses were separated by 4 h; however, this sensitizing effect was no longer present when the interval between doses was greater than 8 h. Additionally, a 'protective' bystander response was observed in these cell lines; exposure to irradiated medium from fish cells caused increased cloning efficiency in unirradiated reporter cells. The data cin unirradiated reporter cells. The data confirm previous conclusions for mammalian cells that the adaptive response and bystander effect are inversely correlated and contrary to expectations probably have different underlying mechanisms

  19. Influence of 2-mercaptopropionylglycine (MPG) on radiation-induced changes in the acid phosphatase activity of mouse intestine and its role in tissue protection

    International Nuclear Information System (INIS)

    Adult male Swiss albino mice were exposed to a 60Cobalt gamma whole-body radiation of 2.5, 5 and 10 Gy with or without a prior intraperitoneal injection of MPG of 20 mg/kg body weight. The acid phosphatase activity was estimated in the ileum and pycnotic nuclei and necrotic cells were counted in the crypts at various post irradiation intervals from 3 h to 14 days. A close correlation was observed between acid phosphatase activity and cell death. It is concluded that the enzyme may have an important role in the development of cell injury. Observation on the MPG-pretreated animals suggests protection of the lysosomal membrane by a radial scavenging action of the drug on the radiation-induced lipid peroxide. (author)

  20. Protective effect of curcumin and its analog on ?-radiation induced DNA damage and lipid peroxidation in cultured human lymphocytes and isolated rat hepatocytes in vitro

    International Nuclear Information System (INIS)

    Ionizing radiation is known to induce oxidative stress through generation of reactive oxygen species (ROS) resulting in an imbalance of the pro-oxidant and antioxidant status in the cells, which is suggested to culminate in cell death. The present work was aimed to evaluate the radioprotective effect of curcumin and its analog on ?-radiation induced toxicity in cultured human lymphocytes and rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The cellular changes were estimated using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). The DNA damage was analyzed by comet assay, cytokinesis blocked micro nucleus assay, dicentric aberrations and translocation frequency. Cell cycle distribution and measurement of the percentage of apoptotic cells were performed by flow cytometry analysis. To investigate whether the dietary agents like curcumin and its analog have a role on cell cycle regulation, we analyzed the changes in cell cycle profiles by using fluorescence activated cell sorter. The increase in the severity of DNA damage was observed with the increase dose (1, 2 and 4 Gy) of ?-radiation in cultured lymphocytes and hepatocytes. TBARS were increased significantly, whereas the levels of GSH and antioxidant enzymes were significantly decreased in ?-irradiated hepatocytes and lymsed in ?-irradiated hepatocytes and lymphocytes. On pretreatment with curcumin and its analog (1, 5 and 10 ?g/ml) showed a significant decrease in the levels of TBARS and DNA damage. The antioxidant enzymes were increased significantly along with the levels of GSH. The maximum protection of hepatocytes and lymphocytes was observed at 10 ?g/ml curcumin and 5 ?g/ml curcumin analog pretreatment. Thus, pretreatment with curcumin and its analog helps in protecting the normal hepatocytes and lymphocytes against ?-radiation induced cellular damage and can be developed as an effective radioprotector during radiotherapy in near future

  1. Glycogen synthase kinase 3? dictates podocyte motility and focal adhesion turnover by modulating paxillin activity: implications for the protective effect of low-dose lithium in podocytopathy.

    Science.gov (United States)

    Xu, Weiwei; Ge, Yan; Liu, Zhihong; Gong, Rujun

    2014-10-01

    Aberrant focal adhesion turnover is centrally involved in podocyte actin cytoskeleton disorganization and foot process effacement. The structural and dynamic integrity of focal adhesions is orchestrated by multiple cell signaling molecules, including glycogen synthase kinase 3? (GSK3?), a multitasking kinase lately identified as a mediator of kidney injury. However, the role of GSK3? in podocytopathy remains obscure. In doxorubicin (Adriamycin)-injured podocytes, lithium, a GSK3? inhibitor and neuroprotective mood stabilizer, obliterated the accelerated focal adhesion turnover, rectified podocyte hypermotility, and restored actin cytoskeleton integrity. Mechanistically, lithium counteracted the doxorubicin-elicited GSK3? overactivity and the hyperphosphorylation and overactivation of paxillin, a focal adhesion-associated adaptor protein. Moreover, forced expression of a dominant negative kinase dead mutant of GSK3? highly mimicked, whereas ectopic expression of a constitutively active GSK3? mutant abolished, the effect of lithium in doxorubicin-injured podocytes, suggesting that the effect of lithium is mediated, at least in part, through inhibition of GSK3?. Furthermore, paxillin interacted with GSK3? and served as its substrate. In mice with doxorubicin nephropathy, a single low dose of lithium ameliorated proteinuria and glomerulosclerosis. Consistently, lithium therapy abrogated GSK3? overactivity, blunted paxillin hyperphosphorylation, and reinstated actin cytoskeleton integrity in glomeruli associated with an early attenuation of podocyte foot process effacement. Thus, GSK3?-modulated focal adhesion dynamics might serve as a novel therapeutic target for podocytopathy. PMID:25239564

  2. Hormesis effect of low dose radiation on cellular DNA repair

    International Nuclear Information System (INIS)

    Objective: To study radio-adaptive response of mutagenesis and repair of DNA double-strand breaks (DSB) in mammalian cells induced by low dose ?-rays, and to detect low dose radiation-induced proteins. Methods: Mouse SR-1 cells were irradiated with 60Co ?-rays. Mutations at hprt locus were assayed by 6-thioguanine selective culture method. DNA DSBs were measured by pulsed field gel electrophoresis. Southwestern blot hybridization was employed to detect radiation-induced proteins. Results: Preexposure of SR-1 cells to 1 cGy at 18 h and 24 h before challenging dose significantly decreased the frequency of hprt gene mutations induced by following 3 Gy challenge. Preexposure of SR-1 cells to single 1 cGy as well as to 1 cGy per day for 10 successive days significantly increased the cellular capacity of rejoining 3 Gy-induced DNA DSBs. A newly synthesized protein bound to damaged DNA was detected at 16 h after 1 cGy exposure. Conclusion: Proteins possibly involved in the process of DNA repair were induced by low dose radiation-up regulating the expression of some specific genes. Such induced proteins lead to increase of cellular DNA repair capacity as well as radio-adaptive response of cells to gene mutations

  3. Radiation induced effects in the developing central nervous system

    International Nuclear Information System (INIS)

    The embryo and the human foetus are particularly sensitive to ionizing radiation and this sensitivity presents various qualitative and quantitative functional changes during intra-uterine development. Apart from radiation induced carcinogenesis, the most serious consequence of prenatal exposure in human beings is severe mental retardation. The principal data on radiation effects on human beings in the development of the central nervous system come form epidemiological studies carried out in individuals exposed in utero during the atomic explosion at Hiroshima and Nagasaki. These observations demonstrate the existence of a time of maximum radiosensitivity between the weeks 8 and 15 of the gestational period, a period in which the proliferation and neuronal migration takes place. Determination of the characteristics of dose-response relationship and the possible existence of a threshold dose of radiation effects on the development of the central nervous system is relevant to radiation protection against low dose radiation and the establishment of dose limits for occupational exposure and the public. Studies were conducted on the generation of nitrous-oxide and its relation with the production of active species of oxygen in brains of exposed rats in utero exposed to doses of up to 1 Gy during their maximum radiosensitivity. The possible role of the mechanism of radiation induced damage in the development of the central nervous system is discussed

  4. Protective effect of peach kernel extracts on radiation-induced DNA damage in human blood lymphocytes in the comet assay

    International Nuclear Information System (INIS)

    The alkaline single-cell gel electrophoresis (SCGE) assay, the comet assay, has been applied to the detection of DNA damage from a number of chemical and biological factors in vivo and in vitro. The comet assay is a novel method to assess DNA single-strand breaks, alkali-labile sites in individual cells. We evaluated the effect of peach kernel extracts on radiation-induced DNA damage in human blood lymphocytes using the comet assay. The lymphocytes, with or without pretreatment of the extracts, were exposed to 0, 0.1, 0.3, 0.5, 1.0 and 2.0 Gy of 60Co gamma ray. Significantly increased tail moment, which was a marker of DNA strand breaks in the comet assay, showed an excellent dose-response relationship. The treatment of the peach kernel extracts prominently reduced the DNA damage in irradiated groups compared to that in non-treated control groups. The result indicated that the extracts showed radioprotective effect on lymphocyte DNA when assessed by the comet assay

  5. 1,4 Naphthoquinone protects radiation induced cell death and DNA damage in lymphocytes by activation Nrf2/are pathway and enhancing DNA repair

    International Nuclear Information System (INIS)

    1,4-Naphthoquinone (NQ) is the parent molecule of many clinically approved anticancer, anti-infective, and antiparasitic drugs such as anthracycline, mitomycin, daunorubicin, doxorubicin, diospyrin, and malarone. Presence of NQ during a-irradiation (4Gy) significantly reduced the death of irradiated murine splenic lymphocytes in a dose dependent manner (0.05-liM), with complete protection at liM as assessed by PI staining. Radioprotection by NQ was further confirmed by inhibition of caspase activation, decrease in cell size, DNA-fragmentation, nuclear-blebbing and clonogenic assay. All trans retinoic acid which is inhibitor of Nrf-2 pathway, completely abrogated the radioprotective effect of NQ, suggesting that radioprotective activity of NQ may be due to activation of Nrf-2 signaling pathways. Further, addition of NQ to lymphocytes activated Nrf-2 in time dependent manner as shown by confocal microscopy, electrophoretic mobility shift assay and quantitative real time PCR. It also increased the expression of Nrf-2 dependent cytoprotective genes like hemeoxygenase-1, MnSOD, catalse as demonstrated by real time PCR and flowcytometry. NQ protected lymphocytes significantly against radiation-induced cell death even when added after irradiation. Complete protection was observed by addition of NQ up to 2 h after irradiation. However, percentage protection decreased with increasing time interval. These results suggested that NQ may offer protection to lymphocytes activating ffer protection to lymphocytes activating repair pathways. Repair of radiation induced DNA strand breaks was studied by comet assay. Pretreatment of lymphocytes with NQ induced single strand breaks up to 6h but not double strand breaks in DNA. However, NQ mediated single strand breaks were repaired completely at longer time intervals. Addition of NQ to lymphocytes prior to 4 Gy a-radiation exposure showed decrease in the yield of DNA double strand breaks. The observed time-dependent decrease in the DNA strand breaks could be attributed to enhanced DNA repair in NQ treated lymphocytes. Furthermore, microarray analysis indicated that treatment of lymphocytes with NQ induces upregulation of several DNA repair genes including mismatch repair (Msh6, Pms2, and Rfc1), nucleotide and base excision repair pathways like pole4, parp1, parp4. Induction of these genes in NQ treated lymphocytes were confirmed by quantitative real time PCR. Further, treatment of lymphocytes with NQ resulted in increased expression of proteins as revealed by 2D protein blot analysis. Proteomic analysis of these spots corresponds to RIKEN protein which is known to exhibits as radio-resistance in the cells. Thus in addition to anti-cancer and anti-parasitic activity, NQ offered protection against a-radiation-induced cell death in lymphocytes via activation of Nrf-2/ARE and DNA repair pathways. (author)

  6. Radiation-induced bystander effects and the DNA paradigm: An 'out of field' perspective

    International Nuclear Information System (INIS)

    Over the past 20 years there has been increasing evidence that cells and the progeny of cells surviving a very low dose of ionizing radiation [?-mGy] can exhibit a wide range of non-monotonic effects such as adaptive responses, low dose hypersensitivity and other delayed effects. These effects are inconsistent with the expected dose-response, when based on extrapolation of high dose data and cast doubt on the reliability of extrapolating from high dose data to predict low dose effects. Recently the cause of many of these effects has been tentatively ascribed to so-called 'bystander effects'. These are effects that occur in cells not directly hit by an ionizing track but which are influenced by signals from irradiated cells and are thus highly relevant in situations where the dose is very low. Not all bystander effects may be deleterious although most endpoints measured involve cell damage or death. In this commentary, we consider how these effects impact the historical central dogma of radiobiology and radiation protection, which is that DNA double strand breaks are the primary radiation-induced lesion which can be quantifiably related to received dose and which determine the probability that a cancer will result from a radiation exposure. We explore the low dose issues and the evidence and conclude that in the very low dose region, the primary determinant of radiation exposure outcome is the genetic and epigenetic background of the individual and not solely the doseof the individual and not solely the dose. What this does is to dissociate dose from effect as a quantitative relationship, but it does not necessarily mean that the effect is ultimately unrelated to DNA damage. The fundamental thesis we present is that at low doses fundamentally different mechanisms underlie radiation action and that at these doses, effect is not quantitatively related to dose

  7. Functional analysis of molecular mechanisms of radiation induced apoptosis, that are not mediated by DNA damages; Funktionelle Analyse molekularer Mechanismen der strahleninduzierten Apoptose, die nicht ueber direkte DNA-Schaeden vermittelt werden

    Energy Technology Data Exchange (ETDEWEB)

    Angermeier, Marita; Moertl, Simone [Helmholtz Zentrum Muenchen, Neuherberg (Germany). Inst. fuer Strahlenbiologie

    2012-09-15

    The effects of low-dose irradiation pose new challenges on the radiation protection efforts. Enhanced cellular radiation sensitivity is displayed by disturbed cellular reactions and resulting damage like cell cycle arrest, DNA repair and apoptosis. Apoptosis serves as genetically determinate parameter for the individual radiation sensitivity. In the frame of the project the radiation-induced apoptosis was mechanistically investigated. Since ionizing radiation induced direct DNA damage and generates a reactive oxygen species, the main focus of the research was the differentiation and weighting of DNA damage mediated apoptosis and apoptosis caused by the reactive oxygen species (ROS).

  8. Protective effect of urinary trypsin inhibitor on the development of radiation-induced lung fibrosis in mice

    International Nuclear Information System (INIS)

    This study aimed to analyze whether Ulinastatin, a urinary trypsin inhibitor (UTI), inhibits the transforming growth factor (TGF)-? signaling pathway and lung fibrosis induced by thoracic irradiation in a lung injury mouse model. The thoraces of 9-week-old female fibrosis-sensitive C57BL/6 mice were irradiated with a single X-ray dose of 12 Gy or 24 Gy. UTI was administrated intraperitoneally at a dose of 200,000 units/kg concurrently with radiation (concurrent UTI) or daily during the post-irradiation period for 8-14 days (post-RT UTI). Mice were sacrificed at 16 weeks after irradiation to assess the histological grade of lung fibrosis and immunohistochemical TGF-? expression. Survival rates of mice given 24 Gy to the whole lung UTI were also compared. Post-RT UTI reduced the score of lung fibrosis in mice, but concurrent UTI had no beneficial effects in irradiated mice. The fibrosis score in post-RT UTI mice was 3.21.0, which was significantly smaller than that of irradiated mice without UTI treatment (RT alone; 6.01.3; p2=0.26, p<0.01). The survival rate at 30 weeks for post-RT UTI mice was significantly better than that of RT alone mice (33% vs. 10%, p<0.05). The administration of post-RT UTI suppressed TGF-? of post-RT UTI suppressed TGF-? expression and radiation-induced lung fibrosis, which resulted in significant survival prolongation of the irradiated mice. (author)

  9. Mechanism of protection of bystander cells by exogenous carbon monoxide: impaired response to damage signal of radiation-induced bystander effect.

    Science.gov (United States)

    Han, W; Yu, K N; Wu, L J; Wu, Y C; Wang, H Z

    2011-05-10

    A protective effect of exogenous carbon monoxide (CO), generated by CO releasing molecule ticarbonyldichlororuthenium (II) dimer (CORM-2), on the bystander cells from the toxicity of radiation-induced bystander effect (RIBE) was revealed in our previous study. In the present work, a possible mechanism of this CO effect was investigated. The results from medium transfer experiments showed that ?-particle irradiated Chinese hamster ovary (CHO) cells would release nitric oxide (NO), which was detected with specific NO fluorescence probe, to induce p53 binding protein 1 (BP1) formation in the cell population receiving the medium, and the release peak was found to be at 1h post irradiation. Treating the irradiated or bystander cells separately with CO (CORM-2) demonstrated that CO was effective in the bystander cells but not the irradiated cells. Measurements of NO production and release with a specific NO fluorescence probe also showed that CO treatment did not affect the production and release of NO by irradiated cells. Protection of CO on cells to peroxynitrite, an oxidizing free radical from NO, suggested that CO might protect bystander cells via impaired response of bystander cells to NO, a RIBE signal in our research system. PMID:21376740

  10. Mechanism of protection of bystander cells by exogenous carbon monoxide: Impaired response to damage signal of radiation-induced bystander effect

    International Nuclear Information System (INIS)

    A protective effect of exogenous carbon monoxide (CO), generated by CO releasing molecule ticarbonyldichlororuthenium (II) dimer (CORM-2), on the bystander cells from the toxicity of radiation-induced bystander effect (RIBE) was revealed in our previous study. In the present work, a possible mechanism of this CO effect was investigated. The results from medium transfer experiments showed that ?-particle irradiated Chinese hamster ovary (CHO) cells would release nitric oxide (NO), which was detected with specific NO fluorescence probe, to induce p53 binding protein 1 (BP1) formation in the cell population receiving the medium, and the release peak was found to be at 1 h post irradiation. Treating the irradiated or bystander cells separately with CO (CORM-2) demonstrated that CO was effective in the bystander cells but not the irradiated cells. Measurements of NO production and release with a specific NO fluorescence probe also showed that CO treatment did not affect the production and release of NO by irradiated cells. Protection of CO on cells to peroxynitrite, an oxidizing free radical from NO, suggested that CO might protect bystander cells via impaired response of bystander cells to NO, a RIBE signal in our research system.

  11. Mechanism of protection of bystander cells by exogenous carbon monoxide: Impaired response to damage signal of radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Han, W. [Department of Physics and Materials Science, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Kowloon (Hong Kong); Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Kowloon (Hong Kong); Wu, L.J. [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Wu, Y.C. [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); School of Nuclear Science and Technology, University of Science and Technology of China, Hefei 230029 (China); Wang, H.Z. [Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China)

    2011-05-10

    A protective effect of exogenous carbon monoxide (CO), generated by CO releasing molecule ticarbonyldichlororuthenium (II) dimer (CORM-2), on the bystander cells from the toxicity of radiation-induced bystander effect (RIBE) was revealed in our previous study. In the present work, a possible mechanism of this CO effect was investigated. The results from medium transfer experiments showed that {alpha}-particle irradiated Chinese hamster ovary (CHO) cells would release nitric oxide (NO), which was detected with specific NO fluorescence probe, to induce p53 binding protein 1 (BP1) formation in the cell population receiving the medium, and the release peak was found to be at 1 h post irradiation. Treating the irradiated or bystander cells separately with CO (CORM-2) demonstrated that CO was effective in the bystander cells but not the irradiated cells. Measurements of NO production and release with a specific NO fluorescence probe also showed that CO treatment did not affect the production and release of NO by irradiated cells. Protection of CO on cells to peroxynitrite, an oxidizing free radical from NO, suggested that CO might protect bystander cells via impaired response of bystander cells to NO, a RIBE signal in our research system.

  12. Low-dose radiation: a cause of breast cancer

    International Nuclear Information System (INIS)

    It is likely that the breast is the organ most sensitive to radiation carcinogenesis in postpubertal women. Studies of different exposed populations have yielded remarkably consistent results, in spite of wide differences in underlying breast cancer rates and conditions of exposure. Excess risk is approximately proportional to dose, and is relatively independent of ionization density and fractionization of dose. This implies that the risk associated with low-dose exposures to ionizing radiation can be estimated with some confidence from higher-dose data. Excess risk is heavily dependent on age at exposure but relatively independent of population differences in normal risk. The temporal patterns after exposure of both radiation-induced and naturally occurring breast cancer are similar, suggesting a strong influence of factors other than radiation on radiation-induced breast cancer. Uncertainties remain about risks from exposures before puberty and after menopause

  13. Characterizing low dose and dose rate effects in rodent and human neural stem cells exposed to proton and gamma irradiation

    Directory of Open Access Journals (Sweden)

    Bertrand P. Tseng

    2013-01-01

    Full Text Available Past work has shown that exposure to gamma rays and protons elicit a persistent oxidative stress in rodent and human neural stem cells (hNSCs. We have now adapted these studies to more realistic exposure scenarios in space, using lower doses and dose rates of these radiation modalities, to further elucidate the role of radiation-induced oxidative stress in these cells. Rodent neural stem and precursor cells grown as neurospheres and human neural stem cells grown as monolayers were subjected to acute and multi-dosing paradigms at differing dose rates and analyzed for changes in reactive oxygen species (ROS, reactive nitrogen species (RNS, nitric oxide and superoxide for 2 days after irradiation. While acute exposures led to significant changes in both cell types, hNSCs in particular, exhibited marked and significant elevations in radiation-induced oxidative stress. Elevated oxidative stress was more significant in hNSCs as opposed to their rodent counterparts, and hNSCs were significantly more sensitive to low dose exposures in terms of survival. Combinations of protons and ?-rays delivered as lower priming or higher challenge doses elicited radioadaptive changes that were associated with improved survival, but in general, only under conditions where the levels of reactive species were suppressed compared to cells irradiated acutely. Protective radioadaptive effects on survival were eliminated in the presence of the antioxidant N-acetylcysteine, suggesting further that radiation-induced oxidative stress could activate pro-survival signaling pathways that were sensitive to redox state. Data corroborates much of our past work and shows that low dose and dose rate exposures elicit significant changes in oxidative stress that have functional consequences on survival.

  14. Low Dose IR Creates an Oncogenic Microenvironment by Inducing Premature

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Zhi-Min [Harvard School of Public Health

    2013-04-28

    Introduction Much of the work addressing ionizing radiation-induced cellular response has been carried out mainly with the traditional cell culture technique involving only one cell type, how cellular response to IR is influenced by the tissue microenvironment remains elusive. By use of a three-dimensional (3D) co-culture system to model critical interactions of different cell types with their neighbors and with their environment, we recently showed that low-dose IR-induced extracellular signaling via the tissue environment affects profoundly cellular responses. This proposal aims at determining the response of mammary epithelial cells in a tissue-like setting.

  15. Effect of low dose radiation on the immune system

    International Nuclear Information System (INIS)

    The aim of the work is to sum-up data concerning the low dose radiation effect on the immune system, the role of some immune factors for the radiosensitivity, as well as to propose methods for assessment of occupationally exposed persons. The question of the impact of such doses on immune parameters is discussed with a certain stimulating effect being also presumed. The application of cell sorting methods by FACS or MACS, as well as the molecular techniques PCR or RT-PCR for amplifying of DNA or RNA sequences, give a clearer idea about radiation-induced changes at cellular or molecular level (author)

  16. Moderate acute intake of de-alcoholised red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo-Results of a comparative in vivo intervention study in younger men

    Energy Technology Data Exchange (ETDEWEB)

    Greenrod, W. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia); Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia (Australia); Stockley, C.S. [Australian Wine Research Institute, South Australia (Australia); Burcham, P. [Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia (Australia); Abbey, M. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia); Fenech, M. [CSIRO Health Sciences and Nutrition, Genome Health and Nutrigenomics Laboratory, PO Box 10041, Adelaide BC, SA 5000 (Australia)]. E-mail: michael.fenech@hsn.csiro.au

    2005-12-11

    Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, dealcoholised red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of dealcoholised red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R = -0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechin.

  17. Moderate acute intake of de-alcoholised red wine, but not alcohol, is protective against radiation-induced DNA damage ex vivo-Results of a comparative in vivo intervention study in younger men

    International Nuclear Information System (INIS)

    Moderate intake of wine is associated with reduced risk of cardiovascular disease and possibly cancer however it remains unclear whether the potential health benefits of wine intake are due to alcohol or the non-alcoholic fraction of wine. We therefore tested the hypothesis that the non-alcoholic fraction of wine protects against genome damage induced by oxidative stress in a crossover intervention study involving six young adult males aged 21-26 years. The participants adhered to a low plant phenolic compound diet for 48 h prior to consuming 300 mL of complete red wine, dealcoholised red wine or ethanol on separate occasions 1 week apart. Blood samples were collected 0.5, 1.0 and 2.0 h after beverage consumption. Baseline and radiation-induced genome damage was measured using the cytokinesis-block micronucleus assay and total plasma catechin concentration was measured. Consumption of dealcoholised red wine significantly decreased the gamma radiation-induced DNA damage at 1 and 2 h post-consumption by 20%. In contrast alcohol tended to increase radiation-induced genome damage and complete wine protected against radiation-induced genome damage relative to alcohol. The observed effects were only weakly correlated with the concentration of total plasma catechin (R = -0.23). These preliminary data suggest that only the non-alcoholic fraction of red wine protects DNA from oxidative damage but this effect cannot be explained solely by plasma catechinby plasma catechin

  18. Low dose radiation and diabetes mellitus

    International Nuclear Information System (INIS)

    Induction of hormesis and adaptive response by low-dose radiatio (LDR) has been extensively indicated. It's mechanism may be related with the protective protein and antioxidants that LDR induced, which take effects on the diabetes mellitus (DM) and other diseases. This review will summarize available dat with emphasis on three points: the preventive effect of LDR on the development of diabetes, the therapeutic effect of LDR on diabetic complications and possible mechanisms by which LDR prevents the development of diabetes and diabetic complications. Finally, the perspectives of LDR clinical, diabetes-related implication are discussed. (authors)

  19. Peroxiredoxin IV Protects Cells From Radiation-Induced Apoptosis in Head-and-Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Purpose: Human peroxiredoxins (Prxs) are known as a family of thiol-specific antioxidant enzymes, among which Prx-I and -II play an important role in protecting cells from irradiation-induced cell death. It is not known whether Prx-IV also protects cells from ionizing radiation (IR). Methods and Materials: To evaluate the protective role of Prx-IV in IR, we transfected full-length Prx-IV cDNA into AMC-HN3 cells, which weakly express endogenous Prx-IV, and knocked down the expression of Prx-IV with siRNA methods using AMC-HN7 cells, which express high levels of endogenous Prx-IV. Radiosensitivity profiles in these cells were evaluated using clonogenic assay, FACS analysis, cell viability, and TUNEL assay. Results: Three Prx-IV expressing clones were isolated. Prx-IV regulated intracellular reactive oxygen species (ROS) levels and made cells more resistant to IR-induced apoptosis. Furthermore, the knockdown of Prx-IV with siRNA made cells more sensitive to IR-induced apoptosis. Conclusion: The results of these studies suggest that Prx-IV may play an important role in protecting cells from IR-induced apoptosis in head-and-neck squamous cell carcinoma

  20. Low-dose energetic protons induce adaptive and bystander effects that protect human cells against DNA damage caused by a subsequent exposure to energetic iron ions.

    Science.gov (United States)

    Buonanno, Manuela; De Toledo, Sonia M; Howell, Roger W; Azzam, Edouard I

    2015-05-01

    During interplanetary missions, astronauts are exposed to mixed types of ionizing radiation. The low 'flux' of the high atomic number and high energy (HZE) radiations relative to the higher 'flux' of low linear energy transfer (LET) protons makes it highly probable that for any given cell in the body, proton events will precede any HZE event. Whereas progress has been made in our understanding of the biological effects of low-LET protons and high-LET HZE particles, the interplay between the biochemical processes modulated by these radiations is unclear. Here we show that exposure of normal human fibroblasts to a low mean absorbed dose of 20 cGy of 0.05 or 1-GeV protons (LET ? 1.25 or 0.2 keV/?m, respectively) protects the irradiated cells (P proton-irradiated cells were co-cultured were also significantly protected from the DNA-damaging effects of the challenge dose. The mitigating effect persisted for at least 24 h. These results highlight the interactions of biological effects due to direct cellular traversal by radiation with those due to bystander effects in cell populations exposed to mixed radiation fields. They show that protective adaptive responses can spread from cells targeted by low-LET space radiation to bystander cells in their vicinity. The findings are relevant to understanding the health hazards of space travel. PMID:25805407

  1. Final Technical Report for the grant entitled "Genetic Factors Affecting Susceptibility to Low-Dose Radiation"

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William, F., Ph.D., D.Sc.

    2006-11-22

    The goal of this proposal was to test the hypothesis that mice heterozygous for the Nijmegen Breakage Syndrome (NBS1) gene are genetically susceptible to low doses of ionizing radiation. The rationale for this is that patients with NBS are radiation sensitive, because of defects in cellular responses to radiation induced genetic damage and haploinsufficiency at this genetic locus provides the potential for genetic susceptibility to low doses of ionizing radiation. Wild type and heterozygous NBS1 mice were irradiated and followed over their lifetime for radiation induced genomic instability, carcinogenesis and non-specific life shortening. No differences in cytogenetic damage, cancer induction or life span were observed between the hypomorphic mice indicating that genetic imbalance at the NBS1 loci does not modulate low dose radiation sensitivity.

  2. Suppression subtractive hybridization in construction of radiation-induced EST library

    International Nuclear Information System (INIS)

    Objective: To clone and identify radiation-induced genes from 0.5 Gy ?-ray irradiated human embryo lung cells (HEL). The identification and functional studies of radiation-induced genes will prompt the elucidation of the molecular mechanisms of low dose radiation-induced biological effects. It will also profit the understanding of the basic processes of cellular metabolisms. Methods: A low dose radiation-induced differentially displaying EST library has been constructed by suppression subtractive hybridization from HEL cells irradiated with 0.5 Gy ?-rays. The EST library was screened by reverse Northern hybridization analysis. Positive clones were sequenced and the similarity was searched against the DNA database in GenBank. Results: Altogether 90 positive cDNA clones with increased expression after 0.5 Gy irradiation were identified which corresponded to 21 individual genes. These genes involved in the processes of cell cycle control, signal transduction, cell skeleton, metabolism and protein synthesis, etc. All these demonstrated the diverse responses of cells to low dose radiation. Moreover, four novel cDNA were obtained. Conclusions: Low dose radiation induces ESTs which relate to cell proliferation, cell cycle control, signal transduction, cell skeleton, metabolism, protein synthesis and stress response etc were cloned and identified by SSH. Authors' data suggest that these genes could play important roles in the biological response of cells to low dose radiatial response of cells to low dose radiation

  3. MELODI - Multidisciplinary European Low dose Initiative - First Draft of Strategic Research Agenda (SRA)

    International Nuclear Information System (INIS)

    The SRA Working Group of MELODI (Multidisciplinary European Low Dose Initiative) was tasked to develop a long-term strategic research agenda (SRA) to guide the coherent integration of national low dose research programmes. Priorities that need to be addressed concern fundamental mechanistic research ranging from radiation track structure and the deposition of energy in biologically important molecules; the resultant homeostatic perturbations and the steps in the cellular and tissue metabolic pathways that eventually lead to disease pathologies. In fact, the main priorities are here the step-wise elucidation of the mechanisms of radiation-induced (oxidative) stress responses and their impact on radiation-induced cancers and non cancer diseases. To achieve this a holistic approach is proposed staring with radiation-specific effects, radiation-induced molecular, biological and pathological effects involving a systems biology approach as well as molecular epidemiology and mathematical modelling in order to come up with more solid low dose health risk assessments. The pathologies considered are outlined in the report where the need is stressed for the MELODI platform to involve a constellation of classical and emerging technologies in a highly multidisciplinary approach. Elucidating the shapes of low-dose response relationships and resolving the question of thresholds is paramount to resolving questions of risk for both populations and individuals. Much is known about radiation-induced cancer in humans and animal models but this needs to be pursued particularly at low doses. More recently, the scientific community has realised that low radiation-induced health effects range well beyond cancer. The priority non-cancer areas that need to be brought into focus are cardiovascular, neurological and ophthalmic. (A.C.)

  4. Molecular Tools and the Biology of Low-dose Effects

    Science.gov (United States)

    Carmel Mothersill (McMaster University; Medical Physics and Applied Radiation Sciences Department)

    2009-09-01

    Most environmental protection issues concern the often chronic exposure of large populations to low doses of chemical toxins and ionizing radiation. However, measuring the effects of low doses on populations exposed over long time periods is highly problematic. Politically driven opinions often tend to take the place of science. Part of the problem is that epidemiology is a weak tool when the level of exposure is low. High background levels of exposure, genetic diversity, and exposure uncertainties all contribute to ??noise? and make dose-response relationships difficult to define. Uncertainty feeds anxiety, leading to polarized politics. This review looks at the promise of molecular technologies for identifying the effects of low doses of radiation and identifies some of the issues involved in defining risk after low-dose exposures. While the main pollutant discussed in this article is ionizing radiation, the analysis could apply equally well to other toxic exposures or to combined radiation and chemical pollutants.

  5. Protective effect of sodium meclofenamate (SM) for radiation induced mucositis of the esophagus, large bowel and urinary bladder: A preliminary report

    International Nuclear Information System (INIS)

    Sodium meclofenamate (SM) is a nonsteroidal anti-inflammatory agent which inhibits the synthesis of both prostaglandins and leukotrienes. In previous studies involving animal models, the authors found that oral SM may protect against radiation induced esophagitis, cystitis and proctitis. Lately, they investigated oral SM for radioprotection of patients irradiated to their esophagus, colon and urinary bladder in a double blind study. A dose of 100 mg tid PO or placebo is given to patients who are irradiated to their chest or their pelvis for different malignancies. Evaluation is based on clinical tolerance to irradiation and histological examination of the involved organs. Twenty-four patients were so far included in the study. Seventeen patients received SM and only 7 were given placebo. A trend was found, the initial toxicity being probably worsened by the meclomen treatment (e.g., diarrhea in 2/7 (28.6%) placebo patients and in 13/17 (76.5%) of SM treated). In contradistinction, during the 12 months followup, signs of late toxicity are significantly lower in the SM treated group (e.g. diarrhea, 4/5 (80%) in the placebo and 1/12 (8.3%) in the SM group). The initial toxicity seems to be troublesome, however, more followup of the accrued patients may be of value regarding prevention of later radiation toxicity

  6. 1,2,3,4,6-penta-?-galloyl-?-D-glucose protects splenocytes against radiation-induced apoptosis in murine splenocytes

    International Nuclear Information System (INIS)

    Antioxidant property and hematopoietic repair capacity are important characteristics of radioprotective agents. Some studies have demonstrated that 1,2,3,4,6-penta-O-galloyl-?-D-glucose (PGG), a molecule isolated from the waterlily, has antioxidant, hematopoietic repair, and anti-inflammatory activities. In this study, we try to determine whether PGG extracted from a lily, Nymphaea tetragona var. angusta, has radioprotective effects on splenocytes in vitro against 60Co ?-ray irradiation with absorption doses of 2 Gy and 4 Gy. Results show that PGG treatment dramatically enhances the proliferation of splenocytes compared with irradiated but untreated controls. In addition, PGG treatment before irradiation protects the splenocytes from lethal effects of irradiation and decreases DNA damages as identified by the alkaline comet assay. PGG-treated cells also show less radiation-induced apoptosis. These cells have lower concentrations of the pro-apoptotic protein p53 and more of the antiapoptotic protein Bcl-2. The results presented in this study suggest that PGG has a cytoprotective effect on immune cells exposed to normally damaging amount of radiation. Thus, PGG could be an effective, non-toxic radioprotective agent. (author)

  7. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

    International Nuclear Information System (INIS)

    Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-?, and lymphotoxin-?) or fibrogenic cytokines (transforming growth factor [TGF]-?) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-?, and lymphotoxin-?) and the fibrogenic cytokine, TGF-?, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapyn clinical radiation therapy

  8. Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice.

