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Sample records for low-dose radiation-induced protective

  1. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    Ali, Haytham [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Galal, Omima [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Abdelrahim, Eman [Department of Medical Histology, Qena Faculty of Medicine, South Valley University (Egypt); Ono, Yusuke [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Mostafa, Emtethal [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Li, Tao-Sheng, E-mail: litaoshe@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2014-09-26

    Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.

  2. The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

    Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit+ stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit+ stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit+ stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms

  3. Radiation-induced stress effects following low dose exposure

    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 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 ionizing radiation induced acoustic neuroma: A putative link?

    Sachin A Borkar

    2012-01-01

    Full Text Available Although exposure to high dose ionizing radiation (following therapeutic radiotherapy has been incriminated in the pathogenesis of many brain tumors, exposure to chronic low dose ionizing radiation has not yet been shown to be associated with tumorigenesis. The authors report a case of a 50-year-old atomic reactor scientist who received a cumulative dose of 78.9 mSv over a 10-year period and was detected to have an acoustic neuroma another 15 years later. Although there is no proof that exposure to ionizing radiation was the cause for the development of the acoustic neuroma, this case highlights the need for extended follow-up periods following exposure to low dose ionizing radiation.

  5. Low-dose radiation-induced endothelial cell retraction

    The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema. (author)

  6. Low-dose radiation-induced endothelial cell retraction

    Kantak, S.S.; Onoda, J.M. (Wayne State Univ., Detroit, MI (United States). School of Medicine); Diglio, C.A. (Wayne State Univ., Detroit, MI (United States). School of Medicine Harper Hospital, Detroit, MI (United States). Gershenson Radiation Oncology Center)

    1993-09-01

    The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema. (author).

  7. Low dose radiation induced bystander effect and its mechanism

    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)

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

    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...

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

    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...

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

    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...

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

    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)

  12. Radiation-induced cancer from low doses of ionizing radiation: risk analysis using the cell dose concept

    High doses of ionizing radiations are known to bear the risk of cancer to the exposed individual. In order to appreciate potential carcinogenesis from low doses also, the action of ionizing radiation in the human body has to be considered in holistic approach: energy depositions to individual cells trigger effects within a hierachical structure of interacting levels of biological systems, consisting consecutively of atoms, molecules, cells and organ tissue. The present paper describes the cell dose concept which is an essential factor in assessing the risk due to the ionizing radiation to the cells and tissues. Low dose of ionizing radiation induces adaptive response in individual cells which could be linked to the action of molecular radicals. Enzyme activities in bone marrow cells and bilayer lipid membranes and radicals are directly related to radiation effects. Temporary improvements of the detoxification of molecular radicals also improve the cellular defence. The risk analysis calls for more attention as it is important for radiation protection and other beneficial effects due to low doses of irradiation. (author). 18 refs

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

    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)

  14. Influence of adaptative response to low dose radiation on radiation-induced thymic lymphoma in mice

    Objective: To search for influence of low dose radiation (LDR) on thymic lymphoma (TL) induced by carcinogenic dose radiation in C57BL /6J mice and its immunologic mechanism. Methods: The model was adopted that C57BL/6J mice were subjected to whole body irradiation with 1.75 Gy X-ray once every week for 4 weeks to induce TL. The incidence of TL was observed by microscopy 6 months after irradiation. The following indexes were examined:splenic NK cytotoxic activity, IL-2 and γ- IFN secretion activity, peritoneal macrophage phagocytosis and its TNFα secretion activity, the changes of thymocyte differentiation in mice irradiated with different dose 1 month after irradiation. Results: The incidences of Tl in mice irradiated with 25mGy or 75m Gy 6h or 12h before 1.75Gy irradiation were all lower than that in mice irradiated with 1.75Gy only, and it is more obvious in mice irradiated with 75mGy prior to carcinogenic dose radiation. Immune parameters mentioned above in mice irradiated with 75mGy 12h before 1.75Gy were higher than those in mice irradiated with 1.75 only and the majority approached to those of the sham-irradiated mice. The number of thymic CD4-CD8 cells or CD4-CD8- cells was lower and CD4+CD 8+ cells was higher in mice irradiated with 75mGy 12h before 1.75Gy than that in mice irradiated with 1.75Gy only. Conclusion: LDR can induce the adaptative response of radiation-induced TL, and prevent or reduce the onset of radiation-induced TL. The suppression mechanism may be related to the immuno-enhancement effect and the adaptive response induced by LDR, decreasing immune function damage caused by carcinogenic dose radiation, eliminating thymic pre-lymphoma cells before they from solid tumor

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

    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)

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

    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 €œSystems 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.

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

    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 low level of radiation may induce protective mechanisms against a relatively large radiation event. - Analysis of signal transduction pathways in CD4+ T cells showed that whole-body priming with 0.01 Gy photons before exposure to simulated SPE protons significantly increased expression of p38MAPK and NF-kappaB, while JNK expression was decreased. Overall, it appears that the p38MAPK signaling pathway may be most important in inducing a radioprotective response.

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

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

    2014-01-01

    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 hema...

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

    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 γ-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 μg 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

  20. Gamma ray radiation induced visible light absorption in P-doped silica fibers at low dose levels

    Lu Ping; Kulkarni, N S; Brown, K

    1999-01-01

    A CCD Fiber Optic Spectrometer has been used to monitor the gamma ray radiation induced loss in P-doped fibers at different dopant concentrations (1, 5 and 10 mol%) with a light source (an incandescent bulb with a temperature of 2800-3000 K). The range of dose rates is limited to that used in medical applications (cancer treatments), that is 0.1 to 1.0 Gray per minute (Gy/min). At low integral dose level (<2.0 Gy) four absorption peaks were observed (470, 502, 540 and 600 nm) within the visible region. It has been observed that the radiation induced loss at 470 and 600 nm depends strongly on dose rate. At dose rates of 0.2 and 0.5 Gy/min the induced loss shows nonlinear relation to the total dose. However, at high dose rate (1.0 Gy/min) and low dose rate (0.1 Gy/min) it seems to have a linear dependence with total dose. The conversion from NBOHCs to GeX centers was observed during gamma radiation at low dose rates (0.1-0.5 Gy/min). At the wavelength of 502 and 540 nm, the radiation induced losses show exce...

  1. Spontaneous and radiation-induced micronucleus frequencies in low dose radiation exposed worker's peripheral blood lymphocytes

    Many studies have been performed to assess the development and application of potentially useful biodosimetry. At present, although chromosome dicentric assay is a sensitive method for dose estimation, it is laborious and requires enough experience for estimation, and without automation its scope for population screening is limited. Therefore, we need an alternative cytogenetic dosimetry to estimate the absorbed dose of victims after low dose exposure such as radiation accidents in hospital workers and workers of radiation related facilities. An alternative and simple cytogenetic technique is the measurement of the micronucleus frequency in cultured human lymphocytes. The reliability of conventional micronucleus (MN) assays is diminished owing to the inclusion of nondividing cells in the estimate, but this problem has been overcome by the development of the cytokinesisblocked (CB) MN assay. The reliable and ease assays of the cytokinesis blocked-approach are obvious advantages in biological monitoring, but there are no developed recognizable and reliable techniques for biological dosimetry of a low dose exposure until recently. Adaptive response is important in determining the biological responses at low doses of radiation and has the potential to impact the shape of the dose-response relationship. We analyzed the frequency of both spontaneous and in vitro 137Cs γ-rays-induced MNs to estimate the low dose radiation-exposed workers as a screening test

  2. cDNA cloning and transcriptional controlling of a novel low dose radiation-induced gene and its function analysis

    Objective: To clone a novel low dose radiation-induced gene (LRIGx) and study its function as well as its transcriptional changes after irradiation. Methods: Its cDNA was obtained by DDRT-PCR and RACE techniques. Northern blot hybridization was used to investigate the gene transcription. Bioinformatics was employed to analysis structure and function of this gene. Results: LRIGx cDNA was cloned. The sequence of LRIGx was identical to a DNA clone located in human chromosome 20 q 11.2-12 Bioinformatics analysis predicted an encoded protein with a conserved helicase domain. Northern analysis revealed a ∼8.5 kb transcript which was induced after 0.2 Gy as well as 0.02 Gy irradiation, and the transcript level was increased 5 times at 4 h after 0.2 Gy irradiation. The induced level of LRIGx transcript by 2.0 Gy high dose was lower than by 0.2 Gy. Conclusion: A novel low dose radiation-induced gene has been cloned. It encodes a protein with a conserved helicase domain that could involve in DNA metabolism in the cellular process of radiation response

  3. Radiation-induced apoptosis in SCID Mousespleen after a low-dose irration

    Ohnishi, T.; Takahashi, A.; Ohnishi, K.

    Purpose: To estimate the effects of space radiation on health of space crews, we aimed to clarify whether pre-irradiation at a low-dose interferes in a p53-centered signal transduction pathway induced by radiation. By using a severe combined immunodeficiency (Scid) mouse defective DNA-PK activity, we examined the role of DNA-PK activity in radioadaptation induced by low-dose irradiation. Methodology: Specific pathogen free 5-week-old fe male mice of Scid and the parental mice (CB-17 Icr+/+) were irradiated with X-rays at 3.0 Gy 1, 2, 3 or 4 weeks after conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after irradiation. Bax on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method using HISTOFINE SAB-PO(R) kit (Nichirei Co., Tokyo, Japan). Apoptosis incidence in the sections was measured by staining with HE staining. Results: The frequency of Bax- and apoptosis -positive cells increased up to 12 h after irradiation at 3.0 Gy in the spleen of CB-17 Icr+/+ and Scid mice. However, they were not observed by irradiation with low dose at 0.15-0.60 Gy. When pre-irradiation at 0.45 Gy 2 weeks before challenging acute irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by irradiation at 3.0 Gy was depressed in the spleen of CB-17 Icr+/+ mice, but not Scid mice. Conclusions: These data suggest that DNA-PKcs (expressed in CB-17 Icr+/+, not Scid mice) might play a major role on radioadaptation induced by pre-irradiation at low dose in mice spleen. We expect that the present findings will provide useful information for the care of space crews' health.

  4. Bio-markers for low dose radiation-induced delayed health effects: oncogenes and growth factors

    The pathophysiological and delayed health effects of high dose radiation exposures have been well documented while the molecular pathways leading to late effects are currently being studied. The discovery that specific genes and their encoded products are involved in those pathways, may provide new targets for intervention. Several molecular 'bio-markers' already identified include specific oncogenes, transcription factors, cytokines, and growth factors. In contrast, delayed health effects due to low dose radiation exposures have not been well characterized and it is unknown if molecular pathways similar to those implicated in cellular response to high dose radiation are involved. We initiated a study to identify molecular bio-markers involved in cellular response to low dose radiation. Using the same in vivo model which previously demonstrated a correlation between radiation injury induced by low dose 60Co and the development of neoplastic disease, our laboratory began a study to determine if exposure to fractionated low-dose gamma radiation in rodents activated the expression of specific oncogene/proto-oncogenes; specifically, genes that are associated with the initiation of neoplastic growth in specific organs, e.g. lung. Results with the in vivo model demonstrated that repeated exposure to 60Co gamma radiation (25 cGy/week/8 weeks) of B6CF1 mice resulted in the activation of specific oncogenes associated with the initiation of neoplastic growth. Northern analysis of animal tissues demonstrated that ras, myc, bcl2, and fos were elevated in both lung and liver tissues 232 days following the radiation regimen. In contrast, lung tissues from animals not exposed to radiation demonstrated only a slight elevation in myc expression; no changes in other oncogenes were detected. (authors)

  5. Radiation induced activation of angiotensin-converting enzyme at low doses of irradiation

    Behaviour of angiotensin-converting enzyme, horseradish peroxidase under in vitro low dose ?- and X-irradiation is studied. Existence takes place of the molecular mechanism of enzyme response to irradiation the key moment of which is in the periodicity of modifications causing the activation and (or) inactivation. Tryptophan and tyrasine residues is supposed to play the considerable role in the appearance of these conformational oscillations

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

    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

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

    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.

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

    Jacob, Peter, E-mail: Jacob@helmholtz-muenchen.de [Helmholtz Zentrum Muenchen, Institute of Radiation Protection, 85764 Neuherberg (Germany); Meckbach, Reinhard; Kaiser, Jan Christian [Helmholtz Zentrum Muenchen, Institute of Radiation Protection, 85764 Neuherberg (Germany); Sokolnikov, Mikhail [Southern Urals Biophysics Institute, Ozyorsk 456780 (Russian Federation)

    2010-05-01

    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.

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

    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.

  10. Low dose rate ionizing radiation induces increased growth capacities of d-deletion retinoblastoma skin fibroblasts

    Skin fibroblasts from normal children and three children with a 13q deletion retinoblastoma (Rb) were exposed to cumulative low doses of gamma rays. The typical response of normal donors was a reduction in the lifespan of irradiated fibroblasts, the precocity of the decline being inversely related to the dose received. In constrast, the lifespan of one Rb cell line (Rb1) was prolonged; irradiated cells with an increased growth potential showed a higher number of cells at confluency and more cells were entering DNA synthesis phase than in non-irradiated cells. Another Rb cell line (Rb2) demonstrated a normal lifespan following irradiation but foci were observed in irradiated cultures. Cytogenetic analysis revealed no selection of abnormal clones in these cell populations. The third Tb line examined (Rb3) responded like a normal cell line. It is suggested that irradiated skin fibroblasts derived from some patients with Rb are in certain cases able to express abnormal growth capacities which may be one of the manifestations of the high susceptibility of the individual's stromal cells to carcinogenic agents. (author)

  11. High and Low Doses of Ionizing Radiation Induce Different Secretome Profiles in a Human Skin Model

    Zhang, Qibin; Matzke, Melissa M.; Schepmoes, Athena A.; Moore, Ronald J.; Webb-Robertson, Bobbie-Jo M.; Hu, Zeping; Monroe, Matthew E.; Qian, Weijun; Smith, Richard D.; Morgan, William F.