    Science.gov (United States)

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Park, Hae-Ran; Jung, Uhee; Jang, Jong Sik; Jo, Sung Kee

    2009-12-01

    The protective properties of an herbal preparation (HemoHIM) against intestinal damage were examined by evaluating its effects on jejunal crypt survival, morphological changes, and apoptosis in gamma-irradiated mice. The mice were whole-body irradiated with 12 Gy for the examination of jejunal crypt survival and any morphological changes and with 2 Gy for the detection of apoptosis and Ki-67 labeling. Irradiation was conducted using (60)Co gamma-rays. HemoHIM treatment was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hours pre-irradiation and 30 minutes post-irradiation or orally at a dosage of 250 mg/kg of body weight/day for 7 or 11 days before necropsy. The HemoHIM-treated group displayed a significant increase in survival of jejunal crypts, when compared to the irradiation controls. HemoHIM treatment decreased intestinal morphological changes such as crypt depth, villus height, mucosal length, and basal lamina length of 10 enterocytes after irradiation. Furthermore, the administration of HemoHIM protected intestinal cells from irradiation-induced apoptosis. These results suggested that HemoHIM may be therapeutically useful to reduce intestinal injury following irradiation. PMID:20041793

  9. COMP-Ang1, angiopoietin-1 variant protects radiation-induced bone marrow damage in C57BL/6 mice

    International Nuclear Information System (INIS)

    Angiopoietin-1 (Ang1) is a vasculogenic factor which is signaled through the endothelial and bone marrow cell-specific, Tie2 receptor tyrosine kinase and has potential therapeutic applications for the induction of angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. In this study, we examined whether Ang1 directly exhibits bone marrow protection after ionizing radiation (IR) using an adenoviral vector of COMP-Ang1 (Ad-COMP-Ang1). This is a variant of Ang1 by replacement of the N-terminal portion of Ang1 with short coiled-coil domains of cartilage oligomeric matrix protein-Angiopoietin 1 (COMP-Ang1) which are, long enough for oligomerization but short enough to avoid problems of aggregation and insolubility. A spleen colony assay after 4.5 Gy whole body radiation, indicated that COMP-Ang1 significantly increased the mean colony numbers. Both the decrease in bone marrow cellularity and increased TUNEL (Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling) positive cells produced by radiation in bone marrow were significantly inhibited by COMP-Ang1 transfer. The expression of the ligands of Ang1 and Tie2 receptors were increased by radiation and, the COMP-Ang1 transfer potentiated this protein expression. Pre-treatment of Ang1 could be beneficial in protecting bone marrow from damage by radiation and COMP-Ang1 may be an effective alternative to native Ang1 for therapeutic purposes. (author)uthor)

  10. Long-term administration of a small molecular weight catalytic metalloporphyrin antioxidant, AEOL 10150, protects lungs from radiation-induced injury

    International Nuclear Information System (INIS)

    Purpose: To determine whether administration of a catalytic antioxidant, Mn(III) tetrakis(N,N'-diethylimidazolium-2-yl) porphyrin, AEOL 10150, with superoxide dismutase (SOD) mimetic properties, reduces the severity of radiation-induced injury to the lung from single-dose irradiation (RT) of 28 Gy. Methods and Materials: Rats were randomly divided into four different dose groups (0, 1, 10, and 30 mg/kg/day of AEOL 10150), receiving either short-term (1 week) or long-term (10 weeks) drug administration via osmotic pumps. Rats received single-dose irradiation (RT) of 28 Gy to the right hemithorax. Breathing rates, body weights, blood samples, histopathology, and immunohistochemistry were used to assess lung damage. Results: There was no significant difference in any of the study endpoints between the irradiated controls and the three groups receiving RT and short-term administration of AEOL 10150. For the long-term administration, functional determinants of lung damage 20 weeks postradiation were significantly worse for RT + phosphate-buffered saline (PBS) and RT + 1 mg/kg/day of AEOL 10150 as compared with the irradiated groups treated with higher doses of AEOL 10150 (10 or 30 mg/kg/day). Lung histology at 20 weeks revealed a significant decrease in structural damage and collagen deposition in rats receiving 10 or 30 mg/kg/day after radiation in comparison to the RT + PBS and 1 mg/kg/day groups. Immunohistochemistry demonstrated a significant reduction in macrophage acd a significant reduction in macrophage accumulation, oxidative stress, and hypoxia in rats receiving AEOL 10150 (10 or 30 mg/kg/day) after lung irradiation compared with the RT + PBS and 1 mg/kg/day groups. Conclusions: The chronic administration of a novel catalytic antioxidant, AEOL 10150, demonstrates a significant protective effect from radiation-induced lung injury. AEOL 10150 has its primary impact on the cascade of events after irradiation, and adding the drug before irradiation and its short-term administration have no significant additional benefits

  11. THE PROTECTIVE ROLE OF ONION OIL (ALLIUM CEPA LINN) AGAINST RADIATION-INDUCED HAZARDS IN MALE ALBINO RATS

    International Nuclear Information System (INIS)

    Radiation poses a major currently irresolvable risk for human. Onion is a major source of dietary flavonoids. The present investigation was carried out to study the protective effects of treating rats with onion oil (150 mg/kg body weight) for consecutive 3 weeks against damages induced by whole body gamma irradiation (7 Gy). Exposure of rats to gamma irradiation caused a significant increase in levels of serum glucose, cholesterol, triglycerides as well as activities of AST, ALT, alkaline phosphatase, creatinine, uric acid and lipid peroxides. Exposure to gamma rays resulted in an increase in the mentioned parameters accompanied by a decrease in urea, total protein, albumin, glutathione content, superoxide dismutase and catalase activities. It could be concluded that onion oil capable of reducing the biological hazards induced by gamma irradiation

  12. Radiation carcinogenesis following low dose or low dose rate exposures

    International Nuclear Information System (INIS)

    A variety of dose responses have been observed for cancer induction following low linear energy transfer (LET) radiation. In general, however, the response is curvilinear, with a rapidly rising component in the intermediate dose range followed by a plateau or decline in incidence at high doses. The response is more linear at low doses, whereas the response at intermediate doses is approximated by a dose-squared relationship. Models for this response are based on the biophysical theory of cellular effects. However, many types of effects contribute to the tumorigenic processes, and host factors play a major role. At low dose rates the carcinogenic effect is generally reduced, which is caused by a dimunition of the dose-squared component and results in a linear response. Effects of fractionation can vary with total dose, fraction size, and fraction interval. High LET radiation is more tumorigenic. The dose-response relationships are more nearly linear and are less dose-rate dependent. The relative biological effectiveness (RBE) varies with dose, dose rate, fractionation, and target tissue. 14 refs., 1 fig

  13. Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

    International Nuclear Information System (INIS)

    Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocyteion of inflammatory activity of splenocytes, and resultant apoptosis of ?-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect ?-cells against superoxide generated by glycation reaction evoked by high glucose environment. Continuous irradiation at 0.63 mGy/hr from 28 days of age elongates life span, and recovers splenic inflammatory response in Klotho-mice bearing ageing syndrome. The radiation increases anti-oxidants in liver, implicating the prevention of ageing through the suppression of cellular oxidative damages. Our results suggest that low dose/low dose-rate radiation effectively ameliorates diseases related to reactive oxygen species, and elongates life span of animals, at least in part through the stimulation of protective responses against oxidative stress. These findings are important not only for clinical use of low dose/low dose-rate radiation for human diseases, but also for non-cancerous risk estimation at dose and dose rate range argued in legal restrictions. (author)

  14. Prophylactic role of melatonin against radiation induced damage in mouse cerebellum with special reference to Purkinje cells

    Energy Technology Data Exchange (ETDEWEB)

    Sisodia, Rashmi; Kumari, Seema; Verma, Rajesh Kumar; Bhatia, A L [Neurobiology Laboratory, Department of Zoology, University of Rajasthan, Jaipur 302004 (India)

    2006-06-15

    Melatonin, a hormone with a proven antioxidative efficacy, crosses all morphophysiological barriers, including the blood-brain barrier, and distributes throughout the cell. The present study is an attempt to investigate the prophylactic influence of a chronic low level of melatonin against an acute radiation induced oxidative stress in the cerebellum of Swiss albino mice, with special reference to Purkinje cells. After 15 days of treatment the mice were sacrificed at various intervals from 1 to 30 days. Biochemical parameters included lipid peroxidation (LPO) and glutathione (GSH) levels as the endpoints. The quantitative study included alterations in number and volume of Purkinje cells. Swiss albino mice were orally administered a very low dose of melatonin (0.25 mg/mouse/day) for 15 consecutive days before single exposure to 4 Gy gamma radiation. Melatonin checked the augmented levels of LPO, by approximately 55%, by day 30 day post-exposure. Radiation induced depleted levels of GSH could be raised by 68.9% by day 30 post-exposure. Radiation exposure resulted in a reduction of the volume of Purkinje cells and their total number. The administration of melatonin significantly protected against the radiation induced decreases in Purkinje cell volume and number. Results indicate the antioxidative properties of melatonin resulting in its prophylactic property against radiation induced biochemical and cellular alterations in the cerebellum. The findings support the idea that melatonin may be used as an anti-irradiation drug due to its potent free radical scavenging and antioxidative efficacy.

  15. Characteristics of repair following very low doses

    International Nuclear Information System (INIS)

    The effects of ionizing radiation on living systems being with the physical processes of energy deposition and develop through many stages of chemical reaction and biological response. The modeling effort attempts to organize the available data and theories of all of these stages into self-consistent models that can be compared and tested. In some cases, important differences among models result in only small differences in cell survival within the ranges of dose and dose rate that are normally investigated. To overcome this limitation, new ways of irradiating cells at extremes of dose rate, or ways of evaluating the effects of very small doses, are developed. Mathematical modeling and cellular studies complement each other. It has recently been found that some mechanisms are not adequate to account for the interaction of dose and repair time as they affect the reproductive survival of plateau-phase Chinese hamster ovary (CHO) cells. Repair of radiation-induced cellular damage plays a central role in the survival of cells exposed to doses of 1 Gy or more. This repair is responsible for the dose rate, split-dose and delayed plating effect and can be evaluated. Because split-dose and dose-rate experiments involve repair during irradiation and delayed plating experiments involve repair after irradiation is completed, it was originally thought that different repair processes were involved. It is now clear that this is not necessarily the case. Appropriately designed models can account for observed effects at conventional doses (1 Gy or more) whether they assume all damage is lethal unless repaired or some damage is innocuous unless it interacts with additional damage. The fact that the survival following a plating delay is always less than the survival following immediate plating at low doses indicates that the damage produced is probably not potentially lethal

  16. Dose and effect relationship of radiation induced cancer and its influencing factors in experimental animals, 1

    International Nuclear Information System (INIS)

    The data of risk evaluation of external irradiation were integrated with animal experiments from the aspects of qualitative generalizations of characteristics of radiation induced tumors. Studies covered competition of cause of death, figure of dose-to-effect relationship, characteristics of low dose rate of irradiation, relative biological effectiveness (RBE) of high LET radiation, effects of feactionated irradiation, complex actions with chemical substances, effects of protectional medium, differences of radiosensitivity by species and strains, and age dependency of sensitivities. Competition of cause of death by time length of latent period and degree of malignancy of the disease. Discussion on competition of death suggested the following idea: 1) incidence of tumor induction in the individual level did not correspond to transformation in the cellular level, and 2) relative incidence of tumor induction after a certain dose of whole body irradiation did not indicate the relative sensitivity of each tissue, for the relationship between tumor incidence and exposure dose was not a linear relationship. The dose-to-effect relationship of tumor induction was decided by following factors: i) sensitivity on transformation of cells, ii) sensitivity on the death of potential tumor cells, and iii) competition of the cause of death. Tumor induction by low dose rate irradiation was also studied by comparing qualitative and quantitative differences between high dose rate single iifferences between high dose rate single irradiation and a series of low dose rate irradiation. (Serizawa, K.)

  17. Protective effect of propolis on radiation-induced chromosomal damage on Chinese hamster ovary cells (CHO-K1)

    International Nuclear Information System (INIS)

    In the last years, particular interest has been given to investigations concerning natural, effective and nontoxic compounds with radioprotective capacity in concert with increasing utilization of different types of ionizing radiation for various applications. Among them, propolis, a resinous mixture of substances collected by honey bees (Apis mellifera) has been considered promising since it presents several advantageous characteristics, i.e., antiinflammatory, anticarcinogenic, antimicrobial and free radical scavenging action. It is, therefore, a direct antioxidant that protects cells and organisms from the adverse effects of ionizing radiation. These relevant biological activities are mainly mediated by the flavonoids, present at relatively high concentrations in the propolis. Considering that the chemical composition and, consequently, the biological activity of propolis is variable according to the environmental plant ecology, the present study was conducted in order to evaluate the radioprotective capacity of Brazilian propolis, collected in the State of Rio Grande do Sul, against genotoxic damages induced by 60Co ?-radiation in Chinese hamster ovary cells (CHO-K1). for this purpose, micronucleus induction was analyzed concerning irreparable damage, specifically related to DNA double-strand breaks, that are potentially carcinogenic. CHO-K1 cells were submitted to different concentrations of propolis (3 - 33 ?g/ml), 1 h before irradiation, with 1 Gy of ? radiation (0.722 Gy/min). The data obtained showed a decreasing tendency in the quantity of radioinduced damage on cells previously treated with propolis. The radioprotective effect was more prominent at higher propolis concentration. The treatment with propolis alone did not induce genotoxic effects on CHO-K1 cells. Beside that, the treatment with propolis, associated or not with radiation, did not influence the kinetics of cellular proliferation. (author)

  18. Protective effect of propolis on radiation-induced chromosomal damage on Chinese hamster ovary cells (CHO-K1)

    Energy Technology Data Exchange (ETDEWEB)

    Spigoti, Geyza; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: kokazaki@ipen.br; Tsutsumi, Shiguetoshi [Amazon Food Ltd., Tokyo (Japan)], e-mail: fwip5138@mb.infoweb.ne.jp

    2009-07-01

    In the last years, particular interest has been given to investigations concerning natural, effective and nontoxic compounds with radioprotective capacity in concert with increasing utilization of different types of ionizing radiation for various applications. Among them, propolis, a resinous mixture of substances collected by honey bees (Apis mellifera) has been considered promising since it presents several advantageous characteristics, i.e., antiinflammatory, anticarcinogenic, antimicrobial and free radical scavenging action. It is, therefore, a direct antioxidant that protects cells and organisms from the adverse effects of ionizing radiation. These relevant biological activities are mainly mediated by the flavonoids, present at relatively high concentrations in the propolis. Considering that the chemical composition and, consequently, the biological activity of propolis is variable according to the environmental plant ecology, the present study was conducted in order to evaluate the radioprotective capacity of Brazilian propolis, collected in the State of Rio Grande do Sul, against genotoxic damages induced by {sup 60}Co {gamma}-radiation in Chinese hamster ovary cells (CHO-K1). for this purpose, micronucleus induction was analyzed concerning irreparable damage, specifically related to DNA double-strand breaks, that are potentially carcinogenic. CHO-K1 cells were submitted to different concentrations of propolis (3 - 33 {mu}g/ml), 1 h before irradiation, with 1 Gy of {gamma} radiation (0.722 Gy/min). The data obtained showed a decreasing tendency in the quantity of radioinduced damage on cells previously treated with propolis. The radioprotective effect was more prominent at higher propolis concentration. The treatment with propolis alone did not induce genotoxic effects on CHO-K1 cells. Beside that, the treatment with propolis, associated or not with radiation, did not influence the kinetics of cellular proliferation. (author)

  19. Double blind test of L-cysteine for protection against radiation-induced side effects in man

    International Nuclear Information System (INIS)

    L-Cysteine (80 mg/capsule of active ingredient) or placebo (lactose) was administered to a total of 127 patients with breast cancer (postoperative irradiation) or uterine cervical cancer (post-operative and intracavitary irradiation). L-Cysteine was effective in 49.3% of all patients and in 52.0% of patients with breast cancer, the difference from the placebo group being statistically significant. Decrease in the white blood cell count was less in the group given L-cysteine than that given placebo, and this difference was significant especially in the 3rd week for all cases. Significant difference was also noted in the 2nd week for postoperative irradiation and in the 2nd and 3rd weeks for postoperative and intracavitary irradiation for uterine cervical cancer. Decrease of white blood cell count to less than 3,000 was significantly small in the group given L-cysteine than in the placebo group. The values of hematocrit and platelets remained within normal limits, but the values in the group treated with L-cysteine was considerably different (0.05< Po<0.10) from those in the placebo group during the 2nd, 4th, and 6th week. The blood sedimentation rate was more stable in the group given L-cysteine than in the placebo group, and considerably different (0.05< Po<0.10) in the 2nd week and significantly different in the 6th week compared to the control. Anorexia was significantly less in the group given L-cysteine, especially in the 3rd week. These results suggest that L-cysted week. These results suggest that L-cysteine can serve as a protective agent against the side effects of radiotherapy. (J.P.N.)

  20. Plants ecotoxicology. A case of low doses and multi pollutant exposure

    International Nuclear Information System (INIS)

    In this report, results of long-term laboratory, 'green-house' and field experiments carried out on different species of wild and agricultural plants (spring barley, Scots pine, spider wort, bulb onion and others) to study toxic and genotoxic effects of low doses and concentrations of such common pollutants as acute and chronic ?-radiation, heavy natural radionuclides, compounds of heavy and alkaline earth metals, pesticides are presented for the first time. Special attention is paid to eco-toxic effects of chronic low dose exposures, the dose-rate effect, synergistic and antagonistic effects of different factors' combined exposures and biological effects of incorporated radionuclides. The results of long-term field experiments in the 30-km Chernobyl NPP zone, in the vicinity of the facility for the processing and storage of radioactive wastes (Leningrad region), in the vicinity of the radium production industry storage cell (Komi Republic), at the site of an underground nuclear explosion (Perm region) are discussed. These findings suggest that the further evolution of investigations in this field would issue in the development of a theoretical bases and practical procedures for environmental protection against radioactivity, taking into account the new experimentally confirmed facts about the presence of such essentially important singularities of the biological effect of low ionizing radiation doses as the nonlinearity of a dose-effect relationship, radiation-induced genomic instability, phenomenon of radio-adaptation, increased probability of synergetic and antagonistic effects of the combined action of different nature factors. A development of a new concept of radiation protection for a human and biota should be based on the clear understanding of these effects and their contribution to the response of biological objects. (author)

  1. Plants ecotoxicology. A case of low doses and multi pollutant exposure

    Energy Technology Data Exchange (ETDEWEB)

    Geras' Kin, S.; Kim, J.; Evseeva, T.; Oudalova, A.; Dikarev, V. [Russian Institute of Agricultural Radiology and Agroecology, Obninsk (Russian Federation)

    2004-07-01

    In this report, results of long-term laboratory, 'green-house' and field experiments carried out on different species of wild and agricultural plants (spring barley, Scots pine, spider wort, bulb onion and others) to study toxic and genotoxic effects of low doses and concentrations of such common pollutants as acute and chronic {gamma}-radiation, heavy natural radionuclides, compounds of heavy and alkaline earth metals, pesticides are presented for the first time. Special attention is paid to eco-toxic effects of chronic low dose exposures, the dose-rate effect, synergistic and antagonistic effects of different factors' combined exposures and biological effects of incorporated radionuclides. The results of long-term field experiments in the 30-km Chernobyl NPP zone, in the vicinity of the facility for the processing and storage of radioactive wastes (Leningrad region), in the vicinity of the radium production industry storage cell (Komi Republic), at the site of an underground nuclear explosion (Perm region) are discussed. These findings suggest that the further evolution of investigations in this field would issue in the development of a theoretical bases and practical procedures for environmental protection against radioactivity, taking into account the new experimentally confirmed facts about the presence of such essentially important singularities of the biological effect of low ionizing radiation doses as the nonlinearity of a dose-effect relationship, radiation-induced genomic instability, phenomenon of radio-adaptation, increased probability of synergetic and antagonistic effects of the combined action of different nature factors. A development of a new concept of radiation protection for a human and biota should be based on the clear understanding of these effects and their contribution to the response of biological objects. (author)

  2. Regulatory aspects of low doses control in Albania

    International Nuclear Information System (INIS)

    In the present paper are described the status of regulatory aspects of low doses control as well as the existing procedures for their implementation in Albania. According to new Radiological Protection Act, approved by Parliament in 1995, the establishment of the infrastructures in radiation protection area is in course, accompanied by the installation and functioning of new equipment for low dose control. Based in many years experience it is concluded that personal doses of the workers added by practices in Albania are 1/10 of dose Emits. Some particular cases of overexposured workers were investigated. Last times the elements of the optimisation procedures (QA and QC) are outlined in the frame of improving regulatory aspects of low doses control. (author)

  3. Radiation-Induced Cancer. Proceedings of a Symposium on Radiation-Induced Cancer

    International Nuclear Information System (INIS)

    The link between radiation and cancer was recognized soon after the discovery of X-rays and natural radioactivity. In the early years after the discovery of ionizing radiations some of the pioneering workers suffered severely from the damaging effects of radiation exposure. These incidents,- generally due to ignorance of the biological consequences of radiation exposure, were instrumental in starting investigations on the subject. Gradually precise information became available on the nature of radiation-induced damage and on the repair phenomena. This information has been advanced by recent progress in molecular biology, cellular biology, cytogenetics, biochemistry, virology, immunology and related disciplines. Contributions of these disciplines to radiation biology and cancer research has resulted in the use of radiation to solve various problems of human health including cancer. At the same time, with knowledge of the effects of radiations on cells and on various organisms including man, it has become possible to state the level of radiation dose that is not an apparent health hazard (i. e. the maximum permissible dose). This work has been vitally important in programs dealing with the occupational safety of personnel working with radiations. Although the present safety standards and devices are generally recognized as adequate, they must be re-evaluated from time to time in the light of the latest findings in radiobiology and other related disciplines. The Symposium on Radiation-Induced Cancer, organized by the International Atomic Energy Agency in collaboration with the World Health Organization, permitted discussion and evaluation of the present understanding of the nature of late biological effects of radiations including cancer, and development of protective as well as curative measures against cancer. Much attention was given to the comparative analysis of the effects of radiation, particularly at low dose levels, on man and experimental mammals. Emphasis was also directed to the dosimetric and radiobiological effects of radiations from internally incorporated nuclides as well as from external sources. The possible importance of such information for radiotherapeutic practices was examined. The Symposium took place in Athens from 28 April to 2 May 1969 at the invitation of the Greek Government. Eighty-four participants attended from 23 countries and a total of 36 papers from 14 countries were presented

  4. Radiologic low-dose pelvimetry

    International Nuclear Information System (INIS)

    In large patient populations from Karolinska Sjukhuset, radiologic pelvimetry data including mean values and correlation of the pelvic diameters have been defined. Overall incidence of contraction and borderline pelvic measurements and the efficacy of selecting by palpation the patients with a narrow pelvis have been evaluated. The indications for pelvimetry were related to an earlier period. By re-evaluation of the clinical application of pelvimetry a modified routine low-dose pelvimetry is proposed. From measurement of the transverse outlet diameters on an orthodiagraphic a.p. film the sum of the outlet diameters is estimated and a supplementary lateral film is exposed in selected cases. Employing pelvimetry in all primigravidae by the orthodiagraphic a.p. film would still result in a lower total population dose than does the presently used routine of complete pelvimetry, consisting of the same a.p. and lateral films, in selected cases. (Auth.)

  5. Low dose radiation and health

    International Nuclear Information System (INIS)

    In the contributions under the first heading, 'Radiobiological questions and methods of measurement', the technique used in measurements of radon is dealt with in brief. Issues related to dose determinations on the basis of physical and biological methods and the influence of the dose rate are discussed in greater detail. Several contributions provide information on the biopositive effects of rays and stimulation of natural defence mechanisms through low dose radiation. A case is given as an object lesson to throw some light on the role of occupational radiation exposure in the development of cancer of the lungs. The second chapter is dedicated to epidemiological questions. Discussed are investigations into the increased incidence of infantile leukaemia in living areas adjacent to nuclear power plants. There are two reports on cases of leukaemia reported in the vicinity of Birkenfeld and infant mortality curves in the Federal Republic after the Chernobyl accident. They are followed by further contributions on the link between radon exposure and pulmonary cancer as well as the most recent statistical analyses of cases of cancer among Hiroshima-Nagasaki survivors. In the third chapter, 'Laws on nuclear energy in juridiction, legislation and execution', the legal aspects of issues related to low dose radiation are discussed along with basic constitutional rights and admendments to acts on radioprotection after the Chernobyl catastrophe. In the introductory parts of the ftrophe. In the introductory parts of the fourth chapter, 'Tailings', a survey is given of redemptive measures now taken in the United States. It also contains a report on the current situation of uranium mills in the former German Democratic Republic. The release of radon from waste dumps in Ellweiler is discussed in connection with planned clean-up activities. The last two contributions to this chapter focus on the special peripheral factors to be considered in the site clean-up at Ellweiler. (orig./MG) With 54 figs

  6. Global DNA methylation responses to low dose radiation exposure

    International Nuclear Information System (INIS)

    Full text: High radiation doses cause breaks in the DNA which are considered the critical lesions in initiation of radiation-induced cancer. However, at very low radiation doses relevant for the general public, the induction of such breaks will be rare, and other changes to the DNA such as DNA methylation which affects gene expression may playa role in radiation responses. We are studying global DNA methylation after low dose radiation exposure to determine if low dose radiation has short- and/or long-term effects on chromatin structure. We developed a sensitive high resolution melt assay to measure the levels of DNA methylation across the mouse genome by analysing a stretch of DNA sequence within Long Interspersed Nuclear Elements-I (LINE I) that comprise a very large proportion of the mouse and human genomes. Our initial results suggest no significant short-term or longterm) changes in global NA methylation after low dose whole-body X-radiation of 10 J1Gyor 10 mGy, with a significant transient increase in NA methylation observed I day after a high dose of I Gy. If the low radiation doses tested are inducing changes in bal DNA methylation, these would appear to be smaller than the variation observed between the sexes and following the general stress of the sham-irradiation procedure itself. This research was funded by the Low Dose Radiation Research Program, Biological and Environmental Research, US DOE, Grant DE-FG02-05ER64104 and MN is the recipient of the FMCF/BHP04 and MN is the recipient of the FMCF/BHP Dose Radiation Research Scholarship.

  7. Radiation Induced Fermion Resonance

    OpenAIRE

    Esposito, S.; Evans, M. W.; Recami, E.

    1998-01-01

    The Dirac equation is solved for two novel terms which describe the interaction energy between the half integral spin of a fermion and the classical, circularly polarized, electromagnetic field. A simple experiment is suggested to test the new terms and the existence of radiation induced fermion resonance.

  8. Modelling radiation-induced bystander effect and cellular communication

    International Nuclear Information System (INIS)

    In the last 10 years evidence has accumulated on the so-called radiation-induced 'non-targeted effects' and in particular on bystander effects, consisting of damage induction in non-irradiated cells most likely following the release of soluble factors by the irradiated ones. These phenomena were observed for different biological endpoints, both lethal and non-lethal for the cell. Although the underlying mechanisms are largely unknown, it is now widely recognised that two types of cellular communication (i.e. via gap junctions and/or release of molecular messengers into the extracellular environment) play a pivotal role. Furthermore, the effects can be significantly modulated by parameters such as cell type and cell-cycle stage, cell density, time after irradiation etc. Theoretical models and simulation codes can be of help to improve our knowledge of the mechanisms, as well as to investigate the possible role of these effects in determining deviations from the linear relationship between dose and risk which is generally applied in radiation protection. In this paper three models, including an approach under development at the Univ. of Pavia, will be presented in detail. The focus will be on the various adopted assumptions, together with their implications in terms of non-targeted radiobiological damage and, more generally, low-dose radiation risk. Comparisons with experimental data will also be discussed. (authors)

  9. Modelling radiation-induced bystander effect and cellular communication.

    Science.gov (United States)

    Ballarini, F; Alloni, D; Facoetti, A; Mairani, A; Nano, R; Ottolenghi, A

    2006-01-01

    In the last 10 years evidence has accumulated on the so-called radiation-induced 'non-targeted effects' and in particular on bystander effects, consisting of damage induction in non-irradiated cells most likely following the release of soluble factors by the irradiated ones. These phenomena were observed for different biological endpoints, both lethal and non-lethal for the cell. Although the underlying mechanisms are largely unknown, it is now widely recognised that two types of cellular communication (i.e. via gap junctions and/or release of molecular messengers into the extracellular environment) play a pivotal role. Furthermore, the effects can be significantly modulated by parameters such as cell type and cell-cycle stage, cell density, time after irradiation etc. Theoretical models and simulation codes can be of help to improve our knowledge of the mechanisms, as well as to investigate the possible role of these effects in determining deviations from the linear relationship between dose and risk which is generally applied in radiation protection. In this paper three models, including an approach under development at the University of Pavia, will be presented in detail. The focus will be on the various adopted assumptions, together with their implications in terms of non-targeted radiobiological damage and, more generally, low-dose radiation risk. Comparisons with experimental data will also be discussed. PMID:17142819

  10. DNA damage-related gene expression as biomarkers to assess low dose radiation exposure

    International Nuclear Information System (INIS)

    Complete text of publication follows. According to the UNSCEAR, the natural rays from the Sun and the Earth transmit about 2,4 mSv to each individual every year. Human activities expose us to an additional radiation dose (1,2 mSv/year), especially the techniques used in non-invasive medical imaging (radiography, CT scanners). Ionizing radiation can induce a large spectrum of DNA lesions, but under optimal DNA repair conditions, the principal residual lesions of importance are misrepaired doublestrand breaks. Predictive markers of intrinsic radio sensitivity in healthy individuals are needed in monitoring their occupational or environmental radiation exposure and may predict a patient's response to radiotherapy. Radiation protection requires a thorough understanding of low dose ionizing radiation. Currently extrapolation from high doses is necessary to estimate the effects of low doses. Furthermore, it is critically important to have an appreciation of the variation in individual responses to radiation among the human population. Present estimates of the risks from radiation exposure are based largely on the 'average' individual in an exposed population. However, clinical observations of adverse reactions to radiotherapy indicate large variations in individual radio sensitivity. Quantification of risk requires the identification of new parameters taking into account these differences in radiation responses. Therefore, a detailed knowledge of the mechanisms by which radd knowledge of the mechanisms by which radiation induces cancer is essential. It is necessary to understand the various steps involved in the multistage process of radiation-induced tumor genesis and to answer the following specific question: Is there a link between radio sensitivity of individuals (short term) and susceptibility to cancer (late after exposure)? Appearance of mutations consist one of more prominent consequence of the radiation action. The aim of our study consisted in the restriction fragment's length polymorphism (RFLP) analysis of pERT87-8/Tag1 and 16intron/Tag1 loci with determining of presence or absence of restriction site in the group of radiologists and in control group. It was demonstrated that the pERT87-8/Tag1 allele frequency on 'mutant' chromosome was 2,4 fold higher than the frequency of this allele on 'normal' chromosome (45,1% in compare with 18,5%, X2=27,7, df=1, p2=78,3, df=1, p<0,01). In the conclusion it is necessary to mention that there are significant difference in the frequency of the polymorph sites pERT87-8/Tag1 and 16intron/Tag1 in the group of radiologists in compare with the control group.

  11. Effect of low dose radiation on apoptosis in mouse spleen

    International Nuclear Information System (INIS)

    Objective: To study the effect of whole body irradiation (WBI) with different doses of X-ray on apoptosis in mouse spleen. Methods: Time course changes and dose-effect relationship of apoptosis in mouse spleen induced by WBI were observed with transmission electron microscopy (TEM) qualitatively and TUNEL method semi-quantitatively. Results: Many typical apoptotic lymphocytes were found by TEM in mouse spleen after WBI with 2 Gy. No marked alterations of ultrastructure were found following WBI with 0.075 Gy. It was observed by TUNEL that the apoptosis of splenocytes increased after high dose radiation and decreased following low dose radiation (LDR). The dose-effect relationship of radiation-induced apoptosis showed a J-shaped curve. Conclusion: The effect of different doses of ionizing radiation on apoptosis in mouse spleen was distinct. And the decrease of apoptosis after LDR is considered a manifestation of radiation hormesis

  12. The researches on the effects of low doses irradiation

    International Nuclear Information System (INIS)

    All research conducted as part of 'Risc-Rad' and those conducted by actors in international programs on low doses allow progress in understanding mechanisms of carcinogenesis associated with irradiation. The data do not question the use in radiation protection, risk estimation models based on a linear increase of the risk with the dose of radiation. Nevertheless, they show that the nature of biological responses induced by low doses of radiation has differences with the responses induced by high doses of radiation. They also show the diversity of effects/dose relationships as the mechanism observed and the importance of genetic predisposition in the individual sensitivity to low doses of radiation. It is therefore essential to continue to bring new data to better understand the complex biological effects and their impact on the establishment of radiation protection standards. In addition, the results have often been at the cellular level. The diversity of responses induced by radiations is also a function of cell types observed, the aging of cells and tissue organization. It is essential to strengthen researches at the tissue and body level, involving in vitro and in vivo approaches while testing the hypothesis in epidemiology with a global approach to systems biology. Over the past four years, the collaboration between partners of 'Risc-Rad' using experimental biology approaches and those using mathematical modeling techniques aimed at developing a new model describing the carcinogenesis induced by low radiation doses. On an other hand, The High level expert group on European low dose risk research (H.L.E.G.) develop programmes in the area of low dose irradiation (Germany, Finland, France, Italy and United Kingdom). It proposed a structure of trans national government called M.E.L.O.D.I. ( multidisciplinary european low dose initiative). Its objective is to structure and integrate European research by gathering around a common programme of multidisciplinary activities the resources and research capacity in the specific area to reduce the fragmentation of European research. (N.C.)

  13. Radiation Induced Non-targeted Response: Mechanism and Potential Clinical Implications

    OpenAIRE

    Hei, Tom K.; Zhou, Hongning; Chai, Yunfei; Ponnaiya, Brian; Ivanov, Vladimir N.

    2011-01-01

    Generations of students in radiation biology have been taught that heritable biological effects require direct damage to DNA. Radiation-induced non-targeted/bystander effects represent a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the biological consequences of exposure to low doses of radiation. Although radiation induced bystander effects have been well documented in a variety ...

  14. Radiation induced oral mucositis

    OpenAIRE

    Satheesh Kumar P; Balan Anita; Sankar Arun; Bose Tinky

    2009-01-01

    Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i) With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii) who also received concomitant chemotherapy; (iii) who received a total dose over 5,000 cGy; and (iv) who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concer...

  15. Low Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation

  16. Molecular targets for radioprotection by low dose radiation exposure

    International Nuclear Information System (INIS)

    Adaptive response is a reduced effect from a higher challenging dose of a stressor after a smaller inducing dose had been applied a few hrs earlier. Radiation induced fibrosarcoma (RIF) cells did not show such an adaptive response, i.e. a reduced effect from a higher challenging dose (2 Gy) of a radiation after a priming dose (1 cGy) had been applied 4 or 7 hrs earlier, but its thermoresistant clone (TR) did. Since inducible HSP70 and HSP25 expressions were different between these two cell lines, the role of inducible HSP70 and HSP25 in adaptive response was examined. When inducible hsp70 or hsp25 genes were transfected to RIF cells, radioresistance in clonogenic survival and reduction of apoptosis was detected. The adaptive response was also acquired in these two cell lines, and inducible hsp70 transfectant showed more pronounced adaptive response than hsp25 transfectant. From these results, inducible HSP70 and HSP25 are at least partly responsible for the induction of adaptive response in these cells. Moreover, when inducible HSP70 or HSP25 genes were transfected to RIF cells, coregulation of each gene was detected and heat shock factor (HSF) was found to be responsible for these phenomena. In continuation of our earlier study on the involvement of heat shock protein (HSP) 25 and HSP70 in the induction of adaptive response, we have now examined the involvement of these proteins in the induction of the adaptive response, using an animal model system. C57BL6 mice wereg an animal model system. C57BL6 mice were irradiated with 5 cGy of gamma radiation 3 times for a week (total of 15cGy) and a high challenge dose (6Gy) was given on the day following the last low dose irradiation. Survival rate of the low dose pre-irradiated mice was increased to 30%. Moreover, high dose-mediated induction of apoptosis was also reduced by low dose pre-irradiation. To elucidate any link existing between HSP and induction of the adaptive response, reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis was performed using splenocytes. High dose radiation up-regulated the expression of HSP25 and especially HSP70; while expression of other HSPs such as HSC70, HSP90, and ?B-crystalline did not change. When splenocytes from HSP70 transgenic mice were pre-irradiated with a low dose of radiation, a reduction in cell death by high dose radiation was observed. These results, suggest that HSP70 is a key molecule in radioprotective effect by low dose radiation

  17. Protective Effect of Adhatoda vascia Nees Against Radiation-Induced Damage at Cellular, Biochemical and Chromosomal Levels in Swiss Albino Mice

    OpenAIRE

    Selvan, Senthamil R.; Begraj Saharan; Ashok Kumar; Madhu Kumar; Ravindra Samarth; Meenal Kumar

    2006-01-01

    Extract of Adhatoda vasica (L) Nees leaves has been used for treatment of various diseases and disorders in Ayurved and Unani medicine. Modulatory effect of ethanolic extract of A. vasica (L) Nees against radiation-induced changes in terms of histological alterations in testis, reduced glutathione (GSH), lipid peroxidation (LPO), acid and alkaline phosphatases levels, and chromosomal alterations in Swiss albino mice was studied at various post-irradiation intervals between 1 and 30 days. Mice...