    2014-03-18

    It is postulated that secreted soluble factors are important contributors of bystander effect and adaptive responses observed in low dose ionizing radiation. Using multidimensional liquid chromatography-mass spectrometry based proteomics, we quantified the changes of skin tissue secretome – the proteins secreted from a full thickness, reconstituted 3-dimensional skin tissue model 48 hr after exposure to 3, 10 and 200 cGy of X-rays. Overall, 135 proteins showed statistical significant difference between the sham (0 cGy) and any of the irradiated groups (3, 10 or 200 cGy) on the basis of Dunnett adjusted t-test; among these, 97 proteins showed a trend of downregulation and 9 proteins showed a trend of upregulation with increasing radiation dose. In addition, there were 21 and 8 proteins observed to have irregular trends with the 10 cGy irradiated group either having the highest or the lowest level among all three radiated doses. Moreover, two proteins, carboxypeptidase E and ubiquitin carboxyl-terminal hydrolase isozyme L1 were sensitive to ionizing radiation, but relatively independent of radiation dose. Conversely, proteasome activator complex subunit 2 protein appeared to be sensitive to the dose of radiation, as rapid upregulation of this protein was observed when radiation doses were increased from 3, to 10 or 200 cGy. These results suggest that different mechanisms of action exist at the secretome level for low and high doses of ionizing radiation.

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

    Furlong, Hayley, E-mail: hayley.furlong@dit.ie [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Mothersill, Carmel [Medical Physics and Applied Radiation Sciences, Nuclear Research Building, 1280 Hamilton, Ontario L8S 4K1 (Canada); Lyng, Fiona M. [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Howe, Orla [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland)

    2013-01-15

    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.

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

    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

  14. Risk of induced cancer by low doses and dose for the radiation protection rate

    With developing knowledge of the effects of ionising radiation, interest has increasingly focused on the effects of low doses and how information on dose response relationships can be used fro setting limits on exposure both for persons who are occupationally exposed and for members of the public. It is now believed that any radiation dose is capable of inducing cancer in exposed persons and that the probability of its occurrence, but not it's severity, depends on the radiation dose. The main source of quantitative information on the risks of radiation-induced cancer comes from the long-term follow-up of the survivors of the atomic bombs in Hiroshima and Nagasaki. This database provides information on a population of more than 90,000 people followed up since 1950 with individuals of different ages exposed to whole body radiation. Information from this follow-up is supplemented by studies on persons exposed for medical reasons, either to external radiation or incorporated radionuclides, and people who have been exposed occupationally, in particular, miners exposed to radon and its decay products and luminisers exposed to radium. In it's most recent 1990 recommendations, the International Commission on Radiological Protection in Publication 60 (ICRP, 1991 a), re-assessed the epidemiological data and this resulted in an increase in estimates of the risks of radiation-induced cancer. Partly this arose as a result of revised dosimetry for the A-bomb survivors and a longer follow-up of the population, but mainly it was attributed to a change in the model now used to project lifetime risks. The development of the risks coefficients for radiation-induced cancer both for the working population and for members of the public, given in Publication 60 are described in this paper, with particular emphasis on the assessment of risks at low doses. More recent data are also included. (Author)

  15. Estrogen Protects against Radiation-Induced Cataractogenesis

    Dynlacht, Joseph R; Valluri, Shailaja; Lopez, Jennifer; Greer, Falon; DesRosiers, Colleen; Caperell-Grant, Andrea; Mendonca, Marc S.; Bigsby, Robert M.

    2008-01-01

    Cataractogenesis is a complication of radiotherapy when the eye is included in the treatment field. Low doses of densely ionizing space radiation may also result in an increased risk of cataracts in astronauts. We previously reported that estrogen (17-β-estradiol), when administered to ovariectomized rats commencing 1 week before γ irradiation of the eye and continuously thereafter, results in a significant increase in the rate and incidence of cataract formation and a decreased latent period...

  16. Spontaneous and radiation-induced micronucleus frequencies in low dose radiation exposed worker's peripheral blood lymphocytes

    Kwon, Hee Kyung; Lee, Hye Jin; Park, Mi Young; Park, Hyun Jin; Kim, Tae Hwan [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Ji, Young Hoon; Kim, Ki Sup; Lee, Su Jae; Lee, Yun Sil; Cho, Chul Koo; Choi, Soo Yong; Kang, Chang Mo [Kyungpook National Univ., Daegu (Korea, Republic of)

    2005-07-01

    Many studies have been performed to assess the development and application of potentially useful biodosimetry. At present, although chromosome dicentric assay is a sensitive method for dose estimation, it is laborious and requires enough experience for estimation, and without automation its scope for population screening is limited. Therefore, we need an alternative cytogenetic dosimetry to estimate the absorbed dose of victims after low dose exposure such as radiation accidents in hospital workers and workers of radiation related facilities. An alternative and simple cytogenetic technique is the measurement of the micronucleus frequency in cultured human lymphocytes. The reliability of conventional micronucleus (MN) assays is diminished owing to the inclusion of nondividing cells in the estimate, but this problem has been overcome by the development of the cytokinesisblocked (CB) MN assay. The reliable and ease assays of the cytokinesis blocked-approach are obvious advantages in biological monitoring, but there are no developed recognizable and reliable techniques for biological dosimetry of a low dose exposure until recently. Adaptive response is important in determining the biological responses at low doses of radiation and has the potential to impact the shape of the dose-response relationship. We analyzed the frequency of both spontaneous and in vitro {sup 137}Cs {gamma}-rays-induced MNs to estimate the low dose radiation-exposed workers as a screening test.

  17. Low-Dose Radiation Induces Cell Proliferation in Human Embryonic Lung Fibroblasts but not in Lung Cancer Cells

    Liang, Xinyue; Gu, Junlian; Yu, Dehai; Wang, Guanjun; Zhou, Lei; Zhang, Xiaoying; Zhao, Yuguang; Chen, Xiao; Zheng, Shirong; Liu, Qiang; Cai, Lu

    2016-01-01

    Hormesis and adaptive responses are 2 important biological effects of low-dose ionizing radiation (LDR). In normal tissue, LDR induces hormesis as evinced by increased cell proliferation; however, whether LDR also increases tumor cell proliferation needs to be investigated. In this study, cell proliferation was assayed by total cell numbers and the Cell Counting Kit 8 assay. Mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3′ -kinase(PI3K)-Akt (PI3K/AKT) phosphorylation were determined by Western blot analysis. Human embryonic lung fibroblast 2BS and lung cancer NCI-H446 cell lines were irradiated with LDR at different doses (20-100 mGy). In response to 20 to 75 mGy X-rays, cell proliferation was significantly increased in 2BS but not in NCI-H446 cells. In 2BS cells, LDR at 20 to 75 mGy also stimulated phosphorylation of MAPK/ERK pathway proteins including ERK, MEK, and Raf and of the PI3K/AKT pathway protein AKT. To test whether ERK1/2 and AKT pathway activation was involved in the stimulation of cell proliferation in 2BS cells, the MAPK/ERK and PI3K/AKT pathways were inhibited using their specific inhibitors, U0126 and LY294002. U0126 decreased the phosphorylation of ERK1/2, and LY294002 decreased the phosphorylation of AKT; each could significantly inhibit LDR-induced 2BS cell proliferation. However, LDR did not stimulate these kinases, and kinase inhibitors also did not affect cell proliferation in the NCI-H446 cells. These results suggest that LDR stimulates cell proliferation via the activation of both MAPK/ERK and PI3K/AKT signaling pathways in 2BS but not in NCI-H446 cells. This finding implies the potential for applying LDR to protect normal tissues from radiotherapy without diminishing the efficacy of tumor therapy. PMID:26788032

  18. Cell protection by low doses of ionizing radiation challenges the concept of linearity

    Ionizing radiation is known to potentially interfere with cellular functions at all levels. Cell death and late effects such as malignant tumors may result. These stem from permanent damage to cellular DNA, which may lead to malignant transformation of the affected cells. Most such studies have used relatively high values of an absorbed dose, D, above about 0.3 Gy. After acute exposures of humans to between 0.3 and 2 Gy, the risk of cancer in the exposed individuals seems proportional to tissue D. For the purpose of radiation protection, this proportionality is assumed to extend down to zero D. This assumption defines the linear-no-threshold, LNT, hypothesis. In addition to DNA damage, altered intracellular signaling results from acute exposure to cell doses below about 0.3 Gy, and involves radiation-induced reactive oxygen species, ROS. In consequence, different mechanisms of protection against DNA lesions may be induced and last from hours to weeks in different cell types. Damage to DNA is continuously and endogenously produced mainly by ROS generated in a normal oxidative metabolism. This DNA damage quantitatively exceeds by several orders of magnitude that caused by low-dose irradiation. Thus, the protective responses following acute low-dose irradiation may be presumed to mainly prevent and reduce endogenously caused DNA damage. Protective responses are physiological and ubiquitous, albeit differently expressed in various cell types and species. Only in few cases has the induction of such responses been studied that occur after acute low-dose irradiation. Their incidence has been described to be nonlinear, increasing initially with D, beginning to decrease with D when D exceeds about 0.1-0.2 Gy, and eventually disappearing at higher D. Accordingly, the model described here uses two dose-effect functions, one linear for causing and a nonlinear one for reducing DNA damage in the irradiated cells and tissues. The resulting net dose-risk function strongly suggests that the incidence of cancer against dose in the irradiated tissues is much less likely to be linear than to exhibit a threshold, or even to fall below the spontaneous incidence, when D to cells is below about 0.2 Gy. This relationship also suggests that alternative definitions of the relative effectiveness for a given type of radiation may be applicable at the cell level. (orig.)

  19. Low-Dose Radiation Induces Cell Proliferation in Human Embryonic Lung Fibroblasts but not in Lung Cancer Cells

    Liang, Xinyue; Gu, Junlian; Yu, Dehai; Wang, Guanjun; Zhou, Lei; Zhang, Xiaoying; Zhao, Yuguang; Chen, Xiao; Zheng, Shirong; Liu, Qiang; Cai, Lu; Cui, Jiuwei; Li, Wei

    2016-01-01

    Hormesis and adaptive responses are 2 important biological effects of low-dose ionizing radiation (LDR). In normal tissue, LDR induces hormesis as evinced by increased cell proliferation; however, whether LDR also increases tumor cell proliferation needs to be investigated. In this study, cell proliferation was assayed by total cell numbers and the Cell Counting Kit 8 assay. Mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3′ -kinas...

  20. Cancer risk from low dose radiation depends directly on the organ mass in a general model of radiation-induced cancer risk.

    Lin, Z W

    2014-04-01

    Current methods of evaluating radiation-induced cancer risk depend on the organ dose but not explicitly on extensive quantities such as the organ mass. However, at the same organ dose, one may expect the larger number of cells in a larger organ to lead to a higher cancer risk. Here the author introduces organ- and radiation type-specific cell cancer risk coefficients and obtains analytical relations between cancer risk and the radiation environment, which contains the dependence of cancer risk on organ masses. The excess cancer risk induced by low dose radiation for an organ is shown to be directly proportional to the organ mass. Therefore the total excess risk for all solid cancers depends directly on organ masses and consequently on body weight or size. This method is also being compared with three existing methods of evaluating the radiation-induced cancer risk, and special cases where this formulation matches each method are demonstrated. The results suggest that the direct dependence of cancer risk on organ masses needs to be checked against existing epidemiological data and, if verified, should be included in the methodology for the evaluation of radiation-induced cancer risk, in particular the individual risk. This dependence is also expected to affect the cancer risk transport from one population group to another that is different in organ mass, body weight or height. PMID:24562066

  1. Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations.

    Cool, Donald A

    2016-03-01

    The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully. PMID:26808877

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

    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

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

    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

  4. Distinctive features of the creation of radiation-induced defects in p-Si by photon-assisted low-dose ion implantation

    Deep-level transient spectroscopy (DLTS) was used to investigate how temperature and in situ photoexcitation affect the creation of radiation-induced defect complexes in p-Si during low-dose ion implantation. Samples of p-Si were simultaneously irradiated by Ar+ ions accelerated to 150 keV in doses of 7x1010 cm-2 and photoexcited with ultraviolet light at temperatures of 300 and 600 K. It was found that nonradiative heating of the samples by the implanted ions increases the total concentration of defect complexes while simultaneously changing the nature of the dominant complex. In contrast, ultraviolet illumination of the semiconductor suppresses defect formation. It was observed that in situ photoexcitation has a progressively smaller effect on the formation of radiation-induced defect complexes as the target temperature increases. The dependence of the concentration of secondary defects created as the accelerated ions are incorporated into the p-Si on the UV illumination intensity is found to be nonmonotonic. The results obtained for p-Si were analyzed and compared with previously known data for n-Si

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

    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 chemically induced developmental anomalies. Combinations of modifying factors with different radiation might deserve further attention. (author)

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

    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

  7. Manganese superoxide dismutase interacts with a large scale of cellular and mitochondrial proteins in low dose radiation-induced adaptive radioprotection

    Eldridge, Angela; Fan, Ming; Woloschak, Gayle; Grdina, David J.; Chromy, Brett A.; Li, Jian Jian

    2012-01-01

    Cellular adaptive response to certain low level genotoxic stresses including the exposure to low dose ionizing radiation (LDIR) shows promise as a tool to enhance radioprotection in normal cells but not in tumor cells. Manganese superoxide dismutase (MnSOD), a fundamental mitochondrial antioxidant in mammalian cells plays a key role in LDIR-induced adaptive response. In this study, we aim to elucidate the signaling network associated with the MnSOD-induced radiation protection. A MnSOD-intera...

  8. Low Dose Radiation Adaptive Protection to Control Neurodegenerative Diseases

    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...

  9. Radiation induced cancer risk, detriment and radiation protection

    Recommendations on radiation protection limits for workers and for the public depend mainly on the total health detriment estimated to be the result of low dose ionizing radiation exposure. This detriment includes the probability of a fatal cancer, an allowance for the morbidity due to non-fatal cancer and the probability of severe hereditary effects in succeeding generations. In a population of all ages, special effects on the fetus particularly the risk of mental retardation at defined gestational ages, should also be included. Among these components of detriment after low doses, the risk of fatal cancer is the largest and most important. The estimates of fatal cancer risk used by ICRP in the 1990 recommendations were derived almost exclusively from the study of the Japanese survivors of the atomic bombs of 1945. How good are these estimates? Uncertainties associated with them, apart from those due to limitations in epidemiological observation and dosimetry, are principally those due to projection forward in time and extrapolation from high dose and dose rate to low dose and dose rate, each of which could after the estimate by a factor of 2 or so. Recent estimates of risk of cancer derived directly from low dose studies are specific only within very broad ranges of risk. Nevertheless, such studies are important as confirmation or otherwise of the estimates derived from the atomic bomb survivors. Recent U.S. British and Russian studies are examined in this light. (author)

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

    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 Investigators 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.