  18. Protection against radiation-induced mutations at the hprt locus by spermine and N,N double-prime-(dithiodi-2,1-ethanediyl)bis-1,3-propanediamine (WR-33278). WR-33278 and spermine protect against mutation induction

    International Nuclear Information System (INIS)

    The polyamine spermine and the disulfide N,N double-prime-(dithiodi-2,1-ethanediyl)bis-1,3-propanediamine (WR-33278) are structurally similar agents capable of binding to DNA. WR-33278 is the disulfide moiety of the clinically studied radioprotective agent S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721). Because of their reported structural and functional similarities, it was of interest to characterize and compare their radioprotective properties using the endpoints of cell survival and mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in Chinese hamster AA8 cells. In order to facilitate both the uptake of WR-33278 into cells and the direct comparison between the protective properties of WR-33278 and spermine, these agents (at concentrations of 0.01 mM and 0.001 mM) were electroporated into cells. The exposure of cells to both electroporation and irradiation gave rise to enhanced cell killing and mutation induction, with the sequence of irradiation followed 3 h later by electroporation being the more toxic protocol. Enhanced cell survival was observed following electroporation of 0.01 mM of spermine and WR-33278 30 min prior to irradiation; protection factors (PF) of 1.3 and 1.8, respectively. Neither agent was protective at a concentration of 0.001 mM. Protection against radiation-induced hprt mutations was observed for both spermine and WR-33278 under all experimental conditions tested. These data suggest that the properties of radioprotection and chemoprevention exhibited by the phosphorothioate (WR-2721) and associated aminothiol (WR-1065) and disulfide (WR-33278) metabolites may be mediated via endogenous spermine-like polyamine processes. Such a mechanism would have important implications with respect to the design and development of new generation drugs for use in radioprotection and chemoprevention

  19. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    International Nuclear Information System (INIS)

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts

  20. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.; Bond, V.P. [Washington State Univ., Richland, WA (United States); Sondhaus, C.A. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Radiology and Radiation Control Office; Altman, K.I. [Univ. of Rochester Medical Center, NY (United States). Dept. of Biochemistry and Biophysics

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  1. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after low dose radiation exposure. Cells viability/cytotoxicity analysis data are currently being analyzed to determine how these endpoints are affected under our experimental conditions. The results from this study will be translatable to risk assessment for assigning limits to radiation workers, pre-dosing for more effective radiotherapy and the consequences of long duration space flight. The data from this study has been presented a various scientific meetings/workshops and a manuscript, containing the findings, is currently being prepared for publication. Due to unforeseen challenges in collecting the data and standardizing experimental procedures, the second and third aims have not been completed. However, attempts will be made, based on the availability of funds, to continue this project so that these aims can be satisfied.

  2. Converting low dose radiation to redox signaling

    OpenAIRE

    Pristov, Jelena Bogdanovi?; Spasi?, Mihajlo; Spasojevi?, Ivan

    2013-01-01

    In contrast to the damaging effects of high doses, low dose radiation (UV, gamma) has been reported to provoke constructive changes in plants. However, the mechanisms by which plants recognize and respond to low dose radiation are not understood. We have shown recently that polygalacturonic acid, cell wall polysaccharide, converts the highly reactive product of radiation - hydroxyl radical into superoxide which may be further dismutated to hydrogen peroxide. Superoxide has been proposed to ac...

  3. Gamma radiation-induced conditioned taste aversions in rats: A comparison of the protective effects of area postrema lesions with differing doses of radiation

    International Nuclear Information System (INIS)

    Lesions which destroy the area postrema (AP) and damage the adjacent nucleus of the solitary tract (NTS) attenuate or abolish conditioned taste aversions (CTA) induced by a variety of pharmacological agents as well as exposure to radiation. In the present experiment, 4 groups of male rats received lesions of AP and 4 groups were given sham lesions. One sham-lesioned and one AP-lesioned group were given a single pairing of 1-hr access to a novel 0.10% sodium saccharin solution followed immediately with exposure to 0, 100, 200, or 400 rad of gamma radiation, respectively. Four days later all groups were given daily two-bottle preference tests (saccharin vs. water) on 4 consecutive days. The sham-lesioned groups exposed to the radiation (100, 200, or 400 rad) developed profound aversions to the saccharin on all test days (p less than 0.001). In contrast, all of the AP-lesioned groups as well as the sham-irradiated (0 rad) sham-lesioned group exhibited strong, comparable (p greater than 0.30) preferences for saccharin. Thus, lesion of AP abolished the radiation-induced CTA at all dose levels of radiation. These results raise the possibility of pharmacological intervention at the level of AP to prevent radiation-induced CTA in cancer patients undergoing radiation therapy

  4. Cyclooxygenase and radiation-induced gastrointestinal injury

    International Nuclear Information System (INIS)

    Prostaglandins is a family of eicosanoids, which have many biological functions. Cyclooxygenase is the key enzyme of the prostaglandins' biosynthesis and is has two isoforms: COX-1 and COX-2. Many researchs indicate that prostaglandins and cyclooxygenase play positive protective role in gastrointestinal tract. In this review, the role of prostaglandins and cyclooxygenase in radiation-induced gastrointestinal injury, as well aas their biochemistry and physiology is summarized. (authors)

  5. Radiation induced pesticidal microbes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Yup; Lee, Y. K.; Kim, J. S.; Kim, J. K.; Lee, S. J.; Lim, D. S

    2001-01-01

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants.

  6. Radiation induced pesticidal microbes

    International Nuclear Information System (INIS)

    To isolate pesticidal microbes against plant pathogenic fungi, 4 strains of bacteria(K1. K3, K4, YS1) were isolated from mushroom compost and hot spring. K4, K1, K3, YS1 strain showed wide antifungal spectrum and high antifungal activities against 12 kinds of fungi. Specific proteins and the specific transcribed genes were found from the YS1 and its radiation-induced mutants. And knock-out mutants of antifungal activity were derived by transposon mutagenesis. From these knock-out mutants, the antifungal activity related genes and its modification by gamma-ray radiation are going to be studied. These results suggested that radiation could be an useful tool for the induction of functional mutants

  7. Induction of Genomic Instability In Vivo by Low Doses of 137Cs gamma rays

    International Nuclear Information System (INIS)

    The overall goal of this project is to determine if low doses (below or equal to the level traditionally requiring human radiation protection, i.e. less than or equal to 10 cGy) of low LET radiation can induce genomic instability. The magnitude of genomic instability was measured as delayed chromosome instability in bone marrow cells of exposed mice with different levels of endogenous DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity, i.e. high (C57BL/6J mice), intermediate (BALB/cJ mice), and extremely low (Scid mice). In addition, at early time points (1 and 4 hrs) following irradiation, levels of activation of nuclear factor-kappa B (NF-?B), a transcription factor known to be involved in regulating the expression of genes responsible for cell protection following stimuli, were measured in these cells. Bone marrow cells were collected at different times following irradiation, i.e. 1 hr, 4 hrs, 1 month, and 6 months. A total of five mice per dose per strain were sacrificed at each time point for sample collection. As a result, a total of 80 mice from each strain were used. The frequency and the type of metaphase chromosome aberrations in bone marrow cells collected from exposed mice at different times following irradiation were used as markers for radiation-induced genomic instability. A three-color fluorescence in situ hybridization (FISH) protocol for mouse chromosomes 1, 2, and 3 was used for the analysis of delayed stable chromosomal aberrations in metaphase cells. All other visible chromatid-type aberrations and gross structural abnormalities involving non-painted chromosomes were also evaluated on the same metaphase cells used for scoring the stable chromosomal aberrations of painted chromosomes. Levels of nuclear factor-kappa B (NF-?B) activation were also determined in cells at 1 and 4 hrs following irradiation (indicative of early responses)

  8. Prophylactic role of melatonin against radiation induced damage in mouse cerebellum with special reference to Purkinje cells

    International Nuclear Information System (INIS)

    Melatonin, a hormone with a proven antioxidative efficacy, crosses all morphophysiological barriers, including the blood-brain barrier, and distributes throughout the cell. The present study is an attempt to investigate the prophylactic influence of a chronic low level of melatonin against an acute radiation induced oxidative stress in the cerebellum of Swiss albino mice, with special reference to Purkinje cells. After 15 days of treatment the mice were sacrificed at various intervals from 1 to 30 days. Biochemical parameters included lipid peroxidation (LPO) and glutathione (GSH) levels as the endpoints. The quantitative study included alterations in number and volume of Purkinje cells. Swiss albino mice were orally administered a very low dose of melatonin (0.25 mg/mouse/day) for 15 consecutive days before single exposure to 4 Gy gamma radiation. Melatonin checked the augmented levels of LPO, by approximately 55%, by day 30 day post-exposure. Radiation induced depleted levels of GSH could be raised by 68.9% by day 30 post-exposure. Radiation exposure resulted in a reduction of the volume of Purkinje cells and their total number. The administration of melatonin significantly protected against the radiation induced decreases in Purkinje cell volume and number. Results indicate the antioxidative properties of melatonin resulting in its prophylactic property against radiation induced biochemical and cellular alterations in the cerebellum. The findings support the idea terebellum. The findings support the idea that melatonin may be used as an anti-irradiation drug due to its potent free radical scavenging and antioxidative efficacy

  9. Reduction of radiation-induced early skin damage (mouse foot) by 0-(?-hydroxyaethyl)-rutoside

    International Nuclear Information System (INIS)

    The effect of a bioflavonoid, 0-(?-hydroxyethyl)-rutoside (HR) on early radiation-induced skin damage was examined, using the mouse foot system; the response to radiation is not species specific and comparison with the clinical situation is therefore possible. The aim was to see whether HR, which is highly effective in protecting against late damage, is also able to reduce early effects. Early reactions were considered to be erythema, swelling and ulceration and occurring up to 30 days after irradiation. It was found that HR significantly reduces early damage, both after a single dose and after fractionated irradiation with low doses. A single pre-treatment dose of HR and pre-treatment together with 30 days post-treatment administration were both found to be effective. The protective effect became more marked with increasing radiation dose (single irradiation). Reduction of late effects is produced iptimally by an interval of 0.25 hours between application of HR and irradiation, and this is also true for early skin damage. The early effects are partly reversible, but there is possibly an interesting correlation between these and irreversible late effects (such as loss of toes); a similar mechanism, presumably affecting the vascular system, may therefore be postulated. The protective action of this well tolesated, highly effective substance, which apparently protects normal tissues from early and late injury, is discussed. (orig.)g.)

  10. Arsenic, mode of action at biologically plausible low doses: What are the implications for low dose cancer risk?

    International Nuclear Information System (INIS)

    Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to ?60 ppb As in their drinking water is often lower than the risk for the unexposed control population. We have found that treatment of human keratinocyte and fibroblast cells with 0.1 to 1 ?M arsenite (AsIII) also produces a low dose protective effect against oxidative stress and DNA damage. This response includes increased transcription, protein levels and enzyme activity of several base excision repair genes, including DNA polymerase ? and DNA ligase I. At higher concentrations (> 10 ?M), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if onse data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues

  11. Does bystander effect by low dose X-ray contribute to breakage of DNA double strand?

    International Nuclear Information System (INIS)

    The purpose of this study is to analyze the effect of low dose radiation (100 mGy or less) in human normal fetal fibroblasts by dose-response curve of phosphorylated ataxia telangiectasia mutated (ATM) foci. The MRC-5 cells were irradiated by X-ray generated in HF320 (Shimadzu Mectem) at 5.67-224 mGy/min (1-100 mGy in total). Phosphorylated ATM was stained by immunocytochemical fluorescence and their foci were counted by fluorescence microscopy using the CCD camera C5810-1 (Hamamatsu Photonics). For dose-response curve, confluent cell cultures on slide glasses were irradiated as above. It was found that with use of phosphorylated ATM as an indicator, the low dose radiation effect could be analyzable; in the low dose range, the relationship between dose and DNA double strand break was not linear; and the radiation-induced bystander effect could be significant even in the lower range than where radiation induced one break per cell in average. Further studies are required for precise evaluation of radiation effect in health risk and in LNT hypothesis. (R.T.)

  12. Accidental chronic exposure to low dose radiation in Taiwan

    International Nuclear Information System (INIS)

    For more than 10 years, about 10,000 people in Taiwan have been chronically exposed to ionizing radiation at low dose rates. Materials used for the construction of their apartments were contaminated by cobalt -60. The incident, discovered in 1992, led to the mapping of contaminated areas and the dosimetry and health consequences since 1993. Measurements were carried out in different places in the apartments and residents wore thermo - luminescent detectors. Annual dose levels about 1 to 140 mSv have been evaluated. Retrospective biological dosimetry studies were realized both by means of analysis of the micronuclei and by the analysis of radiation-induced stable chromosomes translocations. Moreover other studies focused on research on functional or anatomic modifications, complete or not by individual biological dosimetry, were carried out and have shown the particular interest in undertaking the biological and medical surveillance of this population. Beyond the analyses and results published, these prolonged exposures at low dose rates and variable cumulated doses, since they cannot exceed the Gy, have raised the question on radio-adaptation and/or hormesis. One of the underlying questions is whether this population, chronically and heterogeneously exposed to an anthropogenic source, can help characterize the harmful effects or beneficial health effects at these dose levels. Different points of view were expressed in 2003, and a review of scientific publications since 1997 on this subject is presented. In view of the incomplete results, both in physical and biological dosimetry, a study on the people exposed during their childhood would seem to be more useful for re-usable results, to investigate the existence of adaptation to anthropogenic chronic irradiation. (authors)

  13. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kleiman, Norman Jay [Columbia University

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9, influence cataract development and thus radiosensitivity. These observations have direct applicability to various human populations including accidentally exposed individuals, interventional medical workers, astronauts and nuclear plant workers.

  14. Radiation Induced Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.

    2011-03-01

    Radiation induced genomic instability can be observed in the progeny of irradiated cells multiple generations after irradiation of parental cells. The phenotype is well established both in vivo (Morgan 2003) and in vitro (Morgan 2003), and may be critical in radiation carcinogenesis (Little 2000, Huang et al. 2003). Instability can be induced by both the deposition of energy in irradiated cells as well as by signals transmitted by irradiated (targeted) cells to non-irradiated (non-targeted) cells (Kadhim et al. 1992, Lorimore et al. 1998). Thus both targeted and non-targeted cells can pass on the legacy of radiation to their progeny. However the radiation induced events and cellular processes that respond to both targeted and non-targeted radiation effects that lead to the unstable phenotype remain elusive. The cell system we have used to study radiation induced genomic instability utilizes human hamster GM10115 cells. These cells have a single copy of human chromosome 4 in a background of hamster chromosomes. Instability is evaluated in the clonal progeny of irradiated cells and a clone is considered unstable if it contains three or more metaphase sub-populations involving unique rearrangements of the human chromosome (Marder and Morgan 1993). Many of these unstable clones have been maintained in culture for many years and have been extensively characterized. As initially described by Clutton et al., (Clutton et al. 1996) many of our unstable clones exhibit persistently elevated levels of reactive oxygen species (Limoli et al. 2003), which appear to be due dysfunctional mitochondria (Kim et al. 2006, Kim et al. 2006). Interestingly, but perhaps not surprisingly, our unstable clones do not demonstrate a mutator phenotype (Limoli et al. 1997), but they do continue to rearrange their genomes for many years. The limiting factor with this system is the target the human chromosome. While some clones demonstrate amplification of this chromosome and thus lend themselves to prolonged study, many tend to eliminate or rearrange the target chromosome until it is too small for further rearrangement. The observed frequency of induced instability by low and high linear-energy-transfer radiations greatly exceeds that observed for nuclear gene mutations at similar doses; hence, mutation of a gene or gene family is unlikely to be the initiating mechanism. Once initiated however, there is evidence in the GM10115 model system that it can be perpetuated over time by dicentric chromosome formation followed by bridge breakage fusion cycles (Marder and Morgan 1993), as well as recombinational events involving interstitial telomere like repeat sequences (Day et al. 1998). There is also increasing evidence that inflammatory type reactions (Lorimore et al. 2001, Lorimore and Wright 2003), presumably involving reactive oxygen and nitrogen species as well as cytokines and chemokines might be involved in driving the ustable phenotype (Liaikis et al. 2007, Hei et al. 2008). To this end there is very convincing evidence for such reactions being involved in another non-targeted effect associated with ionizing radiation, the bystander effect (Hei et al. 2008). Clearly the link between induced instability and bystander effects suggests common processes and inflammatory type reactions will likely be the subject of future investigation.

  15. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    Science.gov (United States)

    Jiang, Erkang; Wu, Lijun

    2009-04-01

    In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy ?-particle irradiated and non-irradiated bystander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensitive to damage signals. Treated by c-PTIO(2-(4-carboxy-phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide), a nitric oxide (NO) scavenger, the MN frequencies were effectively inhibited, showing that nitric oxide might be very important in mediating the enhanced damage. These results indicated that caffeine enhanced the low dose ?-particle radiation-induced damage in irradiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE).

  16. Oligomer formation in the radiation-induced polymerization of styrene

    International Nuclear Information System (INIS)

    Analyses of the oligomers formed in radiation-induced polymerization of purified styrene were performed. The principal dimeric products were cis- and trans-diphenyl-cyclobutane with a relatively small amount of 1-phenyltetralin; the trimeric products were the optical isomers of 1-phenyl-4-[1'-phenylethyl-(1')]-tetralin in gamma-ray and 60 MeV proton irradiation. Oligomer formation increased with increasing dose, but more gradually than the linear formation of high polymer with dose. The yield was 0.25-3.1 ?mol/J at low doses and decreased to an asymptotic value of 0.15 at higher doses. It appears that oligomers act as chain transfer agents during the polymerization reaction which would account for the observed decrease in molecular weight of the high polymer with increase in dose. Although the thermal and radiation-induced polymerization of styrene have different initiation steps, the oligomers produced by both reactions are similar in composition

  17. Exposure to low doses of ionizing radiations

    International Nuclear Information System (INIS)

    The author discusses the knowledge about the effects of ionizing radiations on mankind. Some of them have been well documented (skin cancer and leukaemia for the pioneer scientists who worked on radiations, some other types of cancer for workers who handled luminescent paints, rock miners, nuclear explosion survivors, patients submitted to radiological treatments). He also evokes the issue of hereditary cancers, and discusses the issue of low dose irradiation where some surveys can now be performed on workers. He discusses the biological effects of these low doses. He outlines that many questions remain about these effects, notably the influence of dose level and of dose rate level on the biological reaction

  18. Enhancing acupuncture by low dose naltrexone.

    Science.gov (United States)

    Hesselink, Jan M Keppel; Kopsky, David J

    2011-06-01

    To find appropriate and effective treatment options for chronic pain syndromes is a challenging task. Multimodal treatment approach has been gaining acceptance for chronic pain. However, combining treatments, such as acupuncture, with rational pharmacology is still in its infancy. Acupuncture influences the opioid and cannabinoid system through releasing endogenous receptor ligands. Low dose naltrexone also acts on both these systems, and upregulates the opioid and cannabinoid receptors. The authors hypothesise that low dose naltrexone could enhance the pain-relieving effect of acupuncture. PMID:21415049

  19. Factors that modify risks of radiation-induced cancer

    International Nuclear Information System (INIS)

    The collective influence of biologic, physical, and other factors that modify risks of radiation-induced cancer introduces uncertainties and assumptions that limit precision of estimates of human cancer risk that can be calculated for populations exposed to low-dose radiation. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, latent periods, time-to-tumor recognition, and individual host (e.g., age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Sources that modify risk also include other carcinogens and biologic factors (e.g., hormonal conditions, immune status, hereditary factors). Discussion includes examples of known influences that modify radiation-associated cancer risks and how they have been dealt with in the risk-estimation process, including extrapolation to low doses, use of relative risk models, and other uncertainties

  20. RIS - radiation induced superheroes

    International Nuclear Information System (INIS)

    We all know & love our Superheroes. Whether we realised it or not when we were kids growing up watching or reading 'Faster than a locomotive...' or ...'he does whatever a spider can...' , the fantasy of these cool hero characters was created, in one way or another, by the influence of RADIATION. Our Radiation Induced Superheroes include such greats as Superman, Spiderman & the Incredible Hulk. There were other lesser known ones which didn't make the cut with this 'bit of fun' poster. Others include names like The Fantastic Four: Mr Fantastic, The Invisible Woman, The Human Torch & Thing - all exposed to high-level cosmic radiation during an outer space scientific mission. Superpowers such as the element of 'Radiation Control' are available to characters like Metallo - a Superman adversary & Ultron - a baddie in the Avengers comics. We all know that the physics makes these characters complete works of fiction, but it's fun to watch their TV shows (Superman is STILL on TV in 'Smallville'), movies go without saying - dozens of them around & still being created & some of us even still read the comics!

  1. Apoptosis and survival parameters during protection from radiation-induced thymocyte death by a candidate radioprotector, GC-2112, from Allium sativum

    International Nuclear Information System (INIS)

    Biomedical studies on nuclear fallout effects show that whole-body exposure to relatively low doses of ionizing radiation (2-10 Gy) induces the hematopoietic syndrome (HS) characterized by severe anemia and immunodeficiency and death within 10-30 days. The thymocyte model applies in many cell death researches and is found to undergo a morphologically and molecularly distinct p53-based apoptosis with DNA-damaging insults, such as radiation exposure. We have shown that exogenously applied radioprotector from allium sativum (garlic), GC-2112, improves total cellular survival for various observation periods concomitantly shifting the LD50/24 from 7 Gy (control) to 21 Gy (GC-2112). This increased survival characteristic of the radioprotected macrophage-free thymocytes, however, fails to correlate with the prevention of apoptosis-associated DNA scissions. Mechanisms to the observed radiomodification may possibly involve cysteine compounds found rich in garlic. These preliminary findings show promise in the applications of selected herbal drugs as dietary prophylaxis against clinical morbidities arising from either medical, occupational or environmental exposures to ionizing radiation. (author)

  2. The OER at low-dose rates

    International Nuclear Information System (INIS)

    There is increasing interest in the treatment of human cancers with multifraction beam therapy at low dose-rates, on the assumption that the OER at low dose-rates is smaller than that at high dose-rates. A comparison has therefore been made of various published values of OER as a function of ? dose-rate for Vicia faba, HeLa cells, P388 cells, hamster cells and chromosome aberrations. The mean value of the OER at low dose-rate was about 20% lower than the mean OER obtained at high dose-rate, although two OER values at low dose-rates were significantly lower than the other reported values. There are technical difficulties associated with maintaining the test systems under hypoxic conditions for long periods of time and the observed decrease in cloning efficiency of hypoxic control cells indicates that cells can be damaged by this treatment alone. It is therefore possible that the high dose-rate OER values would have been reduced if the cells irradiated at high dose-rates under oxic and anoxic conditions had had a pre-treatment period of storage under anoxic conditions. (U.K.)

  3. Stimulation of seeds by low dose irradiation

    International Nuclear Information System (INIS)

    The first section of the bibliography lists materials on the stimulation of seeds by low dose irradiation, with particular reference to stimulation of germination and yield. The second section contains a small number of selected references on seed irradiation facilities. (author)

  4. [DNA-signaling pathway mediating development of a radiation-induced bystander effect in human cells].

    Science.gov (United States)

    Ermakov, A V; Kon'kova, M S; Kostiuk, S V; Ve?ko, N N

    2011-01-01

    Low doses of ionizing radiation induce the adaptive effect (AE) development in human cells which is followed by a number of cell responses. These responses can be transmitted from irradiated cells to non-irradiated ones (bystander effect, BE). The major role in radiation-induced BE is played by an oxidative stress (OS) and a DNA-signaling pathway, in which extracellular DNA fragments (ecDNA) are the factors of stress-signalization. We propose the following sequence of events in this signaling system: irradiation-OS-DNA modification-apoptosis of irradiated cells-ecDNA-signal acceptance by non-irradiated cells-OS-DNA modification, etc. We observed a radiation-induced BE which is accompanied by DNA-signaling pathway in differentiated and undifferentiated human cells forming monolayer or suspension cultures. Here we discuss several aspects of the radiation-induced BE mechanism and its persistence possibilities. PMID:22384714

  5. Experimental observation of lens damage after low doses of ?-ray irradiation to rabbit eyes

    International Nuclear Information System (INIS)

    Objective: To investigate and evaluate low dose ?-ray radiation induced lens damage. Methods: Both eyes of each rabbit were exposed to a single dose of 25 or 50 cGy ?-rays in two groups, respectively. Samples were examined by transmission electron microscopy (TEM) and slit lamp microscopy (SLM)after irradiation. Results: Three days after 25 and 50 cGy irradiation,the epithelial cells of lens equator al region showed marked swelling and many vacuoles formed in intercellular space and cytoplasm,and accompanied by increased multi-lamellar bodies. Five months after irradiation, SLM of both groups showed that the posterior sub-capsule cortex exhibited clusters of vacuoles; 11 months after 50 cGy irradiation,the posterior sub-capsule and deep cortex manifested marked cloudy opacities. Conclusion: Low doses of ?-ray (25 and 50 cGy) irradiation can markedly damage lens of rabbits

  6. Bystander responses in low dose irradiated cells treated with plasma from gamma irradiated blood

    Science.gov (United States)

    Acheva, A.; Georgieva, R.; Rupova, I.; Boteva, R.; Lyng, F.

    2008-02-01

    There are two specific low-dose radiation-induced responses that have been the focus of radiobiologists' interest in recent years. These are the bystander effect in non-irradiated cells and the adaptive response to a challenge dose after prior low dose irradiation. In the present study we have investigated if plasma from irradiated blood can act as a 'challenge dose' on low dose irradiated reporter epithelial cells (HaCaT cell line). The main aim was to evaluate the overall effect of low dose irradiation (0.05 Gy) of reporter cells and the influence of bystander factors in plasma from 0.5 Gy gamma irradiated blood on these cells. The effects were estimated by clonogenic survival of the reporter cells. We also investigated the involvement of reactive oxygen species (ROS) as potential factors involved in the bystander signaling. Calcium fluxes and mitochondrial membrane potential (MMP) depolarization were also examined as a marker for initiation of apoptosis in the reporter cells. The results show that there are large individual differences in the production of bystander effects and adaptive responses between different donors. These may be due to the specific composition of the donor plasma. The observed effects generally could be divided into two groups: adaptive responses and additive effects. ROS appeared to be involved in the responses of the low dose pretreated reporter cells. In all cases there was a significant decrease in MMP which may be an early event in the apoptotic process. Calcium signaling also appeared to be involved in triggering apoptosis in the low dose pretreated reporter cells. The heterogeneity of the bystander responses makes them difficult to be modulated for medical uses. Specific plasma characteristics that cause these large differences in the responses would need to be identified to make them useful for radiotherapy.

  7. Bystander responses in low dose irradiated cells treated with plasma from gamma irradiated blood

    International Nuclear Information System (INIS)

    There are two specific low-dose radiation-induced responses that have been the focus of radiobiologists' interest in recent years. These are the bystander effect in non-irradiated cells and the adaptive response to a challenge dose after prior low dose irradiation. In the present study we have investigated if plasma from irradiated blood can act as a 'challenge dose' on low dose irradiated reporter epithelial cells (HaCaT cell line). The main aim was to evaluate the overall effect of low dose irradiation (0.05 Gy) of reporter cells and the influence of bystander factors in plasma from 0.5 Gy gamma irradiated blood on these cells. The effects were estimated by clonogenic survival of the reporter cells. We also investigated the involvement of reactive oxygen species (ROS) as potential factors involved in the bystander signaling. Calcium fluxes and mitochondrial membrane potential (MMP) depolarization were also examined as a marker for initiation of apoptosis in the reporter cells. The results show that there are large individual differences in the production of bystander effects and adaptive responses between different donors. These may be due to the specific composition of the donor plasma. The observed effects generally could be divided into two groups: adaptive responses and additive effects. ROS appeared to be involved in the responses of the low dose pretreated reporter cells. In all cases there was a significant decrease in MMP which may be an early event in the an MMP which may be an early event in the apoptotic process. Calcium signaling also appeared to be involved in triggering apoptosis in the low dose pretreated reporter cells. The heterogeneity of the bystander responses makes them difficult to be modulated for medical uses. Specific plasma characteristics that cause these large differences in the responses would need to be identified to make them useful for radiotherapy

  8. Radiation-induced intestinal inflammation

    OpenAIRE

    Moll, Meritxell; Pans, Julin

    2007-01-01

    Radiation induces an important inflammatory response in the irradiated organs, characterized by leukocyte infiltration and vascular changes that are the main limiting factor in the application of this therapeutic modality for the treatment of cancer. Recently, a considerable investigative effort has been directed at determining the molecular mechanisms by which radiation induces leukocyte recruitment, in order to create strategies to prevent intestinal inflammatory damage. In these review, we...

  9. From Chernobyl to Fukushima: the effect of low doses

    International Nuclear Information System (INIS)

    This Power Point presentation describes the Fukushima's reactors, recalls some data about the earthquake and tsunami, and indicates their consequences for the operation of the power station (notably the loss of cooling means). It identifies some design errors for the Chernobyl's and Fukushima's power stations, outlines differences between these two cases. It gives assessment of doses receives by external irradiation around Fukushima, of the dose rate evolution, of the sea contamination. It gives some data about the Chernobyl accident (radioactivity evolution). After some data about health consequences of Chernobyl, health risks and more particularly biological risks associated to low doses are described. Protection measures are evoked, as well as psycho-social impacts

  10. Ionizing radiation: effects of low doses

    International Nuclear Information System (INIS)

    This article deals with the important and delicate subject posed by the study of the action on Man's health of low doses of ionizing radiation. A number of fundamental notions whose knowledge is indispensable in order to avoid doubtful meanings or misunderstandings are noted in this article. Following the reminder of these notions, the characteristics of the various types of pathological effects of radiation are indicated, as well as how it is possible for effects which are named ''aleatory'' to be evaluated with care so as to limit risks at low doses. The reader will easily understand that this article has to be somewhat didactic - it seemed best to proceed by well defined stages and to clearly specify numerous concepts whose meanings are not always clearly defined when such problems are treated

  11. The effects of low-dose radiation

    International Nuclear Information System (INIS)

    Three pieces of evidence in the debate on the effects of low-dose radiation are discussed. These are evidence from the television programme, 'The Nuclear Laundry' which showed that the incidence of childhood cancers close to the Sellafield reprocessing plant is greater than the national average, the findings of the Black Committee set up by the Government which concluded that the levels of radiation in the area were far too low to be associated with such an increase, and evidence from the Oxford Survey of Childhood Cancers which suggests that even a small dose of ionizing radiation may be sufficient to initiate a disease process which leads to a cancer death any time in the following 10, 20 or 30 years. The conclusion is that the risks from low dose radiation must be reassessed in the light of new evidence. (U.K.)

  12. Biological effects of low doses of radiation at low dose rate

    International Nuclear Information System (INIS)

    The purpose of this report was to examine available scientific data and models relevant to the hypothesis that induction of genetic changes and cancers by low doses of ionizing radiation at low dose rate is a stochastic process with no threshold or apparent threshold. Assessment of the effects of higher doses of radiation is based on a wealth of data from both humans and other organisms. 234 refs., 26 figs., 14 tabs

  13. Estimation of radiation risks at low dose

    International Nuclear Information System (INIS)

    The report presents a review of the effects caused by radiation in low doses, or at low dose rates. For the inheritable (or ''genetic''), as well as for the cancer producing effects of radiation, present evidence is consistent with: (a) a non-linear relationship between the frequency of at least some forms of these effects, with comparing frequencies caused by doses many times those received annually from natural sources, with those caused by lower doses; (b) a probably linear relationship, however, between dose and frequency of effects for dose rates in the region of that received from natural sources, or at several times this rate; (c) no evidence to indicate the existence of a threshold dose below which such effects are not produced, and a strong inference from the mode of action of radiation on cells at low dose rates that no such thresholds are likely to apply to the detrimental, cancer-producing or inheritable, effects resulting from unrepaired damage to single cells. 19 refs

  14. Genomic Instability Induced by Low Dose Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Evans, Helen H.

    2006-07-15

    The goal of this project was to determine if genomic instability could be initiated by poorly repaired DNA damage induced by low doses of ionizing radiation leading to a mutator phenotype. Human cells were irradiated, then transfected with an unirradiated reporter gene at various times AFTER exposure. The vector carried an inactive GFP gene that fluoresced when the gene was activated by a delayed mutation. Fluorescent cells were measured in the interval of 50 hours to four days after transfection. The results showed that delayed mutations occurred in these cells after exposure to relatively low doses (0.3-1.0 Gy) of low or high ionizing radiation, as well as after treatment with hyrodgen peroxide (30-100 micromolar). The occurrence was both dose and time dependent, often decreasing at higher doses and later times. No marked difference was observed between the response of mis-match repair-proficient and -deficient cell lines. Although the results were quite reproducible within single experiments, difficulties were observed from experiment to experiment. Different reagents and assays were tested, but no improvement resulted. We concluded that this method is not sufficiently robust or consisent to be useful in the assay of the induction of genomic instability by low doses of radiation, at least in these cell lines under our conditions.

  15. The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

    Energy Technology Data Exchange (ETDEWEB)

    Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.; Lien, Katie A.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Sacksteder, Colette A.

    2012-12-01

    Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-?, IL-2, MIP-1?, were significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-?, MIP-1?, TNF ?, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1?, IL-8, MIP-1?, MIP-1?, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.

  16. A legacy of Hiroshima and Nagasaki : risk estimates for radiation induced cancer

    International Nuclear Information System (INIS)

    The atomic bombs dropped on Hiroshima and Nagasaki fifty years ago ended the war in the Pacific and set the world agog at the prospect of new and frightening weapons for the future. Many residents of these cities, exposed to lesser than lethal amounts of radiation, survived to constitute the most remarkable radioepidemiological study of late radiation effects any of us could have imagined. These survivors and those relatively few among them who died of cancers attributable to radiation, provide us with our primary source of risk estimates for radiation induced cancer. As cancer is the principal low dose radiation effect these estimates are today at the core of our radiation protection system for workers and the public. In 1977 it was the risk estimates mainly from the LSS (Lifespan Study of the A-bomb survivors) estimated at about 1%/Sv that enabled ICRP to confirm the existing worker limit of 50mSv/y. In 1987, NCRP introduced a new and more restrictive occupational guideline because risk estimates from the LSS were known to be 'going up'. Continued surveillance of radioepidemiological studies and especially the LSS is a vital part of the scientific background of radiation protection. (author)

  17. Low-Dose Aspirin Treatment Alleviates Gamma Irradiation Impaired Fertility in Female Albino Rats

    International Nuclear Information System (INIS)

    Recent experimental evidence suggests that Aspirin (acetylsalicylic acid), the extensively prescribed analgesic, can improve female fertility by suppressing the prostaglandin (PG) biosynthesis and modulating the uterine circulation. Aspirin has also been found to exhibit a protective ability on the radiation induced oxidative stress. Thus the present work aims to investigate the effect of oral low-dose Aspirin treatment on the radiation induced female reproductive disturbance. Adult female rats were used in the current experiment. All rat group treatments started at the onset of the proestrus phase and terminated at the diestrus encompassing 2 complete estrus cycles. Subsequently, the rats were divided into 4 equal groups: Group 1-Control: female rats receiving distilled water via an oral gavage; Group 2- Irradiation: female rats subjected to 6 Gy gamma rays at the proestrus cycle and receiving distilled water; Group 3-Aspirin: rats orally administered a daily dose of 7mg/kg body weight aspirin dissolved in distilled water via an oral gavage and Group 4- Irradiation + Aspirin: female rats irradiated as group 2 and receiving aspirin treatment. A number of rats from each experimental group were allowed to mate following every treatment to serve as Control mated (Subgroup 1), Irradiated mated (Subgroup 2), Aspirin administered mated (Subgroup 3) and Irradiated + Aspirin treated mated (Subgroup 4). At the assigned day of the second estrus cycle completion, blood was collected from Groups 1-4 for subsequent hormonal assay, lipid peroxides and glutathione (GSH) estimation whereas Subgroups 1-4 were carefully monitored for reproduction and infertility rates. Results have shown that the 6 Gy ?- irradiation of the rats at the proestrus cycle (Group 2) caused a decrease in follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and estradiol (E2) levels associated with a drastic increase in the progesterone levels in addition to the significant elevated malondialdehyde (MDA) and reduced glutathione (GSH) levels compared to the related serum control values. The radiation effect was extended to Subgroup 2 that revealed apparent infertility. Moreover, Aspirin oral daily administration caused a remarkable reduction in both FSH and LH hormones alongside with elevated progesterone and PRL levels with no noted E2 level changes (Group 3). However the same treatment accelerated both the fertility and re productivity rates of Subgroup 3. However, the results of the present study revealed the potency of the anti-inflammatory drug Aspirin when administered post radiation exposure (Group 4) in ameliorating the abrupt irradiation induced hormonal imbalance and the significant elevation in serum MDA in addition to its ability in alleviating the radiation induced reproductive disorders (Subgroup 4). In conclusion, oxidative stress caused by radiation exposure of cycling female rats induced marked disturbance in their hormonal balance leading to negative fertility outcomes that has been ameliorated by Aspirin therapy.

  18. Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

    Science.gov (United States)

    Matsumoto, H.; Ohnishi, T.

    There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

  19. N-acetyl cysteine protects against ionizing radiation-induced DNA damage but not against cell killing in yeast and mammals

    International Nuclear Information System (INIS)

    Ionizing radiation (IR) induces DNA strand breaks leading to cell death or deleterious genome rearrangements. In the present study, we examined the role of N-acetyl-L-cysteine (NAC), a clinically proven safe agent, for it's ability to protect against ?-ray-induced DNA strand breaks and/or DNA deletions in yeast and mammals. In the yeast Saccharomyces cerevisiae, DNA deletions were scored by reversion to histidine prototrophy. Human lymphoblastoid cells were examined for the frequency of ?-H2AX foci formation, indicative of DNA double strand break formation. DNA strand breaks were also measured in mouse peripheral blood by the alkaline comet assay. In yeast, NAC reduced the frequency of IR-induced DNA deletions. However, NAC did not protect against cell death. NAC also reduced ?-H2AX foci formation in human lymphoblastoid cells but had no protective effect in the colony survival assay. NAC administration via drinking water fully protected against DNA strand breaks in mice whole-body irradiated with 1 Gy but not with 4 Gy. NAC treatment in the absence of irradiation was not genotoxic. These data suggest that, given the safety and efficacy of NAC in humans, NAC may be useful in radiation therapy to prevent radiation-mediated genotoxicity, but does not interfere with efficient cancer cell killing.

  20. Global DNA methylation responses to low dose radiation exposure

    International Nuclear Information System (INIS)

    At high radiation doses, breaks in the DNA are considered the critical lesions in initiation of radiation- induced cancer. However, at the very low radiation doses relevant for the general public, the induction of such breaks will be rare, and other changes to the DNA such as DNA methylation may play a role in radiation responses. DNA methylation is the addition of a methyl group to cytosine in the DNA, usually where a cytosine is adjacent to a guanine (CpG). Methylation affects the way in which genes are read, and is inherited from cell to cell on replication. It is known that high dose radiation can cause changes in methylation in the genome but less is known about the effect of low dose radiation on methylation. We developed a sensitive assay to measure the levels of DNA methylation across the mouse genome by analysing a stretch of DNA sequence within Long Interspersed Nuclear Elements-1(LINE1) that comprise a very large proportion of the mouse and human genomes. Using bisulphite modification followed by quantitative real-time polymerase chain reaction (PCP) and high- resolution melt analysis, a very large pool of DNA sequences from throughout the genome can be studied indicating gain or loss of methylation. We validated the assay in vitro using the chemical demethylating agent 5'-aza-2' -deoxycytidine with changes at as few as 3% of CpG's being reproducibly detected. We have demonstrated a difference in the baseline levels of in vivo DNA methylation between male and female mice and between different tissues. Our initial results suggest no significant short-term or long-term changes in global DNA methylation after low dose whole-body X-radiation of 10 -Gy or 10 mGy, with a significant transient increase in DNA methylation observed 1 day after a high dose of 1 Gy. If the low radiation doses tested are inducing changes in global DNA methylation, these would appear to be smaller than the natural variation observed between the sexes and following the general stress of the sham-irradiation procedure itself.

  1. Proceedings of the 8. LOWRAD: International conference on the effects of low doses and very low doses of ionizing radiation on human health and biotopes

    International Nuclear Information System (INIS)

    Theoretical and experimental papers are presented in these proceedings covering the following subjects: radiation protection, dosimetry, radiation dosimetry, cells, technetium, plutonium, uranium, thorium, low dose irradiation, radiation doses, cesium, radiation chemistry, nuclear medicine, safety and occupational exposure, neoplasm, cytology and radioisotopes

  2. Quantitative Proteomic Profiling of Low Dose Ionizing Radiation Effects in a Human Skin Model

    Energy Technology Data Exchange (ETDEWEB)

    Hengel, Shawna; Aldrich, Joshua T.; Waters, Katrina M.; Pasa-Tolic, Ljiljana; Stenoien, David L.

    2014-07-29

    To assess molecular responses to low doses of radiation that may be encountered during medical diagnostic procedures, nuclear accidents, or terrorist acts, a quantitative global proteomic approach was used to identify protein alterations in a reconstituted human skin tissue treated with 10 cGy of ionizing radiation. Subcellular fractionation was employed to remove highly abundant structural proteins and provide insight on radiation induced alterations in protein abundance and localization. In addition, peptides were post-fractionated using high resolution 2-dimensional liquid chromatography to increase the dynamic range of detection of protein abundance and translocation changes. Quantitative data was obtained by labeling peptides with 8-plex isobaric iTRAQ tags. A total of 207 proteins were detected with statistically significant alterations in abundance and/or subcellular localization compared to sham irradiated tissues. Bioinformatics analysis of the data indicated that the top canonical pathways affected by low dose radiation are related to cellular metabolism. Among the proteins showing alterations in abundance, localization and proteolytic processing was the skin barrier protein filaggrin which is consistent with our previous observation that ionizing radiation alters profilaggrin processing with potential effects on skin barrier functions. In addition, a large number of proteases and protease regulators were affected by low dose radiation exposure indicating that altered proteolytic activity may be a hallmark of low dose radiation exposure. While several studies have demonstrated altered transcriptional regulation occurs following low dose radiation exposures, the data presented here indicates post-transcriptional regulation of protein abundance, localization, and proteolytic processing play an important role in regulating radiation responses in complex human tissues.

  3. Protection of nucleated bone marrow cells of mice against effect of radiation-induced micronucleus formation by using polysaccharides extracted from 'Zi Zhi' (a ganoderma)

    International Nuclear Information System (INIS)

    This paper describes the influence of polysaccharides extracted from 'Zi Zhi' (Ganoderma Sinese Zhao, Xu et Zhang) on the frequency of micronucleated cells induced by 60Co gamma irradiation at different doses in bone marrow of mice. These polysaccharides of 'Zi Zhi' were shown to be of ability to protect nucleated bone marrow cells from micronucleus formation in irradiated mice. For Swiss mice, a dose reduction factor (DRF) was found to be 1.72 in the range of 0 to 4.728 Gy and for LACA mice, to be 1.73 in the range of 0 to 3.152 Gy. Such findings indicate that these polysaccharides are comparable to L-cysteine in their effeciency of protection

  4. The principal phenolic and alcoholic components of wine protect human lymphocytes against hydrogen peroxide- and ionising radiation-induced DNA damage in vitro

    International Nuclear Information System (INIS)

    We have tested the hypothesis that the alcoholic and phenolic components of wine are protective against the DNA damaging and cytotoxic effects of hydrogen peroxide and gamma radiation in vitro. The components of wine tested were ethanol, glycerol, a mixture of the phenolic compounds catechin and caffeic acid, and tartaric acid, all at concentrations that were 2.5% or 10.0% of the concentration in a typical Australian white wine Riesling. These components were tested individually or combined as a mixture and compared to a white wine stripped of polyphenols as well as a Hanks balanced salt solution control which was the diluent for the wine components. The effect of the components was tested in lymphocytes, using the cytokinesis-block micronucleus assay, after 30 minutes incubation in plasma or whole blood for the hydrogen peroxide or gamma-radiation challenge respectively. The results obtained showed that ethanol, glycerol, the catechin-caffeic acid mixture, the mixture of all components, and the stripped white wine significantly reduced the DNA damaging effects of hydrogen peroxide and gamma radiation (ANOVA P = 0.043 - 0.001). The strongest protective effect against DNA damage by gamma irradiation was observed for the catechin-caffeic acid mixture and mixture of all components (30% and 32% reduction respectively). These two treatments as well as ethanol produced the strongest protective effects against DNA damage by hydrogen peroxide (24%, 25% and 18% respectively) .peroxide (24%, 25% and 18% respectively) . The protection provided by the mixture did not account for the expected additive protective effects of the individual components suggesting that the components may be exerting their effects through similar mechanisms which are saturated at the concentrations tested. Ethanol was the only component that significantly increased base-line DNA damage rate, however, this effect was negated in the mixture. In conclusion our results suggest that the main phenolic and alcoholic components of wine can reduce the DNA damaging effects of two important oxidants ie hydrogen peroxide and ionising radiation, in this physiologically relevant in vitro system

  5. Biological effect of low dose radiation

    International Nuclear Information System (INIS)

    This document describes the recent findings in studies of low dose radiation effect with those by authors' group. The low dose radiation must be considered in assessment of radiation effects because it induces the biological influence unexpected hitherto; i.e., the bystander effect and genetic instability. The former is a non-targeted effect that non-irradiated cells undergo the influence of directly irradiated cells nearby, which involves cell death, chromosome aberration, micronucleus formation, mutation and carcinogenesis through cellular gap junction and/or by signal factors released. Authors' group has found the radical(s) possessing as long life time as >20 hr released from the targeted cells, a possible mediator of the effect; the generation of aneuploid cells as an early carcinogenetic change; and at dose level <10 Gy, activation of MAPK signal pathway leading to relaxation of chromatin structure. The genetic instability means the loss of stability where replication and conservation of genome are normally maintained, and is also a cause of the late radiation effect. The group has revealed that active oxygen molecules can affect the late effect like delayed cell death, giant cell formation and chromosome aberration, all of which lead to the instability, and is investigating the hypothesis that the telomere instability resulted from the abnormal post-exposure interaction with its nuclear membrane or between chromatin and nuclear matrix, is enhanced by structural nuclear matrix, is enhanced by structural distortion of nuclear genes. As well, shown is the possible suppression of carcinogenesis by p53. The group, to elucidate the mechanism underlying the low dose radiation effect, is conducting their studies in consideration of the sequential bases of physical, chemical and biological processes. (R.T.)

  6. Markers of the Low Dose Radiation Response

    International Nuclear Information System (INIS)

    One of the major challenges in the field of radiation biology is to correlate the results of biochemical studies with the process of DNA repair as it occurs in the living cell. The overall goal of this project is to develop better methods for visualizing DNA doublestrand breaks and double-strand break repair complexes in situ, in irradiated cells. Technologies are particularly needed to study repair complexes induced by low doses of radiation, where only one or a few breaks may be present

  7. Low doses: myth or true danger

    International Nuclear Information System (INIS)

    The question of low doses and the existence of a threshold dose is discussed here. The opinions are shared between scientists of nuclear energy and doctors who think there is a threshold, under it there is no detected effect for health, and the partisans of a zero risk who think that radiations are dangerous at any level. If elementary principles of precaution want that exposure standards continue to decrease, it can be appear for the public as a confirmation of soundness of zero dose thesis, and consequently generate a trust crisis between public and scientists. (N.C.)

  8. Food preservation by irradiation at low doses

    International Nuclear Information System (INIS)

    This work describes the use of food irradiation process at low doses, evidencing its potential and several applications and effects, among other issues. An special emphasis has been given to sensorial changes in several kinds of food, irradiated with doses between 0.75 kGy and 3.0 kGy. Sensorial effects originated from the irradiated frozen or refrigerated, and concentrated or diluted juices were investigated. The possible mechanisms that could account for the observed sensorial effects were also discussed. The present work has the objective of filling some still existing gaps in the national literature related to food irradiation process, such as, sensorial and physiological changes. (author)

  9. Radiation-induced peritoneal mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Babcock, T.L.; Powell, D.H.; Bothwell, R.S.

    1976-01-01

    A case report of a patient who developed peritoneal mesothelioma 7 years after internal and external irradiation for carcinoma of the cervix is reported. No previous reports of induction of this tumor by irradiation have been found. The subject of radiation-induced tumors and peritoneal mesothelioma is briefly discussed.

  10. Radiation-induced peritoneal mesothelioma

    International Nuclear Information System (INIS)

    A case report of a patient who developed peritoneal mesothelioma 7 years after internal and external irradiation for carcinoma of the cervix is reported. No previous reports of induction of this tumor by irradiation have been found. The subject of radiation-induced tumors and peritoneal mesothelioma is briefly discussed

  11. Radiation-induced changes in rat endocrine system and their correction by means of adaptogens

    International Nuclear Information System (INIS)

    Endocrine status of experimental animals under chronic influence of both external and internal irradiation in low doses was researched in this work. The influence of adaptation medication preparation (biopolymer Spiruline - BS) on studied indexes is also evaluated. Application of preparation with adaptation-inducing properties - the biopolymer Spiruline for experimental animals at the early irradiation stage partially or completely prevents the development of radiation-induced damages

  12. Low-dose radiation exposure and carcinogenesis

    International Nuclear Information System (INIS)

    Absorption of energy from ionizing radiation by the genetic material in the cell leads to damage to DNA, which in turn leads to cell death, chromosome aberrations and gene mutations. While early or deterministic effects result from organ and tissue damage caused by cell killing, latter two are considered to be involved in the initial events that lead to the development of cancer. Epidemiological studies have demonstrated the dose-response relationships for cancer induction and quantitative evaluations of cancer risk following exposure to moderate to high doses of low-linear energy transfer radiation. A linear, no-threshold model has been applied to assessment of the risks resulting from exposure to moderate and high doses of ionizing radiation; however, a statistically significant increase has hardly been described for radiation doses below 100 mSv. This review summarizes our current knowledge of the physical and biological features of low-dose radiation and discusses the possibilities of induction of cancer by low-dose radiation. (author)

  13. Genes activated by low dose radiation

    International Nuclear Information System (INIS)

    Gene expression profiles were examined in the mouse kidney and testis in order to investigate the molecular mechanisms of the life span-shortening effect of low dose-rate radiation. C57BL/6J male mice (7-8 wks old) were irradiated by cesium-137 gamma-rays for 485 days at rates of 0, 32, 650 and 13,000 nGy/min and organs were excised out. Gene expression was analyzed with cDNA microarray Illumina Sentrix Mouse-6. In the kidney, 4 genes concerning mitochondrial respiration (oxidative phosphorylation) were found to be up-regulated at the middle and high dose rates (expression level changed in >1.6 folds by irradiation). Significantly modulated genes were in 16 clusters, which exerted elevated expression level dose rate-dependently and found to be categorized in cytoplasm/mitochondria/energy pathways by the database ''Gene Ontology''. In the testis, gene expression pattern was different from that in kidney. Clustering analysis and database revealed that up-regulated genes belonged to ''DNA repair'', ''response to DNA damage'', DNA replication'' and ''Mitotic cell cycles''. Thus low dose radiation can cause the cellular oxidative stress by elevated respiratory activity in the kidney, and a type of emergent biological response in the testis. (R.T.)

  14. Oxygen radiosensitisation at low dose rate

    International Nuclear Information System (INIS)

    Oxygen radiosensitisation has been studied at dose rate of 600, 3.37 and 0.89 Gy/h at pO2 levels of 0.001, 0.03, 0.1, 0.3, 1, 3, 10 and 21% in the gas phase. The oxygen enhancement ratio (OER), evaluated at 2% cellular survival, exhibited a decrease with dose rate from a value of 3.2 at the acute dose rate, to 2.4 at the lowest dose rate. This observation results from a decreased dose-rate effect on hypoxic cells, which is attributed to the partial suppression of sublethal damage (SLD) repair under hypoxic conditions. Oxygen radiosensitisation at the acute dose rate agrees with the calculated values based on the oxygen fixation hypothesis. Direct application of the Howard-Flanders and Moore equation to results obtained at low dose rate is not appropriate due to the influence of pO2 on SLD repair which affects radiosensitivity at low dose rate. When cells are irradiated at 3.37 Gy/h under nutrient-deprived condition (i.e. in Hanks balanced salt solution without glucose), low levels of oxygen appear to be more radioprotective than extreme hypoxia. Specifically, cells irradiated with 0.03% and 0.1% O2 are more radioresistant than cells under N2, with enhancement factors of 0.7 and 0.8, respectively. (author)

  15. Implications of effects ''adaptive response'', ''low-dose hypersensitivity'' und ''bystander effect'' for cancer risk at low doses and low dose rates

    International Nuclear Information System (INIS)

    A model for carcinogenesis (the TSCE model) was applied in order to examine the effects of ''Low-dose hypersensitivity (LDH)'' and the ''Bystander effect (BE)'' on the derivation of radiation related cancer mortality risks. LDH has been discovered to occur in the inactivation of cells after acute exposure to low LET radiation. A corresponding version of the TSCE model was applied to the mortality data on the Abomb survivors from Hiroshima and Nagasaki. The BE has been mainly observed in cells after exposure to high LET radiation. A Version of the TSCE model which included the BE was applied to the data on lung cancer mortality from the workers at the Mayak nuclear facilities who were exposed to Plutonium. In general an equally good description of the A-bomb survivor mortality data (for all solid, stomach and lung tumours) was found for the TSCE model and the (conventional) empirical models but fewer parameters were necessary for the TSCE model. The TSCE model which included the effects of radiation induced cell killing resulted in non-linear dose response curves with excess relative risks after exposure at young ages that were generally lower than in the models without cell killing. The main results from TSCE models which included cell killing described by either conventional survival curves or LDH were very similar. A sub multiplicative effect from the interaction of smoking and exposure to plutonium was found to result from the analysis of the Mayak lung cancer mortthe analysis of the Mayak lung cancer mortality data. All models examined resulted in the predominant number of Mayak lung cancer deaths being ascribed to smoking. The interaction between smoking and plutonium exposures was found to be the second largest effect. The TSCE model resulted in lower estimates for the lung cancer excess relative risk per unit plutonium dose than the empirical risk model, but this difference was not found to be statistically significant. The excess relative risk dose responses were linear in the empirical model and linear below 1Sv, but strongly non-linear above 1Sv, in the TSCE model. Excess relative risk effect modification by age attained was found to be clearly weaker in the TSCE models than in the empirical models, for lung doses smaller than 10Sv. A BE was not compatible with the data. (orig.)

  16. Heavy-ion radiation induced bystander effect in mice

    Science.gov (United States)

    Liang, Shujian; Sun, Yeqing; Zhang, Meng; Wang, Wei; Cui, Changna

    2012-07-01

    Radiation-induced bystander effect is defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, Low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic, metabolomics and proteomics play significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male mice head were exposed to 2000mGy dose of 12C heavy-ion radiation and the distant organ liver was detected on 1h, 6h, 12h and 24h after radiation, respectively. MSAP was used to monitor the level of polymorphic DNA methylation changes. The results show that heavy-ion irradiate mouse head can induce liver DNA methylation changes significantly. The percent of DNA methylation changes are time-dependent and highest at 6h after radiation. We also prove that the hypo-methylation changes on 1h and 6h after irradiation. But the expression level of DNA methyltransferase DNMT3a is not changed. UPLC/Synapt HDMS G2 was employed to detect the proteomics of bystander liver 1h after irradiation. 64 proteins are found significantly different between treatment and control group. GO process show that six of 64 which were unique in irradiation group are associated with apoptosis and DNA damage response. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo.

  17. Low doses ionizing radiation enhances the invasiveness of breast cancer cells by inducing epithelial-mesenchymal transition

    International Nuclear Information System (INIS)

    Highlights: ? Low doses ionizing irradiation would enhance the invasiveness of breast cancer cells by inducing EMT. ? Low doses ionizing radiation induced morphologic changes in breast cancer cells. ? Low doses ionizing radiation led to upregulation of mesenchymal markers and down-regulation of epithelial markers. ? Low doses ionizing radiation increased migration and invasion of breast cancer cells. -- Abstract: Epithelial-mesenchymal transition (EMT) is a process cellular morphologic and molecular alterations facilitate cell invasion. We hypothesized that low dose ionizing irradiation (LDIR) enhances the invasiveness of breast cancer cells by inducing EMT. The effects of LDIR on cellular morphology and the EMT markers of MCF-7 breast cancer cells were analyzed by western blot/RT-PCR and migration/invasion was examined using the transwell assay. We found that LDIR led to the phenotypic changes of EMT in MCF-7 cells and down-regulation of epithelial differentiation markers and transcriptional induction of mesenchymal markers. Furthermore, the radiated cells demonstrated enhanced migration/invasion MCF-7 cells compared with non-radiated cells. In summary, LDIR promotes the invasiveness of breast cancer cells through epithelial to mesenchymal transition. These findings may ultimately provide a new targeted approach for improving the therapeutic effectiveness of radiation in breast cancer.

  18. Radiation leukaemogenesis at low doses DE-FG02-05 ER 63947 Final Technical Report 15 May 2005 ???????????????¢???????????????????????????????? 14 May 2010

    Energy Technology Data Exchange (ETDEWEB)

    Simon Bouffler

    2010-07-28

    This report provides a complete summary of the work undertaken and results obtained under US Department of Energy grant DF-FG02-05 ER 63947, Radiation leukaemogenesis at low doses. There is ample epidemiological evidence indicating that ionizing radiation is carcinogenic in the higher dose range. This evidence, however, weakens and carries increasing uncertainties at doses below 100-200 mSv. At these low dose levels the form of the dose-response curve for radiation-induced cancer cannot be determined reliably or directly from studies of human populations. Therefore animal, cellular and other experimental systems must be employed to provide supporting evidence on which to base judgements of risk at low doses. Currently in radiological protection a linear non-threshold (LNT) extrapolation of risk estimates derived from human epidemiological studies is used to estimate risks in the dose range of interest for protection purposes. Myeloid leukaemias feature prominently among the cancers associated with human exposures to ionising radiation (eg UNSCEAR 2006; IARC 2000). Good animal models of radiation-induced acute myeloid leukaemia (AML) are available including strains such as CBA, RFM and SJL (eg Major and Mole 1978; Ullrich et al 1976; Resnitzky et al 1985). Early mechanistic studies using cytogenetic methods in these mouse models established that the majority of radiation-induced AMLs carried substantial interstitial deletions in one copy of chromosome (chr) 2 (eg Hayata et al 1983; Trakhtenbrot et al 1988; Breckon et al 1991; Rithidech et al 1993; Bouffler et al 1996). Chr2 aberrations are known to occur in bone marrow cells as early as 24 hours after in vivo irradiation (Bouffler et al 1997). Subsequent molecular mapping studies defined a distinct region of chr2 that is commonly lost in AMLs (Clark et al 1996; Silver et al 1999). Further, more detailed, analysis identified point mutations at a specific region of the Sfpi1/PU.1 haemopoietic transcription factor gene which lies in the commonly deleted region of chr2 (Cook et al 2004; Suraweera et al 2005). These lines of evidence strongly implicate the Sfpi1/PU.1 gene as a tumour suppressor gene, dysregulation of which leads to myeloid leukaemia. The main focus of this project was to utilize the CBA mouse model of radiation leukaemogenesis to explore mechanisms of low dose and low dose-rate leukaemogenesis. A series of mechanistic investigations were undertaken, the central aim of which was to identify the events that convert normal cells into myeloid leukaemia cells and explore the dose-response relationships for these. Much of the work centred on the Sfpi1/PU.1 gene and its role in leukaemogenesis. Specific studies considered the dose-response and time-course relationships for loss of the gene, the functional consequences of Sfpi1/PU.1 loss and mutation on transcriptional programmes and developing an in vivo reporter gene system for radiation-induced alterations to PU.1 expression. Additional work sought further genetic changes associated with radiation-induced AMLs and a better characterization of the cell of origin or 'target cell' for radiation-induced AML. All the information gathered is of potential use in developing biologically realistic mathematical models for low dose cancer risk projection.

  19. Radiation-induced bystander effects. Mechanisms, biological implications, and current investigations at the Leipzig LIPSION facility

    International Nuclear Information System (INIS)

    Background: The bystander effect is a relatively new area of radiobiological research, which is aimed at studying post-radiation changes in neighboring non-hit cells or tissues. The bystander effect of ionizing irradiation is important after low-dose irradiation in the range of up to 0.2 Gy, where a higher incidence of stochastic damage was observed than was expected from a linear-quadratic model. It is also important when the irradiation of a cell population is highly non-uniform. Objective: This review summarizes most of the important results and proposed bystander effect mechanisms as well as their impact on theory and clinical practice. The literature, in parts contradictory, is collected, the main topics are outlined, and some basic papers are described in more detail. In order to illustrate the microbeam technique, which is considered relevant for the bystander effect research, the state of the Leipzig LIPSION nanoprobe facility is described. Results: The existence of a radiation-induced bystander effect is now generally accepted. The current state of knowledge on it is summarized here. Several groups worldwide are working on understanding its different aspects and its impact on radiobiology and radiation protection. Conclusion: The observation of a bystander effect has posed many questions, and answering them is a challenging topic for radiobiology in the future. (orig.)

  20. Protective Effect of Phoenix dactylifera-L Extracts against Radiation-Induced Cardio-Toxicity and Some Biochemical Changes in Male Albino Rats

    International Nuclear Information System (INIS)

    The Antioxidant properties of the date palm fruit; Phoenix dactylifera-L in mitigation of cellular injury following free radicals release by ionizing radiation has been investigated. Forty-eight male albino rats divided equally into 6 groups were used in this study. Group 1 (G.1) acted as control, G.2 received date extract orally (4 ml/ kg/ day) for 21 days, G.3 was exposed to a single dose of gamma irradiation (6 Gy), G.4 received date extract orally at an identical dose and duration to G.2 and irradiation to G.3, G.5 received the daily date extract for 7 days post irradiation and G.6 received the daily date extract for 21 days before and for 7 days after irradiation. Heart tissue was examined histologically and biochemical testing for total cholesterol (TC), triglycerides (TG), high and low density lipoprotein-cholesterol (HDL-C and LDL-C), creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) was performed for each rat group. Data from the investigation showed that gamma irradiation caused histopathological damage to the heart tissue and disturbances in most parameters related to cardiac function. Administration of date extracts pre-irradiation provided evidence of a potential protective effect against irradiation hazard

  1. The application of microbeam in the research on radiation-induced bystander effects

    International Nuclear Information System (INIS)

    There has been more and more attention to the phenomenon known as radiation-induced bystander effects, which will have a tremendous effect on the research in low -dose radiation biological effects. However, due to the stochastic nature of energy deposition and the random position of tracts, direct evidence for bystander effects and exact results of single particle interacts with a cell cannot be provided by using conventional broad-field irradiation. The availability of microbeam, especially the single particle microbeam in the world, whereby individual cells or precise location of cells can be irradiated with either a single or an exact number of particles provides a useful tool for the research on radiation-induced bystander effects. The author describes the radiation -induced bystander effect and the application of microbeam in the research on it

  2. The effect of degree of deacetylation on the radiation induced degradation of chitosan

    International Nuclear Information System (INIS)

    Radiation-induced degradation of chitosan having different degree of deacetylation (DD) ratios was investigated. Chitosan samples were irradiated with gamma rays in air at ambient temperature in the solid state at a low dose rate. Change in their molecular weights was followed by size exclusion chromatography. Changes in their viscosity values as a function of dose, were also determined. Chains scission yields, G(S), and degradation rates were calculated. It was observed that the DD ratio was an important factor controlling the G(S) and degradation rate of chitosan. The change in the scission yield was attributed to the change in the crytallinity of the chitosan chains that was a result of a change in DD. - Highlights: Radiation-induced degradation of chitosan described. The influences of the DD on the radiation-induced degradation of chitosan were examined. G(S) and degradation rate of chitosan were calculated by using molecular weights data obtained from size exclusion chromatography

  3. Low-dose effects hypothesis and results

    International Nuclear Information System (INIS)

    Full text: Introduction: In the modern world the use of different ionizing radiation sources is almost ubiquitous. They find applications in industry, medicine, science, agriculture and others. The doses received by workers exposed to occupational exposure are comparable to those of natural background radiation. The published data about the health effects of occupational exposure persons are contradictory. The question about negative (bystander effects, genomic instability) and positive (adaptive response, radiation hormesis) effects of low doses exposure is essential and has significant social and economic impact. What you will learn: In this lecture we will summarize information about: Primary radiation damage; Influence of defense mechanisms; Model for risk assessment, Epidemiological studies and results; Molecular mechanisms

  4. How to understand low dose risks

    International Nuclear Information System (INIS)

    It is well established that those who were exposed to ionizing radiation have increased risks of developing malignancies. The magnitude of the risk varies depending on not only the dose but also age at the time of exposure, gender, background incidence rate etc. In the case of atomic bomb survivors, the relative risk of cancer is linearly related to the dose, and the sex averaged relative risk (exposure age is 30, risk calculation is when they reached age 70) is 1.5 at 1 Gy. Because the increased risks below 100 to 200 mGy are too small and not statistically significant, there are arguments in interpreting the risks at the low dose range. (author)

  5. Health effects of low dose radiation

    International Nuclear Information System (INIS)

    Studies of 30,000 children born to atomic bomb survivors exposed to an average of 400 mSv revealed no statistically significant increase in the genetic indicators when compared with 40,000 control children. Nevertheless, UNSCEAR reports in 2001 gave estimates of hereditary effects of radiation using experimental data on mice. Four cases (people living at a high background radiation area in China, British radiologists, European airline pilots and children in Belarus exposed to high level of radioactive fallout from the Chernobyl accident) of epidemiologic data are presented to show that cancer incidences after chronic exposure to radiation at the level of a few mSv to 100 mSv are not higher than those after exposure to the normal level of natural radiation. Radiation, when given at a low dose, is safe. (author)

  6. Low dose irradiation creep of pure nickel

    International Nuclear Information System (INIS)

    A detailed climb-controlled glide model of low dose irradiation creep has been developed to rationalize irradiation creep data of pure nickel irradiated in a light ion irradiation creep apparatus. Experimental irradiation creep data were obtained to study the effects of initial microstructure and stress on low dose irradiation creep in pure nickel. Pure nickel specimens (99.992% Ni), with three different microstructures, were irradiated with 17 or 15 MeV deuterons at 473 K and stresses ranging from 0.35 to 0.9 of the unirradiated yield stress. Transmission electron microscopy revealed that the microstructure following irradiation to 0.05 dpa consisted of a high density of small dislocation loops, some small voids and network dislocations. The creep model predicted creep rates proportional to the mobile dislocation density and a comparison of experimental irradiation creep rates as a function of homologous stress revealed a dependence on initial microstructure of the magnitude predicted by the measured dislocation densities. The three microstructures that were irradiated consisted of 85% and 25% cold-worked Ni specimens and well-annealed Ni specimens. A weak stress dependence of irradiation creep was observed in 85% cold-worked Ni in agreement with experimental determinations of the stress dependence of irradiation creep by others. The weak stress dependence was shown to be a consequence of the stress independence of the dislocation climb velocity and the weak stress dependence of the barrier removal process. The irradiation creep rate was observed to be proportional to the applied stress. This linear stress dependence was suggested to be due to the stress dependence of the mobile dislocation density. 101 references, 27 figures, 11 tables

  7. Mitochondrial-Derived Oxidants and Cellular Responses to Low Dose/Low LET Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Spitz, Douglas R.

    2009-11-09

    Exposure to ionizing radiation results in the immediate formation of free radicals and other reactive oxygen species (ROS). It has been assumed that the subsequent injury processes leading to genomic instability and carcinogenesis following radiation, derive from the initial oxidative damage caused by these free radicals and ROS. It is now becoming increasingly obvious that metabolic oxidation/reduction (redox) reactions can be altered by irradiation leading to persistent increases in steady-state levels of intracellular free radicals and ROS that contribute to the long term biological effects of radiation exposure by causing chronic oxidative stress. The objective during the last period of support (DE-FG02-05ER64050; 5/15/05-12/31/09) was to determine the involvement of mitochondrial genetic defects in metabolic oxidative stress and the biological effects of low dose/low LET radiation. Aim 1 was to determine if cells with mutations in succinate dehydrogenase (SDH) subunits C and D (SDHC and SDHD in mitochondrial complex II) demonstrated increases in steady-state levels of reactive oxygen species (ROS; O2- and H2O2) as well as demonstrating increased sensitivity to low dose/low LET radiation (10 cGy) in cultured mammalian cells. Aim #2 was to determine if mitochondrially-derived ROS contributed to increased sensitivity to low dose/low LET radiation in mammalian cells containing mutations in SDH subunits. Aim #3 was to determine if a causal relationship existed between increases in mitochondrial ROS production, alterations in electron transport chain proteins, and genomic instability in the progeny of irradiated cells. Evidence gathered in the 2005-2009 period of support demonstrated that mutations in genes coding for mitochondrial electron transport chain proteins (ETC); either Succinate Dehydrogenase (SDH) subunit C (SDHC) or subunit D (SDHD); caused increased ROS production, increased genomic instability, and increased sensitivity to low dose/low LET radiation that could be mitigated by over expression of the H2O2 metabolizing enzyme, catalase, and/or the mitochondrial form of superoxide dismutase (MnSOD). Furthermore, using radiation-induced genomically unstable cells, it was shown that steady-state levels of H2O2 were significantly elevated for many cell generations following exposure, catalase suppressed the radiation-induced mutator phenotype when added long after radiation exposure, unstable clones showed evidence of mitochondrial dysfunction some of which was characterized by improper assembly of SDH subunits (particularly subunit B), and chemical inhibitors of SDH activity could decrease steady-state levels of H2O2 as well as mutation frequency. These results support the hypotheses that 1) SDH mutations could contribute to transformation by inducing genomic instability and a mutator phenotype via increasing steady-state levels of ROS; 2) metabolic sources of O2- and H2O2 play a significant role in low dose radiation induced injury and genomic instability; and 3) increased mutation rates in irradiated mammal cells can be suppressed by scavengers of H2O2 (particularly catalase) long after radiation exposure. Overall the results obtained during this period of support provide clear evidence in support of the hypothesis that abnormal oxidative metabolism in mitochondria that result in increases in steady-sate levels of H2O2 and other ROS are capable of significantly contributing to radiation-induced mutator phenotypes in mammalian cells.