  11. Protection against radiation-induced performance decrement in mice

    Recognizing 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, 1 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 Ca2+ 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. (author). 23 refs., 2 figs

  12. Risk estimates for radiation-induced cancer and radiation protection standards

    At low doses, the primary biological effects of concern are stochastic in nature, i.e., they are more probable at higher doses, but their severity is independent of the dose. In the last decade, a new epidemiological information on radiation-induced cancer in humans has become available. In the Japanese survivors three new cycles of data (11 yr of experience) have accumulated, and a revised dosimetry system (DS86) has been introduced. UNSCEAR [United Nations Scientific Committee on the Effects of Atomic Radiation] reevaluated the risk of cancer from all human sources, which include other human populations such as those treated for ankylosing spondylitis and for cancer of the cervix. UNSCEAR has also evaluated the cancer risk for each of nine organs. For radiation protection purposes (low doses and dose rates, adult populations mainly), nominal values of risk since the 1977-80 period have been ?1%/Sv. This value will need to be increased in the light of the new estimates. Also, risk estimates for various tissues must be reconsidered, and weighting factors used by International Commission on Radiological Protection need to be reexamined. Recommendations on occupational and public dose limits must also be reconsidered. The National Council on Radiation Protection and Measurements is in a comparatively good position with a recently produced set of recommendations that had higher cancer risk estimates in mind

  13. Inducible HSP70 Protects Radiation-Induced Salivary Gland Damage

    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

  14. Low dose, radiation-induced adaptive response against cancer in high-dose-exposed, cancer-prone, Trp53 heterozygous mice

    Full text: Mice that are heterozygous for Trp53 are both cancer-prone and sensitive to high radiation doses. Groups of 7-8-week-old female Trp53 heterozygous mice were exposed to 4 Gy of 60Co-gamma radiation at either high (0.5 Gy/min) or low (0.5 mGy/min) dose rate. Other groups received a 10-mGy or 100-mGy dose, given at low dose rate (0.5 mGy/min) 24 h prior to the 4 Gy dose. Tumor frequency and latency were measured over the lifespan of the animals. Compared to animals receiving only 4 Gy at high dose rate, mice receiving a prior 10-mGy adapting exposure had significantly extended lifespan and increased latency for all malignant tumors taken together. However, the latency responses were tumor type specific. The prior 10-mGy exposure increased latency for lymphomas and hemangiosarcomas, but decreased latency for spinal osteosarcomas. Increasing the adapting dose to 100 mGy eliminated the tumor latency increase and significantly reduced lifespan. A 10-mGy adapting dose given prior to a 4 Gy exposure at low dose rate generally showed either a reduced effect or no effect. Adapting exposures had no significant effect on tumor frequency. We conclude that adaptive responses are induced by low doses of radiation in radiation sensitive, cancer prone Trp53 +/ - mice, and that these responses are expressed as an increase in tumor latency that reduces the carcinogenic effects of a subsequent large exposure. The dose at which protective effects give way to detrimental effects is tumor type specific

  15. Protection from ionizing radiation induced damages by phytoceuticals and nutraceuticals

    Exposure of living systems to ionizing radiation cause a variety of damages to DNA and membranes due to generation of free radicals and reactive oxygen species. The radiation induced lesions in the cellular DNA are mainly strand breaks, damage to sugar moiety, alterations and elimination of bases, cross links of the intra and inter strand type and cross links to proteins while peroxidation of the lipids and oxidation of proteins constitute the major lesions in the membranes. The radioprotectors elicit their action by various mechanisms such as i) by suppressing the formation of reactive species, ii) detoxification of radiation induced species, iii) target stabilization and iv) enhancing the repair and recovery processes. The radioprotective compounds are of importance in medical, industrial, environmental, military and space science applications. Radiation protection might offer a tactical advantage on the battlefield in the event of a nuclear warfare. Radioprotectors might reduce the cancer risk to populations exposed to radiations directly or indirectly through industrial and military applications. The antioxidant and radioprotective properties a few of these agents under in vitro and in vivo conditions in animal models will be discussed

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

    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.)

  17. Application of radiation-induced apoptosis in radiation oncology and radiation protection

    A rapid assay of the ability of lymphocytes to respond to radiation-induced damage is presented. Age and genetic dependence of radiation response have been quantified. The assay is sensitive to low doses of radiation. Its ability to assess the cytotoxic response of blood capillaries to radiation has been evaluated. (author)

  18. HSP25 Protects Radiation-Induced Salivary Gland Damage

    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

  19. Protection of radiation-induced DNA damage in albino rats by Zingiber Montanum extract

    The tropical ginger, Zingiber montanum (J. König) A. Dietr, has potentials in scavenging free radicals and affording protection from radiation-induced chromosomal aberrations. The present investigation aims at determining antioxidant and radioprotective properties of the rhizome extract. Sulphur free radical, DPPH and superoxide scavenging assays were carried out for assessing antioxidant activities. Radiation-induced (500 cGy) DNA damage in pBR322 in vitro could be significantly reduced upto 71% (P < 0.05) by treatment with 60% ethanol extract (20 μg). Acute toxicity of the 60% ethanol extract was determined and suitable injectable dose was selected for intra-peritoneal administration in albino rats (Rattus norvegicus). The LD50 of extract calculated for 72 hrs was found to be 2.9 g/kg, and maximum tolerated dose (MTD) of rhizome extract was 1.3 g/kg. Rhizome extract (0.5 g/kg) in 60% ethanol was intra-peritoneally injected to albino rats and exposed to 100, 300 and 500 cGy. Radioprotective effect of the extract was determined by alkaline single cell comet assay. Significant reduction (P < 0.05) of comet DNA (68%) and length (61%)in rat bone marrow cells was observed at a radiation dose of 500 cGy. The results demonstrate that tropical ginger possess free radical scavenging properties and can protect bone marrow cells from radiation-induced DNA damages. The results on radiation induced DNA damage using plasmid pBR322 DNA obviously justify that the extract at a low dose can protect DNA from undergoing strand breakage due to gamma radiation exposure. Versatility of Zingiber montanum in different chemical assays in terms of its radical scavenging potential shows that this non-conventional food plant as a lot of potential in maintaining human health through dietary supplementation as nutraceutical. This candidate plant also can possibly be a promising candidate in clinical radiotherapy perhaps as a substitute of or the well-know radioprotector amifostine. (author)

  20. Low-dose carbon monoxide inhalation protects neuronal cells from apoptosis after optic nerve crush.

    Chen, Zeli; Wang, Ruobing; Wu, Jiangchun; Xia, Fangzhou; Sun, Qinglei; Xu, Jiajun; Liu, Lin

    2016-01-22

    Glaucomatous optic neuropathy, including axonal degeneration and apoptotic death of retinal ganglion cells (RGCs), eventually leads to irreversible visual impairment. Carbon monoxide (CO) acts as a therapeutic agent against neural injury via its anti-apoptotic effect. Here we hypothesized that low-dose CO inhalation can protect RGCs in a rat model of optic nerve crush (ONC). ONC was performed on adult male Sprague Dawley rats to imitate glaucomatous optic damage. Low-dose CO (250ppm) or air was inhaled for 1h immediately after ONC, and all the tests were carried out 2 weeks later. Flash visual evoked potentials (FVEP) and pupil light relax (PLR) were recorded for the assessment of visual function. RGC density was evaluated by hematoxylin and eosin staining and Fluorogold labeling. Retinal apoptotic process was assessed by TUNEL staining and caspase-3 activity measurement. Low-dose CO treatment significantly ameliorated the abnormalities of FVEP and PLR induced by ONC. As expected, the RGC density was increased remarkably by CO inhalation after the glaucomatous optic nerve insult. Moreover, CO treatment after ONC significantly decreased the number of TUNEL-positive cells in ganglion cell layer and attenuated the retinal caspase-3 activity. Low-dose CO inhalation protects RGCs from optic nerve injury via inhibiting caspase-3 dependent apoptosis. PMID:26707638

  1. Protective Effect of HSP25 on Radiation Induced Tissue Damage

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Bae, Sang-Woo; Lee, Yun-Sil [Korea Institute of Radiological Medical Sciences, Seoul (Korea, Republic of); Kim, Sung Ho [Chonnam National University, 300 Yongbong-Dong, Puk-Ku, Gwangju (Korea, Republic of)

    2007-10-15

    Control of cancer by irradiation therapy alone or in conjunction with combination chemotherapy is often limited by organ specific toxicity. Ionizing irradiation toxicity is initiated by damage to normal tissue near the tumor target and within the transit volume of radiotherapy beams. Irradiation-induced cellular, tissue, and organ damage is mediated by acute effects, which can be dose limiting. A latent period follows recovery from the acute reaction, then chronic irradiation fibrosis (late effects) pose a second cause of organ failure. HSP25/27 has been suggested to protect cells against apoptotic cell death triggered by hyperthermia, ionizing radiation, oxidative stress, Fas ligand, and cytotoxic drugs. And several mechanisms have been proposed to account for HSP27-mediated apoptotic protection. However radioprotective effect of HSP25/27 in vivo system has not yet been evaluated. The aim of this study was to evaluate the potential of exogenous HSP25 expression, as delivered by adenoviral vectors, to protect animal from radiation induced tissue damage.

  2. Protective Effect of HSP25 on Radiation Induced Tissue Damage

    Control of cancer by irradiation therapy alone or in conjunction with combination chemotherapy is often limited by organ specific toxicity. Ionizing irradiation toxicity is initiated by damage to normal tissue near the tumor target and within the transit volume of radiotherapy beams. Irradiation-induced cellular, tissue, and organ damage is mediated by acute effects, which can be dose limiting. A latent period follows recovery from the acute reaction, then chronic irradiation fibrosis (late effects) pose a second cause of organ failure. HSP25/27 has been suggested to protect cells against apoptotic cell death triggered by hyperthermia, ionizing radiation, oxidative stress, Fas ligand, and cytotoxic drugs. And several mechanisms have been proposed to account for HSP27-mediated apoptotic protection. However radioprotective effect of HSP25/27 in vivo system has not yet been evaluated. The aim of this study was to evaluate the potential of exogenous HSP25 expression, as delivered by adenoviral vectors, to protect animal from radiation induced tissue damage

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

    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...

  4. Radiation induced diffusion as a method to protect surface

    Radiation induced diffusion forms a coating adeherent and without interface on the surface of metalic substrates. This coating improves the behaviour of metal to corrosion and abrasion. The effect of radiation induced diffusion of tin and calcium on pure iron surface is described and analyzed in this work. (author)

  5. Recent research on the effects of low dose radiation: implications to radiation protection

    Radiation protection specialists unanimously agree that radiation at high dose levels can cause cancer. At low dose levels, the results are not conclusive. Specialists accept the Linear-No-Threshold (LNT) dose-effect relationship as a practical approach in radiation protection. That means that the dose-effect relation is linear without a threshold; any dose however small will have some deleterious effect. Application of LNT without appreciating that it is just a pragmatic concept leads to unreasonable fear about radiation. This adversely impact acceptance of nuclear power as a source of energy

  6. Evaluation of the detriment associated with exposure at low doses and low dose rates in the radiation protection system

    Questions about quantifying the radiological risk associated with exposure to ionising radiation have been debated repeatedly for a variety of exposure situations, including, among others, medical irradiation, discharges from nuclear facilities, transportation of radioactive waste, and potential nuclear accidents. This paper aims to shed light on the link between exposure and risk, focusing on the items that constitute the detriment associated with this exposure. The management of the risk associated with it relies on a cautious hypothesis of a linear no-threshold relation between exposure and risk of death or detriment. The International Commission on Radiological Protection (ICRP) published General Recommendations in 1966 that recognised this relation, but did not publish a quantification of the risk until 1977. The Commission introduced the concept of effective dose as a risk indicator that makes it possible to determine dose limits according to the risk associated with them. In 1990, the Commission proposed a revision of the quantification and construction of detriment. New limits, based on risk quantification and, for the first time, risk tolerability, were proposed. The optimisation of radiation protection - keeping radiation exposure as low as reasonably achievable in light of the economic and social context - became the key principle of the radiation protection system. The use of detriment makes it possible to use economic tools to guide the decision process for this optimisation - by assessing the monetary value of human life. This concept, widely used in health economics during the 1980's, has been criticised by many and must be used cautiously. ICRP published the latest quantifications of detriment in 2007. Detriment is thus an indicator that assesses the risk of death associated with exposure to ionising radiation for an average individual. Its construction relies on simplifying assumptions that are needed to implement a robust and effective radiation protection system. (authors)

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

    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.

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

    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

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

    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 α-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 β1/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

  10. 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

    Morgan, William F; Kovalchuk, Olga; Dolinoy, Dana C; Dubrova, Yuri E; Coleman, Matthew A; Schär, 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.

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

    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...

  12. Low-Dose Radiation Induces Cell Proliferation in Human Embryonic Lung Fibroblasts but not in Lung Cancer Cells: Importance of ERK1/2 and AKT Signaling Pathways.

    Liang, Xinyue; Gu, Junlian; Yu, Dehai; Wang, Guanjun; Zhou, Lei; Zhang, Xiaoying; Zhao, Yuguang; Chen, Xiao; Zheng, Shirong; Liu, Qiang; Cai, Lu; Cui, Jiuwei; Li, Wei

    2016-01-01

    Hormesis and adaptive responses are 2 important biological effects of low-dose ionizing radiation (LDR). In normal tissue, LDR induces hormesis as evinced by increased cell proliferation; however, whether LDR also increases tumor cell proliferation needs to be investigated. In this study, cell proliferation was assayed by total cell numbers and the Cell Counting Kit 8 assay. Mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3' -kinase(PI3K)-Akt (PI3K/AKT) phosphorylation were determined by Western blot analysis. Human embryonic lung fibroblast 2BS and lung cancer NCI-H446 cell lines were irradiated with LDR at different doses (20-100 mGy). In response to 20 to 75 mGy X-rays, cell proliferation was significantly increased in 2BS but not in NCI-H446 cells. In 2BS cells, LDR at 20 to 75 mGy also stimulated phosphorylation of MAPK/ERK pathway proteins including ERK, MEK, and Raf and of the PI3K/AKT pathway protein AKT. To test whether ERK1/2 and AKT pathway activation was involved in the stimulation of cell proliferation in 2BS cells, the MAPK/ERK and PI3K/AKT pathways were inhibited using their specific inhibitors, U0126 and LY294002. U0126 decreased the phosphorylation of ERK1/2, and LY294002 decreased the phosphorylation of AKT; each could significantly inhibit LDR-induced 2BS cell proliferation. However, LDR did not stimulate these kinases, and kinase inhibitors also did not affect cell proliferation in the NCI-H446 cells. These results suggest that LDR stimulates cell proliferation via the activation of both MAPK/ERK and PI3K/AKT signaling pathways in 2BS but not in NCI-H446 cells. This finding implies the potential for applying LDR to protect normal tissues from radiotherapy without diminishing the efficacy of tumor therapy. PMID:26788032

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

    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 prejudice

  14. Low dose radiation induced adaptive response upon salt stress and vacuum stress: a possible mechanism for the effect of saddle-like dose response curve

    To explore mechanism for the effect of saddle-like dose-response curve, the relationship of irradiation-vacuum stress, and irradiation-salt stress, was investigated with rice seeds irradiated to 60-560 Gy by 60Co ?-rays. The dose-response curve was simulated based on seedling height data, which showed obedient to linear-quadratic model. During germination,the irradiated rice seeds were stressed by 10-3 Pa vacuum, or by NaCl in different concentrations. After that, the dose-response curve manifested a saddle-like shape. The results indicate that while low dose irradiation could retard seedling growth synergistically with vacuum stress and salt stress, it could also induce adaptive response upon vacuum stress and salt stress. Low dose irradiation induced adaptive response upon environmental adverse factors could contribute to the mechanism for the effect of saddle-like dose-response curve. (authors)

  15. 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

    Olga Loseva

    2014-07-01

    Full Text Available 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 chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

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

    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 β1 (TGF-β1)/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 α-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 β1/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

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

    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 β1 (TGF-β1)/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 α-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 β1/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.

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

    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.)

  19. Radiation-induced chromosome aberrations in lymphocytes from man and crab-eating monkey. The dose-response relationships at low doses

    Takahashi, E.; Hirai, M.; Tobari, I.; Utsugi, T.; Nakai, S. (National Inst. of Radiological Sciences, Chiba (Japan). Div. of Genetics)

    1982-01-01

    To obtain information on the relation between yield of chromosome aberrations and dose at low-dose levels, experiments were conducted with 5, 10, 20, 30 and 50 rad of /sup 137/Cs ..gamma..-rays, on lymphocytes from man and crab-eating monkey (Macaca fascicularis). The dose-response relationship for dicentrics was obtained from the combined data of these low-dose experiments with those of our previous ones at high doses (100-400 rad). When the difference between observed yields and those expected from the linear-quadratic model were computed, the dose-response curve had a good fit for man, but not for the monkey. The linear regression lines between 0 and 30 rad were calculated, because the expected values of ..cap alpha../..beta.. for man and monkey would be about 100 and 60 rad. The human data gave a satisfactory fit to a linear model, i.e., a linear increase in aberration frequency with dose, whereas this was not so for those of the monkey. Furthermore, there was some suggestive evidence for the existence of a plateau in dicentric yields between 10 and 30 rad for the monkey and between 20 and 30 rad for human lymphocytes, but more data would be needed to verify this suggestion, particularly for human lymphocytes.

  20. Does smoking protect against radiation-induced pneumonitis?

    The overall aim of the project reported here was to investigate the inflammatory reaction in the otherwise healthy human lung after ionizing irradiation. The tool used was the well accepted and now safe technique of bronchoalveolar lavage. The causality between smoking and the development of different forms of cancer, especially lung cancer, is well established. However, the possible effects of smoking on cancer treatment per se has been studied less. The authors observed, in addition to the expected inflammatory reactions in the lung parenchyma, that smoking during post-operative treatment of breast cancer seems to depress the grade of radiation-induced pneumonitis. (author)

  1. Reduced protection of stem spermatogonia by WR-2721 at low doses of irradiation

    The radioprotection of normal cells with WR-2721 at low doses of radiation (about 2 Gy per fraction) was investigated using testicular stem cells. Survival of stem spermatogonia to single doses of irradiation, measured using sperm head counts at 56 days postirradiation, indicated no protection factor (PF = 1.00) at 2 GY by 400 mg/kg WR-2721, but a significant PF = 1.44 at 12 Gy. Stem cell survival was also measured after 5 fractions. When daily fractionation was used with 300 mg/kg WR-2721, given prior to each irradiation, little or no protection was observed at 2 Gy using the sperm head assay (PF = 0.98) or at 2.4 Gy using counts of repopulating tubules at 35 days postirradiation (PF = 1.12). In contrast, there was more significant protection (PF's = 1.22 and 1.27) for these two assays when 300 mg/kg WR-2721 was used with single high doses of radiation. When 4-hour fractionation was used with 300 mg/kg WR-2721, given prior to the first dose and 150 mg/kg prior to subsequent doses, minimal protection was observed at 2 Gy/fraction using the sperm head assay (PF = 0.98) and the repopulating tubule assay (PF = 1.09). Thus, protection of these cells in the clinical dose range is much lower than that observed at doses above 10 Gy. These results may be explained by a decrease in the intrinsic ability of WR-2721 to protect at lower radiation doses plus a cytotoxic effect of WR-2721

  2. Repair of low dose γ-radiation induced DNA strand breaks in eukaryotic cells in vitro: biphasic repair curve in plasmid transfected SCID and +/+ cells

    Full text: The efficiency and characteristics of inherent repair system(s) decide the criticality of radiation induced damage in DNA. The interplay of the inflicted damage and its repair finally dictates the biological response to the exposure in form of the well-being and survival of a cell or an organism. In our continuing effort to use a plasmid model to understand the process at molecular level, this study has been initiated to understand the kinetics of γ-radiation induced DNA strand breaks and repair of the breaks in an eukaryotic system. Earlier studies using a plasmid DNA construct pMTa4 transformed into E. coli have revealed (a) vulnerability of GC-rich nucleotide sequences to γ-irradiation generating pre-mutagenic lesions in a non-random way and (b) critical roles of RecF-RecA proteins, especially RecA protein, in high fidelity rejoining of strand breaks in prokaryotes. In this study a reporter plasmid construct pGFP incorporating reported green fluorescent protein gene was transfected into repair proficient or deficient eukaryotic cell lines (+/+ and SCID). The transfected cells were γ-irradiating to medically relevant doses of 0.5, 1 and 2 Gy. The plasmid was recovered from the sham-irradiated and γ-irradiated cell lines under repair permissive (R+) and non-permissive (R-) conditions and analyzed for induction and repair of single strand breaks (SSB) and double strand breaks (DSB). The efficiency of transfection was, in general, higher for radio-hypersensitive SCID cells (clonogenic survival ≤ 1% at 2 Gy) than its radioresistant +/+ (wild) counterpart (clonogenic survival ≅ 80% at 2 Gy). γ-irradiation up to a dose of 2 Gy did not affect the difference in transfection efficiency. While +/+ cells showed a near-dose dependent increase in induction of SSB and DSB and near-complete repair under R+ condition, SCID cells failed to do so. The slope of curve for induction of strand breaks was biphasic; higher slope at lower dose. No cell cycle arrest was noticed up to 1 cell cycle after irradiation. Differences in damage fixation in SCID and +/+ cell lines seem critical to processing repair of the induced damage. The presentation shall focus on implication of these findings on genome instability

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

    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 (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

  4. 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

    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)

  5. Low dose docosahexaenoic acid protects normal colonic epithelial cells from araC toxicity

    Meckling Kelly A

    2005-03-01

    Full Text Available Abstract Background The nucleoside analogue arabinosylcytosine (araC has been used for many years in the treatment of acute leukemia. Evidence in the literature suggests that araC may inhibit the growth of human colon carcinoma cell lines as well. Because araC action interferes with normal nucleoside metabolism, it is highly toxic to a number of normal cell types including bone marrow and intestinal mucosa cells. Here we investigate whether the omega-3 fatty acid docosahexaenoic acid (DHA could selectively target araC toxicity toward colonic tumor cells while protecting the normal cells in vitro. Results Cultures of normal rat colonic epithelial cells (4D/WT and those transformed by v-src (D/v-src were supplemented with graded concentrations of DHA or arachidonic acid (AA alone or in combination with araC. AraC was only 1.6 fold more toxic to D/v-src than 4D/WT in cultures without added fatty acids. Supplementing with as little as 3 ?M of either AA or DHA increased araC toxicity by more than 30-fold in the tumorigenic cells. The toxic effect of araC on the normal cells was also increased by the fatty acid supplementation. IC50 values were decreased 1.7 fold by DHA in the 4D/WT cells but a more than 7-fold decrease was observed during AA supplementation. As a result, the therapeutic index of araC (IC50 normal/IC50 tumor was more than 3-fold higher in the DHA than the AA supplemented cells. The expression of protein kinase C isoform epsilon was decreased in AA alone supplemented D/v-src cultures but in combination with araC decreased only in DHA supplemented 4D/WT cells. Conclusion Low dose DHA supplementation may enhance araC chemotherapy in colon cancer while protecting normal tissues, possibly through control of PKC signalling pathways.

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

    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

  7. Protective Effect of Curcumin on γ - radiation Induced Chromosome Aberrations in Human Blood Lymphocytes

    The present work is aimed at evaluating the radioprotective effect of curcumin on γ 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 γg/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 γ-radiation induced chromosome aberration at certain doses. (author)

  8. A Low-dose Arsenic-induced p53 Protein-mediated Metabolic Mechanism of Radiotherapy Protection*

    Ganapathy, Suthakar; Xiao, Shaowen; Yang, Mei; Qi, Min; Choi, Doo Eun; Ha, Chul S.; Little, John B.; Yuan, Zhi-Min

    2014-01-01

    Radiotherapy is the current frontline cancer treatment, but the resulting severe side effects often pose a significant threat to cancer patients, raising a pressing need for the development of effective strategies for radiotherapy protection. We exploited the distinct metabolic characteristics between normal and malignant cells for a metabolic mechanism of normal tissue protection. We showed that low doses of arsenic induce HIF-1α, which activates a metabolic shift from oxidative phosphorylation to glycolysis, resulting in increased cellular resistance to radiation. Of importance is that low-dose arsenic-induced HIF-1α requires functional p53, limiting the glycolytic shift to normal cells. Using tumor-bearing mice, we provide proof of principle for selective normal tissue protection against radiation injury. PMID:24391088

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

    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 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

  10. Glycine betaine, a beer component, protects radiation-induced injury

    Human whole-blood was exposed to 137Cs ?-rays or 50 keV/?m carbon ions in the presence or absence of glycine betaine, a beer component in vitro. The dicentrics of chromosome aberrations in human lymphocytes were significantly (p<0.05) reduced by glycine betaine after irradiation with 4 Gy of either ?-rays or carbon ions. The maximum protection by glycine betaine for ?-rays or carbon ions was 37% and 20%, respectively. C3H/He female mice, aged 14 weeks, received an intraperitoneal (i.p.) injection of glycine betaine 15 mm before whole-body irradiation with ?-rays or 50 keV/?m carbon ions. Glycine betaine significantly (p<0.05) increased the percent survival of irradiated mice with either ?-rays or carbon ions. In conclusion, glycine betaine is a potent protector against damages caused by low- and high-linear energy transfer (LET) radiation. (author)

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

    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.

  12. Sucralfate protects intestinal epithelial cells from radiation-induced apoptosis in rats

    Radiotherapy for malignant pelvic disease is often followed by acute radiation colitis (ARC). It has been reported that sucralfate treatment has a protective effect against ARC, though the mechanisms of action are unknown. The effects of sucralfate on X-ray radiation-induced apoptosis was studied at 4 Gy in the colonic crypt cells of rats. Sucralfate enemas given prior to radiation resulted in the following: reduction in number of apoptotic colonic crypt cells; reduction in number of caspase-3 positive cells; decreases in p53 accumulation and p21 expression; decreases of Bax/Bcl-2 ratio. The protective effects of sucralfate against ARC may be partially due to the suppression of radiation-induced apoptosis by way of p53 in the colon and the protection of the colonic epithelial stem cell region. (author)

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

    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...

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

    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

  15. Polymorphisms of uridine glucuronosyltransferase gene and irinotecan toxicity: low dose does not protect from toxicity

    Tziotou, Marianna; Kalotychou, Vassiliki; Ntokou, Anna; Tzanetea, Revekka; Armenis, Iakovos; Varsou, Marianna; Konstantopoulos, Konstantinos; Tsavaris, Nicolas; Rombos, Yannis

    2014-01-01

    Uridine glucuronosyltransferase (UGT) gene polymorphisms have been linked to irinotecan toxicity. Our purpose was to study the association between UGT1A1*28, UGT1A7*2, and UGT1A7*3 polymorphisms and irinotecan toxicity in Greek patients receiving low-dose weekly irinotecan. Blood samples were collected for 46 patients. DNA was extracted and UGT1A1 promoter and UGT1A7 exon 1 genotyping was carried out. Laboratory tests and physical examination were performed on regular basis for the assessment...

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

    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

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

    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 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)

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

    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 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.)

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

    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, α-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, γ-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

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

    McConnell, Kevin W; Muenzer, Jared T; Chang, Kathy C; Davis, Chris G; McDunn, Jonathan E; Coopersmith, Craig M; Hilliard, Carolyn A; Hotchkiss, Richard S; Grigsby, Perry W; Hunt, Clayton R

    2007-04-01

    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 15Gy radiation. In mice exposed to 5Gy 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. PMID:17307150

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

    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) 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)

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

    Schöllnberger, 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...