  8. Radiological risk and low doses: between false debate and experience

    International Nuclear Information System (INIS)

    The information of the workers and the public on ionizing radiation and their potential effects is very superficial. The scientific community, as well as the experts in charge of establishing basic radiation protection standards, have never really succeeded to transmit a clear and constructive message on the fundamental principles underlying the assessment and management of radiological risk. The on-going debate on low doses is a good illustration of the deficit in knowledge in this field. An educational effort, with ''direct experience'' of radioactivity in all domains, should, in the future, facilitate the emergence of a true radiological risk culture. This should help both in reconciling the public with the techniques and the people involved and restoring the trust in the institutions in charge of the evaluation and the management of radiological risk. (author). 9 refs

  9. Radiation induced crosslinking of polytetrafluoroethylene

    International Nuclear Information System (INIS)

    The Irradiation temperature effect on polytetrafluoroethylene (PTFE) from room temperature to 380degC was investigated by tensile test and thermal analysis. The behavior of tensile properties and changes of crystallinity on irradiation indicated the formation of a network structure in PTFE by radiation induced crosslinking in inert gas in the molten state just above the melting temperature of PTFE (327degC). The crosslinked PTFE showed a much improved radiation resistance in an atmospheric radiation field. (author)

  10. The health effects of low-dose ionizing radiation

    International Nuclear Information System (INIS)

    It has been established by various researches, that high doses of ionizing radiation are harmful to health. There is substantial controversy regarding the effects of low doses of ionizing radiation despite the large amount of work carried out (both laboratory and epidemiological). Exposure to high levels of radiation can cause radiation injury, and these injuries can be relatively severe with sufficiently high radiation doses. Prolonged exposure to low levels of radiation may lead to cancer, although the nature of our response to very low radiation levels is not well known at this time. Many of our radiation safety regulations and procedures are designed to protect the health of those exposed to radiation occupationally or as members of the public. According to the linear no-threshold (LNT) hypothesis, any amount, however small, of radiation is potentially harmful, even down to zero levels. The threshold hypothesis, on the other hand, emphasizes that below a certain threshold level of radiation exposure, any deleterious effects are absent. At the same time, there are strong arguments, both experimental and epidemiological, which support the radiation hormesis (beneficial effects of low-level ionizing radiation). These effects cannot be anticipated by extrapolating from harmful effects noted at high doses. Evidence indicates an inverse relationship between chronic low-dose radiation levels and cancer incidence and/or mortality rates. Examples are drawn from: 1) state srates. Examples are drawn from: 1) state surveys for more than 200 million people in the United States; 2) state cancer hospitals for 200 million people in India; 3) 10,000 residents of Taipei who lived in cobalt-60 contaminated homes; 4) high-radiation areas of Ramsar, Iran; 5) 12 million person-years of exposed and carefully selected control nuclear workers; 6) almost 300,000 radon measurements of homes in the United States; and 7) non-smokers in high-radon areas of early Saxony, Germany. This evidence conforms to the hypothesis that adequate ionizing radiation protects against cancer and promotes health. In this paper we provide special focus on the health effects due to low-dose ionizing radiation. (author)

  11. Radiation-induced genomic instability

    International Nuclear Information System (INIS)

    Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome. (author)

  12. Radiation-induced genomic instability

    Science.gov (United States)

    Kronenberg, A.

    1994-01-01

    Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.

  13. Increased interleukin-1? levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    Directory of Open Access Journals (Sweden)

    Mayado Andrea

    2011-11-01

    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1? and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1?, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1? were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1? levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1? at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 ?g, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1? (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1? plays an important role in the development of delayed preconditioning by low dose MDMA.

  14. Study on excited effect of low dose radiation and clinical application

    International Nuclear Information System (INIS)

    Ionizing radiation exist extensively in life environment. Low dose radiation can induce adaptive response of the body, the mechanism including DNA damage repair, promote intracellular information transfer of T cell, the produce of protective protein and the effection of reactive oxygen species. It also can enhance immunity, inhibit growth and metastasis of tumor and can effect the adverse reaction of chemotherapy. (authors)

  15. Radiation-induced bystander effect: early process and rapid assessment.

    Science.gov (United States)

    Wang, Hongzhi; Yu, K N; Hou, Jue; Liu, Qian; Han, Wei

    2015-01-01

    Radiation-induced bystander effect (RIBE) is a biological process that has received attention over the past two decades. RIBE refers to a plethora of biological effects in non-irradiated cells, including induction of genetic damages, gene expression, cell transformation, proliferation and cell death, which are initiated by receiving bystander signals released from irradiated cells. RIBE brings potential hazards to normal tissues in radiotherapy, and imparts a higher risk from low-dose radiation than we previously thought. Detection with proteins related to DNA damage and repair, cell cycle control, proliferation, etc. have enabled rapid assessment of RIBE in a number of research systems such as cultured cells, three-dimensional tissue models and animal models. Accumulated experimental data have suggested that RIBE may be initiated rapidly within a time frame as short as several minutes after radiation. These have led to the requirement of techniques capable of rapidly assessing RIBE itself as well as assessing the early processes involved. PMID:24139967

  16. Factors that modify risks of radiation-induced cancer

    International Nuclear Information System (INIS)

    The collective influence of biologic and physical factors that modify risks of radiation-induced cancer introduces uncertainties sufficient to deny precision of estimates of human cancer risk that can be calculated for low-dose radiation in exposed populations. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, minimum latent period, time-to-tumor recognition, and the influence of individual host (age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Other modifying factors include other carcinogens, and other biological sources (hormonal status, immune status, hereditary factors)

  17. In vitro study on the cellular effects of low dose combined exposures

    International Nuclear Information System (INIS)

    Complete text of publication follows. Objectives: Low dose alpha particles derived from radon, induce non-targeted effects such as bystander phenomenon, adaptive response or genomic instability, which may increase or decrease the risk of lung cancer. Our study was aimed to investigate whether the low radiation dose induced effects are involved in carcinogenesis induced by multiple environmental exposures. Methods: The interaction of low dose (mGy) alpha particles and the environmental PAHs (polycyclic aromatic hydrocarbons), cadmium, nickel and asbestos exposures were investigated on human lung cell lines (BEAS-2B and HFL1). Cells were treated separately and in combinations with alpha irradiation. PAH-DNA adduct levels were determined by 32P-postlabelling. DNA strand breaks were measured by Comet-assay. Micronucleus frequency, apoptosis and proliferation were also followed. Results: Alpha irradiation (10 mGy) prior to PAH's treatment, substantially de-creased the adduct level. Alpha irradiation significantly induced DNA strand breaks, whereas the PAHs at 0.2 ?M did not have measurable effect by the Comet assay. In combination of alpha irradiation and the PAHs, only benzo[a]-pyrene had a modifying, ie. additive effect to alpha irradiation. Metal compounds (Cd and Ni-chloride; ) in low concentration (0,5-1?M) reduced the cytotoxicity of alpha particles, depending on the compound, incubation time, cell line treated and also low doses of radiation (mGy-s) red also low doses of radiation (mGy-s) reduced the cytotoxic effect of metals (cross adaptive response). Further increases in concentrations and/or doses caused additive cytotoxic responses. The rejoining of DNA breaks was more efficient when the cells were treated in combination with glass fibres and low dose radiation then after each single exposures. The radio-adaptive response induced by 10 mGy alpha particles was diminished by Cd (24-48 h) incubation. Cd (0,01 mM) enhanced the radiosensitivity of cells. Bystander cells found to be more sensitive to Cd, then directly irradiated ones. In the presence of Cd the re-joining of the radiation induced DNA breaks slowed down. The data on proliferation and micronuclei induction indicated that the genetic changes were detected in the progeny of irradiated and Cd-treated cells. Conclusion: It can be concluded that low dose radiation effects must be taken into consideration in estimating the health risk from combined multiple environmental exposures. This research was supported by NKFP-1B/047/2004 and GVOP 3.1.1.-2004-05-0432/3.0 grants.

  18. Prevention of radiation induced taste aversion in rats

    International Nuclear Information System (INIS)

    Diltiazem, a calcium channel blocker, and a cardiovascular therapeutic agent offers significant protection to mice against lethal dose of ionizing radiation. Considering the potential efficacy of diltiazem as a radioprotector for human use, it was deemed necessary to investigate its influence on radiation-induced behavioural changes like nausea, vomiting, learning, memory and performance. In the present studies, conditioned taste aversion (CTA) test based on consumption of saccharin solution, was used as a marker of behavioural changes. Significant CTA (972%) was observed in rats irradiated with 60Co gamma rays (absorbed dose 1 Gy). Administration of diltiazem at doses greater than 10 mg/kg, body wt, evoked CTA in a dose-dependent manner and that was found to be further aggravated on irradiation. At a lower dose of 5 mg/kg, body wt, diltiazem did not evoke CTA and protected against radiation induced aversion significantly (623%). The results suggest that diltiazem at concentrations lower than 10 mg/kg, body wt, in rats may be useful in preventing radiation induced behavioural changes. This observation could be of particular significance in clinical radiotherapy where radiation induced nausea and vomiting are of great concern. (author)

  19. low dose irradiation growth in zirconium

    International Nuclear Information System (INIS)

    Low dose neutron irradiation growth in textured and recrystallized zirconium, is studied, at the Candu Reactors Calandria temperature (340 K) and at 77 K. It was necessary to design and build 1: A facility to irradiate at high temperatures, which was installed in the Argentine Atomic Energy Commission's RA1 Reactor; 2: Devices to carry out thermal recoveries, and 3: Devices for 'in situ' measurements of dimensional changes. The first growth kinetics curves were obtained at 365 K and at 77 K in a cryostat under neutron fluxes of similar spectra. Irradiation growth experiments were made in zirconium doped with fissionable material (0,1 at %235U). In this way an equivalent dose two orders of magnitude greater than the reactor's fast neutrons dose was obtained, significantly reducing the irradiation time. The specimens used were bimetallic couples, thus obtaining a great accuracy in the measurements. The results allow to determine that the dislocation loops are the main cause of irradiation growth in recrystallized zirconium. Furthermore, it is shown the importance of 'in situ' measurements as a way to avoid the effect that temperature changes have in the final growth measurement; since they can modify the residual stresses and the overconcentrations of defects. (M.E.L.)

  20. Contraception. Low-dose pill launched.

    Science.gov (United States)

    1993-01-01

    At a vibrant ceremony in Kampala, Uganda, the Minister of Women in Development, Youth and Culture launched the new low-dose oral contraceptive Pilplan which provides women more options for birth spacing. Diplomats, physicians, government officials, and business leaders attended the ceremony at the Sheraton Hotel Kampala. A dance group did an interpretation of "Women in Uganda: Gaining Momentum." The Minister considered the introduction of this new pill as a turning point for reproductive rights. A baseline survey among Ugandan women has shown that although almost all women were familiar with the pill, only 36% have ever used it and only 15% were currently using it. 80% thought that pill use was preferable to having an unplanned pregnancy. These findings convinced the Minister that ignorance and misconception keep women from using the pill. The government, health providers, and others need to educate women about Pilplan and how to use it correctly. A bilateral agreement between the Ministry of Health and USAID set in motion a social marketing project which has now launched two contraceptive methods: Pilplan in 1993 and the Protector condom in 1990. USAID vowed to continue to support Pilplan, particularly if men could also help in supporting birth spacing. A Uganda-based pharmaceutical firm will distribute Pilplan in Uganda through pharmacies, clinics, and health facilities. Pilplan targets all middle- to low-income women. PMID:12319754

  1. Effects of low dose mitomycin C on experimental tumor radiotherapy

    International Nuclear Information System (INIS)

    Objective: To evaluate the possibility of low dose mitomycin C(MMC) as an adjunct therapy for radiotherapy. Methods: Change in tumor size tumor-bearing mice was measured. Radioimmunoassay was used to determine immune function of mice. Results: Low dose Mac's pretreatment reduced tumor size more markedly than did radiotherapy only. The immune function in mice given with low dose MMC 12h before radiotherapy was obviously higher than that in mice subjected to radiotherapy only (P<0.05), and was close to that in the tumor-bearing mice before radiotherapy. Conclusion: Low dose MMC could improve the radiotherapy effect. Pretreatment with low dose MMC could obviously improve the immune suppression state in mice caused by radiotherapy. The mechanism of its improvement of radiotherapeutic effect by low dose of MMC might be due to its enhancement of immune function and induction of adaptive response in tumor-bearing mice

  2. Chromosome aberrations induced by low doses of X-rays in human lymphocytes in vitro

    International Nuclear Information System (INIS)

    Curves derived from the dose-response data for the yield of aberrations in human lymphocytes can be represented by a quadratic equation at all but low dose ranges. A calibration curve has therefore been determined at a low dose range of X-radiation (11.5 to 57.5 rad). The frequencies of dicentrics plus centric rings, and of acentrics were better fitted by linear dose-response models than quadratic. The linearity of the relationship indicated that asymmetrical chromosome exchanges at low doses of radiation are produced predominantly by a single track mechanism. A dose-response curve for dicentrics plus centric rings (5 to 60 rad) has also been derived by pooling published data with the results of this study. This calibration curve is relevant to cytogenetic dosimetry in radiological protection. (UK)

  3. Effects of low dose radiation on antioxidant enzymes after radiotherapy of tumor-bearing mice

    International Nuclear Information System (INIS)

    Objective: To search for effects of low dose radiation on the activities of antioxidant enzymes after radiotherapy of tumor-bearing mice. Methods: Superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) were all determined by chemical colorimetry. Results: Low dose radiation increase the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) in serum of tumor-bearing mice more markedly than those in the unirradiated controls. The activities of antioxidant enzymes SOD, GST, CAT in serum of tumor-bearing mice (d5, d3) irradiated with 5cGy 6h before 2.0 Gy radiation are obviously higher than those of the group (c3, c5) given with radiotherapy only. Conclusion: The increase in the activities of antioxidant enzymes in serum of tumor-bearing mice triggered by low dose radiation could partly contribute to the protective mechanism. (authors)

  4. Radiation induced oxidation of phenylalanine

    International Nuclear Information System (INIS)

    For the detection of irradiation in food it has been proposed to use radiation-induced conversion of phenylalanine into o-tyrosin as a marker. The strong variation of the slope of yield-dose plots with the experimental conditions may well make the method impractical for the determination of the exact dose received by a certain food. Because of this situation it's worthwile to consider some basic question as to how O-Tyr might be formed when Phe-containing protein is irradiated . It's the intention of this paper to present some fundamental studies on the ?-radiolysis of Phe in aqueous solution. 11 refs

  5. Cellular and molecular aspects of radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Thymocytes are highly radiosensitive and show 'interphase death' within a few hours after low doses of irradiation. Now it is proved to be a typical apoptosis. Separation of the dead thymocyte fraction from irradiated thymocyte suspensions by centrifugation on Percoll gradient provided homogeneous populations of dead cells suitable for detailed study. Using this method, radiation-induced apoptosis of thymocytes was found to involve a sharp but transient increase in buoyant density, concomitant with the appearance of distinctive morphologic changes which included disappearance of microvilli and blistering of the cell surface. The chromatin in the apoptotic cells fragmented into oligonucleosomomal units. Immediate population was not detected. Apoptosis thus proceed a discrete, abrupt transition from the normal state and is not merely the consequence of progressive and degenerative changes. Furthermore, morphological and biochemical chages of the cell death are inhibited by cycloheximide and actinomycin D, suggesting the need for RNA and protein synthesis on apoptotic transition. Thymocytes undergo necrosis after massive doses irradiation. Radiation-induced apoptosis of various cells, including proliferating cells is currently under active investigation. Today's great interest promises progress in the future. (J.P.N.)

  6. Biological effects of low-dose irradiation

    International Nuclear Information System (INIS)

    For a long time, radiation, biological research concentrated on the diagnosis and the effect chains to be taken into consideration in the case of acute and chronic radiation effects due to intensive irradiation. Approximately at the beginning of the Thirties, the research results of the geneticist Mueller and the radiation-biologists Oliver and Timofeef-Ressovsky brought a fundamental change in the way of looking at things in radiation biology. From the results then obtained it can be deduced that even the smallest quantities of radiation can cause effects. Basically, two processes leading to different radiation reactions have to be recognized: 1) A change in the genetical code, especially by direct irradiation of the nucleus. The effects thus arising are called stochastic effects. 2) A change of the cell in total by inactivation of the cell division or by cell death. These are called non-stochastic effects. Here, a threshold dose is existent. In these cases, the degree of the effects depends on the quantity of the dose. Therefore, the stochastic effects are paid special attention when determining radiation effects with low doses. Here, the emphasis of the research was moved from the genetic effects to the generation of somatic effects, especially the generation of malign neoformations and the shortening of the life connected with them. In the generation of malign neoformations by ionising radiation, probably only the transformation of a single cell is necessary, however only then when ionising radiation is absorbed in the nucleus several times (multi-hit theory). This leads to the assumption that the induction of malignant neoformations possesses a linear quadratic function, at least in the region of medium doses. (orig./MG)

  7. Effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Several groups of human have been irradiated by accidental or medical exposure, if no gene defect has been associated to these exposures, some radioinduced cancers interesting several organs are observed among persons exposed over 100 to 200 mSv delivered at high dose rate. Numerous steps are now identified between the initial energy deposit in tissue and the aberrations of cell that lead to tumors but the sequence of events and the specific character of some of them are the subject of controversy. The stake of this controversy is the risk assessment. From the hypothesis called linear relationship without threshold is developed an approach that leads to predict cancers at any tiny dose without real scientific foundation. The nature and the intensity of biological effects depend on the quantity of energy absorbed in tissue and the modality of its distribution in space and time. The probability to reach a target (a gene) associated to the cancerating of tissue is directly proportional to the dose without any other threshold than the quantity of energy necessary to the effect, its probability of effect can be a more complex function and depends on the quality of the damage produced as well as the ability of the cell to repair the damage. These two parameters are influenced by the concentration of initial injuries in the target so by the quality of radiation and by the dose rate. The mechanisms of defence explain the low efficiency of radiation as carcinogen and then the linearity of effects in the area of low doses is certainly the least defensible scientific hypothesis for the prediction of the risks. (N.C.)

  8. Particle radiation-induced genetic damage in vivo

    International Nuclear Information System (INIS)

    Full text: Assessment of radiation-induced alterations in the genomic is important to determine both short and long-term effects after exposure. Transgenic mouse mutation model systems, based on the insertion of specific target genes into the genome of every cell of the animals, provide a rapid and efficient means to obtain statistically reliable results on the frequencies of mutations in all tissues without requiring prior drug selection and clonal expansion of the target cells. We are using the plasmid-based lacZ transgenic mouse model system to measure the dose- and temporal-dependent particle-radiation induced responses. We measured cytogenetic damage to the hematopoietic system as well as mutations in the transgene in both the brain and spleen tissues after an acute dose of 250 MeV/amu protons or 1 GeV/amu iron ions. The level of peripheral blood micronucleated reticulocytes (MN-RET) increased dramatically within 48 h after whole body exposure for both proton or iron irradiated animals and returned to control levels within 1 week after treatment suggesting that these severely damaged transient cell populations are rapidly eliminated from the body. Mutation frequencies (MF) of the lacZ transgene increased as a function of proton dose in the spleen and brain tissues at 1, 8 and 16 wks post irradiation. We demonstrated that the MF of the lacZ target transgene was responsive to low doses of protons with significant increases in the MF (p0.5 Gy iron ions. The overall magnitude of induction of lacZ MF in the brain is lower than that of the spleen, suggesting that radiation-induced genetic effects are tissue-specific, and tissue physiology plays a role in determining the late effects after particle radiation. This work was supported by NASA/NSBRI NCC 9-58-163

  9. The induction of a tumor suppressor gene (p53) expression by low-dose radiation and its biological meaning

    International Nuclear Information System (INIS)

    I report the induced accumulation of wild-type p53 protein of a tumor suppressor gene within 12 h in various organs of rats exposed to X-ray irradiation at low doses (10-50 cGy). The levels of p53 in some organs of irradiated rats were increased about 2- to 3-fold in comparison with the basal p53 levels in non-irradiated rats. Differences in the levels of p53 induction after low-dose X-ray irradiation were observed among the small intestine, bone marrow, brain, liver, adrenal gland, spleen, hypophysis and skin. In contrast, there was no obvious accumulation of p53 protein in the testis and ovary. Thus, the induction of cellular p.53 accumulation by low-dose X-ray irradiation in rats seems to be organ-specific. I consider that cell type, and interactions with other signal transduction pathways of the hormone system, immune system and nervous system may contribute to the variable induction of p53 by low-dose X-ray irradiation. I discussed the induction of p53 by radiation and its biological meaning from an aspect of the defense system for radiation-induced cancer. (author)

  10. Radiation-induced leiomyosarcoma of the oropharynx

    Directory of Open Access Journals (Sweden)

    Maier Wolfgang

    2006-08-01

    Full Text Available Abstract Leiomyosarcoma is a malignant mesenchymal tumor originating from smooth muscle cells, which most frequently develops in the myometrium and in the gastro-intestinal tract. Reviewing the international literature, radiation-induced sarcoma arise in 0.035 to 0.2 % of all irradiated patients. Especially in the head and neck region, radiation-induced leiomyosarcoma is an extremely rare lesion. The authors report a case of a radiation-induced leiomyosarcoma of the tonsillar region of the oropharynx in a 51-year-old male patient, who had undergone radiation therapy of this region 38 years before. The lesion was treated by radical surgery. Diagnostic steps, histological presentation and therapy are described in detail and the literature concerning radiation induced malignancies in general as well as radiation induced leiomyosarcoma in particular is reviewed. The highlights of this case are an extremely uncommon location and a rare pathological entity of radiation induced malignancies.

  11. Measurement of 60CO gamma radiation induced attenuation in multimode step-index POF at 530 nm

    Directory of Open Access Journals (Sweden)

    Kova?evi? Milan S.

    2013-01-01

    Full Text Available As optical fibres are used ever more extensively in space applications, nuclear industry, medicine and high-energy physics experiments, it has become essential to investigate the influence of ionizing radiation on their characteristics. In this work, the radiation-induced attenuation at 530 nm is investigated experimentally in step-index multimode polymethyl-methacrylate plastic optical fibres exposed to low dose-rate gamma radiation. Cumulative doses ranged from 50 Gy to 500 Gy. The radiation induced attenuation has been empirically found to obey the power law RIA= aDb, where D is the total radiation dose and a and b are the constants determined by fitting.

  12. Radiation-induced cardiovascular effects

    Science.gov (United States)

    Tapio, Soile

    Recent epidemiological studies indicate that exposure to ionising radiation enhances the risk of cardiovascular mortality and morbidity in a moderate but significant manner. Our goal is to identify molecular mechanisms involved in the pathogenesis of radiation-induced cardiovascular disease using cellular and mouse models. Two radiation targets are studied in detail: the vascular endothelium that plays a pivotal role in the regulation of cardiac function, and the myocardium, in particular damage to the cardiac mitochondria. Ionising radiation causes immediate and persistent alterations in several biological pathways in the endothelium in a dose- and dose-rate dependent manner. High acute and cumulative doses result in rapid, non-transient remodelling of the endothelial cytoskeleton, as well as increased lipid peroxidation and protein oxidation of the heart tissue, independent of whether exposure is local or total body. Proteomic and functional changes are observed in lipid metabolism, glycolysis, mitochondrial function (respiration, ROS production etc.), oxidative stress, cellular adhesion, and cellular structure. The transcriptional regulators Akt and PPAR alpha seem to play a central role in the radiation-response of the endothelium and myocardium, respectively. We have recently started co-operation with GSI in Darmstadt to study the effect of heavy ions on the endothelium. Our research will facilitate the identification of biomarkers associated with adverse cardiac effects of ionising radiation and may lead to the development of countermeasures against radiation-induced cardiac damage.

  13. Radiation-induced sarcoma in spine

    OpenAIRE

    Kam, Lok Sang; Anthony, Marina Portia; Shek, H.

    2013-01-01

    Although radiotherapy is a part of treatment in cancers, it can also induce malignancy as a late complication. The presence of radiation-induced sarcomas in bone, although not very common, is acknowledged. The onset of radiation-induced sarcoma in the spine however, is not well recognized. We present here a case of radiation-induced fibrosarcoma in the T1 lamina and spinous process in a patient with a history of breast cancer treated with radiotherapy 30 years prior.

  14. Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses.

    Science.gov (United States)

    Tomita, Masanori; Maeda, Munetoshi

    2015-03-01

    Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or ?-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. PMID:25361549

  15. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these non-targeted responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and ?-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim to uncover protein mediators of the bystander responses using advanced proteomic screening of factors released from irradiated, bystander and unstable cells. Integral to these studies will be an assessment of the role of genetic susceptibility in these responses, using CBA/H and C57BL/6J mice. The relevance of in vivo interactions between stem cells and the stem cell niche will be explored in the future by re-implantation techniques of previously irradiated cells. The above studies will provide fundamental mechanistic information relating genetic predisposition to important low dose phenomena, and will aid in the development of Department of Energy policy, as well as radiation risk policy for the public and the workplace. We believe the proposed studies accurately reflect the goals of the DOE low dose program.

  16. Radiation Induced Degradation of Galactomannan Polysaccharides

    International Nuclear Information System (INIS)

    Galactomannans are neutral polysaccharides that occur in substantial amounts in the endosperm of the seeds of some leguminous plants. Structurally they consist of a ?(1-4)-D-mannose backbone to which galactose units are attached ?(1-6). Among various galactomannans known, guar gum (GG), tara gum (TG) and locust bean gum (LBG) are the most widely used in applications in, for example, the food, pharmaceutical, and chemical industries as thickening agents or stabilizers due mainly to the high viscosity they impart at low concentrations. In many industrial applications, the use of low molecular weight polysaccharides is essential. For example, guar solutions, which are used as hydraulic fracturing fluids in oil and gas recovery, need to be degraded to facilitate the outflow of oil. In addition, to understand the solution properties of guar as well as other water-soluble biopolymers, it is often necessary to degrade the native polymer to prepare samples with various molecular weights (MW. Degradation of polysaccharides has been widely studied. Though acid and enzymatic hydrolysis are most common, other methods such as thermal, ?-irradiation, extrusion, ultrasonication and free radical degradation are also reported. In this study, radiation induced degradation of galactomannan polysaccharides has been investigated. GG, TG and LBG samples were irradiated with gamma rays in air at ambient temperature in the solid state at low dose rate. The change in their molecular weights was determined by SEC analysis and the change in their viscosity values as a function of temperature and irradiation dose was determined. Chain scission yields, G(S), and degradation rates were calculated. As a result of irradiation the molecular weight and viscosity of all galactomannans sharply decreased up to 50 kGy, no significant change was observed beyond this dose value. We observed that mannose-to-galactose ratio is an important factor controlling the G(S) and degradation rate of galactomannans. The G(S) values were found to follow an order of guar gum > tara gum > locust bean gum. When the chemical structures of these gums are examined it is seen that GG has one galactomannan unit attached to the backbone per two monomeric units of the backbone. This is one per three monomeric units for TG and one per four monomeric units for LBG. It can be concluded that the G(S) value increases with an increase in the galactose to mannose ratio and/or molecular weight of the unirradiated sample

  17. Radiation induced lipid peroxidation: role for Ca2+

    International Nuclear Information System (INIS)

    Effect of Ca2+ on radiation induced lipid peroxidation of ghost membranes prepared from mice erythrocytes was studied at a dose rate 1.01 Gy/s. Ca2+ provided significant protection against lipid peroxidation in concentration dependent manner. Ca2+ is known to modify membrane dynamics and might be the reason for inhibition of lipid peroxidation. Post-irradiation treatment with Ca2+ also resulted in significant inhibition of lipid peroxidation. The diminition of protective effect in presence of A23187 suggests that the extracellular pool of Ca2+ may provide protection against the effect of radiation on plasma membrane. (author)

  18. Radiation induced non-targeted response: mechanism and potential clinical implications.

    Science.gov (United States)

    Hei, Tom K; Zhou, Hongning; Chai, Yunfei; Ponnaiya, Brian; Ivanov, Vladimir N

    2011-06-01

    Generations of students in radiation biology have been taught that heritable biological effects require direct damage to DNA. Radiation-induced non-targeted/bystander effects represent a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the biological consequences of exposure to low doses of radiation. Although radiation induced bystander effects have been well documented in a variety of biological systems, including 3D human tissue samples and whole organisms, the mechanism is not known. There is recent evidence that the NF-?B-dependent gene expression of interleukin 8, interleukin 6, cyclooxygenase-2, tumor necrosis factor and interleukin 33 in directly irradiated cells produced the cytokines and prostaglandin E2 with autocrine/paracrine functions, which further activated signaling pathways and induced NF-?B-dependent gene expression in bystander cells. The observations that heritable DNA alterations can be propagated to cells many generations after radiation exposure and that bystander cells exhibit genomic instability in ways similar to directly hit cells indicate that the low dose radiation response is a complex interplay of various modulating factors. The potential implication of the non-targeted response in radiation induced secondary cancer is discussed. A better understanding of the mechanism of the non-targeted effects will be invaluable to assess its clinical relevance and ways in which the bystander phenomenon can be manipulated to increase therapeutic gain in radiotherapy. PMID:21143185

  19. Reduction of background mutation by low dose irradiation at a low dose rate

    International Nuclear Information System (INIS)

    The dose-response relationship of ionizing radiation and its stochastic effects has been thought to be linear without any thresholds for a long time. The linear dose-response relationship was reported as early as 1930 using a sex-linked recessive lethal assay in mature sperm of the fruit fly Drosophila melanogaster. However, mature sperm has no DNA repair function. We have previously reported that somatic mutation frequency was not proportional to the X-ray dose and that there was a threshold at around 1 Gy. Furthermore, the threshold value was dependent on the DNA repair function. In this paper, we examined the dose-response relationship of X-ray irradiation and mutation in repair proficient immature sperm of Drosophila, and found that a low dose irradiation at a low dose rate caused a decrease, rather than increase, of mutation frequency compared to the non-irradiated control. The threshold was again dependent on the DNA repair function. It was indicated that the DNA repair function contributes to establishing of the threshold and that the so-called linear non-threshold (LNT) model is valid only in repair deficient cells. (author)

  20. Radiation-induced apoptosis in microvascular endothelial cells.

    OpenAIRE

    Langley, R. E.; Bump, E. A.; Quartuccio, S. G.; Medeiros, D; Braunhut, S. J.

    1997-01-01

    The response of the microvasculature to ionizing radiation is thought to be an important factor in the overall response of both normal tissues and tumours. It has recently been reported that basic fibroblast growth factor (bFGF), a potent mitogen for endothelial cells, protects large vessel endothelial cells from radiation-induced apoptosis in vitro. Microvessel cells are phenotypically distinct from large vessel cells. We studied the apoptotic response of confluent monolayers of capillary en...

  1. A review of the bystander effect and its implications for low-dose exposure

    International Nuclear Information System (INIS)

    Current models for the interaction between ionising radiation and living cells or tissues are based on direct genetic damage produced by energy deposition in cellular DNA. An important observation which has questioned this basic assumption is radiation-induced bystander response, in which cells which have not been directly targeted respond if their neighbours have been exposed. This response predominates at low doses of relevance to radiation risk analysis (<0.2 Gy) and therefore needs to be fully characterised. The development of microbeams, which allow individual cells within populations to be targeted with precise doses of radiation, has provided a useful tool for quantifying this response. The authors' studies have targeted individual human and mouse cells with counted protons and helium ions and monitored neighbouring cells for the production of bystander responses. Bystander responses have been measured after exposures as low as a single proton or helium ion delivered to an individual cell. An important aspect is that these responses saturate with increasing dose to the single target cell, thus the relative roles of direct and indirect (non-targeted) responses change with dose. Studies with multicellular, tissue-based models are providing evidence that bystander responses may have a complex phenotype involving multiple pathways and the overall response may be a balance between multiple signalling processes and responses to radiation exposure. Current models for to radiation exposure. Current models for radiation risk assume a linear non-threshold response and have generally been extrapolated from high-dose exposures. The involvement of competing processes at low doses may have important consequences for understanding the effects of low-dose exposure. (author)

  2. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Eric Y. Chuang

    2006-08-31

    It has been long recognized that a significant fraction of the radiation-induced genetic damage to cells are caused by secondary oxidative species. Internal cellular defense systems against oxidative stress play significant roles in countering genetic damage induced by ionizing radiation. The role of the detoxifying enzymes may be even more prominent in the case of low-dose, low-LET irradiation, as the majority of genetic damage may be caused by secondary oxidative species. In this study we have attempted to decipher the roles of the superoxide dismutase (SOD) genes, which are responsible for detoxifying the superoxide anions. We used adenovirus vectors to deliver RNA interference (RNAi or siRNA) technology to down-regulate the expression levels of the SOD genes. We have also over-expressed the SOD genes by use of recombinant adenovirus vectors. Cells infected with the vectors were then subjected to low dose ?-irradiation. Total RNA were extracted from the exposed cells and the expression of 9000 genes were profiled by use of cDNA microarrays. The result showed that low dose radiation had clear effects on gene expression in HCT116 cells. Both over-expression and down-regulation of the SOD1 gene can change the expression profiles of sub-groups of genes. Close to 200 of the 9000 genes examined showed over two-fold difference in expression under various conditions. Genes with changed expression pattern belong to many categories that include: early growth response, DNA-repair, ion transport, apoptosis, and cytokine response.

  3. Radiation-induced thermoacoustic imaging

    International Nuclear Information System (INIS)

    This invention provides a new technique for obtaining information non-invasively on the composition and structures of a material or body by detecting radiation-induced thermoacoustic image features. This is accomplished by utilizing the acoustic wave generated by sudden thermal stress. The sudden thermal stress is induced by a pulse of radiation which deposits energy causing a rapid, but very small, rise of temperature (typically, ?T approximately 10sup(-6) - 10sup(-5) deg C). The radiation may be ionizing radiation, such as high energy electrons, photons (x-rays), neutrons, or other charged particles or it may be non-ionizing radiation, such as R.F. and microwave electromagnetic radiation and ultrasonic radiation. The choice of radiation depends on the nature of the body to be imaged and the type of information desired

  4. Low Dose Studies with Focused X-Rays in cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

    Energy Technology Data Exchange (ETDEWEB)

    Kathy Held; Kevin Prise; Barry Michael; Melvyn Folkard

    2002-12-14

    The management of the risks of exposure of people to ionizing radiation is important in relation to its uses in industry and medicine, also to natural and man-made radiation in the environment. The vase majority of exposures are at a very low level of radiation dose. The risks are of inducing cancer in the exposed individuals and a smaller risk of inducing genetic damage that can be indicate that they are low. As a result, the risks are impossible to detect in population studies with any accuracy above the normal levels of cancer and genetic defects unless the dose levels are high. In practice, this means that our knowledge depends very largely on the information gained from the follow-up of the survivors of the atomic bombs dropped on Japanese cities. The risks calculated from these high-dose short-duration exposures then have to be projected down to the low-dose long-term exposures that apply generally. Recent research using cells in culture has revealed that the relationship between high- and low-dose biological damage may be much more complex than had previously been thought. The aims of this and other projects in the DOE's Low-Dose Program are to gain an understanding of the biological actions of low-dose radiation, ultimately to provide information that will lead to more accurate quantification of low-dose risk. Our project is based on the concept that the processes by which radiation induces cancer start where the individual tracks of radiation impact on cells and tissues. At the dose levels of most low-dose exposures, these events are rare and any individual cells only ''sees'' radiation tracks at intervals averaging from weeks to years apart. This contrasts with the atomic bomb exposures where, on average, each cell was hit by hundreds of tracks instantaneously. We have therefore developed microbeam techniques that enable us to target cells in culture with any numbers of tracks, from one upwards. This approach enables us to study the biological ha sis of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in low-dose radiation risk. This project therefore also examines how cells are damaged by treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and therefore it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.

  5. Radiation-induced cancers in the rat, an experimental study

    International Nuclear Information System (INIS)

    Radiation carcinogenesis at low doses raises a major radiological protection problem; we have attempted to deal with it through animal investigations involving over 3,000 rats. For various radiation types, dose-effect relationships as well as possible synergies with endogenous or exogenous chemical factors were studied. The chief problem being the possibility of extrapolation to man, a comparison was made between man and rat with the only human data available from radon inhalation in uranium miners

  6. Measurement of 60CO gamma radiation induced attenuation in multimode step-index POF at 530 nm

    OpenAIRE

    Kova?evi? Milan S.; ?or?evi? Aleksandar; Savovi? Svetislav; Baji? Jovan S.; Stupar Dragan Z.; Slankamenac Milo P.; Kova?evi? Milojko

    2013-01-01

    As optical fibres are used ever more extensively in space applications, nuclear industry, medicine and high-energy physics experiments, it has become essential to investigate the influence of ionizing radiation on their characteristics. In this work, the radiation-induced attenuation at 530 nm is investigated experimentally in step-index multimode polymethyl-methacrylate plastic optical fibres exposed to low dose-rate gamma radiation. Cumulative doses ranged from 50 Gy to 500 Gy. The ra...

  7. Spatially Fractionated Radiation Induces Cytotoxicity and Changes in Gene Expression in Bystander and Radiation Adjacent Murine Carcinoma Cells

    OpenAIRE

    Asur, Rajalakshmi S.; Sharma, Sunil; Chang, Ching-Wei; Penagaricano, Jose; Kommuru, Indira M.; Moros, Eduardo G.; Corry, Peter M.; GRIFFIN, ROBERT J.

    2012-01-01

    Radiation-induced bystander effects have been extensively studied at low doses, since evidence of bystander induced cell killing and other effects on unirradiated cells were found to be predominant at doses up to 0.5 Gy. Therefore, few studies have examined bystander effects induced by exposure to higher doses of radiation, such as spatially fractionated radiation (GRID) treatment. In the present study, we evaluate the ability of GRID treatment to induce changes in GRID adjacent (bystander) r...

  8. Low-dose doxepin: in the treatment of insomnia.

    Science.gov (United States)

    Weber, Juliane; Siddiqui, M Asif A; Wagstaff, Antona J; McCormack, Paul L

    2010-08-01

    Doxepin binds with high specificity and affinity to the histamine H(1) receptor compared with other receptors. Therefore, at low doses, doxepin selectively antagonises H(1) receptors, which is believed to promote the initiation and maintenance of sleep. In three large, well designed, phase III trials in adult or elderly patients with chronic primary insomnia, oral, low-dose doxepin 3 or 6 mg once daily improved wake time after sleep onset, total sleep time and sleep efficiency to a significantly greater extent than placebo. Significant between-group differences in polysomnographic sleep recordings that favoured low-dose doxepin were evident after a single administration of the drug. Other efficacy measures, including patient-reported sleep quality, also favoured low-dose doxepin over placebo. Symptom control was maintained for up to 12 weeks of low-dose doxepin administration and there was no evidence of physical dependence or worsening insomnia after doxepin withdrawal. Oral, low-dose doxepin 6 mg was also significantly more effective than placebo in a large, well designed trial modelling transient insomnia in healthy adults, according to polysomnographic recordings (e.g. in latency to persistent sleep). Oral, low-dose doxepin was generally well tolerated in clinical trials. PMID:20658801

  9. The Effects of G2-Phase Enrichment and Checkpoint Abrogation on Low-Dose Hyper-Radiosensitivity

    International Nuclear Information System (INIS)

    Purpose: An association between low-dose hyper-radiosensitivity (HRS) and the 'early' G2/M checkpoint has been established. An improved molecular understanding of the temporal dynamics of this relationship is needed before clinical translation can be considered. This study was conducted to characterize the dose response of the early G2/M checkpoint and then determine whether low-dose radiation sensitivity could be increased by synchronization or chemical inhibition of the cell cycle. Methods and Materials: Two related cell lines with disparate HRS status were used (MR4 and 3.7 cells). A double-thymidine block technique was developed to enrich the G2-phase population. Clonogenic cell survival, radiation-induced G2-phase cell cycle arrest, and deoxyribonucleic acid double-strand break repair were measured in the presence and absence of inhibitors to G2-phase checkpoint proteins. Results: For MR4 cells, the dose required to overcome the HRS response (approximately 0.2 Gy) corresponded with that needed for the activation of the early G2/M checkpoint. As hypothesized, enriching the number of G2-phase cells in the population resulted in an enhanced HRS response, because a greater proportion of radiation-damaged cells evaded the early G2/M checkpoint and entered mitosis with unrepaired deoxyribonucleic acid double-strand breaks. Likewise, abrogation of the checkpoint by inhibition of Chk1 and Chk2 also increased low-dose radiosensitivity. These effects were not evident in 3.vity. These effects were not evident in 3.7 cells. Conclusions: The data confirm that HRS is linked to the early G2/M checkpoint through the damage response of G2-phase cells. Low-dose radiosensitivity could be increased by manipulating the transition of radiation-damaged G2-phase cells into mitosis. This provides a rationale for combining low-dose radiation therapy with chemical synchronization techniques to improve increased radiosensitivity.

  10. Treatment of puberty trichotillomania with low-dose aripiprazole

    OpenAIRE

    Sasaki, Tsuyoshi; Iyo, Masaomi

    2015-01-01

    The present case is of a 14-year-old female with trichotillomania (TTM) that was treated with a low dose of aripiprazole (ARP) 1.5 mg/day. To our knowledge, this is the first published report to show an improvement of pubertal TTM using an ultra-low dose of ARP. In this case, a 50-mg fluvoxamine monotherapy for 2 years and a subsequent 4-month comprehensive cognitive behavioral therapy (CBT) monotherapy did not improve her hair-pulling symptoms. However, the treatment with a low-dose ARP of 1...

  11. Interplay between photo- and radiation-induced darkening in ytterbium-doped fibers.

    Science.gov (United States)

    Duchez, Jean-Bernard; Mady, Franck; Mebrouk, Yasmine; Ollier, Nadge; Benabdesselam, Mourad

    2014-10-15

    This Letter demonstrates a remarkable interplay between photo- and radiation-induced darkening of ytterbium-doped alumino-silica optical fibers operated in amplifying conditions and harsh environments (as, e.g., in space-based applications). Influences of the pump power, ionizing dose, and dose rate on this interaction are characterized. The pump is capable of accelerating or slowing down the radiation-induced darkening build-up depending on the ionizing dose. The steady-state photo-radio-darkening level is independent of the dose and at least equal to the equilibrium level of pure photo-darkening. This lower limit is notably reached at low dose rates, including those encountered in space. We, therefore, argue that photo-resistant ytterbium-doped fibers will resist against a space mission, whatever the dose. PMID:25361132

  12. Gene expression profiling distinguishes between spontaneous and radiation-induced rat mammary carcinomas

    International Nuclear Information System (INIS)

    The ability to distinguish between spontaneous and radiation-induced cancers in humans is expected to improve the resolution of estimated risk from low dose radiation. Mammary carcinomas were obtained from Sprague-Dawley rats that were either untreated (n=45) or acutely ?-irradiated (1 Gy; n=20) at seven weeks of age. Gene expression profiles of three spontaneous and four radiation-induced carcinomas, as well as those of normal mammary glands, were analyzed by microarrays. Differential expression of identified genes of interest was then verified by quantitative polymerase chain reaction (qPCR). Cluster analysis of global gene expression suggested that spontaneous carcinomas were distinguished from a heterogeneous population of radiation-induced carcinomas, though most gene expressions were common. We identified 50 genes that had different expression levels between spontaneous and radiogenic carcinomas. We then selected 18 genes for confirmation of the microarray data by qPCR analysis and obtained the following results: high expression of Plg, Pgr and Wnt4 was characteristic to all spontaneous carcinomas; Tnfsf11, Fgf10, Agtr1a, S100A9 and Pou3f3 showed high expression in a subset of radiation-induced carcinomas; and increased Gp2, Areg and Igf2 expression, as well as decreased expression of Ca3 and noncoding RNA Mg1, were common to all carcinomas. Thus, gene expression analysis distinguished between spontaneous and radiogenic carcinomas, suggesting possible differenccarcinomas, suggesting possible differences in their carcinogenic mechanism. (author)

  13. Low Dose Studies with Focused X-rays in Cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

    Energy Technology Data Exchange (ETDEWEB)

    Barry D. Michael; Kathryn Held; Kevin Prise

    2002-12-19

    The management of the risks of exposure of people to ionizing radiation is important in relation to its uses in industry and medicine, also to natural and man-made radiation in the environment. The vase majority of exposures are at a very low level of radiation dose. The risks are of inducing cancer in the exposed individuals and a smaller risk of inducing genetic damage that can be transmitted to children conceived after exposure. Studies of these risks in exposed population studies with any accuracy above the normal levels of cancer and genetic defects unless the dose levels are high. In practice, this means that our knowledge depends very largely on the information gained from the follow-up of the survivors of the atomic bombs dropped on Japanese cities. The risks calculated from these high-dose short-duration exposures then have to be projected down to the low-dose long-term exposures that apply generally. Recent research using cells in culture has revealed that the relations hi between high- and low-dose biological damage may be much more complex than had previously been thought. The aims of this and other projects in the DOE's Low-Dose Program are to gain an understanding of the biological actions of low-dose radiation, ultimately to provide information that will lead to more accurate quantification of low-dose risk. Our project is based on the concept that the processes by which radiation induces cancer start where the individual tracks of radiation impact on cells and tissues. At the dose levels of most low-dose exposures, these events are rare and any individual cells only ''sees'' radiation tracks at intervals averaging from weeks to years apart. This contracts with the atomic bomb exposures where, on average, each cell was hit by hundreds of tracks instantaneously. We have therefore developed microbeam techniques that enable us to target cells in culture with any number of tracks, from one upwards. This approach enables us to study the biological basis of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and there it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure.

  14. Experimental studies on stimulatory effects of low dose ionizing radiation

    International Nuclear Information System (INIS)

    The experimental data of low dose low LET radiation effects on immune functions, chromosome aberrations, and DNA damage repair in mice were reported. Radiation hormesis appeared following both single low dose whole-body X-irradiation and continuous low level gamma-irradiation, expressed as: 1) immunoenhancement, including augmentation of antibody formation, increase in I1-2 production and increase in NK activity by the splenocytes, and increase of thymocyte proliferation; 2) induction of cytogenetic adaptive response, which resulted from an exposure in advance to low dose radiation leading to reduction of chromosome aberrations caused by a subsequent larger radiation dose; 3) increase of UDS and DNA polymerase activity in the splenocytes. The mechanism and implications of the hormetic effects of low dose radiation are discussed

  15. Topics on study of low dose-effect relationship

    International Nuclear Information System (INIS)

    It is not exceptional but usually observed that a dose-effect relationship in biosystem is not linear. Sometimes, the low dose-effect relationship appears entirely contrary to the expectation from high dose-effect. This is called a 'hormesis' phenomena. A high dose irradiation inflicts certainly an injury on biosystem. No matter how low the dose may be, an irradiation might inflict some injury on biosystem according to Linear Non-Threshold hypothesis(LNT). On the contrary to the expectation, a low dose irradiation stimulates immune system, and promotes cell proliferation. This is called 'radiation hormesis'. The studies of the radiation hormesis are made on from four points of view as follows: (1) radiation adaptive response, (2) revitalization caused by a low dose stimulation, (3) a low dose response unexpected from the LNT hypothesis, (4) negation of the LNT hypothesis. The various empirical proofs of radiation hormesis are introduced in the report. (M . Suetake)

  16. Radiation induced sulfur dioxide removal

    International Nuclear Information System (INIS)

    The biggest source of air pollution is the combustion of fossil fuels, were pollutants such as particulate, sulfur dioxide (SO2), nitrogen oxides (NOx), and volatile organic compounds (VOC) are emitted. Among these pollutants, sulfur dioxide plays the main role in acidification of the environment. The mechanism of sulfur dioxide transformation in the environment is partly photochemical. This is not direct photooxidation, however, but oxidation through formed radicals. Heterogenic reactions play an important role in this transformation as well; therefore, observations from environmental chemistry can be used in air pollution control engineering. One of the most promising technologies for desulfurization of the flue gases (and simultaneous denitrification) is radiation technology with an electron accelerator application. Contrary to the nitrogen oxides (NOx) removal processes, which is based on pure radiation induced reactions, sulfur dioxide removal depends on two pathways: a thermochemical reaction in the presence of ammonia/water vapor and a radiation set of radiochemical reactions. The mechanism of these reactions and the consequent technological parameters of the process are discussed in this paper. The industrial application of this radiation technology is being implemented in an industrial pilot plant operated by INCT at EPS Kaweczyn. A full-scale industrial plant is currently in operation in China, and two others are under develo in China, and two others are under development in Japan and Poland. (author)

  17. Development of Plant Application Technique of Low Dose Radiation

    International Nuclear Information System (INIS)

    The project was carried out to achieve three aims. First, development of application techniques of cell-stimulating effects by low-dose radiation. Following irradiation with gamma-rays of low doses, beneficial effects in crop germination, early growth, and yield were investigated using various plant species and experimental approaches. For the actual field application, corroborative studies were also carried out with a few concerned experimental stations and farmers. Moreover, we attempted to establish a new technique of cell cultivation for industrial mass-production of shikonin, a medicinal compound from Lithospermum erythrorhizon and thereby suggested new application fields for application techniques of low-dose radiation. Second, elucidation of action mechanisms of ionizing radiation in plants. By investigating changes in plant photosynthesis and physiological metabolism, we attempted to elucidate physiological activity-stimulating effects of low-dose radiation and to search for radiation-adaptive cellular components. Besides, analyses of biochemical and molecular biological mechanisms for stimulus-stimulating effects of low-dose radiation were accomplished by examining genes and proteins inducible by low-dose radiation. Third, development of functional crop plants using radiation-resistant factors. Changes in stress-tolerance of plants against environmental stress factors such as light, temperature, salinity and UV-B stress after exposed to low-dose gamma-rays were investigated. Concerned reactive oxygen species, antioxidative enzymes, and antioxidants were also analyzed to develop high value-added and environment-friendly functional plants using radiation-resistant factors. These researches are important to elucidate biological activities increased by low-dose radiation and help to provide leading technologies for improvement of domestic productivity in agriculture and development of high value-added genetic resources

  18. Development of Plant Application Technique of Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Byung Yeoup; Kim, Jae Sung; Lim, Yong Taek (and others)

    2007-07-15

    The project was carried out to achieve three aims. First, development of application techniques of cell-stimulating effects by low-dose radiation. Following irradiation with gamma-rays of low doses, beneficial effects in crop germination, early growth, and yield were investigated using various plant species and experimental approaches. For the actual field application, corroborative studies were also carried out with a few concerned experimental stations and farmers. Moreover, we attempted to establish a new technique of cell cultivation for industrial mass-production of shikonin, a medicinal compound from Lithospermum erythrorhizon and thereby suggested new application fields for application techniques of low-dose radiation. Second, elucidation of action mechanisms of ionizing radiation in plants. By investigating changes in plant photosynthesis and physiological metabolism, we attempted to elucidate physiological activity-stimulating effects of low-dose radiation and to search for radiation-adaptive cellular components. Besides, analyses of biochemical and molecular biological mechanisms for stimulus-stimulating effects of low-dose radiation were accomplished by examining genes and proteins inducible by low-dose radiation. Third, development of functional crop plants using radiation-resistant factors. Changes in stress-tolerance of plants against environmental stress factors such as light, temperature, salinity and UV-B stress after exposed to low-dose gamma-rays were investigated. Concerned reactive oxygen species, antioxidative enzymes, and antioxidants were also analyzed to develop high value-added and environment-friendly functional plants using radiation-resistant factors. These researches are important to elucidate biological activities increased by low-dose radiation and help to provide leading technologies for improvement of domestic productivity in agriculture and development of high value-added genetic resources.

  19. Detection of the proteins with different arginine methylation status induced by low dose irradiation

    International Nuclear Information System (INIS)

    Complete text of publication follows. Objective: The objective of this study is to detect the noble proteins that were functionally regulated by change of arginine methylation through irradiation of the low dose. The increase of the arginine methylation which is induced by low dose gamma-ray will have meaningful Introduction: Exposure of cells to low doses of radiation has well documented biological effect, but the underlying regulatory mechanisms are still poorly understood. Arginine methylation is a post translational modification that results in the formation of asymmetrical and symmetrical dimethylated arginines. Post-translational methylation of arginine residues of proteins involved in a growing number of cellular processes, including transcriptional regulation, cell signaling, RNA processing and DNA repair, biological influence. Methods: Human normal cell line Chang-liver was irradiation by gamma-ray of 0.02Gy, 0.2Gy. After irradiation, cells were incubated for 4h, 8h, 24h, and then harvested to prepare protein extracts. ASYM24(anti-dimethyl-Arginine, asymmetric) antibody was used to Western blot and immunoprecipitation. Proteins that show different degrees of intensity between the two samples were analyzed by Mass spectrometry. Results: We detected increased asymmetric arginine methylation of two proteins at 24h after a dose of 0.2Gy irradiation. The mass spectrometry identified that it is 27kDa and 73kDa proteins. The 27kDa is hypothetical protein that functi 27kDa is hypothetical protein that function does not know. The 73kDa protein is Mortalin, a member of the Heat shock 70 protein family, which correlate with the radioresistance response, control of cell proliferation and act as a chaperone. Conclusion: Low dose radiation induces the change of asymmetric arginine methylation modification of arginine residues of hypothetical protein and mortalin. We expect that increase of arginine methylation in mortarin and hypothetical protein correlates with the radioresistance, the functional study for these proteins is necessary to clarify the biological effects in radioadaptive response.

  20. Radiation-induced myelopathy and vertebral necrosis

    International Nuclear Information System (INIS)

    Radiation-induced myelopathy is a well-known delayed complication of radiotherapy. Its exact mechanism is unknown and the diagnosis is often not confirmed by complementary modalities or pathological studies. We report a patient who developed a ''Brown-Sequard plus'' syndrome two years after radiotherapy for a mediastinal neoplasm. We suggest that, in addition to the usual criteria, the presence of another radiation-induced lesion (such as aseptic vertebral necrosis) adjacent to the spinal cord lesion supports the radiation-induced origin of the myelopathy. (orig.)

  1. Transient radiation-induced conductivity in polymers

    International Nuclear Information System (INIS)

    The radiation-induced conductivity of some polymers is investigated under pulse irradiation conditions in vacuum at room temperature. Two mechanisms of radiation-induced conductivity are shown to be operative in polymers. One due mainly to free charge carriers escaping geminate recombination and partly to electrons generated in short tracks and the other associated with geminate electrons localized at deep traps. It is noted that non-Gaussian dispersive transport of charge carriers accounts well for the major features of radiation-induced current transients in polymers. (author)

  2. Low dose radiation effects on the transcription of consensus radiation response genes in primary and immortalized human fibroblast cells

    International Nuclear Information System (INIS)

    Complete text of publication follows. OBJECTIVE: The linear non-threshold model suggests that tumors might be induced even by low radiation doses. Still, most of the conventional methods are unable to detect damages below 100 mGy. We have studied whether transcriptional responses of consensus radiation response genes can be detected after low dose radiation exposure in directly exposed or bystander primary human fibroblast cells. The short term proliferation capacity of primary fibroblast cells in culture limits their long term application. Therefore we tried to immortalize the cells by the introduction of the human telomerase gene using retroviral vectors. METHODS: Primary human fibroblast cell lines were established from skin biopsies of cancer patients and foreskin samples of young children. To create immortalized cell lines the human telomerase gene was cloned into a retroviral vector. Primary fibroblast cells were transduced and their proliferation capacity studied. To investigate radiation induced transcriptional alterations, cells were irradiated with 60Co ?-rays (0; 0.01; 0,04; 0,1; 2 and 8 Gy) and 2 hours later total cellular RNA was isolated both from directly exposed and bystander cells. Transcriptional alterations were followed in consensus radiation response genes (CDKN1, GADD45, GDF15, IER5, PLK3, TP53INP1) with quantitative real time PCR (Corbett/ SybrGreen). RESULTS: There is an elevated expression of CDKN1, GADD45, GDF15, PLK3, TP53INP1 inf CDKN1, GADD45, GDF15, PLK3, TP53INP1 in the exposed cells. We see only for the PLK3 a dose-dependent increase which manifested also at low doses. It seems this gene is the most sensitive to radiation at low doses. The hTERT-immortalized cells were morphologically identical to the primary cells. the radiation-induced transcriptional profile of immortalized cells were very similar to the primary ones. CONCLUSIONS: hTERT immortalized cells can be used to mimic alterations in primary cells. Low dose irradiation doesn't influence the expression of most of the studied genes. PLK3 might be an efficient marker to estimate individually low dose effects.

  3. Cytogenetic effects of low doses of energetic carbon ions on rice after exposures of dry seeds, wet seeds and seedlings

    International Nuclear Information System (INIS)

    In order to investigate the biological effects of heavy ion radiation at low doses and the different radiosensitivities of growing and non-growing plants, rice at different lift stages (dry seed, wet seed and seedling) were exposed to carbon ions at doses of 0.02, 0.2, 2 and 20 Gy. Radiobiological effects on survival, root growth and mitotic activity, as well as the induction of chromosome aberrations in root meristem, were observed. The results show that radiation exposure induces a stimulatory response at lower dose and an inhibitory response at higher dose on the mitotic activity of wet seeds and seedlings. Cytogenetic damages are induced in both seeds and seedlings by carbon ion radiation at doses as low as 0.02 Gy. Compared with seedlings, seeds are more resistant to the lethal damage and the growth rate damage by high doses of carbon ions, but are more sensitive to cytogenetic damage by low doses of irradiation. Different types of radiation induced chromosome aberrations are observed between seeds and seedlings. Based on these results, the relationships between low dose heavy ion-induced biological effects and the biological materials are discussed. (author)

  4. Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials

    Science.gov (United States)

    Charlebois, Audrey; Jacques, Mario; Archambault, Marie

    2014-01-01

    Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. This study was undertaken to address these issues. Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277). Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. Exposure to low doses of some of these antimicrobials tended to lead to a diminution of the biofilm formed. However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin, and monensin. Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. Matrix composition analysis showed the presence of proteins, beta-1,4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine. This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials. PMID:24795711

  5. Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials

    Directory of Open Access Journals (Sweden)

    MarieArchambault

    2014-04-01

    Full Text Available Clostridium perfringens is an opportunistic pathogen that can cause food poisoning in humans and various enterotoxemia in animal species. Very little is known on the biofilm of C. perfringens and its exposure to subminimal inhibitory concentrations of antimicrobials. This study was undertaken to address these issues. Most of the C. perfringens human and animal isolates tested in this study were able to form biofilm (230/277. Porcine clinical isolates formed significantly more biofilm than the porcine commensal isolates. A subgroup of clinical and commensal C. perfringens isolates was randomly selected for further characterization. Biofilm was found to protect C. perfringens bacterial cells from exposure to high concentrations of tested antimicrobials. Exposure to low doses of some of these antimicrobials tended to lead to a diminution of the biofilm formed. However, a few isolates showed an increase in biofilm formation when exposed to low doses of tylosin, bacitracin, virginiamycin and monensin. Six isolates were randomly selected for biofilm analysis using scanning laser confocal microscopy. Of those, four produced more biofilm in presence of low doses of bacitracin whereas biofilms formed without bacitracin were thinner and less elevated. An increase in the area occupied by bacteria in the biofilm following exposure to low doses of bacitracin was also observed in the majority of isolates. Morphology examination revealed flat biofilms with the exception of one isolate that demonstrated a mushroom-like biofilm. Matrix composition analysis showed the presence of proteins, beta 1-4 linked polysaccharides and extracellular DNA, but no poly-beta-1,6-N-acetyl-D-glucosamine (PNAG. This study brings new information on the biofilm produced by C. perfringens and its exposure to low doses of antimicrobials.

  6. Non-targeted effects of radiation: applications for radiation protection and contribution to LNT discussion

    International Nuclear Information System (INIS)

    According to the target theory of radiation induced effects (Lea, 1946), which forms a central core of radiation biology, DNA damage occurs during or very shortly after irradiation of the nuclei in targeted cells and the potential for biological consequences can be expressed within one or two cell generations. A range of evidence has now emerged that challenges the classical effects resulting from targeted damage to DNA. These effects have also been termed non-(DNA)-targeted (Ward, 1999) and include radiation-induced bystander effects (Iyer and Lehnert, 2000a), genomic instability (Wright, 2000), adaptive response (Wolff, 1998), low dose hyper-radiosensitivity (HRS) (Joiner, et al., 2001), delayed reproductive death (Seymour, et al., 1986) and induction of genes by radiation (Hickman, et al., 1994). An essential feature of non-targeted effects is that they do not require a direct nuclear exposure by irradiation to be expressed and they are particularly significant at low doses. This new evidence suggests a new paradigm for radiation biology that challenges the universality of target theory. In this paper we will concentrate on the radiation-induced bystander effects because of its particular importance for radiation protection

  7. Radiation-induced DNA damage

    International Nuclear Information System (INIS)

    Ionizing radiation directly and indirectly induces DNA damage at the base and deoxyribose moieties. However, in spite of the complicated formation of DNA damage, ESR experiments at 77K showed that only two ionic radicals (guanine cation G+ and thymine T- or cytosine anion C-) were produced at the base moiety in hydrated DNA. Electron affinic radiosensitizers as misonidazole when added in hydrated DNA inhibit the formation of T- (or C-) by scavenging electrons liberated from DNA, resulting in the suppression of strand breaks at the thymine or cytosine moiety. This means that T- (or C-) is surely a precursor of strand break of DNA, though this result is incompatible with the fact that electron-affinic compounds generally sensitize the cell killing effects of ionizing radiation. Our recent studies showed that the spin-trapping agent, n-tert-butyl-?-phenylnitrone (PBN), sensitized the radiation-induced formation of 8-hydroxy-2'-deoxyguanine (8-OHdG) in DNA. Since G+ is considered as a common precursor of both 8-OHdG and strand break, this compound was employed to modify radiation-chemical processes from G+ to strand break. Application of this compound to X-irradiated Chinese hamster V79 cells proved that PBN inhibited the formation of DNA double-strand breaks and enhanced the formation of 8-OHdG, suggesting that G+ was surely a precursor of DNA strand break. However, the survivals of X-irradiated cells were lower in PBN-containing cells than those in control cells. From these results it was concluded that DNA double-strand breaks were not necessarily responsible for cell death and the complex structures of DNA damage containing strand breaks, base alterations and abasic sites might contribute to cellular response to ionizing radiation. (J.P.N.)

  8. Radiation-induced carcinoma of the penis

    International Nuclear Information System (INIS)

    Two patients with carcinoma of the penis were treated with interstitial radiation. They were cured of their disease for 17 and 21 years respectively and then developed radiation-induced tumours. (author)

  9. Low dose radiation effects: an integrative european approach (Risc-Rad Project) coordinated by the Cea

    International Nuclear Information System (INIS)

    RISC-RAD (Radiosensitivity of Individuals and Susceptibility to Cancer induced by ionizing Radiations) is an Integrated Project funded by the European Commission under 6. Framework Programme / EURATOM. RISC-RAD started on 1. January 2004 for a duration of four years. Coordinated by Cea (Dr Laure Sabatier), it involves 11 European countries (Austria, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Spain, Sweden and the United Kingdom) and 29 research institutions. Objectives: Exposures to low and protracted doses of ionizing radiation are very frequent in normal living environment, at work places, in industry and in medicine. Effects of these exposures on human health cannot be reliably assessed by epidemiological methods, nor is thoroughly understood by biologists. RISC-RAD project proposes to help bridging the gap of scientific knowledge about these effects. To achieve this goal, a necessary key step is to understand the basic mechanisms by which radiation induces cancer. Studying this multistage process in an integrated way, the project offers a new biological approach characterised by and clear-cut and objective-driven scientific policy: the project is focused on the effects of low doses (less than 100 mSv) and protracted doses of radiation. It aims at identifying new parameters that take into account the differences in radiation responses between individuals. A group of modelers works closely with the experimental teams in order to better quantxperimental teams in order to better quantify the risks associated with low and protracted doses. Research work is divided into five work packages interacting closely with each other. WP1 is dedicated to DNA damage. Ionizing Radiation (IR) produce a broad spectrum of base modifications and DNA strand breaks of different kinds, among which double-strand breaks and 'clustered damage' which is thought to be a major feature in biological effectiveness of IR. The aim of Work Package 1 is to improve understanding of the initial DNA damage induced by IR and of the impact of the major defence pathways (DNA repair, cell cycle checkpoints, apoptosis) on radiation induced damage and radiosensitivity. Chromosomal abnormalities and gene mutations induced by IR are thought to be transmitted to future cell generations. The topic of WP2 is to characterize the delayed and epigenetic effects of IR in the progeny of irradiated cells and in non-irradiated neighbourhood. A major challenge is to understand the interplay between cellular ageing and genomic instability in the progeny of irradiated cells. WP3 overall objective is to obtain a more precise description of the temporal sequence of genetic and epigenetic events which underlie radiation carcinogenesis in skin, intestine, bone, lung and the haematopoietic system. Using animal model systems, these studies aim to provide quantitative information on the events leading to radiation induced cancer. In this regard, very early stage pre-neoplastic lesions need to be studied. WP4 aims to provide a biological basis for the inclusion of molecular genetic parameters in models of low dose radiation risk. In order to more accurately reflect the genetic component of risk WP4 has initiated experiments designed to identify the genes that modify individual susceptibility. The work of WP4 is designed to exploit animal models of radiation carcinogenesis as a tool for the discovery of critical modifier genes. Contributing to the project's objectives, WP5 utilizes other WP experimental results to provide models aimed at improving quantitative risk assessment of the effects of low doses. (author)

  10. Radiation Induced Bystander Effect in vivo

    OpenAIRE

    Chai, Yunfei; Hei, Tom K.

    2008-01-01

    Radiation-induced bystander effect is defined as the induction of biological effects in cells that are not directly traversed by radiation, but merely in the presence of cells that are. Although radiation induced bystander effects have been well defined in a variety of in vitro models using a range of endpoints including clonogenic survival, mutations, neoplastic transformation, apoptosis, micronucleus, chromosomal aberrations and DNA double strand beaks, the mechanism(s) as well as the prese...

  11. Radiation-induced apoptosis: relevance to radiotherapy

    International Nuclear Information System (INIS)

    Radiation-induced apoptosis is reviewed in terms of: (a) the identification of apoptotic and necrotic cells, (b) observations in vitro and in vivo of radiation-induced apoptosis, (c) genes controlling apoptosis, (d) evidence that the target may be the plasma membrane or nuclear DNA, (e) quantitative comparisons of apoptotic death and reproductive (clonogenic) death, (f) the importance of radiation-induced apoptosis in radiotherapy, and (g) studies of radiation-induced apoptosis that are needed. High priority should be placed on determining the molecular pathways that are important in the expression and modulation of radiation-induced apoptosis. Specifically, the events that modulate the apoptosis that occurs in interphase before the cell can divide should be distinguished from the events before division that modulate the misrepair of DNA damage, that results in chromosomal aberrations observed in mitotic cells, which in turn cause the progeny of the dividing cell with aberrations to die by either apoptosis or necrosis. Then, molecular events that determine whether a cell that divides with or without a chromosomal aberration will produce progeny that apoptose or necrose need to be identified. These considerations are important for determining how modulation of radiation-induced apoptosis will affect the ultimate clonogenic survival, and possibly genomic instability in the surviving progeny

  12. Pulmonary injury after combined exposures to low-dose low-LET radiation and fungal spores.

    LENUS (Irish Health Repository)

    Marples, B

    2012-02-01

    Exposure to infectious microbes is a likely confounder after a nuclear terrorism event. In combination with radiation, morbidity and mortality from an infection may increase significantly. Pulmonary damage after low-dose low-LET irradiation is characterized by an initial diffuse alveolar inflammation. By contrast, inhaled fungal spores produce localized damage around pulmonary bronchioles. In the present study, we assessed lung injury in C57BL\\/6 mice after combined exposures to whole-body X radiation and inhaled fungal spores. Either animals were exposed to Aspergillus spores and immediately irradiated with 2 Gy, or the inoculation and irradiation were separated by 8 weeks. Pulmonary injury was assessed at 24 and 48 h and 1, 2, 4, 8, and 24 weeks later using standard H&E-stained sections and compared with sham-treated age-matched controls. Immunohistochemistry for invasive inflammatory cells (macrophages, neutrophils and B and T lymphocytes) was performed. A semi-quantitative assessment of pulmonary injury was made using three distinct parameters: local infiltration of inflammatory cells, diffuse inflammation, and thickening and distortion of alveolar architecture. Radiation-induced changes in lung architecture were most evident during the first 2 weeks postexposure. Fungal changes were seen over the first 4 weeks. Simultaneous combined exposures significantly increased the duration of acute pulmonary damage up to 24 weeks (P < 0.01). In contrast, administration of the fungus 8 weeks after irradiation did not produce enhanced levels of acute pulmonary damage. These data imply that the inhalation of fungal spores at the time of a radiation exposure alters the susceptibility of the lungs to radiation-induced injury.

  13. An extracellular DNA mediated bystander effect produced from low dose irradiated endothelial cells.

    Science.gov (United States)

    Ermakov, Aleksei V; Konkova, Marina S; Kostyuk, Svetlana V; Smirnova, Tatiana D; Malinovskaya, Elena M; Efremova, Liudmila V; Veiko, Natalya N

    2011-07-01

    The human umbilical vein endothelial cells culture was exposed to X-ray radiation in a low dose of 10cGy. The fragments of extracellular genomic DNA (ecDNA(R)) were isolated from the culture medium after the short-term incubation. A culture medium of unirradiated endothelial cells was then supplemented with ecDNA(R), followed by analysing the cells along the series of parameters (bystander effect). The exposed cells and bystander endotheliocytes showed similar response to low doses: approximation of the 1q12 loci of chromosome 1 and their transposition into the cellular nucleus, change in shape of the endotheliocytic nucleus, activation of the nucleolus organizing regions (NORs), actin polymerization, and an elevated level of DNA double-stranded breaks. Following blockade of TLR9 receptors with oligonucleotide-inhibitor or chloroquine in the bystander cells these effects - except of activation of NORs - on exposure to ecDNA(R) disappeared, with no bystander response thus observed. The presence of the radiation-induced apoptosis in the bystander effect being studied suggests a possibility for radiation-modified ecDNA fragments (i.e., stress signaling factors) to be released into the culture medium, whereas inhibition of TLR9 suggests the binding these ligands to the recipient cells. A similar DNA-signaling pathway in the bystander effect we previously described for human lymphocytes. Integrity of data makes it possible to suppose that a similar signaling mechanism which we demonstrated for lymphocytes (humoral system) might also be mediated in a monolayer culture of cells (cellular tissue) after the development of the bystander effect in them and transfer of stress signaling factors (ecDNA(R)) through the culture medium. PMID:21392514

  14. An extracellular DNA mediated bystander effect produced from low dose irradiated endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Ermakov, Aleksei V., E-mail: avePlato@mail.ru [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Konkova, Marina S.; Kostyuk, Svetlana V.; Smirnova, Tatiana D.; Malinovskaya, Elena M.; Efremova, Liudmila V.; Veiko, Natalya N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation)

    2011-07-01

    The human umbilical vein endothelial cells culture was exposed to X-ray radiation in a low dose of 10 cGy. The fragments of extracellular genomic DNA (ecDNA{sup R}) were isolated from the culture medium after the short-term incubation. A culture medium of unirradiated endothelial cells was then supplemented with ecDNA{sup R}, followed by analysing the cells along the series of parameters (bystander effect). The exposed cells and bystander endotheliocytes showed similar response to low doses: approximation of the 1q12 loci of chromosome 1 and their transposition into the cellular nucleus, change in shape of the endotheliocytic nucleus, activation of the nucleolus organizing regions (NORs), actin polymerization, and an elevated level of DNA double-stranded breaks. Following blockade of TLR9 receptors with oligonucleotide-inhibitor or chloroquine in the bystander cells these effects - except of activation of NORs - on exposure to ecDNA{sup R} disappeared, with no bystander response thus observed. The presence of the radiation-induced apoptosis in the bystander effect being studied suggests a possibility for radiation-modified ecDNA fragments (i.e., stress signaling factors) to be released into the culture medium, whereas inhibition of TLR9 suggests the binding these ligands to the recipient cells. A similar DNA-signaling pathway in the bystander effect we previously described for human lymphocytes. Integrity of data makes it possible to suppose that a similar signaling mechanism which we demonstrated for lymphocytes (humoral system) might also be mediated in a monolayer culture of cells (cellular tissue) after the development of the bystander effect in them and transfer of stress signaling factors (ecDNA{sup R}) through the culture medium.