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

    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 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

  4. Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model

    Liu, Hao; XUE, JIAN-XING; Li, Xing; Ao, Rui; You LU

    2013-01-01

    In the present study, the hypothesis that quercetin liposomes are able to effectively protect against radiation-induced pulmonary injury in a murine model was tested. C57BL/6J mice receiving whole-thorax radiotherapy (16 Gy) were randomly divided into three groups: control, radiation therapy plus saline (RT+NS) and RT plus quercetin (RT+QU). At 1, 4, 8 and 24 weeks post-irradiation, lung injury was assessed by measuring oxidative damage and the extent of acute pneumonitis and late fibrosis. I...

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

    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 redox status of cells. The results will be helpful in understanding the mechanistic aspects and development of sesamol based radioprotector. (author)

  6. Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model.

    Liu, Hao; Xue, Jian-Xing; Li, Xing; Ao, Rui; Lu, You

    2013-08-01

    In the present study, the hypothesis that quercetin liposomes are able to effectively protect against radiation-induced pulmonary injury in a murine model was tested. C57BL/6J mice receiving whole-thorax radiotherapy (16 Gy) were randomly divided into three groups: control, radiation therapy plus saline (RT+NS) and RT plus quercetin (RT+QU). At 1, 4, 8 and 24 weeks post-irradiation, lung injury was assessed by measuring oxidative damage and the extent of acute pneumonitis and late fibrosis. In the lung tissues from the RT+NS group, the malondialdehyde (MDA) levels were significantly elevated and superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were significantly reduced; the total cell counts and inflammatory cell proportions in the bronchoalveolar lavage fluid (BALF), plasma tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 concentrations and the hydroxyproline (HP) content were significantly increased. Quercetin liposome administration significantly reduced the MDA content and increased SOD and GSH-PX activities in the lung tissues, and reduced the total cell counts and inflammatory cell proportions in the BALF, plasma TNF-α and TGF-β1 concentrations and the HP content in the lung tissues. A histological examination revealed suppression of the inflammatory response and reduced TGF-β1 expression and fibrosis scores. Radiation-induced oxidative damage ranged from pneumonitis to lung fibrosis. Quercetin liposomes were shown to protect against radiation-induced acute pneumonitis and late fibrosis, potentially by reducing oxidative damage. PMID:24137346

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

    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)

  8. ''Low dose'' and/or ''high dose'' in radiation protection: A need to setting criteria for dose classification

    The ''low dose'' and/or ''high dose'' of ionizing radiation are common terms widely used in radiation applications, radiation protection and radiobiology, and natural radiation environment. Reading the title, the papers of this interesting and highly important conference and the related literature, one can simply raise the question; ''What are the levels and/or criteria for defining a low dose or a high dose of ionizing radiation?''. This is due to the fact that the criteria for these terms and for dose levels between these two extreme quantities have not yet been set, so that the terms relatively lower doses or higher doses are usually applied. Therefore, setting criteria for classification of radiation doses in the above mentioned areas seems a vital need. The author while realizing the existing problems to achieve this important task, has made efforts in this paper to justify this need and has proposed some criteria, in particular for the classification of natural radiation areas, based on a system of dose limitation. (author)

  9. The Protective Effect of Curcumin on Ionizing Radiation-induced Cataractogenesis in Rats

    Fatma Nesrin Turan

    2012-12-01

    Full Text Available Objective: The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. Material and Methods: Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO, Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px, and the malondialdehyde (MDA were measured.Results: 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin.Conclusion: Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis.

  10. Low doses of flagellin-L2 multimer vaccines protect against challenge with diverse papillomavirus genotypes.

    Kalnin, Kirill; Tibbitts, Timothy; Yan, Yanhua; Stegalkina, Svetlana; Shen, Lihua; Costa, Victor; Sabharwal, Robert; Anderson, Stephen F; Day, Patricia M; Christensen, Neil; Schiller, John T; Jagu, Subhashini; Roden, Richard B S; Almond, Jeffrey; Kleanthous, Harold

    2014-06-12

    Genetically modified bacterial flagellin (Fla), a Toll-like receptor-5 (TLR5) ligand, was evaluated as a fusion partner for human papillomavirus (HPV) L2-based immunogens in two animal challenge models; either cutaneous inoculation of rabbits with HPV 'quasivirions' containing cottontail rabbit papillomavirus (CRPV) genomes that induce warts, or intra-vaginal inoculation of mice with HPV 'pseudovirions' encapsidating a luciferase reporter plasmid and measurement of bioluminescence to determine infectivity. An Escherichia coli production system was developed for flagellin-L2 (Fla-L2) fusions containing either monomeric HPV-16 L2 a.a. 11(11-200) or oligomeric L2 comprising a fusion of the a.a. 11-88 peptides of five (Fla?511-88) or eight (Fla?811-88) genital HPV types. Immunogenicity and bioactivity of Fla-L2 constructs were assessed using an in vitro neutralization and cell-based TLR-5 binding assay, respectively. Efficacy was evaluated following active immunization of rabbits or mice administered 3 intramuscular doses of Fla-L2 recombinants without exogenous adjuvant, followed by challenge. In addition, passive immunization studies of nave rabbits with serial dilutions of pooled immune sera were used to determine End-Point Protection Titers (EPPT) for each formulation against a broader spectrum of HPV quasivirions. Efficacy was assessed for up to 10 weeks on the basis of wart volume induced following challenge and results compared to licensed L1-VLP vaccines (Gardasil and Cervarix). Following active immunization at doses as low as 1 ?g, Fla-L2 fusions afforded complete protection against infection (mice) and disease (rabbits) following either homologous or heterologous HPV challenge. Passive immunization with anti-L2 immune sera discriminated between the different vaccine candidates under evaluation, demonstrated the protective role of antibody and suggested the superiority of this oligomeric L2-TLR5 agonist fusion approach compared to L1-based vaccines in its ability to cross-protect against non-vaccine HPV types. PMID:24780250

  11. Mitochondrial protection by low doses of insulin-like growth factor-Iin experimental cirrhosis

    Raquel Prez, Mara Garca-Fernndez, Matas Daz-Snchez, Juan E Puche, Gloria Delgado, Marian Conchillo, Jordi Muntan, Inma Castilla-Cortzar

    2008-05-01

    Full Text Available AIM: To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-I(IGF-I therapy (4 wk is able to induce beneficial effects on damaged mitochondria leading to cellular protection.METHODS: Wistar rats were divided into three groups: Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF-Itreatment (2 ?g/100 g bw/d. Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three experimental groups.RESULTS: Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3; an increase of intramitochondrial reactive oxigen species (ROS generation and a significant reduction of ATPase activity. IGF-Itherapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes Iand III was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF-Itherapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis.CONCLUSION: These results show that IGF-Iexerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.

  12. Protective effect of flax seed oil against radiation induced hematological alterations in mammals

    Human beings are exposed to ionizing and non ionizing radiation from natural as well as manmade sources. Ionizing radiations are one of the predominant exogenous factors that have deleterious consequences to human life. Exposure to ionizing radiations damages the hematopoietic, gastrointestinal or central nervous systems, depending on radiation dose. Hence, there is an urgent need to prevent such deleterious effects caused due to ionizing radiations. Chemical protection involves the use of synthetic and natural products against planned radiation exposure. Medicinal plants are rich in antioxidants and their chemical constituents may be the potential source for radioprotective agents. Linum usitatissimum plant (family: Linaceae), source of flaxseed oil (FSO), is well known for its anticarcinogenic, antidiabetic, cardioprotector, antiulcer properties owing to the presence of various phytochemicals. The present study has been focused to find out the preventive action of flaxseed oil against radiation induced hematological and biochemical lesions in mammals. For this purpose, FSO (50μL/animal/day) was orally administered to Swiss albino mice for five days, prior to 6 Gy gamma radiation exposure. The animals were sacrificed on 1st, 3rd, 7th, 15th and 30th day after irradiation. Radiation treated control group exhibited significant reduction in erythrocytes count, hemoglobin content, hematocrit value and total WBC count in peripheral blood. In contrast, pretreatment with FSO significantly increased all these blood constituents. Further, the antioxidant parameters such as reduced glutathione, catalase, and superoxide dismutase showed a significant elevation in FSO pretreated group which were reduced in irradiated control group. Similarly, radiation induced increase lipid peroxidation in blood was significantly inhibited after FSO treatment. The present results indicate that the flaxseed oil has the ability to debilitate the radiation induced adverse alterations in the peripheral blood throughout the experiment in mammals. (author)

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

    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, 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)

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

    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)

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

    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)

  16. The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application

    Cem Uzal

    2012-03-01

    Full Text Available Objective: The aim of the study was to evaluate the radioprotective efficacy of intrarectal administration of amifostine in radiation-induced proctitis compared to intraperitoneal administration.Materials and Methods: Thirty-two Sprague-Dawley rats were randomly divided into four groups: Control (CONT, irradiation alone (RT, intraperitoneal amifostine plus irradiation (IPAMI, and intrarectal amifostine plus irradiation (IRAMI. The rats in the RT, IPAMI and IRAMI groups were irradiated individually with a single dose of 17.5 Gy to the pelvis. Amifostine was administered by the intraperitoneal (200 mg/kg or intrarectal (2000 mg/kg route before irradiation. Histopathologic analysis of the rectum was performed 14 days after irradiation. Results: Significant radiation damage appeared in all histopathologic parameters and was reduced by amifostine. Pretreatment with IPAMI significantly reduced the inflammatory infiltrate in the lamina propria (p=0.021, cryptitis (p=0.002 and crypt abscess (p=0.015. However, the protective effect of IRAMI was significant for all parameters with equal or higher significance than IPAMI, including the eosinophil leucocytes count (p=0.02, and distortion of the crypts (p=0.008, and was also significant for regenerative/reparative atypia (p=0.013. Conclusion: Intrarectal high dose topical administration of amifostine is more effective in the prevention of radiation-induced proctitis compared to its intraperitoneal systemic administration.

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

    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-α, IL-1β 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 potential to support a successful radiotherapy by protecting against radiation-induced enteritis. (author)

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

    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

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

    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

  20. Grape Seed Oil Extract Protects Against Radiation-Induced Oxidative Damage in Rats Eyes

    The present study was carried out to investigate the beneficial effects of grape seed oil on radiation-induced oxidative stress in the irradiated rat eyes. The rats were divided into three groups; control group that received distilled water, irradiated group (R) that exposed to gamma radiation as a single dose of 6.4 Gy and irradiated + grape seed oil group (R+GSO) that administered grape seed oil for seven consecutive days then exposed to the same single gamma radiation dose followed by grape seed oil for seven additional days. Histopathological results revealed protective effect of grape seed oil on the eye tissues of rat. The results lead to the conclusion that administration of GSO prior to radiation exposure may be a promising attempt in attenuating the extent of oxidative damage accompanying radiotherapy

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

    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 γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-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 γ-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

  2. Protection against radiation induced cytogenetic damage in mouse bone marrow by vitamin E

    It appears that pre-treatment of vitamin E could significantly prevent clastogenic alterations in the form of chromosomal aberrations and micronuclei formation against radiation induced cytogenetic damage

  3. Protective effect of zingerone, a dietary compound against radiation induced genetic damage and apoptosis in human lymphocytes.

    Rao, Bhuvanagiri Nageshwar; Archana, Parampalli Raghavendra; Aithal, Balkudru Kiran; Rao, Bola Sadashiva Satish

    2011-04-25

    Zingerone a dietary compound was investigated for its ability to protect against radiation induced genotoxicity and apoptosis in human lymphocytes growing in vitro. The radiation antagonistic potential of zingerone was assessed by alkaline comet, cytokinesis-block micronucleus, apoptosis and reactive oxygen species inhibition assays. Treatment of lymphocytes with zingerone (10?g/ml) prior exposure to 2Gy gamma radiation resulted in a significant reduction of frequency of micronuclei as compared to the control set of cells evaluated by cytokinesis blocked micronucleus assay. Similarly, treatment of lymphocytes with zingerone prior to radiation exposure showed significant decrease in the DNA damage as assessed by comet parameters, such as percent tail DNA and Olive tail moment. Further, treatment with zingerone (10?g/ml) before irradiation significantly decreased the percentage of apoptotic cells analyzed microscopically method and by DNA ladder assay. Similarly, the radiation induced reactive oxygen species levels were significantly (Pzingerone. Our study demonstrates the protective effect of zingerone against radiation induced DNA damage and antiapoptotic effect in human lymphocytes, which may be partly attributed to scavenging of radiation induced free radicals and also by the inhibition of radiation induced oxidative stress. PMID:21335001

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

    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.

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

    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

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

    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 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

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

    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 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

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

    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

  9. The protection of glutamine on radiation-induced intestinal mucosa injury in rats

    Objective: To observe the protection of glutamine on radiation-induced intestinal mucosa injury. Methods: Thirty rats were randomly divided into normal control group (group A), radiation control group (group B) and glutamine protection group (group C). The rats were received abdominal radiation of 1000 cGy. Feeding glutamine began since the day before radiation in group C. Four days later, the rats were killed, and the intestinal bacterial 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, and much lighter in group C than in group B. The concentration of endotoxin in blood was very low in group A, very high in group B, but much lower in group C than in group B. The villus edema, mucosa infiltrated with informative cells and epithelial exuviation were found in group B, but these pathological changes were much lighter in group C, and not found in group A. Conclusion: Whole abdomen radiation will evidently cause intestinal mucosa injury in rats, and bacteria translocation and endotoxemia would occur. Glutamine can prevent those changes

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

    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)

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

    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 cardiotoxicity

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

    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)

  13. Protection from radiation induced changes in liver and serum transaminase of whole body gamma irradiated rats

    Whole body gamma irradiation of rats with a dose of 5.5 Gy induced significant changes in the activity of liver and serum transaminase. The results indicated that this radiation dose caused a significant increase in the activity of serum Got and GPT on the third and seventh days after irradiation. This was followed by significant decreases on the fourteenth post-irradiation day. The activity of Got returned to is control activity, while the activity of GPT was significantly above the control on the twenty ones post-irradiation day. The activity of Got, in the liver of irradiated rats was elevated during the post-irradiation days, but on the twenty one day activity was about the normal value. The activity of liver GPT firstly decreased and then increased very much but attained the control level on the fourteenth after irradiation. The intraperitoneal injection of testosterone-vitamin E mixture 10 days before whole body gamma irradiation caused complete recovery for the activity of liver and serum Got. No indication of remarkable recovery in the case of GPT activity was recorded either in liver or in serum of irradiated rats. The applied mixture could protect against radiation induced changes in Got activity of liver and serum but could not protect or ameliorate the changes which occurred in the activity of GPT of the two tissues. 2 tab

  14. Biology responses to low dose radiation

    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)

  15. 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

    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...