  15. An extracellular DNA mediated bystander effect produced from low dose irradiated endothelial cells

    International Nuclear Information System (INIS)

    The human umbilical vein endothelial cells culture was exposed to X-ray radiation in a low dose of 10 cGy. The fragments of extracellular genomic DNA (ecDNAR) were isolated from the culture medium after the short-term incubation. A culture medium of unirradiated endothelial cells was then supplemented with ecDNAR, followed by analysing the cells along the series of parameters (bystander effect). The exposed cells and bystander endotheliocytes showed similar response to low doses: approximation of the 1q12 loci of chromosome 1 and their transposition into the cellular nucleus, change in shape of the endotheliocytic nucleus, activation of the nucleolus organizing regions (NORs), actin polymerization, and an elevated level of DNA double-stranded breaks. Following blockade of TLR9 receptors with oligonucleotide-inhibitor or chloroquine in the bystander cells these effects - except of activation of NORs - on exposure to ecDNAR disappeared, with no bystander response thus observed. The presence of the radiation-induced apoptosis in the bystander effect being studied suggests a possibility for radiation-modified ecDNA fragments (i.e., stress signaling factors) to be released into the culture medium, whereas inhibition of TLR9 suggests the binding these ligands to the recipient cells. A similar DNA-signaling pathway in the bystander effect we previously described for human lymphocytes. Integrity of data makes it possible to suppose that a simia makes it possible to suppose that a similar signaling mechanism which we demonstrated for lymphocytes (humoral system) might also be mediated in a monolayer culture of cells (cellular tissue) after the development of the bystander effect in them and transfer of stress signaling factors (ecDNAR) through the culture medium.

  16. Effect of low doses of gamma radiation in tomato seeds

    International Nuclear Information System (INIS)

    Tomato dry seeds of the hybrid 'Gladiador' Fl were exposed to low doses of gamma radiation from 60Co source at 0. 509 kGy tax rate in order to study stimulation effects of radiation on germination and plant growth. Eight treatments of different radiation doses were applied as follows: 0 (control); 2.5, 5.0, 7.5, 10.0, 12.5, 15.0, 20.0 Gy. Seed germination as well as green fruits number, harvested fruit number, fruit weight and total production were assessed to identify occurrence of stimulation. Tomato seeds and plants were handled as for usual tomato production in Brazil. Low doses of gamma radiation treatment in the seeds stimulate germination and substantially increase fruit number and total production up to 86% at 10 Gy dose. There are evidences that the use of low doses of gamma radiation can stimulate germination and plant production thus, showing hormetic effects. (author)

  17. Low-Dose Risk, Decisions, and Risk Communication

    International Nuclear Information System (INIS)

    To conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low dose exposures. This involves the study of existing knowledge and the evaluation of science information presented within a variety of formats, as educational information, news media stories, and alternative communication methods (personal contact, small group interaction, email and internet, etc.). Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low- dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

  18. Radiation induced changes in electrical conductivity of chemical vapor deposited silicon carbides under fast neutron and gamma-ray irradiations

    International Nuclear Information System (INIS)

    The radiation-induced changes in the volume electrical conductivities of chemical vapor deposited silicon carbides (CVD-SiCs) were in-site investigated by performing irradiation using 1.17 and 1.33-MeV gamma-ray and 14-MeV fast neutron beams in air and vacuum. Under gamma-ray irradiation at ionization dose rates of 3.6 and 5.9 Gy/s and irradiation temperature of approximately 300 K, the initial rapid increase in electrical conductivity; this is indicative of radiation-induced conductivity (RIC), occurred due to electronic excitation, and a more gradual increase followed up to a dose of approximately 10-50 kGy corresponding to the results in base conductivity without radiation; this is indicative of radiation-induced electrical degradation (RIED). However, the radiation-induced phenomena were not observed at irradiation temperatures above 373 K. Under neutron irradiation at a further low dose rate below approximately 2.1 Gy/s, a fast neutron flux of 9.2 x 1014 n/m2 s, and 300 K, the RIED-like behavior according to radiation-induced modification of the electrical property occurred with essentially no displacement damage, but ionizing effects (radiolysis).

  19. Effects of low dose radiation and epigenetic regulation

    International Nuclear Information System (INIS)

    Purpose: To conclude the relationship between epigenetics regulation and radiation responses, especially in low-dose area. Methods: The literature was examined for papers related to the topics of DNA methylation, histone modifications, chromatin remodeling and non-coding RNA modulation in low-dose radiation responses. Results: DNA methylation and radiation can regulate reciprocally, especially in low-dose radiation responses. The relationship between histone methylation and radiation mainly exists in the high-dose radiation area; histone deacetylase (HDAC) inhibitors show a promising application to enhance radiation sensitivity, no matter whether in low-dose or high-dose areas; the connection between ?-H2AX and LDR has been remained unknown, although ?-H2AX has been shown no radiation sensitivities with 1-15 Gy irradiation; histone ubiquitination play an important role in DNA damage repair mechanism. Moreover, chromatin remodeling has an integral role in DSB repair and the chromatin response, in general, may be precede DNA end resection. Finally, the effect of radiation on miRNA expression seems to vary according to cell type, radiation dose, and post-irradiation time point. Conclusion: Although the advance of epigenetic regulation on radiation responses, which we are managing to elucidate in this review, has been concluded, there are many questions and blind blots deserved to investigated, especially in low-dose radiation area. However, as progress on epigenetics, a. However, as progress on epigenetics, we believe that many new elements will be identified in the low-dose radiation responses which may put new sights into the mechanisms of radiation responses and radiotherapy. (authors)

  20. Radiation-induced-radioresistance: mechanisms and modification radioprotection

    International Nuclear Information System (INIS)

    Full text: The term radiation-induced-radioresistance (RIR) has been chosen to explain a particular class of resistance against lethal doses of radiation, which is transient and is induced by pre-exposure to low doses of radiation. This is a genetically governed phenomenon and is different from adaptation which in one of its several senses, refers to evolutionary transformation into new behavioural patterns. RIR is understood to be an evolutionarily conserved fundamental cellular defense mechanism. Small doses of radiation acting as stress stimuli evoke a concerted action of molecular pathways which help the organism to cope-up with the genotoxic effects of lethal doses of radiation given subsequently. Such molecular pathways are a complex interplay of genetic and biochemical entities and are increasingly becoming the focus of research world over. Most of our information on this subject has been gathered from prokaryotes, simpler eukaryotes, human cells and the epidemiological studies. A number of genes such as GADD 45, CDKN1A, PBP74, DIR1, DDR have been reported by to participate in RIR. However, till date, the mechanism of RIR remain poorly understood. In this deliberation some of our findings on mechanisms of RIR will be presented. Further, modification of RIR by a metabolic modifier, presently under clinical investigations for tumor radiotherapy, will also be presented

  1. Hybrid model of the radiation-induced bystander effect

    International Nuclear Information System (INIS)

    The radiation-induced bystander effect (RIBE) refer to biological alterations in non-irradiated cells that occupy the same medium (culture or tissue) of irradiated cells. The biochemical mechanisms of the RIBE are not completely elucidated. However, several experiments indicate its existence. The objective of this work is to quantify the effect via stochastic and deterministic approaches. The hypotheses of the model are: a) one non-irradiated healthy cell interacts with signals that propagate through the medium. These signals are released by irradiated cells. At the time of interaction cell-signal, the cell can become damaged and signaling or damage and not signaling; b) Both types of damage cells repair with certain rate becoming health cells; c) The diffusion of signals obey the discrete diffusion equation with decay in two dimensions. d) The signal concentration released by irradiated cells depends on the dose in the low dose range (< 0.3 Gy) and saturates for higher dose values. As expected, the temporal analysis of the model as a function of the repair rate shows that the survival fraction decreases as the repair rate is reduced. The analysis of the extent of damage triggered by a signal concentration released by a single irradiated cell at time zero show that the damage grows with the maximum simulation time. The results show good agreement with the experimental data. The stochastic and deterministic methods used are in qualitative agreement, as expected. (author)

  2. Hybrid model of the radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Braga, Viviane V.B.; Faria, Fernando Pereira de; Grynberg, Suely Epsztein, E-mail: vitoriabraga06@gmail.com, E-mail: fernandopereirabh@gmail.com, E-mail: seg@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    The radiation-induced bystander effect (RIBE) refer to biological alterations in non-irradiated cells that occupy the same medium (culture or tissue) of irradiated cells. The biochemical mechanisms of the RIBE are not completely elucidated. However, several experiments indicate its existence. The objective of this work is to quantify the effect via stochastic and deterministic approaches. The hypotheses of the model are: a) one non-irradiated healthy cell interacts with signals that propagate through the medium. These signals are released by irradiated cells. At the time of interaction cell-signal, the cell can become damaged and signaling or damage and not signaling; b) Both types of damage cells repair with certain rate becoming health cells; c) The diffusion of signals obey the discrete diffusion equation with decay in two dimensions. d) The signal concentration released by irradiated cells depends on the dose in the low dose range (< 0.3 Gy) and saturates for higher dose values. As expected, the temporal analysis of the model as a function of the repair rate shows that the survival fraction decreases as the repair rate is reduced. The analysis of the extent of damage triggered by a signal concentration released by a single irradiated cell at time zero show that the damage grows with the maximum simulation time. The results show good agreement with the experimental data. The stochastic and deterministic methods used are in qualitative agreement, as expected. (author)

  3. Radiation-Induced Bystander Response: Mechanism and Clinical Implications.

    Science.gov (United States)

    Suzuki, Keiji; Yamashita, Shunichi

    2014-01-01

    Significance: Absorption of energy from ionizing radiation (IR) to the genetic material in the cell gives rise to damage to DNA in a dose-dependent manner. There are two types of DNA damage; by a high dose (causing acute or deterministic effects) and by a low dose (related to chronic or stochastic effects), both of which induce different health effects. Among radiation effects, acute cutaneous radiation syndrome results from cell killing as a consequence of high-dose exposure. Recent advances: Recent advances in radiation biology and oncology have demonstrated that bystander effects, which are emerged in cells that have never been exposed, but neighboring irradiated cells, are also involved in radiation effects. Bystander effects are now recognized as an indispensable component of tissue response related to deleterious effects of IR. Critical issues: Evidence has indicated that nonapoptotic premature senescence is commonly observed in various tissues and organs. Senesced cells were found to secrete various proteins, including cytokines, chemokines, and growth factors, most of which are equivalent to those identified as bystander factors. Secreted factors could trigger cell proliferation, angiogenesis, cell migration, inflammatory response, etc., which provide a tissue microenvironment assisting tissue repair and remodeling. Future directions: Understandings of the mechanisms and physiological relevance of radiation-induced bystander effects are quite essential for the beneficial control of wound healing and care. Further studies should extend our knowledge of the mechanisms of bystander effects and mode of cell death in response to IR. PMID:24761341

  4. A Commentary on: "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008".

    Science.gov (United States)

    Brooks, Antone L

    2015-04-01

    This commentary provides a very brief overview of the book "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008" ( http://lowdose.energy.gov ). The book summarizes and evaluates the research progress, publications and impact of the U.S. Department of Energy Low Dose Radiation Research Program over its first 10 years. The purpose of this book was to summarize the impact of the program's research on the current thinking and low-dose paradigms associated with the radiation biology field and to help stimulate research on the potential adverse and/or protective health effects of low doses of ionizing radiation. In addition, this book provides a summary of the data generated in the low dose program and a scientific background for anyone interested in conducting future research on the effects of low-dose or low-dose-rate radiation exposure. This book's exhaustive list of publications coupled with discussions of major observations should provide a significant resource for future research in the low-dose and dose-rate region. However, because of space limitations, only a limited number of critical references are mentioned. Finally, this history book provides a list of major advancements that were accomplished by the program in the field of radiation biology, and these bulleted highlights can be found in last part of chapters 4-10. PMID:25768839

  5. Low Dose Gamma Irradiation Potentiates Secondary Exposure to Gamma Rays or Protons in Thyroid Tissue Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Green, Lora M

    2006-05-25

    We have utilized our unique bioreactor model to produce three-dimensional thyroid tissue analogs that we believe better represent the effects of radiation in vivo than two-dimensional cultures. Our thyroid model has been characterized at multiple levels, including: cell-cell exchanges (bystander), signal transduction, functional changes and modulation of gene expression. We have significant preliminary data on structural, functional, signal transduction and gene expression responses from acute exposures at high doses (50-1000 rads) of gamma, protons and iron (Green et al., 2001a; 2001b; 2002a; 2002b; 2005). More recently, we used our DOE funding (ending Feb 06) to characterize the pattern of radiation modulated gene expression in rat thyroid tissue analogs using low-dose/low-dose rate radiation, plus/minus acute challenge exposures. Findings from these studies show that the low-dose/low-dose rate priming exposures to radiation invoked changes in gene expression profiles that varied with dose and time. The thyrocytes transitioned to a primed state, so that when the tissue analogs were challenged with an acute exposure to radiation they had a muted response (or an increased resistance) to cytopathological changes relative to un-primed cells. We measured dramatic differences in the primed tissue analogs, showing that our original hypothesis was correct: that low dose gamma irradiation will potentiate the repair/adaptation response to a secondary exposure. Implications from these findings are that risk assessments based on classical in vitro tissue culture assays will overestimate risk, and that low dose rate priming results in a reduced response in gene expression to a secondary challenge exposure, which implies that a priming dose provides enhanced protection to thyroid cells grown as tissue analogs. If we can determine that the effects of radiation on our tissue analogs more closely resemble the effects of radiation in vivo, then we can better estimate the risks and modify assign limits to radiation worker and astronauts. Additionally, confirmation that tissue analogs represent a realistic in vivo response to radiation will allow scientists to perform tissue relevant experiments without the expense of using animals. Confirmation of the in vivo approximation of our model will strengthen our findings from the recent completion of our DOE funding which is the subject of the current proposal.

  6. Reduction of the background mutation by a low dose irradiation of drosophila spermatocytes at a low dose-rate

    International Nuclear Information System (INIS)

    Complete text of publication follows. Objective: As the Linear Non Threshold model was first established in 1930, based on the results of a genetic study using Drosophila, we tried to indicate the conditions under which LNT holds. Methods: A sex-linked recessive lethal mutation assay was performed in Drosophila melanogaster. DNA repair proficient immature spermatocytes and spermatogonia were irradiated with X-rays at a high or low dose-rate. Results and discussion: Mutation frequency in the sperms irradiated with a low total dose (0.2Gy) at a low dose-rate (0.05Gy/min) was significantly lower than that in the sham-irradiated group whereas irradiation with a high dose (10Gy) at the same dose-rate resulted in a significant increase in the mutation frequency. It was obvious that the dose response relationship was not linear, but U-shaped. A low dose irradiation at a high dose-rate (0.5Gy/min) did not cause a significant reduction in mutation frequency. Mutation in the high dose, high dose-rate group was more frequent than in the high dose, low dose-rate group. A dose-rate effect was evident. When mutant male flies defective in DNA excision repair function were used instead of wild type flies, a low dose irradiation at a low dose-rate did not cause the reduction in the mutation frequency. These observations suggest that the dose response relationship is dependent not only on the dose-rate, but also on the DNA repair function. It is inferred that error-free DNA repair funcs inferred that error-free DNA repair functions were activated by a low dose of low dose-rate irradiation, and this repaired spontaneous DNA damage rather than the X-ray induced one, thus forming a practical threshold. As the human somatic cells are usually repair function proficient, we conclude that LNT can not estimate the human cancer risks properly.

  7. Low-dose computed tomography screening in Japan.

    Science.gov (United States)

    Nawa, Takeshi; Nakagawa, Tohru; Mizoue, Tetsuya; Endo, Katsuyuki

    2015-03-01

    Lung cancer is a leading cause of cancer death in both male and female individuals in Japan. The effect of screening using chest radiography is assumed to be limited. In Japan, screening using low-dose computed tomography (CT) was initiated in 1993, and its dissemination has progressed with studies evaluating its efficacy, although it is not officially recommended. In addition to the academic activities of the Japanese Society of CT Screening, certification of physicians and radiologic technologists by the Japan Accreditation Council for CT Screening has been progressing. Currently, several hundred thousand low-dose CT screenings are performed annually in Japan. In Hitachi City, Ibaraki Prefecture, low-dose CT screening among employees and in communities started in 2001, and it was estimated that 40% of 50- to 69-year-old citizens had undergone screening at least once by March 2009. The lung cancer mortality rate in citizens in this age group decreased by 24% in 2005 to 2009 compared with the national statistics. Low-dose CT screening targeting the general population may be effective, but it is necessary to consider the target and interval of screening separately from those for the high-risk group. Observational study may play a role in evaluating the efficacy of screening in Japan. PMID:25658475

  8. Glyphosate Applied at Low Doses Can Stimulate Plant Growth

    Science.gov (United States)

    Glyphosate blocks the shikimic acid pathway, inhibiting the production of aromatic amino acids and several secondary compounds derived from these amino acids. Non-target plants can be exposed to low doses of glyphosate by herbicide drift of spray droplets and contact with treated weeds. Previous s...

  9. Molecular mechanism of adaptive response to low dose radiation

    International Nuclear Information System (INIS)

    Adaptive response is a term used to describe the ability of a low, priming dose of ionizing radiation to modify the effects of a subsequent higher, challenge dose. Molecular mechanism of adaptive response to low dose radiation is involved in signal transduction pathway, reactive oxygen species, DNA damage repair

  10. Biological effects of low dose radiation and tritium biology

    International Nuclear Information System (INIS)

    The amount of tritium introduced into the thermonuclear reactor is not small. Therefore, it is important to explore the minimum amount (dose rate) of tritium allowable for the human health and safety. In the present paper, recent research activities on biological effects of low-dose radiations and tritium biology are reviewed. (J.P.N.)

  11. Low-dose radioimmuno-therapy of cancer.

    Science.gov (United States)

    Pollycove, Myron; Feinendegen, Ludwig E

    2008-02-01

    Four decades of genomic, cellular, animal and human data have shown that low-dose ionizing radiation stimulates positive genomic and cellular responses associated with effective cancer prevention and therapy and increased life span of mammals and humans.( 1-8) Nevertheless, this data is questioned because it seems to contradict the well demonstrated linear relation between ionizing radiation dose and damage to DNA without providing a clear mechanistic explanation of how low-dose radiation could produce such beneficial effects. This apparent contradiction is dispelled by current radiobiology that now includes DNA damage both from ionizing radiation and from endogenous metabolic free radicals, and coupled with the biological response to low-dose radiation. Acceptance of current radiobiology would invalidate long established recommendations and regulations of worldwide radiation safety organizations and so destroy the basis of the very expensive existing system of regulation and remediation. More importantly, current radiobiology would facilitate urgently needed clinical trials of low dose radiation (LDR) cancer therapy. PMID:18480144

  12. Study on effects of low dose radiation on biological function

    International Nuclear Information System (INIS)

    In this research, the characteristics that the relation of active oxygen which is considered to be the cause of ageing with the enzyme that cancels it (superoxide dismutase, SOD), the amount of lipid peroxide (LPO) which becomes the index of ageing, and cell membrane function changed by low dose X-ray irradiation were examined by animal experiment, and the activation phenomena of chemical defense function were to be evaluated. It was clarified that accompanying low dose irradiation, SOD was synthesized by induction, by genetic analysis, and SOD activity increased. It was found that the quantity of LPO in cell membranes decreased by low dose irradiation, and the membrane fluidity rose, and the change of approaching to the young age value arose. Further, the pump action for adjusting the concentration of Na+ and K+ indispensable for living bodies inside and outside cells was activated. DNA damage was completely inhibited by the administration of SOD. HB-SOD markedly decreased the blood pressure of rats. The expression of mRNA for SOD in both hemopoietics and immune is responsible for the induction of SOD activity by low dose radiation. Also the effect of radon inhalation on central neurotransmission is reported. (K.I.) 104 refs

  13. Low-dose ionizing radiation is it harmful to health?

    International Nuclear Information System (INIS)

    A conference on the health effects of low-dose ionizing radiation organized in London earlier this year by the British Nuclear Energy Society brought together epidemiologists who have been investigating the mortality of workers from the nuclear industry in an attempt to put low-level radiation risk estimates on a scientific basis

  14. Topics on study of low dose-effect relationship

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Takeshi [Toho Univ., School of Medicine, Tokyo (Japan); Ohyama, Harumi

    1999-09-01

    It is not exceptional but usually observed that a dose-effect relationship in biosystem is not linear. Sometimes, the low dose-effect relationship appears entirely contrary to the expectation from high dose-effect. This is called a 'hormesis' phenomena. A high dose irradiation inflicts certainly an injury on biosystem. No matter how low the dose may be, an irradiation might inflict some injury on biosystem according to Linear Non-Threshold hypothesis(LNT). On the contrary to the expectation, a low dose irradiation stimulates immune system, and promotes cell proliferation. This is called 'radiation hormesis'. The studies of the radiation hormesis are made on from four points of view as follows: (1) radiation adaptive response, (2) revitalization caused by a low dose stimulation, (3) a low dose response unexpected from the LNT hypothesis, (4) negation of the LNT hypothesis. The various empirical proofs of radiation hormesis are introduced in the report. (M . Suetake)

  15. Malignant melanoma of the tongue following low-dose radiation

    International Nuclear Information System (INIS)

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented

  16. Malignant melanoma of the tongue following low-dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  17. Research on the effects of low doses of irradiation

    International Nuclear Information System (INIS)

    The issue of risks related to low doses of irradiation is a concern for the entire scientific community, in France, in Europe and internationally. Currently, a review is being undertaken at the European level, to designate research priorities for the next twenty years. (authors)

  18. Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation

    International Nuclear Information System (INIS)

    Previous studies have shown that high NaCl can be genotoxic, either alone or combined with irradiation. However, little is known about the relationship between environmental NaCl at elevated conditions and radiation-induced bystander effects (RIBE). RIBE, which has been considered as non-targeted bystander responses, has been demonstrated to occur widely in various cell lines. In the present study, RIBE under the elevated NaCl culture condition was assessed in AG 1522 cells by both the induction of ?-H2AX, a reliable marker of DNA double-strand break (DSB) for the early process (G-methyl-L-arginine, an inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells was effecton of foci-positive cells was effectively inhibited both in 0.2 cGy ?-particle irradiated and adjacent non-irradiated regions under either normal or elevated NaCl conditions. These results suggested that the cultures with elevated NaCl medium magnified the damage effects induced by the low dose ?-particle irradiation and nitric oxide generated by irradiation was also very important in this process

  19. Dosimetric characterisation of aqueous solution of brilliant green for low-dose food irradiation dosimetry

    International Nuclear Information System (INIS)

    Dosimetric characterisation of aqueous solution of brilliant green has been studied spectrophotometrically for possible applications in low-dose food irradiation dosimetry. Absorption spectra of unirradiated and irradiated solutions were determined which showed two absorption bands with peaks at 427 and 626 nm and a decrease in absorption as the radiation dose is increased. Radiation-induced bleaching of the dye was measured at wavelengths of maximum absorbance (427 and 626 nm) as well as at 550 and 570 nm. At all these wavelengths, the decrease in absorbance of the dosimeter was linear with respect to the absorbed dose from 20 to 120 Gy. However, the upper dose limit was increased to 200 Gy when the negative logarithm of the absorbance (-log A) was plotted versus absorbed dose. The stability of dosimetric solution during post-irradiation storage in dark at room temperature showed that after some initial bleaching within the first 5 h of irradiation the response was stable for about 18 days. The effect of different light and temperature conditions to which a dosimeter may be exposed during commercial irradiation has been discussed

  20. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Engelward, Bevin P

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells remember radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy iron particle radiation on large scale sequence rearrangements and we have discovered tissue specific differences in sensitivity to homologous recombination. DOE support has given rise to critical new knowledge about the biological impact of low dose rate radiation and about the underlying mechanisms that govern genomic stability in response to radiation exposure. This work has spurred interest in radiation among MIT scientists, and has fostered ongoing research projects that will continue to contribute toward our understanding of the biological effects of low dose radiation exposure.

  1. Cohort studies on cancer mortality among nuclear workers exposed to low-dose ionizing radiation: a meta-analysis

    International Nuclear Information System (INIS)

    To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for low-dose ionising radiation exposure. Published papers referring to 20 low-dose ionising radiation-exposed cohorts among nuclear industry workers with Standardized Mortality Ratios (SMR) were recta-analyzed in fixed and random effect models. The significantly deficient Meta-SMRs for all deaths (0.73; 95% CI: 0.66-0.80), all cancers (0.83; 95% CI: 0.77- 0.91), lung cancer (0.93; 95% CI: 0.90-0.95), non-Hodgkin lymphoma (0.88; 95% CI: 0.78- 0.99), esophagus cancer (0.83; 95% CI:0.76-0.91), colorectal cancer (0.88; 95% CI: 0.83-0.94), stomach cancer (0.81; 95% CI: 0.76-0.86) were observed. The Meta-SMRs for leukemia, multiple myeloma, Hodgkin's disease were found to be no significant difference with normal populations. There was no excessive risk of cancers among nuclear workers exposed to low-doses and low-dose rates ionizing radiation. (authors)

  2. Hazard of the radiation induced thyroid cancer

    International Nuclear Information System (INIS)

    The level of thyroid cancer in Belarus before Chernobyl accident was low and made in different age and sex groups 0,03-2,5 (male) and 0,1-3,9 (female) per 100000 correspondingly. Different risk factors, which can influence the thyroid cancer development, are being taken into account. They are the factors of environment (strong external irradiation, long-time irradiation for medical purposes or in result of disaster), endo gen factors (hormonal, reproductive, genetic predisposition), some medicinal preparations and other. The protective effect of vegetable and fish consumption was found out. Among the factors of thyroid cancer development one of the most important is radiation. There is a point of view, which assumes that one of the reasons of thyroid cancer cases increase among the population of developed countries is increase of radiation induced thyroid cancer. The results of first research testify the influence of radiation factor on thyroid cancer development. During the period 1920 -1960 in the USA X-ray therapy was applied for the treatment of different good-quality diseases. Thyroid got in the zone of irradiation during the complex treatment with using of radiation. The results of the research of 1970 revealed that 70% of children with thyroid cancer were exposed to radiation in children's age. The subsequent researches of by-effects from the side of a thyroid at beam therapy of various diseases alongside with the results of the estimation of consequences of ints of the estimation of consequences of inhabitants of Hiroshima and Nagasaki irradiation owing to nuclear bombardment have shown the influence of irradiation of a thyroid on cancer development. High quantity of radio-epidemiological researches was directed to the studying of the consequences of thyroid external irradiation at young age. In all carried out researches the quantity of observed thyroid cancer cases among irradiated people has exceeded number of expected. The influence of thyroid internal irradiation by I-131 at young age was investigate on the groups, exposed to the diagnostic procedures with the using of I-131 in the USA and Sweden, on the population of irradiated owing to nuclear tests people in the state of Utah. The data received pointed on lower I-131 efficiency in the induction of radiation cancer in comparison with external irradiation. The quantitative expression of probability of the radiating factor influence on the induction of thyroid cancer is the concept of risk (absolute and relative). Risk coefficients received in separate research to the certain extend expressed the specificity of population irradiated and irradiation conditions (kind and duration of irradiation, dose capacity). The consequences of the Chernobyl accident are the precondition of the research of the role of radiation factor expansion, and especially of I-131, in the induction of thyroid cancer. The population of Belarus has suffered from the Chernobyl accident in the greatest extends. Meteorological conditions of the air masses spreading during the first weeks after disaster have determined the radioactive fall outs formation in north-west and north-east directions. Consequently, the main territory of Belarus was contaminated by iodine. The population of areas suffered got various dose loading on thyroid. Formed irradiation doses of thyroid created preconditions of radiation induced cancer development. Ecological investigation in the area of radiation epidemiology includes the comparative analysis of the level diseases of population from different areas and time periods. The research by a method 'case-control' assumes comparison of groups of people observing who have and do not have thyroid gland cancer. It allows revealing the influence of radiation factor. In the result of ecological researches can be received detail information that quantitatively describes the level of extra diseases during an early period after irradiation as such researches operate by all the cancer cases registered. During the post Chernobyl accident period numerous data were received. The

  3. Radiation-induced brain injury: A review

    Directory of Open Access Journals (Sweden)

    MichaelRobbins

    2012-07-01

    Full Text Available Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (> 6 months to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses > 30 Gy; white matter necrosis occurs at fractionated doses > 60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as we

  4. Radiation-induced electric conductivity of polymers

    International Nuclear Information System (INIS)

    Radiation-induced electric conductivity of polystyrene, polyethylene and polypropylene, excited by pulses of accelerated (60 keV) electrons of 1 ms to 10 s duration with a change in electric field to prebreak down voltage (? 2x108 V/m) in vacuum at room temperature was studied. Specific features of recombination effects at increased dose rate were considered. General theoretic problems of radiation-induced electric conductivity of the polymers, especially of heminal mechanism realized in polypropylene, and for pulses of radiation shorter than 0.1 s in polyethylene, as well, are discussed

  5. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

    International Nuclear Information System (INIS)

    The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16INKa and DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16INKa promoter methylation upon LDR exposure. In male liver tissue, p16INKa promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16INKa promoter methylation were noted in the muscle tissue of exposed males and females.uscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16INKa and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure

  6. Marked depression of time interval between fertilization period and hatching period following exposure to low-dose X-rays in zebrafish

    International Nuclear Information System (INIS)

    In recent years there has been growing concern over the stimulating effects of very low-dose X -rays. Our laboratory had observed that zebrafish irradiated with low-dose X-rays tended to emerge earlier than sham controls. This observation led us to quantitatively examine the effects of low-dose X irradiation on a series of stages of development in the zebrafish. The embryos were fertilized simultaneously in vitro and incubated at an optimal temperature without crowding. Following exposure of the cleavage period (1.5 h after fertilization) to 0.025-Gy X-rays, the duration to hatching was slightly shorter than that of the sham controls. This tendency was increased when the X-ray exposure occurred during the blastula period (3.5 h). In these embryos, the duration to hatching decreased significantly by an average of 6 h sooner than for sham controls. No differences in duration to hatching were seen when irradiation was given during either the zygote period (45 min) or the segmentation period (12 h). On the contrary, upon exposure to 0.5-Gy X-rays during the blastula period, the duration to hatching increased significantly relative to that of sham controls. These results suggest that the radiation-induced early hatching effect is observed for low doses of X-rays

  7. Role of extracellular DNA oxidative modification in radiation induced bystander effects in human endotheliocytes

    International Nuclear Information System (INIS)

    The development of the bystander effect induced by low doses of irradiation in human umbilical vein endothelial cells (HUVECs) depends on extracellular DNA (ecDNA) signaling pathway. We found that the changes in the levels of ROS and NO production by human endothelial cells are components of the radiation induced bystander effect that can be registered at a low dose. We exposed HUVECs to X-ray radiation and studied effects of ecDNAR isolated from the culture media conditioned by the short-term incubation of irradiated cells on intact HUVECs. Effects of ecDNAR produced by irradiated cells on ROS and NO production in non-irradiated HUVECs are similar to bystander effect. These effects at least partially depend on TLR9 signaling. We compared the production of the nitric oxide and the ROS in human endothelial cells that were (1) irradiated at a low dose; (2) exposed to the ecDNAR extracted from the media conditioned by irradiated cells; and (3) exposed to human DNA oxidized in vitro. We found that the cellular responses to all three stimuli described above are essentially similar. We conclude that irradiation-related oxidation of the ecDNA is an important component of the ecDNA-mediated bystander effect.

  8. Comparison of hyperuricemia in type 2 diabetics on low dose aspirin and not on low dose aspirin

    International Nuclear Information System (INIS)

    Objective: To compare the frequency of hyperuricemia in type 2 diabetes patients who are taking low dose aspirin with those patients who are not taking low dose aspirin. Study design: Quasi experimental study. Place and duration of study: This study was carried out at Military Hospital Rawalpindi for a period of two years (June 2006-May 2008). Patients and Methods: Sixty diabetic patients were selected who were taking low dose aspirin comparing group A and sixty diabetic patients who were not taking aspirin were placed in group B. These patients were selected from the OPD through non probability convenience sampling. All these patients were being followed up in medical outpatient quite regularly on fort-nightly basis. Data had been collected through a carefully designed questionnaire. Results: In group A, 90% of the patients had uric acid less than 445 micro mol/l and 10% of the patients had uric acid more than 445micro mol/l. Whereas in group B 100% of the patients had uric acid less than 445umol/l, there was a statistically significant difference between the two groups (p< 0.05). Conclusion: Aspirin in low doses cause hyperuricemia and regular monitoring of uric acid is mandatory to prevent its adverse effects. (author)

  9. State of the art in research into the risk of low dose radiation exposurefindings of the fourth MELODI workshop

    International Nuclear Information System (INIS)

    The fourth workshop of the Multidisciplinary European Low Dose Initiative (MELODI) was organised by STUKRadiation and Nuclear Safety Authority of Finland. It took place from 12 to 14 September 2012 in Helsinki, Finland. The meeting was attended by 179 scientists and professionals engaged in radiation research and radiation protection. We summarise the major scientific findings of the workshop and the recommendations for updating the MELODI Strategic Research Agenda and Road Map for future low dose research activities. (memorandum)

  10. [Influence of low-dose-rate red and near-infrared radiations on the level of reactive oxygen species, the genetic apparatus and the tumor growth in mice in vivo].

    Science.gov (United States)

    Zaichkina, S I; Rozanova, O M; Diukina, A R; Simonova, N B; Romanchenko, S P; Sorokina, S S; Aptikaeva, G F; Iusupov, V I

    2013-01-01

    The effect of low-dose-rate red and near-infrared radiations from the matrix of light emitted diode (650 nm and 850 nm) and a He-Ne laser (633 nm) on activation of the reserve of a natural defense system in the mice exposed to radiation in vivo was studied by the level of reactive oxygen species (ROS) production in blood cells, the induction of cytogenetic adaptive response in bone marrow cells, thymus and spleen, and the rate of Ehrlich ascites carcinoma growth in a solid form. As a positive control animals were irradiated with X-rays by the scheme of the radiation-induced adaptive response (0.1 Gy + 1.5 Gy). The levels of ROS production was assessed in whole blood by luminol-dependent chemiluminescence, of cytogenetic damage--by the "micronucleus test" in the bone marrow, the weight of the thymus and spleen--by index of organ, and the rate of tumor growth--according to its size for 30 days after inoculation. Adaptogenic and anticarcinogenic effects of studied radiations were revealed. The values of these effects were not different from those in animals pre-irradiated with the X-rays. The relationship between the level of ROS production and adaptive response induction in the mice under the influence of non-ionizing radiation was first ascertained. The experimental data obtained may indicate a similar mechanism of induction of protective responses to ionizing and non-ionizing radiations in mice in vivo. PMID:25481959

  11. Radiation Induced Bystander Effect in vivo

    Science.gov (United States)

    Chai, Yunfei; Hei, Tom K.