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

    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.)

  17. Grapevine fruit extract protects against radiation-induced oxidative stress and apoptosis in human lymphocyte

    Ionizing radiation (IR) causes oxidative stress through overwhelming generation of reactive oxygen species (ROS) in the living cells leading the oxidative damage further to biomolecules. Grapevine (Vitis vinifera L.) posses several bioactive phytochemicals and is the richest source of antioxidants. In this study, we investigated V. vinifera for its phytochemical content, enzymes profile and, ROS-and oxidant-scavenging activities. We have also studied the fruit extract of four different grapevine viz., Thompson seedless, Flame seedless, Kishmish chorni and Red globe for their radioprotective actions in human lymphocytes. The activities of ascorbic acid oxidase and catalase significantly (P < 0.01) differed among extracts within the same cultivar, while that of peroxidase and polyphenol oxidase did not differ significantly. The superoxide radical-scavenging activity was higher in the seed as compared to the skin or pulp of the same cultivar. Pretreatment with grape extracts attenuated the oxidative stress induced by 4 Gy γ-radiation in human lymphocytes in vitro. Further, γ-radiation-induced increase in caspase 3/7 activity was significantly attenuated by grape extracts. These results suggest that grape extract serve as a potential source of natural antioxidants against the IR-induced oxidative stress and also inhibit apoptosis. Furthermore, the protective action of grape depends on the source of extract (seed, skin or pulp) and type of the cultivars. (author)

  18. Grapevine fruit extract protects against radiation-induced oxidative stress and apoptosis in human lymphocyte.

    Singha, Indrani; Das, Subir Kumar

    2015-11-01

    Ionizing radiation (IR) causes oxidative stress through overwhelming generation of reactive oxygen species (ROS) in the living cells leading the oxidative damage further to biomolecules. Grapevine (Vitis vinifera L.) posses several bioactive phytochemicals and is the richest source of antioxidants. In this study, we investigated V. vinifera for its phytochemical content, enzymes profile and, ROS- and oxidant-scavenging activities. We have also studied the fruit extract of four different grapevine viz., Thompson seedless, Flame seedless, Kishmish chorni and Red globe for their radioprotective actions in human lymphocytes. The activities of ascorbic acid oxidase and catalase significantly (P skin or pulp of the same cultivar. Pretreatment with grape extracts attenuated the oxidative stress induced by 4 Gy γ-radiation in human lymphocytes in vitro. Further, γ-radiation-induced increase in caspase 3/7 activity was significantly attenuated by grape extracts. These results suggest that grape extract serve as a potential source of natural antioxidants against the IR-induced oxidative stress and also inhibit apoptosis. Furthermore, the protective action of grape depends on the source of extract (seed, skin or pulp) and type of the cultivars. PMID:26669019

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

    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 α-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)

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

    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)

  1. Glycogen synthase kinase 3β inhibitors protect hippocampal neurons from radiation-induced apoptosis by regulating MDM2-p53 pathway

    Thotala, D K; Hallahan, D E; Yazlovitskaya, E M

    2011-01-01

    Exposure of the brain to ionizing radiation can cause neurocognitive deficiencies. The pathophysiology of these neurological changes is complex and includes radiation-induced apoptosis in the subgranular zone of the hippocampus. We have recently found that inhibition of glycogen synthase kinase 3β (GSK-3β) resulted in significant protection from radiation-induced apoptosis in hippocampal neurons. The molecular mechanisms of this cytoprotection include abrogation of radiation-induced accumulat...

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

    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 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

  3. Protective effects of WR-2721 against radiation-induced injury of murine gut, testis, lung, and lung tumor nodules

    WR-2721 (S-3-(3 aminopropylamino) ethylphosphorothioic acid) has been investigated for its ability to protect gut, lung, and testis, as well as fibrosarcoma (FSa) tumor nodules, in the lungs of mice from gamma-radiation injury. This compound greatly protected jejunum and testis epithelial cells. FSa micrometastases in the lung were protected in a lesser extent than jejunum and testis. Conversely, WR-2721 was not able to protect the lung against radiation-induced enhancement of tumor metastases formation generated by intravenously injected FSa cells

  4. Protective effects of parathyroid hormone on radiation-induced hematopoietic damage in mice

    Objective: To study the protective effects of parathyroid hormone (PTH) on radiation-induced hematopoietic damage in mice. Methods: A total of sixty male C57 mice were irradiated by 60Co γ-rays to induce hematopoietic injuries, and then the mice were randomly divided into PTH and control group.The PTH-treated group was treated with PTH (80 μg· kg-1 · d-1) intraperitoneally everyday. The control group was given equivalent volume saline. Peripheral blood cell number, bone marrow mononuclear cell number,granulocyte-macrophage colony forming units (CFU-GM) and CD34 positive cells in bone marrow were detected. Results: With the whole post-irradiation period, the WBC and bone marrow mononuclear cell numbers in PTH-treated mice were significantly higher than those in saline-treated mice (t=6.32, 9.19, 11.18, 7.44 and 4.42, P<0.05). The RBC numbers in PTH-treated mice were significantly higher than those in control mice at 10 d, 15 d and 20 d post-irradiation (t =6.48, 3.66 and 4.98, P<0.05). The PLT numbers in PTH-treated mice were significantly higher than those in control group at 5 and 30 d post-irradiation (t=2.57 and 3.10, P<0.05). PTH increased CD34 positive cell and CFU-GM numbers in bone marrow after irradiation (t=16.12, 7.82 and 20.00, P<0.05). Conclusions: PTH could improve the hematopoietic recovery after irradiation. (authors)

  5. 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

    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

  6. Studies on protective effects of superoxide dismutase on radiation induced-chromosomal aberrations

    This study demonstrates that radiation induced-chromosomal aberrations are not only due to the direct effect of radiation hit, but the indirect effect of free radical as well. Therefore, chromosome damage induced by radiation may be reduced by adding exogenous SOD into the radiation exposed lymphocyte culture to eliminate the superoxide free radical which damages DNA. On the other hand, however, the radiosensitivity of lymphocytes can be raised by adding SOD inhibitor (DDC) into the lymphocyte culture, which makes radiation induced-chromosomal damages more severely

  7. A novel topical protectant for the prevention of ?-radiation induced moist desquamation

    Full text: Effective therapies for the prevention of radiation-induced skin burns that could be readily deployed under a nuclear accident or nuclear terrorism scenario are urgently needed. In this report we describe the efficacy of a novel radioprotectant (DMZ911) in a model of b-radiation induced moist desquamation (MD) in pig skin. DMZ911 is a nitroxide-based topical cream that effectively delivers the nitroxide into viable skin cells. Stable nitroxide compounds have been shown to be effective against both X-ray and ?-ray-induced damage in vivo and in vitro. A pig skin model of ?-radiation-induced MD was employed in this study. Exposure to 30 Gy was used to induce skin lesions involving >80% moist desquamation in prescribed test sites on flank skin of female Large White pigs. DMZ911 or placebo was applied to various test sites 2 hours prior to radiation exposure. Lesions were scored based on the area of the test site containing 50% MD (severe) as determined by clinical assessment using blinded observers. Treatment with DMZ911 resulted in a 31% net reduction in MD when compared to placebo treated sites following an 8-week study period. This reduction was observed whether all sites or only those with severe MD were considered. Skin damage (as indicated by MD) from radiation exposure was significantly reduced by 31% (p = 0.05) following pretreatment with the novel topical radioprotectant DMZ911. This observation suggests that skin lesion development from radiation-induced oxidative damage cascades may be successfully inhibited by treatment with DMZ911. This topical therapeutic agent represents a novel treatment for nuclear radiation induced skin injury. DMZ911 may have unique applications in radiation oncology, cosmetic and therapeutic UV, laser, glycolic and dermabrasion procedures

  8. Corticosterone protects against memory impairments and reduced hippocampal BDNF levels induced by a chronic low dose of ethanol in C57BL/6J mice.

    Ebada ME; Latif LM; Kendall DA; Pardon MC

    2014-01-01

    Acute low doses of ethanol can produce reversible memory deficits, but it is unknown whether they persist upon chronic use. We investigated whether the chronic intake of a low dose of ethanol induces memory impairments in the ethanol-preferring C57BL/6J mouse strain. Because stress precipitates alcohol abuse and the stress hormone corticosterone contributes to memory processes, ethanol consumption and toxic effects, we also determined the impact of co-treatment with corticosterone on these effects. BDNF contributes to memory function and toxic effects of ethanol, therefore its levels were quantified in the hippocampus and frontal cortex. Ethanol (1% in drinking water) and corticosterone (250 ?g/mL) were administered using the two-bottle choice test to monitor their appetitive properties. Spatial and non-spatial memory performance was assessed using the spontaneous alternation, object recognition and object location tests. The chronic exposure to a low dose of ethanol caused spatial and non-spatial memory deficits after withdrawal associated with a reduction in hippocampal BDNF levels, which were prevented by co-treatment with corticosterone (~21 mg/kg/day). The protective effect of corticosterone on memory was no longer observed at higher doses (~41 mg/kg/day), but persisted for hippocampal BDNF levels. C57BL/6J mice did not develop an appetence for 1% ethanol, but the addition of corticosterone increased voluntary consumption of and preference for the ethanol+corticosterone solutions. Although acute low doses of corticosterone (1 mg/kg) were found to rescue established memory impairments, this is the first report of a protective effect of chronic doses of corticosterone in the range of 20-32 mg/kg, and particularly against memory deficits induced by alcohol.

  9. Corticosterone protects against memory impairments and reduced hippocampal BDNF levels induced by a chronic low dose of ethanol in C57BL/6J mice.

    Ebada, Mohamed Elsaed; Latif, Liaque M; Kendall, David A; Pardon, Marie Christine

    2014-01-01

    Acute low doses of ethanol can produce reversible memory deficits, but it is unknown whether they persist upon chronic use. We investigated whether the chronic intake of a low dose of ethanol induces memory impairments in the ethanol-preferring C57BL/6J mouse strain. Because stress precipitates alcohol abuse and the stress hormone corticosterone contributes to memory processes, ethanol consumption and toxic effects, we also determined the impact of co-treatment with corticosterone on these effects. BDNF contributes to memory function and toxic effects of ethanol, therefore its levels were quantified in the hippocampus and frontal cortex. Ethanol (1% in drinking water) and corticosterone (250 ?g/mL) were administered using the two-bottle choice test to monitor their appetitive properties. Spatial and non-spatial memory performance was assessed using the spontaneous alternation, object recognition and object location tests. The chronic exposure to a low dose of ethanol caused spatial and non-spatial memory deficits after withdrawal associated with a reduction in hippocampal BDNF levels, which were prevented by co-treatment with corticosterone (~21 mg/kg/day). The protective effect of corticosterone on memory was no longer observed at higher doses (~41 mg/kg/day), but persisted for hippocampal BDNF levels. C57BL/6J mice did not develop an appetence for 1% ethanol, but the addition of corticosterone increased voluntary consumption of and preference for the ethanol+corticosterone solutions. Although acute low doses of corticosterone (1 mg/kg) were found to rescue established memory impairments, this is the first report of a protective effect of chronic doses of corticosterone in the range of 20-32 mg/kg, and particularly against memory deficits induced by alcohol. PMID:25611260

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

    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

  11. Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells

    Current management of radiation-induced liver injury is limited. Sinusoidal endothelial cell (SEC) apoptosis and inflammation are considered to be initiating events in hepatic damage. We hypothesized that mesenchymal stem cells (MSCs) possess anti-apoptotic and anti-inflammatory actions during hepatic irradiation, acting via paracrine mechanisms. This study aims to examine whether MSC-derived bioactive components are protective against radiation-induced liver injury in rats. MSC-conditioned medium (MSC-CM) was generated from rat bone marrow–derived MSCs. The effect of MSC-CM on the viability of irradiated SECs was examined by flow cytometric analysis. Activation of the Akt and ERK pathways was analyzed by western blot. MSC-CM was also delivered to Sprague–Dawley rats immediately before receiving liver irradiation, followed by testing for pathological features, changes in serum hyaluronic acid, ALT, and inflammatory cytokine levels, and liver cell apoptosis. MSC-CM enhanced the viability of irradiated SECs in vitro and induced Akt and ERK phosphorylation in these cells. Infusion of MSC-CM immediately before liver irradiation provided a significant anti-apoptotic effect on SECs and improved the histopathological features of injury in the irradiated liver. MSC-CM also reduced the secretion and expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines. MSC-derived bioactive components could be a novel therapeutic approach for treating radiation-induced liver injury. (author)

  12. Protection against radiation induced biochemical changes in cerebrum of Swiss albino mice by Grewia asiatica fruit extract

    Full text: The aim of the present study was to evaluate the radioprotective effect of Grewia asiatica fruit pulp extract (GAE) on Swiss albino mice exposed to gamma radiation. In the present study radioprotective efficacy of Grewia asiatica (rich in anthocyanin, carotenes, Vit.C, etc.) was studied against radiation induced biochemical alterations in mice cerebrum. For experimental study, healthy Swiss Albino mice were selected from an inbred colony and divided into four groups. Group I (normal) did not receive any treatment. Group II was orally supplemented (GAE) once daily at the dose of 700 mg/Kg.b.wt/day for fifteen consecutive days. Group III (control) received distilled water orally equivalent to GAE for fifteen days than exposed to 5 Gy of gamma radiation. Group IV (IR+Drug) was administered orally (GAE) for 15 consecutive days once daily after exposed to single dose of 5Gy of gamma radiation respectively. Mice were sacrificed at different autopsy intervals viz. 1, 3, 7, 15 and 30 days and cerebrum were removed for various biochemical estimations viz. glutathione (GSH), lipid peroxidation (LPO) and protein. GAE post treatment renders protection against various biochemical changes in mice cerebrum. Radiation induced augmentation in the levels of LPO was significantly ameliorated by GAE post-treatment. Radiation-induced depletion in the level of GSH, protein was checked significantly by GAE administration

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

    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...

  14. PHD Inhibition Mitigates and Protects Against Radiation-Induced Gastrointestinal Toxicity via HIF2

    Taniguchi, Cullen M; Miao, Yu Rebecca; Diep, Anh N.; Wu, Colleen; Rankin, Erinn B.; Atwood, Todd F.; Xing, Lei; Amato J. Giaccia

    2014-01-01

    Radiation-induced gastrointestinal (GI) toxicity can be a major source of morbidity and mortality after radiation exposure. There is an unmet need for effective preventative or mitigative treatments against the potentially fatal diarrhea and water loss induced by radiation damage to the GI tract. We report that prolyl hydroxylase inhibition by genetic knockout or pharmacologic inhibition of all PHD isoforms by the small molecule dimethyloxyallylglycine (DMOG) increases HIF expression, improve...

  15. The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction

    Although the protective effect of the polyhydroxylated fullerene derivative C60(OH)n against ionizing radiation is an area of much interest, the mechanisms relating to how polyhydroxylated fullerene derivatives improve mitochondrial dysfunction remain unknown. In order to find new and effective radioprotective agents, we synthesized a new polyhydroxylated fullerene molecule with 24 hydroxyl groups of known positions on C60 and studied its protective effects in mice subjected to irradiation. Mice were pretreated with C60(OH)24 for 2 weeks (daily, 40 mg/kg i. p.), then subjected to a lethal dose of whole body ?-irradiation (from a 60Co source). Survival was observed for 30 days after irradiation. Immune and mitochondrial dysfunction and oxidative damage were analyzed in mice with the same C60(OH)24 pretreatment and irradiation except that the animals were euthanized at day 5 after the irradiation. It was found that 2-week C60(OH)24 pretreatment effectively reduced whole body irradiation-induced mortality without apparent toxicity. C60(OH)24 pretreatment also showed significant protective effects against ionizing-radiation-induced decreases in immune and mitochondrial function and antioxidant defense in the liver and spleen. These results suggest that the polyhydroxylated fullerene derivative C60(OH)24 protects against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.

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

    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 one¡¯s 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 ¡Ý 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 ¡Ý 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 combined exposure to low- and high-LET radiations when based on the LNT or other models that exclude RR < 1. Our results for high-LET radiation are consistent with the LNT hypothesis but only where there is no additional low-LET contribution (e.g., gamma rays) to the total dose. For high-LET neutron sources, gamma rays arise (especially in vivo) for large mammals such as humans from neutron interactions with tissue. The gamma rays might provide some protection from low-dose-related stochastic effects via inducing the protective bystander apoptosis effect that is considered to contribute to tissue cleansing via removal of problematic cells.

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

    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 γ-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 μg/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 μg/ml and the filtrate at 50, 100, 200 μg/ 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 μ-radiation induced oxidative stress protection activity.

  18. Acemannan (a polysaccharides of Aloe vera gel) protects against radiation induced mortality by modulation of immunosuppression

    Acemannan (poly-acetylated mannose) is an active component of Aloe vera gel and has been reported to have anticancerous, antimicrobial and shown to stimulate the development and proliferation of the hematopoietic cells. The anticancerous properties of acemannan have been attributed to the modulation of immune system rather then cytotoxicity. Therefore objective of the present study was to evaluate radioprotective efficacy of acemannan against radiation induced immune suppression using Swiss albino mice as a model system. For In-vivo studies mice were treated for 7 days orally prior to irradiation (5 Gy). Animals were sacrificed at different time point to study the effect on cellular proliferation, DNA damage, apoptosis and ROS level, cytokines level, antioxidant enzymes, nitric oxide and protein expression. For survival studies mice were treated with acemannan for 7 days pre or post irradiation and survival was monitored for 30 days. Acemannan showed a significant induction of proliferation of splenocytes in radiation treated groups. Beside a decrease in radiation induced ROS and DNA damage resulted in the reduction of apoptosis in murine splenocytes. Acemannan restored the antioxidant enzyme level (catalase, SOD, DTD and GST) and maintained the proper redox status via GSH, in irradiated mice. Further acemannan was shown to induce the hematopoiesis (peripheral lymphocytes cells, spleen colony cells, spleen index) by increasing the level of the pro-hematopoiesis cytokines (IL-1, TNF-α). Being an immunomodulator, acemannan reduced the level of the inflammation (IL-6, nitric oxide). Also the multiple mechanisms operational at cellular and molecule levelled to the reduction of radiation induced mortality of mice in both pre and post-irradiation studies. On the basis of the above results it can be concluded that radioprotective effects of the acemannan was due to its immunomodulatory activity and could have application for radio-therapeutic purposes. (author)

  19. Hydrogen-rich PBS protects cultured human cells from ionizing radiation-induced cellular damage

    Qian Liren

    2010-01-01

    Full Text Available Hydroxyl radicals play an important role in ionizing radiation-induced cellular damage, while hydrogen can selectively reduce hydroxyl radicals in vitro. This study was designed to test the hypothesis that hydrogen-rich PBS may be an effective radioprotective agent in vitro. Compared to cells pretreated without hydrogen, we demonstrated that treating cells with hydrogen-rich PBS before irradiation could significantly inhibit IR-induced apoptosis, increase viability of human intestinal crypt cells, significantly increase endogenous antioxidant, and decrease malondialdehyde and 8-hydroxydeoxyguanosine concentrations of human lymphocyte AHH-1 cells. It is concluded that hydrogen has a potential as an effective and safe radioprotective agent.

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

    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

  1. Possible protective and curative role of thiamine pyrophosphate against radiation induced biochemical and histological changes in male albino rats

    The present study has been performed to investigate the possible curative and protective role of thiamine pyrophosphate (TPP) in minimizing the radiation-induced changes in certain biochemical and histological parameters in the liver and kidney of rats. The activity of liver alanine aminotransferase (ALT), aspartate aminotransferase (AST) and g-glutamyl transferase (g-GT) as well as kidney creatinine and urea concentrations were measured. In addition, histological changes in the liver and kidney tissues were examined.The results obtained revealed that whole body g-irradiation of rats at 5 Gy (single dose) induced significant increase in the activity of liver g-GT, ALT and AST and also significant increase in the concentration of creatinine and urea in the kidney at 1, 2, 3, and 4 weeks post-irradiation. Exposure to radiation induced also distortion in the architecture pattern of the liver as well as degenerative changes of the proximal convoluted tubules of the kidney.The intraperitoneal administration of TPP at a concentration of 2mg/Kg body weight to unirradiated rats for 5 consecutive days did not induce any significant changes in biochemical and histological parameters studied at all the experimental periods. TPP given to rats for 5 consecutive days either before or after irradiation ameliorated the intensity of changes induced due to radiation exposure. Accordingly, it was concluded that TPP could exert a beneficial protective and curative role against some radiation-induced biochemical and histological disorders in liver and kidney. Extrapolation of the results obtained in the present study to patients who need such treatments and undergoing radiotherapy requires further investigations

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

    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 (γ-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 was associated 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

  3. Risperidone in ultra low dose protects against stress in the rodent cold restraint model by modulating stress pathways.

    Krishnamurthy, Sairam; Garabadu, Debapriya; Reddy, Nagannathahalli Ranga; Joy, Keerikkattil P

    2011-10-01

    The present investigation evaluates the anti-stress activity of risperidone (RIS) in the cold restraint stress (CRS) model and related stress pathways. Rats were pretreated with RIS (0.1 and 1.0 mg/kg) for 21 days before subjecting to CRS. Ultra low dose of RIS (ULD; 0.1 mg/kg) in contrast to higher dose (1.0 mg/kg) significantly reduced stress in terms of ulcer index. ULD also reversed stress-induced increase in plasma corticosterone and norepinephrine levels used as markers for the function of hypothalamo-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) respectively. ULD caused dose and brain region (hippocampus, prefrontal cortex and striatum) specific changes to stress-induced perturbations of serotonin, dopamine and its metabolites indicating modulation of brain monoaminergic system (BMS). ULD did not show any extrapyramidal side effects. Thus, the anti-stress effect ULD is probably mediated through the HPA axis, SNS and BMS. The study indicates a potential use of ULD in stress disorders. PMID:21660590

  4. Protective effects of catecholomic acid derivatives on radiation-induced damage of rat liver mitochondria

    Objective: To evaluate the effects of catecholomic acid derivatives 9501, 9502 and 7601 (CBMIDA) against radiation-induced injury of rat liver mitochondria in vitro. Methods: The injury of rat liver mitochondria was induced by γ-irradiation in vitro. The contents of MDA were assayed by spectrophotometry of TBA. The absorption value at 520 nm was measured to detect swelling of mitochondria. The electron microscopic samples of mitochondria were prepared. Results: All 9501 (5 x 10-6 mol/L), 9502(10-5 mol/L), and 7601 (10-5 mol/L) significantly inhibited radiation-induced increase of MDA information.The swelling of mitochondria induced by irradiation was also prevented by 9501, 7601. The electron micrographs also showed that 9501 markedly reduced the pathological damage of mitochondria induced by γ-irradiation. The mechanisms of anti-oxidative action of catecholomic acid derivatives was discussed. Conclusion: Injurious effect of radiation on rat liver mitochondria can be prevented by catecholomic acid derivatives 9501, 9502 and 7601 (CBMIDA)

  5. Protective effect of superoxide dismutase in radiation-induced intestinal inflammation

    Purpose: To analyze the therapeutic value of Cu/Zn-superoxide dismutase (SOD1) supplementation in an experimental model of radiation-induced intestinal inflammation and explore its mechanistic effects. Methods and materials: Mice were subjected to abdominal irradiation with 10 Gy or sham irradiation and studied 24 or 72 hours after radiation. Groups of mice were treated with 0.1, 4, or 6 mg/kg/day of SOD1 or vehicle. Leukocyte-endothelial cell interactions in intestinal venules were assessed by intravital microscopy. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was determined with radiolabeled antibodies. Effects of SOD1 on histologic damage and levels of lipid hydroperoxides were also measured. Results: A significant increase in the flux of rolling leukocytes and number of firmly adherent leukocytes in intestinal venules was observed at 24 and 72 hours after irradiation. Treatment with SOD1 had no effect on leukocyte rolling but significantly and dose-dependently decreased firm leukocyte adhesion to intestinal venules. Treatment with SOD1 at doses that reduced leukocyte recruitment abrogated the increase in hydroperoxides in intestinal tissue and ICAM-1 upregulation in intestinal endothelial cells. The inflammatory score, but not a combined histology damage score, was also significantly reduced by SOD1. Conclusions: Treatment with SOD1 decreases oxidative stress and adhesion molecule upregulation in response to abdominal irradiation. This is associated with an attenuation of the radiation-induced intestinal inflammatory response

  6. New risk estimates at low doses

    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

  7. Synergistic protective effects of escin and low?dose glucocorticoids on blood?retinal barrier breakdown in a rat model of retinal ischemia.

    Zhang, Fenglan; Li, Yuanbin; Zhang, Leiming; Mu, Guoying

    2013-05-01

    Escin, a natural mixture of triterpenoid saponins isolated from the seed of the horse chestnut (Aesculushippocastanum), has been demonstrated to possess glucocorticoid (GC)?like anti?edematous and anti?in?ammatory effects. The aim of the present study was to investigate whether escin exhibits synergistic protective effects on blood?retinal barrier (BRB) breakdown when combined with GCs in a rat model of retinal ischemia. Low concentrations of escin and triamcinolone acetonide (TA) alone did not affect BRB permeability. However, when administered together, low?dose escin and TA significantly reduced BRB permeability following ischemia. Furthermore, low?dose escin and TA alone did not affect the expression of occludin in the ischemic retina; however, when administered together, they significantly increased occludin expression in the ganglion cell layer of the ischemic retina. This indicates that escin and GCs have synergistic protective effects on BRB breakdown and the molecular mechanisms may be correlated with the upregulation of occludin. Therefore, the administration of escin may allow a reduction in the dose of GCs for the treatment of macular edema. The combination of escin with GCs is potentially a beneficial treatment method for BRB breakdown and warrants further investigation. PMID:23525122

  8. Protective effect of hypoxia against radiation induced fibrosis in the rat gut

    The protective effect of hypoxia, induced by degradable microspheres, against the development of fibrosis was investigated after single-dose irradiation of exteriorized rat ileum. Evaluation, based upon microscopy and analysis of hydroxyproline in protected and non-protected gut segments, demonstrated an evident protective effect at doses of 15 to 25 Gy. (Auth.)

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

    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.)

  10. Protective effect of N-acetyl cysteine on radiation-induced DNA damage in rat bone

    Can DEMİREL

    2008-01-01

    Full Text Available OBJECTIVES: To evaluate the potential radioprotective effects of N-acetylcysteine (NAC against genocytotoxicity. As representative of a clinically used radioprotector, the effect of WR-2721 was compared with that of NAC using chromosomal aberration (CA and mitotic index (MI in the irradiated rat’s femoral bone marrow cells. METHODS: The rats (n=48 were divided randomly and equally into six groups as: Control (C, NAC (received 1000 mg/kg NAC, WR-2721 (200 mg/kg WR-2721, Radiation (R, received irradiation, R + NAC (received irradiation and 1000 mg/kg NAC, and R + WR-2721 (received irradiation and 200 mg/kg WR-2721. All the irradiated groups received whole-body gamma irradiation as a single dose of 6 Gy. At 72th hours, the rats were sacrificed and bone marrow cells were bilaterally collected from rats’ femur. Then, cytogenetic and cytotoxicity tests were performed according to convantional methods. RESULTS: Group R showed significantly higher CA and lower MI values when compared to C. R + NAC and R + WR-2721 groups showed significantly lower CA and higher MI averages when compared to R. CONCLUSION: The results give clues about the beneficial effects of NAC against radiation-induced genocytotoxicity.