    2010-01-01

    Radiation-induced bystander effect is defined as the induction of biological effects in cells that are not directly traversed by radiation, but merely in the presence of cells that are. Although radiation induced bystander effects have been well defined in a variety of in vitro models using a range of endpoints including clonogenic survival, mutations, neoplastic transformation, apoptosis, micronucleus, chromosomal aberrations and DNA double strand beaks, the mechanism(s) as well as the presence of such an effect in vivo are not well described. In this review, we summarize the evidence of radiation induced bystander effect in various in vivo systems including rodents, fish and plants. Many biological endpoints such as epigenetic changes, DNA damage, miRNA, apoptosis, cell proliferation, gene expression and tumorgenesis have been demonstrated in the non-targeted regions in vivo. Although the bystander effect is evolutionarily conserved in rodent systems, the bystander response depends on gender, tissue and strain. However, the studies about mechanism of radiation induced bystander effect in vivo are still limited. PMID:20634916

  12. Radiation induced bystander effect in vivo

    International Nuclear Information System (INIS)

    Radiation-induced bystander effect is defined as the induction of biological effects in cells that are not directly traversed by radiation, but merely in the presence of cells that are. Although radiation induced bystander effects have been well defined in a variety of in vitro models using a range of endpoints including clonogenic survival, mutations, neoplastic transformation, apoptosis, micronucleus, chromosomal aberrations and DNA double strand breaks, the mechanism(s) as well as the presence of such an effect in vivo are not well described. In this review, we summarize the evidence of radiation induced bystander effect in various in vivo systems including rodents, fish and plants. Many biological endpoints such as epigenetic changes, DNA damage, miRNA, apoptosis, cell proliferation, gene expression and tumorgenesis have been demonstrated in the non-targeted regions in vivo. Although the bystander effect is evolutionarily conserved in rodent systems, the bystander response depends on gender, tissue and strain. However, the studies about mechanism of radiation induced bystander effect in vivo are still limited. (author)

  13. Radiation-induced evaporation of austenitic steels

    International Nuclear Information System (INIS)

    The influence of radiation effect on vaporability of chromium manganese (EP-838) and chromium-nickel (316) austenitic steels is studied. It is shown experimentally that helium ion bombardment essentially increases the process of austenitic steels evaporation, a stronger effect of radiation-induced evaporation being observed in chromium manganese steel

  14. Displacement of atoms and radiation induced defects

    International Nuclear Information System (INIS)

    Physical radiation effects of fast neutrons on DT fusion reactor materials are reviewed. First fundamental processes of displacement and the cascade damage of materials induced by high-energy particles are explained. Next the annihilation process and bias effect of radiation-induced defects are discussed. Finally, the definition of dpa, a measure of displacement is given. (J.P.N.)

  15. Radiation Induced Bystander Effect in vivo.

    Science.gov (United States)

    Chai, Yunfei; Hei, Tom K

    2008-01-01

    Radiation-induced bystander effect is defined as the induction of biological effects in cells that are not directly traversed by radiation, but merely in the presence of cells that are. Although radiation induced bystander effects have been well defined in a variety of in vitro models using a range of endpoints including clonogenic survival, mutations, neoplastic transformation, apoptosis, micronucleus, chromosomal aberrations and DNA double strand beaks, the mechanism(s) as well as the presence of such an effect in vivo are not well described. In this review, we summarize the evidence of radiation induced bystander effect in various in vivo systems including rodents, fish and plants. Many biological endpoints such as epigenetic changes, DNA damage, miRNA, apoptosis, cell proliferation, gene expression and tumorgenesis have been demonstrated in the non-targeted regions in vivo. Although the bystander effect is evolutionarily conserved in rodent systems, the bystander response depends on gender, tissue and strain. However, the studies about mechanism of radiation induced bystander effect in vivo are still limited. PMID:20634916

  16. Comparison of protein expression profile changes in human fibroblasts induced by low doses of gamma rays and energetic protons

    Science.gov (United States)

    Zhang, Ye; Clement, Jade; Gridley, Diala; Rohde, Larry; Wu, Honglu

    Extrapolation of known radiation risks to the risks from low dose and low dose-rate exposures of human population, especially prolonged exposure of astronauts in the space radiation environment, relies in part on the mechanistic understanding of radiation induced biological consequences at the molecular level. While some genomic data at the mRNA level are available for cells or animals exposed to radiation, the data at the protein level are still lacking. Here, we studied protein expression profile changes using Panorama antibody microarray chips that contain antibodies to more than 200 proteins (or modified proteins) involved in cell signaling that included mostly apoptosis, cytoskeleton, cell cycle and signal transduction. Normal human fibroblasts were cultured till fully confluent and then exposed to 2 cGy of gamma rays at either low (1 cGy/hr) or high (0.2 Gy/min) dose-rate, or to 2 cGy of 150 MeV protons at high dose-rate. The proteins were isolated at 2 and 6 hours after exposure and labeled with Cy3 for the irradiated cells and with Cy5 for the control samples before loaded onto the protein microarray chips. The intensities of the protein spots were analyzed using ScanAlyze software and normalized by the summed fluorescence intensities and the housekeeping proteins. Comparison of the overall protein expression profiles in gamma-irradiated cells showed significantly higher inductions at the high dose-rate than at the low dose-rate. The protein profile in cells after the proton exposure showed a much earlier induction pattern in comparison to both the high and low dose-rate gamma exposures. The same expression patterns were also found in individual cell signaling cascades. At 6 hours post irradiation, high dose-rate gamma rays induced cellular protein level changes (ratio to control 2) mostly in apoptosis, cell cycle and cytoskeleton, while low dose-rate gamma rays induced similar changes with smaller fold-change values. In comparison, protons induced protein changes mainly in the cell cycle category. Thus, at the total dose of 2 cGy, high dose-rate gamma rays may generate more cellular responses through protein level and modification changes to regulate cell signaling and cell-cell communication. Protons presented the less effect, possibly due to the different track distribution compared with gamma radiation.

  17. Induction of chromosome aberrations in G0 human lymphocytes by low doses of ionizing radiations of different quality

    International Nuclear Information System (INIS)

    Human peripheral blood lymphocytes from two donors were exposed to low doses (0.05 to 2.0 Gy) of ? rays, X rays, or fast neutrons of different energies. Chromosome aberrations were analyzed in metaphase of first-division cells after a culture time of 45-46 hr. Different dose-response relationships were fitted to the data by using a maximum likelihood method; best fits for radiation-induced dicentric aberrations were obtained with the linear-quadratic law for all radiations. The linear component of this equation predominated, however, for neutrons in the range of doses studied. The RBE increased with decreasing neutron dose and with decreasing neutron energy from d(50)+Be to d(16)+Be neutrons. The limiting RBE at low doses (RBEo) was calculated to be about 1.5 for X rays and 14.0, 6.2, and 4.7 for the d(16)+Be, d(33)+Be, and d(50)+Be neutrons, respectively

  18. Radio-adaptive Response: An Implication for the Biological Consequences of Low Dose-rate Exposure to X-Ray

    International Nuclear Information System (INIS)

    Radiation induced adaptive response is described as the reduced damaging effect of a challenging radiation dose when induced by a previous low priming dose. To verify the radio-adaptive response that can be induced by occupationally (in vivo) received chronic low dose of X-ray, chromosomal aberration (CA) analysis, micronucleus test (MN), interleukin-1? (IL-1?) and nitric oxide (NO) concentrations were investigated for both the occupationally exposed and control groups before and after exposure to 2 Gy ?-rays as a challenge dose. The results showed that an elevated frequency of CA, MN and nucleoplasmic bridge (NPB) was recorded in radiation workers (exposed group) compared to control group. However, after 2Gy in vitro irradiation of lymphocytes of exposed and control groups, the exposed group was found to be lower than that of control group. On the other hand, IL-1? and NO concentrations in plasma were elevated in exposed group more than in control group. While, after 2Gy irradiation for both groups, there are higher increment in the concentrations of IL-1? and NO in exposed group than the increment difference observed for control group after in vitro irradiation as compared to the same group before irradiation. The present results suggested the existence of an in vivo cytogenetic adaptive response in individuals occupationally exposed to low dose of X-ray. In addition, the results showed that NO radicals and IL-1? have a role in the induction of radio-resistance due to in vivo exposure that may intermediate this radiation.

  19. Changing of expression level of fas-antigen (CD95), cytokines synthesis and production after irradiation in low doses

    International Nuclear Information System (INIS)

    It is known that bone marrow progenitor (CD34+), tymocytes and peripheral blood lymphocytes (PBL) are most radiosensitive than other cell types. Even low doses of radiation induce apoptosis. The investigators suggest that it is possible relationship between synthesis and production of cytokines and apoptotic process. With the purpose to determine correlation between expression of Fas-antigen and synthesis of cytokines after low doses irradiation the experiments by irradiation PBL of healthy persons in vitro were held. Cells were X-irradiated by 12,5, 25 and 50 cGy. In consequence of the experiments increasing of Fas-antigen was revealed. This increasing correlated with changing in synthesis and production of cytokines. Also the Chernobyl's accident liquidators (CAL) were investigated. After comparison data in the group CAL (I) with data in the control group (II) increasing of Fas-antigen expression was revealed. Also in I group was discovered increasing of the cell number sinthesied interleukine-4 (IL-4) and interleukine-6 (IL-6). Interleukine-l? (IL-1 ?) producing pell were decreased. These changes have been correlated with degree of immunodeficiency at CAL. These data allow to consider the apoptosis as cell mechanism included in pathogenesis of diseases, which can be showed later long time after irradiation. (author)

  20. Low-dose effects hypothesis and observations on NPP personal

    International Nuclear Information System (INIS)

    In the modern world the use of various sources of ionizing radiation is nearly ubiquitous. They have numerous applications in industry, medicine, science, agriculture, etc. Radiation doses to workers nevertheless are commensurable to the natural background exposure. Published data on the health effects of occupational radiation exposure are often contradictory. Addressing the issue of negative (bystander effects, genomic instability) and positive (adaptive response, radiation hormesis) effects of low doses is important and has a significant social and economic impact. In this paper we summarize the results of our extensive monitoring of nuclear power plant (NPP) staff. We believe it is a cohort suitable for analysis of health effects at low doses, because of their good medical and dosimetric control. Our results rather support the idea of absence of adverse health effects in NPP workers. (author)

  1. Treatment of refractory catatonic schizophrenia with low dose aripiprazole

    Directory of Open Access Journals (Sweden)

    Sasaki Tsuyoshi

    2012-05-01

    Full Text Available Abstract This case is of 54-year-old female with catatonic schizophrenia, characterized by treatment resistance to the pharmacotherapy with olanzapine, risperidone, flunitrazepam, and ECT. Olanzapine and risperidone and flunitrazepam did not improve her catatonic and psychotic symptoms, and induced the extrapyramidal symptoms. The effects of ECT did not continue even for a month. However, the treatment with low-dose aripiprazole dramatically improved the patients psychotic symptoms and extrapyramidal symptoms. The mechanisms underlying the effects of low-dose aripiprazole in this case remain unclear, but unlike other antipsychotics, aripiprazole is a dopamine D2 partial agonist. In this regard, our results suggest that aripiprazole has numerous advantages, especially in cases of stuporous catatonia and a defective general status.

  2. Immunological effect of low dose radiation and its mechanism

    International Nuclear Information System (INIS)

    A series of changes in the immune functions in mice were found after low dose radiation with either single X-rays or continuous ?-rays. The plaque-forming cell (PFC) reaction in the spleen was stimulated. The ratio of Ts to Th did not change. Neither Ts activity in the spleen induced by ConA nor the short life-span Ts activity of splenocytes and thymocytes was inhibited. The T cell functions were activated. DNA, RNA and protein synthesis in the response to ConA were significantly enhanced. The IL-2 production by the splenocytes also increased. Simultaneously, the contents of norepinephrine and epinephrine in the spleen increased and the concentrations of enkephalins in the hypothalamus markedly decreased. These results indicated that the changes of neuroendocrine regulative functions might be involved in the stimulatory effects of immune functions after low dose radiation

  3. Immunological adaptive response induced by low dose X-rays

    International Nuclear Information System (INIS)

    Objective: To find out whether or not low dose radiation could induce resistance to challenge dose-induced depression of immune functions. Methods: The following techniques were employed in this experiment: flow cytometry with immunofluorescence for the expression of TCR/CD3 receptor, 3H-TdR incorporation technique for the spontaneous proliferation of thymocytes and the mitogen-induced proliferation of splenocytes as well as a bioassay with CTLL cells for IL-2 production. Results: The following optimal conditions for the induction of immunological adaptive response were determined: 0.025 to 0.1 Gy for the conditioning doses (D1), 1.0 to 1.5 Gy for the challenge doses (D2), and 6 to 12 h for the intervals between D1 and D2. Conclusion: Immunological adaptive response could be induced by low dose radiation

  4. Cystoid macular edema induced by low doses of nicotinic Acid.

    Science.gov (United States)

    Domanico, Daniela; Carnevale, Carmela; Fragiotta, Serena; Verboschi, Francesca; Altimari, Simona; Vingolo, Enzo Maria

    2013-01-01

    Cystoid macular edema (CME) is a condition that involves the macula, causing painless vision loss. In this paper, we report a case of niacin-induced bilateral cystoid macular edema (CME) in a middle-age woman taking low dose of niacin (18?mg of nicotinic acid). Optical coherence tomography (OCT) showed retinal thickening and cystoid spaces in both eyes, whereas fluorescein angiography (FA; HRA 2, Heidelberg Engineering) revealed the absence of fluorescein leakage also in later phases. Four weeks after discontinuation of therapy there were a complete disappearance of macular edema at funduscopic examination and an improvement of visual acuity in both eyes. Furthermore OCT showed a normal retinal profile in both eyes. In our opinion considering the wide availability of niacin, medical monitoring and periodical examination should be considered during niacin administration. To our knowledge, this is the first report in the literature that described the very low-dose niacin-induced bilateral niacin maculopathy. PMID:23662229

  5. A Case of Lichen Amyloidosis Treated with Low Dose Acitretin

    Directory of Open Access Journals (Sweden)

    Fatma Pelin Cengiz

    2014-12-01

    Full Text Available Primary localized cutaneous amyloidosis (PCA is a rare disorder characterized by amyloid deposition in dermis without systemic involvement. There are three different types of primary localized cutaneous amyloidosis: Lichen amyloidosis, macular amyloidosis and nodular amyloidosis. The lesions of lichen amyloidosis are characterized by pruritic papules. Although, topical or intralesional treatment with corticosteroids, topical dimethyl sulfoxide, ultraviolet B, oral psoralen plus ultraviolet A, retinoic acid derivatives are the recommended treatment for lichen amyloidosis, the results are often unsatisfactory. In the literature, there have been only a few reports evaluating the efficacy of low dose acitretin in the treatment of lichen amiloidosis. In this article, we report a case of lichen amyloidosis with pruritic hyperkeratotic papules on the back and chest of 5 years duration, successfully treated with low dose acitretin.

  6. Pathogenic effects of low dose irradiation: dose-effect relationships

    International Nuclear Information System (INIS)

    There is no evidence of pathogenic effects in human groups exposed to less than 100 mSv at low dose-rate. The attributed effects are therefore the result of extrapolations from higher doses. The validity of such extrapolations is discussed from the point of view of epidemiology as well as cellular and molecular biology. The Chernobyl accident resulted in large excess of thyroid cancers in children; it also raised the point that some actual sanitary effects among distressed populations might be a direct consequence of low doses. Studies under the control of UN have not confirmed this point identifying no dose-effect relationship and 'severe socio-economic and psychological pressures... poverty, poor diet and living conditions, and lifestyle factors' as the main cause for depressed health. Some hypothesis are considered for explaining the dose-dependence and high prevalence of non-cancer causes of death among human groups exposed to more than 300 mSv. (author)

  7. Thioredoxin: Inducible radioprotective protein by low-dose radiation

    International Nuclear Information System (INIS)

    Thioredoxin (TRX), that has many biological activities, is radioprotector and a key protein in regulating cellular functions through redox reaction. We observed time course and dose dependent alteration of TRX gene expression in human peripheral lymphocytes after low-dose irradiation. TRX mRNA level increased to a peak, 5.7-fold higher than the control at maximum, 6 h after irradiation, and then decreased. The optimum radiation dose for enhancement of induction of the TRX mRNA was 0.25 Gy. The TRX protein, also increased to a peak, a 3-fold increase at maximum, with the same timing as that for TRX mRNA. Induction of the expression of TRX gene mess followed after ionizing irradiation of lymphocytes from human donors. The similarity of time course between TRX gene expression and induction of radioadaptive response by low-dose radiation suggests that TRX may be involved in adaptive response. (author)

  8. Effect of low-dose radiation on ocular circulation

    International Nuclear Information System (INIS)

    We treated 6 eyes of unilateral age-related macular degeneration by low-dose radiation. Each eye received daily dose of 2 Gy by 4MV lineac totalling 20 Gy over 2 weeks. Color doppler flowmetry was used to determine the mean blood flow velocity (Vmean) and vascular resistive index (RI) in the short posterior ciliary artery, central retinal artery and ophthalmic artery in the treated and fellow eyes before and up to 6 months of treatment. There were no significant differences in Vmean and RI before and after treatment. The findings show the absence of apparent influence of low-dose radiation on the ocular circulation in age-related macular degeneration. (author)

  9. Low Dose, Low Energy 3d Image Guidance during Radiotherapy

    Science.gov (United States)

    Moore, C. J.; Marchant, T.; Amer, A.; Sharrock, P.; Price, P.; Burton, D.

    2006-04-01

    Patient kilo-voltage X-ray cone beam volumetric imaging for radiotherapy was first demonstrated on an Elekta Synergy mega-voltage X-ray linear accelerator. Subsequently low dose, reduced profile reconstruction imaging was shown to be practical for 3D geometric setup registration to pre-treatment planning images without compromising registration accuracy. Reconstruction from X-ray profiles gathered between treatment beam deliveries was also introduced. The innovation of zonal cone beam imaging promises significantly reduced doses to patients and improved soft tissue contrast in the tumour target zone. These developments coincided with the first dynamic 3D monitoring of continuous body topology changes in patients, at the moment of irradiation, using a laser interferometer. They signal the arrival of low dose, low energy 3D image guidance during radiotherapy itself.

  10. Irradiation - Patients - mechanisms of Action of adult stem cells on radiation-induced inflammation

    International Nuclear Information System (INIS)

    Radiotherapy is essential for treating pelvic cancers. Its aim is to control the tumor while minimizing damage to surrounding healthy tissues, as such damage can lead to gastro-intestinal complications that can sometimes be severely incapacitating. IRSN's research seeks to improve understanding of the physiopathology of radiation-induced lesions to develop treatments that provide better protection of healthy tissue. (author)

  11. Effects of low doses; Effet des faibles doses

    Energy Technology Data Exchange (ETDEWEB)

    Le Guen, B. [Electricite de France (EDF-LAM-SCAST), 93 - Saint-Denis (France)

    2001-07-01

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  12. Role of animal studies in low-dose extrapolation

    International Nuclear Information System (INIS)

    Current data indicate that in the case of low-LET radiation linear, extrapolation from data obtained at high doses appears to overestimate the risk at low doses to a varying degree. In the case of high-LET radiation, extrapolation from data obtained at doses as low as 40 rad (0.4 Gy) is inappropriate and likely to result in an underestimate of the risk

  13. Cystoid Macular Edema Induced by Low Doses of Nicotinic Acid

    OpenAIRE

    Daniela Domanico; Carmela Carnevale; Serena Fragiotta; Francesca Verboschi; Simona Altimari; Enzo Maria Vingolo

    2013-01-01

    Cystoid macular edema (CME) is a condition that involves the macula, causing painless vision loss. In this paper, we report a case of niacin-induced bilateral cystoid macular edema (CME) in a middle-age woman taking low dose of niacin (18?mg of nicotinic acid). Optical coherence tomography (OCT) showed retinal thickening and cystoid spaces in both eyes, whereas fluorescein angiography (FA; HRA 2, Heidelberg Engineering) revealed the absence of fluorescein leakage also in later phases. Four we...

  14. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    OpenAIRE

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2012-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsycholog...

  15. Biological effects of low doses of ionising radiation

    International Nuclear Information System (INIS)

    A study was performed with the aim to examine whether the progeny of cells that had been repeatedly irradiated with low doses of gamma rays will change their sensitivity to cytotoxic agents. Four mammalian cell lines were used in the experiment. It was found that the progeny of cells irradiated in this way do not change their sensitivity to gamma rays but would change their sensitivity to various cytostatics drugs. (A.K.)

  16. Exercise and Sport Performance with Low Doses of Caffeine

    OpenAIRE

    Spriet, Lawrence L.

    2014-01-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (513mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (

  17. Low-Dose Naltrexone for Pruritus in Systemic Sclerosis

    OpenAIRE

    Tracy Frech; Kirsten Novak; Revelo, Monica P.; Maureen Murtaugh; Boaz Markewitz; Nathan Hatton; Mary Beth Scholand; Edward Frech; David Markewitz; Sawitzke, Allen D.

    2011-01-01

    Pruritus is a common symptom in systemic sclerosis (SSc), an autoimmune disease which causes fibrosis and vasculopathy in skin, lung, and gastrointestinal tract (GIT). Unfortunately, pruritus has limited treatment options in this disease. Pilot trials of low-dose naltrexone hydrochloride (LDN) for pruritus, pain, and quality of life (QOL) in other GIT diseases have been successful. In this case series we report three patients that had significant improvement in pruritus and total GIT symptoms...

  18. Early Outcomes Following Low Dose Naltrexone Enhancement of Opioid Detoxification

    OpenAIRE

    Mannelli, Paolo; Patkar, Ashwin A.; Peindl, Kathleen; Gottheil, Edward; Wu, Li-tzy; Gorelick, David A.

    2009-01-01

    Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) o...

  19. Therapeutic rationale for low dose doxepin in insomnia patients

    OpenAIRE

    Katwala, Jigar; Kumar, Ananda K; Sejpal, Jaykumar J; Terrence, Marcelle; Mishra, Manish

    2013-01-01

    Histamine is an excitatory neurotransmitter in central nervous system. It plays an important role in the regulation of the sleep-wake cycle. Antidepressant with sleep-promoting effects, for example, doxepin, promotes sleep not through a sedative action but through resynchronisation of circadian cycle. The stimulation of the H1 receptor is thought to play an important role in mediating arousal. Doxepin has a high affinity for the H1 receptor, making it a selective H1 antagonist at low dose and...

  20. Ageing effects of polymers at very low dose-rates

    International Nuclear Information System (INIS)

    The equipment irradiation dose-rate into the containment is variable from 10-6 to 10-4 gray per second for the most exposed materials. During qualification, safety equipments are submitted in France to dose-rates around 0.28 gray per second. This study purpose is to now if a so large irradiation dose-rate increase is reasonable. Three elastomeric materials used in electrical cables, o'rings seals and connectors, are exposed to a very large dose-rates scale between 2.1.10-4 and 1.4 gray per second, to 49 KGy dose. This work was carried out during 3.5 years. Oxygen consumption measurement of the air in contact with polymer materials, as mechanical properties measurement show that: - at very low dose-rate, oxygen consumption is maximum at the same time (1.4 year) for the three elastomeric samples. Also, mechanical properties simultaneously change with oxygen consumption. At very low dose-rate, for the low irradiation doses, oxygen consumption is at least 10 times more important that it is showed when irradiation is carried out with usual material qualification dose-rate. At very low dose-rate, oxygen consumption decreases when absorbed irradiation dose by samples increases. The polymer samples irradiation dose is not still sufficient (49 KGy) to certainly determine, for the three chosen polymer materials, the reasonable irradiation acceleration boundary during nuclear qualification tests

  1. Exercise and sport performance with low doses of caffeine.

    Science.gov (United States)

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (body mass,~200mg) are also ergogenic in some exercise and sport situations, although this has been less well studied. Lower caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200mg of caffeine before and/or during training and competitions is ergogenic on an individual basis. PMID:25355191

  2. Health surveys, epidemiology and low-dose radiation risks

    International Nuclear Information System (INIS)

    In the past decade, several international studies on population groups exposed to low radiation doses have arrived at varied conclusions. While the residential radon studies in North America and Europe and the 15 country pooled study of occupational workers conducted by International Agency of Research on Cancer (IARC) have shown positive indications of risks at moderate exposure levels, the results of studies on elevated natural background radiation areas in India and China have not yielded any excess risks. Also, the recent studies on the low dose groups of the Japanese A-Bomb survivor populations suggest elevated risks for certain noncancer diseases. These results have been debated in considerable detail by international bodies such as UNSCEAR, ICRP and WHO in order to develop a balanced and integrated view o flow dose radiation risks. Although it is quite clear that it is impossible to detect radiation attributable health effects at doses below 100 mSv, several questions are being raised by general public and press regarding instituting epidemiological study programmes in the vicinity of nuclear facilities, Efforts have also been made in some quarters to establish causal relations from the data of various health surveys conducted for different purposes, without first examining whether they really qualify to be epidemiological studies. This presentation discusses these issues in the light of an overwhelming body of international opinion on low dose questions and prional opinion on low dose questions and principles of radiation epidemiology. (author)

  3. Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females

    International Nuclear Information System (INIS)

    Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5 Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results snesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes

  4. Radiation-induced transmission spectral variations of Ce3+-doped heavy germanate glasses

    International Nuclear Information System (INIS)

    Radiation-induced transmission spectral variations of Ce3+-doped heavy germanate glasses used as scintillating materials are presented. Glass matrix contains mainly GeO2, BaO and Gd2O3 with a density higher than 5 g/cm3. Glasses are melted in the different atmosphere. The transmission spectra of glasses before and after radiation treatments are measured and compared. Unlike exhibiting the monotonous deterioration effect on the glass matrix, radiation plays the radiation protection role, even making enhanced transmission of Ce3+-doped glasses, depending upon glass melting atmosphere and radiation dose. Radiation-induced reducing and oxidizing mechanism is proposed to explain phenomena

  5. Radiation induced membrane effects at the apoptotic cell death

    International Nuclear Information System (INIS)

    Lymphocytes are rather sensitive towards radiation induced apoptosis. The hypothesis can be tried that the cellular membrane (or intracellular membranes) be the primary target for the radiation induced apoptosis. Chemically induced and radiation induced apoptosis follow, at least partially, common mechanistic patterns. It involves a fluidisation of the cellular membrane. Rigidisation of the membrane by incorporation of cholesterol interferes with the radiation induced apoptosis. (orig.)

  6. Plants as warning signal for exposure to low dose radiation

    International Nuclear Information System (INIS)

    The stamen-hair system of Tradescantia for flower colour has proven to be one of the most suitable materials to study the frequency of mutations induced by low doses of various ionizing radiations and chemical mutagens. The system has also been used successfully for detecting mutagenic synergisms among chemical mutagens and ionizing radiations as well as for studying the variations of spontaneous mutation frequency. In this study of radiobiology, the main objective is to observe somatic mutation (occurrence of pink cells from blue cells) induced on stamen hairs of five Tradescantia sp. available in Malaysia after exposure to low doses of chronic gamma irradiation using Gamma Green House. Pink cells appeared only on Tradescantia Pallida Purpurea stamen hairs after 13 days of exposure to irradiation with different doses of gamma rays. The highest number of stamens with pink cells was recorded from flowers irradiated with the highest dose of 6.37 Gy with 0.07 Gy/ h of dose rate. The lowest number of stamens with pink cells was recorded with an average of 0.57, irradiated with the lowest dose of 0.91 Gy with 0.01 Gy/ h of dose rate. There were no pink cells observed on Tradescantia Spathaceae Discolor after exposure to different doses of gamma rays. Similar negative results were observed for the control experiments. The principal cells in this assay are the mitotic stamen hair cells developing in the young flower buds. After exposure to radiation, the heterozygous dominant blue character of the stamen hair cell is prevented, resulting in the appearance of the recessive pink color. Furthermore, no pink cell appears on all species of Tradescantia spathaceae after irradiated with different doses of gamma rays. The sensitivity of the Tradescantia has been used widely and has demonstrated the relation between radiation dose and frequency of mutation observed at low doses which can contribute to the effects of low doses and their consequences for human health. This system carries the advantage of observing meaningful data in a short period of time, being able to meditate effects on human health and to prevent possible accidents, when adopted as periodical monitoring. Tradescantia Pallida Purpurea can be regarded as a biosensor plant or a biological warning signal for exposure to low dose radiation which exhibits a noticeable quantity of cell alteration in a short time following exposure to radiation. Hence, the effects caused on the environment might be anticipated, and by extension on the human being, as a result of its occupation exposition level. The use of this method can be recommended for radiation monitoring, therefore into the environment acclimatization, and may be used, in addition, in the prevention of radiological accidents. (author)

  7. Implication of prostaglandins and histamine H1 and H2 receptors in radiation-induced temperature responses of rats

    International Nuclear Information System (INIS)

    Exposure of rats to 1-15 Gy gamma radiation (60Co) induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxygenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu-receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H1 and H2 receptors may be involved in radiation-induced hypothermia, since both the H1 receptor antagonist, mepyramine, and H2 receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggest that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiationsting from accidental irradiations

  8. Micronuclei: sensitivity for the detection of radiation induced damage

    International Nuclear Information System (INIS)

    The in vitro cytokinesis-block (CB) micronucleus (MN) assay for human peripheral blood has been used extensively for the assessment of chromosomal damage induced by ionizing radiation and chemicals and considered a suitable biological dosimeter for estimating in vivo whole body exposures, particularly in the case of large scale radiation accidents. One of the major drawbacks of the MN assay is its reduced sensitivity for the detection of damage induced by low doses of low LET radiation, due to the high variability among the spontaneous MN frequencies. It is suggested that age, smoking habit and sex are the main confounding factors that contribute to the observed variability. Previous work in our laboratory, shows a significant positive correlation of the spontaneous and radiation induced MN frequencies with age and smoking habit, the latter being the strongest confounder. These findings led to in vitro studies of the dose-response relationships for smoking and non smoking donors evaluated separately, using 60Co ? rays. The objectives of the present work are: 1-To increase the amount of data of the dose-response relationships, using ? rays from a 60Co source, for smoking and non smoking donors, in order to find, if applicable, a correction factor for the calibration curve that takes into account the smoking habit of the individual in the case of accidental overexposure dose assessment, particularly in the low dose range. 2-To establish general conclusions on the current state of the technique. The sample for smoking and non smoking calibration curves was enlarged in the range of 0Gy to 2Gy. The fitting of both curves, performed up to the 2Gy dose, resulted in a linear quadratic model. MN distribution among bi nucleated cells was found to be over dispersed with respect to Poisson distribution, the average ratio of variance to mean being 1.13 for non smokers and 1.17 for smokers. Each fitted calibration curve, for smoking and non smoking donors, fell within the 95% confidence curves of the other, with the exception of the spontaneous frequency values of both calibration curves. Thus, for the accidental overexposure dose assessment it seems to be appropriate to use a pooled data (smokers + non smokers) calibration curve and in the case of dose assessment up to 0.5Gy, it is convenient to use the corresponding spontaneous term in the yield equation; associated to the individual smoking habit condition. General conclusions: 1-The high and variable spontaneous MN frequency prevents an adequate dose estimation below 0.2-0.3Gy of low LET radiation. 2-At high doses, of low LET radiation, the sensitivity of the MN test is lower than the conventional aberration methods (dicentrics) due to the smaller squared term in the yield equation. 3-Radiation induced MN tend to be over dispersed with respect to Poisson distribution. Over dispersion increases the standard error on the observed yield and thus the uncertainties on the dose estimation. (author)

  9. Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract.

    Science.gov (United States)

    Sinha, Mahuya; Das, Dipesh Kr; Datta, Sanjukta; Ghosh, Santinath; Dey, Sanjit

    2012-03-01

    Protective effect of Moringa oleifera leaf extract (MoLE) against radiation-induced lipid peroxidation has been investigated. Swiss albino mice, selected from an inbred colony, were administered with MoLE (300 mg/kg body wt) for 15 days before exposing to a single dose of 5 Gy 60Co-gamma radiation. After treatments, animals were necropsied at different post irradiation intervals (days 1, 7 and 15) and hepatic lipid peroxidation and reduced glutathione (GSH) contents were estimated to observe the relative changes due to irradiation and its possible amelioration by MoLE. It was observed that, MoLE treatment restored GSH in liver and prevented radiation induced augmentation in hepatic lipid peroxidation. Phytochemical analysis showed that MoLE possess various phytochemicals such as ascorbic acid, phenolics (catechin, epicatechin, ferulic acid, ellagic acid, myricetin) etc., which may play the key role in prevention of hepatic lipid peroxidation by scavenging radiation induced free radicals. PMID:22439436

  10. Mint oil (Mentha spicata Linn.) offers behavioral radioprotection: a radiation-induced conditioned taste aversion study.

    Science.gov (United States)

    Haksar, A; Sharma, A; Chawla, R; Kumar, Raj; Lahiri, S S; Islam, F; Arora, M P; Sharma, R K; Tripathi, R P; Arora, Rajesh

    2009-02-01

    Mentha spicata Linn. (mint), a herb well known for its gastroprotective properties in the traditional system of medicine has been shown to protect against radiation-induced lethality, and recently its constituents have been found to possess calcium channel antagonizing properties. The present study examined the behavioral radioprotective efficacy of mint oil (obtained from Mentha spicata), particularly in mitigating radiation-induced conditioned taste aversion (CTA), which has been proposed as a behavioral endpoint that is mediated by the toxic effects of gamma radiation on peripheral systems, primarily the gastrointestinal system in the Sprague-Dawley rat model. Intraperitoneal administration of Mentha spicata oil 10% (v/v), 1 h before 2 Gy gamma radiation, was found to render significant radioprotection against CTA (p Mentha spicata can be effectively utilized in preventing radiation-induced behavioral changes. PMID:18853399

  11. Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract

    International Nuclear Information System (INIS)

    Protective effect of Moringa oleifera leaf extract (MoLE) against radiation-induced lipid peroxidation has been investigated. Swiss albino mice, selected from an inbred colony, were administered with MoLE (300 mg/kg body wt) for 15 days before exposing to a single dose of 5 Gy 60Co-gamma radiation. After treatments, animals were necropsied at different post irradiation intervals (days 1, 7 and 15) and hepatic lipid peroxidation and reduced glutathione (GSH) contents were estimated to observe the relative changes due to irradiation and its possible amelioration by MoLE. It was observed that, MoLE treatment restored GSH in liver and prevented radiation induced augmentation in hepatic lipid peroxidation. Phytochemical analysis showed that MoLE possess various phytochemicals such as ascorbic acid, phenolics (catechin, epicatechin, ferulic acid, ellagic acid, myricetin) etc., which may play the key role in prevention of hepatic lipid peroxidation by scavenging radiation induced free radicals. (author)

  12. Detection of DNA damage in mouse tissue cells induced by low dose or low dose-rate irradiation

    International Nuclear Information System (INIS)

    We modified a single cell gel electrophoresis assay (cement assay) to detect DNA damage induced by X-rays as low as 50mGy in peripheral blood lymphocytes and 100mGy in splenocytes in mice. We compared the amount of DNA damage in the splenocytes induced by 0.5Gy of X-rays at a high dose-rate (1.6Gy/min) and that by the same dose of gamma-rays at a low dose rate (1.2mGy/hr), subsequently observing a significant increase after the high dose rate but no significant increase after the low dose-rate irradiation. We also examined the effect of low dose rate pre-irradiation on the amount of DNA damage by 1Gy X-rays. A certain decrease, though not significant, was observed by a pre-irradiation of 0.5Gy at 1.2 mGy/hr. (author)

  13. European low-dose radiation risk research strategy: future of research on biological effects at low doses.

    Science.gov (United States)

    Salomaa, Sisko; Averbeck, Dietrich; Ottolenghi, Andrea; Sabatier, Laure; Bouffler, Simon; Atkinson, Michael; Jourdain, Jean-Ren

    2015-04-01

    In 2009, the European High Level and Expert Group identified key policy and scientific questions to be addressed through a strategic research agenda for low-dose radiation risk. This initiated the establishment of a European Research Platform, called MELODI (Multidisciplinary European Low Dose Research Initiative). In 2010, the DoReMi Network of Excellence was launched in the Euratom 7th Framework Programme. DoReMi has acted as an operational tool for the sustained development of the MELODI platform during its early years. A long-term Strategic Research Agenda for European low-dose radiation risk research has been developed by MELODI. Strategic planning of DoReMi research activities is carried out in close collaboration with MELODI. The research priorities for DoReMi are designed to focus on objectives that are achievable within the 6-y lifetime of the project and that are in areas where stimulus and support can help progress towards the longer-term strategic objectives. PMID:25520379

  14. Radiation-induced preventive bystander response and adaptive response

    International Nuclear Information System (INIS)

    Radiation-induced bystander response (BR) is a phenomenon not observed in cells irradiated directly but in cells nearby. Recently, the relationship between BR and adaptive response (AR) has been studied and BR is suggested to be one of important mechanisms involved in AR induction through key molecules like reactive oxygen (RO) and nitrogen species. In this paper, the possible contribution of BR to AR is discussed on recent findings including author's ones. Many biological responses in bystander cells, cultured tissues and mice by cell-cell communication molecules