  11. Low-dose CT of the paranasal sinuses with eye lens protection: effect on image quality and radiation dose

    Hein, Eike; Rogalla, Patrik; Klingebiel, Randolph; Hamm, Bernd [Department of Diagnostic and Interventional Radiology, Charite Hospital, Humboldt-Universitaet zu Berlin (Germany)

    2002-07-01

    The purpose of the study was to assess the effect of lens protection on image quality and radiation dose to the eye lenses in CT of the paranasal sinuses. In 127 patients referred to rule out sinusitis, an axial spiral CT with a lens protection placed on the patients eyes was obtained (1.5/2/1, 50 mAs, 120 kV). Coronal views were reconstructed at 5-mm interval. To quantify a subjective impression of image quality, three regions of interest within the eyeball were plotted along a line perpendicular to the protection at 2, 5, and 9 mm beneath skin level on the axial images. Additionally, dose reduction of a bismuth-containing latex shield was measured using a film-dosimetry technique. The average eyeball density was 17.97 HU (SD 3.7 HU). The relative increase in CT density was 180.6 (17.7), 103.3 (11.7), and 53.6 HU (9.2), respectively. There was no diagnostic information loss on axial and coronal views observed. Artifacts were practically invisible on images viewed in a bone window/level setting. The use of the shield reduced skin radiation from 7.5 to 4.5 mGy. The utilization of a radioprotection to the eye lenses in paranasal CT is a suitable and effective means of reducing skin radiation by 40%. (orig.)

  12. Low-dose CT of the paranasal sinuses with eye lens protection: effect on image quality and radiation dose

    The purpose of the study was to assess the effect of lens protection on image quality and radiation dose to the eye lenses in CT of the paranasal sinuses. In 127 patients referred to rule out sinusitis, an axial spiral CT with a lens protection placed on the patients eyes was obtained (1.5/2/1, 50 mAs, 120 kV). Coronal views were reconstructed at 5-mm interval. To quantify a subjective impression of image quality, three regions of interest within the eyeball were plotted along a line perpendicular to the protection at 2, 5, and 9 mm beneath skin level on the axial images. Additionally, dose reduction of a bismuth-containing latex shield was measured using a film-dosimetry technique. The average eyeball density was 17.97 HU (SD 3.7 HU). The relative increase in CT density was 180.6 (17.7), 103.3 (11.7), and 53.6 HU (9.2), respectively. There was no diagnostic information loss on axial and coronal views observed. Artifacts were practically invisible on images viewed in a bone window/level setting. The use of the shield reduced skin radiation from 7.5 to 4.5 mGy. The utilization of a radioprotection to the eye lenses in paranasal CT is a suitable and effective means of reducing skin radiation by 40%. (orig.)

  13. Protective action of testosterone propionate and vitamin E for recovery from radiation induced changes in serum nitrogen of irradiated rats

    A mixture of testosterone propionate and vitamin E has no influence on the serum protein nitrogen of rats. It was found that the intraperitoneal injection of 5 mg testosterone propionate and 10 mg vitamin E/100 g body weigh, or even ten times more than this concentration, could not exert any toxic effects. When this mixture was used as radioprotector, the rats were injected 10 days before whole body gamma -irradiation by dose of 5.5 Gy. These changes were characterized by significant increase in both protein and nonprotein nitrogen levels all post-irradiation periods. Testosterone mixture succeeded in providing complete protection for the radiation induced changes in the contents of protein nitrogen in the serum of irradiated rats. The significant changes which were recorded in irradiated rats ultimately disappeared 3 days after whole body gamma-irradiation of rats, previously treated with the mixture of testosterone and vitamin E.1 fig

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

    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.)

  15. Protection against radiation induced hematopoietic damage in bone marrow of Swiss albino mice by Mentha piperita (Linn)

    The protective effects of Mentha piperita (Linn) extract against radiation induced hematopoietic damage in bone marrow of Swiss albino mice have been studied. Mice were given either double distilled water or leaf extract of M. piperita orally (1 g/kg b.wt./day) once a day for three consecutive days, and after 30 min of treatments on the third day were exposed to 8 Gy gamma radiation. Mice were autopsied at 12, 24, 48 hrs and 5, 10 and 20 days post-irradiation to evaluate the percentage of bone marrow cells, frequency of micronuclei and erythropoietin level in serum. An exposure to gamma radiation resulted in a significant decline in the number of bone marrow cells such as leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes. Pretreatment with leaf extract of M. piperita followed by radiation exposure resulted in significant increases in the numbers of leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes in bone marrow as compared to the control group. Pretreatment with leaf extract of M. piperita followed by radiation exposure also resulted in significant decreases in micronucleus frequencies in bone marrow of Swiss albino mice. A significant increase in erythropoietin level was observed at all the studied intervals in leaf extract of M. piperita pretreated irradiated animals as compared to control animals (radiation alone). The results of the present investigation suggest the protective effects of leaf extract of M. piperita against radiation induced hematopoietic damage in bone marrow may be attributed to the maintenance of erythropoietin (EPO) level in Swiss albino mice. (author)

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

    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)

  17. Radiation induced bystander effects

    Full text: In recent years, radiation induced bystander effects have been reported in cells which were not themselves irradiated but were either in the vicinity of irradiated cells or exposed to medium from irradiated cells. The effects have been clearly shown to occur both in vivo and in vitro. This work has led to a paradigm shift in radiobiology over the last 5-10 years. The target theory of radiation induced effects is now being challenged because of an increasing number of studies which demonstrate non (DNA)-targeted effects. These effects appear to be particularly important at low doses. Considerable evidence now exists relating to radiation induced bystander effects but the mechanisms involved in the transduction of the signal are still unclear. Cell-cell communication through gap junctions and/or secretion of a cytotoxic factor into the medium are thought to be important in both mechanisms. Signalling pathways leading to apoptosis, such as calcium, MAP kinase, mitochondrial and reactive oxygen species (ROS) signaling are shown. The importance of oxidative metabolism and calcium signaling in bystander responses are demonstrated. Further investigations of these signalling pathways may aid in the identification of novel therapeutic targets

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

    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.

  19. Protection of rat primary hepatocytes from radiation-induced apoptosis by hepatocyte growth factor (HGF)

    Purpose: Radiation hepatopathy can be a life-threatening treatment complication limiting the therapeutic intervention of irradiation in upper abdominal malignancies. Understanding the mechanisms of radiation-induced liver injury will help us develop methods for the prevention and treatment of this complication. Both liver endothelial cell and hepatocyte injury contribute to the development of radiation hepatopathy. The objective of the present study is to examine the effects of irradiation on primary hepatocyte injury and to investigate how the irradiation effect is modified by the presence of non-parenchymal cells and hepato trophic growth factors such as HGF. Methods: Primary hepatocytes and liver non parenchymal cells were isolated from collagenase perfused Fischer 344 rat livers by a two-step percoll gradient centrifugation. Hepatocytes (>90% viable by Trypan blue exclusion) were cultured in modified Chee medium on collagen-coated Nunc Permanox plates. HGF was added at a concentration of 100 ng/ml. Survival of hepatocytes was determined after 30Gy of Co60 irradiation by Trypan blue dye exclusion and counting Hoechst-33258 stained apoptotic nuclei by fluro scent microscopy. Results: After irradiation, primary hepatocytes exhibited apoptosis which was observed at 6 hours, peaked at 24 hrs and continued up to 72 hours (the last time point in this study). A dose of 30 Gy induced apoptosis in 10-15% of hepatocytes, while unirradiated controls showed >3.0% of apoptotic cells. HGF (100ng/ml) could inhibit the induction of apoptosis in irradiated hepatocytes by 75-80% to the basal level of spontaneous apoptosis, present in unirradiated controls. Daily supplementation of HGF maintained this inhibition of apoptosis for the entire observation period (72 hours). Co incubation of non parenchymal liver cells sensitized hepatocytes to the irradiation-induced apoptosis by three fold. Conclusion: Cultured primary rat hepatocytes undergo apoptosis following irradiation. The rate of apoptosis is enhanced by the presence of non-parenchymal liver cells and is inhibited by HGF

  20. Pro-inflammatory agents LPS and IL-6 protect monocytic cell line RAW264.7 from radiation induced cell death

    Our earlier studies have shown that increased glycolysis protects cells from radiation induced cell death. Pro-inflammatory molecules like LPS have been shown to reduce radiation induced gastro-intestinal syndrome, while IL-6 protects cardiomyocytes from ischemia induced oxidative stress. Interestingly, both pro-inflammatory molecules, LPS and IL-6 induce glycolysis in cells and mimic the high glycolytic phenotype. Therefore, we hypothesize that LPS and IL-6 can protect the hematopoietic cells from radiation induced cell death by inducing glycolysis. To validate our hypothesis, we investigated the response of RAW264.7 cells stimulated with LPS (10 ng/ml) and IL-6 (1 ng/ml), 2 hours prior to irradiation (2 Gy, gamma rays, 60Co). Both LPS and IL-6 protected cells from radiation induced growth inhibition with > 50% increase in cell number as compared to radiation alone. Under these conditions, IL-6 showed more than 2 fold increase in glycolysis, measured by lactate production, which correlated with increased cell number. To understand the mechanisms underlying IL-6 induced radio-resistance, we examined the effects of IL-6 on anti-oxidant defence and mitochondrial status in irradiated cells. Cells treated with IL-6 showed nearly 40% reduced levels of radiation induced delayed reactive oxygen species (ROS), measured at 24 hours after exposure using DCFH2-DA. The decrease in ROS was linked to increased mitochondrial membrane potential (MMP), thereby suggesting that IL-6 induced reduction in ROS levels and high MMP protects the cell from radiation induced cell death. Our results show that both mitochondrial uncouplers and pro-inflammatory molecules (LPS and IL-6) lead to similar metabolic shift in the form of increased glycolysis leading to enhanced radio-resistance. Therefore, we propose that stimulation of glycolysis can be an useful radioprotective strategy, irrespective of the nature of stimulants. Further studies to understand mechanisms underlying IL-6 induced radioprotection of cells are under progress. (author)

  1. Pretreatment by low-dose fibrates protects against acute free fatty acid-induced renal tubule toxicity by counteracting PPARα deterioration

    Development of a preventive strategy against tubular damage associated with proteinuria is of great importance. Recently, free fatty acid (FFA) toxicities accompanying proteinuria were found to be a main cause of tubular damage, which was aggravated by insufficiency of peroxisome proliferator-activated receptor alpha (PPARα), suggesting the benefit of PPARα activation. However, an earlier study using a murine acute tubular injury model, FFA-overload nephropathy, demonstrated that high-dose treatment of PPARα agonist (0.5% clofibrate diet) aggravated the tubular damage as a consequence of excess serum accumulation of clofibrate metabolites due to decreased kidney elimination. To induce the renoprotective effects of PPARα agonists without drug accumulation, we tried a pretreatment study using low-dose clofibrate (0.1% clofibrate diet) using the same murine model. Low-dose clofibrate pretreatment prevented acute tubular injuries without accumulation of its metabolites. The tubular protective effects appeared to be associated with the counteraction of PPARα deterioration, resulting in the decrease of FFAs influx to the kidney, maintenance of fatty acid oxidation, diminution of intracellular accumulation of undigested FFAs, and attenuation of disease developmental factors including oxidative stress, apoptosis, and NFκB activation. These effects are common to other fibrates and dependent on PPARα function. Interestingly, however, clofibrate pretreatment also exerted PPARα-independent tubular toxicities in PPARα-null mice with FFA-overload nephropathy. The favorable properties of fibrates are evident when PPARα-dependent tubular protective effects outweigh their PPARα-independent tubular toxicities. This delicate balance seems to be easily affected by the drug dose. It will be important to establish the appropriate dosage of fibrates for treatment against kidney disease and to develop a novel PPARα activator that has a steady serum concentration regardless of kidney dysfunction. - Graphical Abstract: Massive proteinuria introduces free fatty acid toxicity to proximal tubular epithelial cells (PTECs). PPARα activationvia clofibrate pretreatment maintains fatty acid catabolism and attenuates oxidative stress, apoptosis, and NFκB activation, resulting in protection of PTECs. The favorable properties of fibrates are evident when PPARα-dependent tubular protective effects outweigh their PPARα-independent tubular toxicities. Display Omitted Highlights: → Clofibrate pretreatment protects against acute FFA-induced tubular toxicity. → PPARα activation decreases FFA influx and maintains fatty acid catabolism. → PPARα activation attenuates oxidative stress, apoptosis, and NFκB activation. → Protective effects must outweigh PPARα-independent tubular toxicities of fibrates.

  2. Protection of ionizing radiation-induced cytogenetic damage by hydroalcoholic extract of Cynodon dactylon in Chinese hamster lung fibroblast cells and human peripheral blood lymphocytes.

    Rao, Bola Sadashiva Satish; Upadhya, Dinesh; Adiga, Satish Kumar

    2008-01-01

    The radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (family: Poaceae) against radiation-induced cytogenetic damage was analyzed using Chinese hamster lung fibroblast (V79) cells and human peripheral blood lymphocytes (HPBLs) growing in vitro. Induction of micronuclei was used as an index of cytogenetic damage, evaluated in cytokinesis blocked binucleate cells. The hydroalcoholic Cynodon dactylon extract (CDE) rendered protection against the radiation-induced DNA damage, as evidenced by the significant (pacid) (ABTS); superoxide anion (O2*-); hydroxyl radical (OH*) and nitric oxide radical (NO*) generated in vitro. Also, an excellent (70%) inhibition of lipid peroxidation in vitro was observed at a dose of 300 microg/ml CDE, attaining the saturation point at higher doses. The present findings demonstrated the radioprotective effect of CDE, also rendering protection against radiation-induced genomic instability and DNA damage. The observed radioprotective effect may be partly attributed to the free radical scavenging and antilipid peroxidative potential of CDE. PMID:18540846

  3. Dried Plum Protects From Radiation-Induced Bone Loss by Attenuating Pro-Osteoclastic and Oxidative Stress Responses

    Globus, Ruth

    2015-01-01

    Future space explorations beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure plays a major role in progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Our long-term goals are to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures. We had previously reported that exposure to low or high-LET radiation correlates with an acute increase in the expression of pro-osteoclastic and oxidative stress genes in bone during the early response to radiation followed by pathological changes in skeletal structure. We then conducted systematic screening for potential countermeasures against bone loss where we tested the ability of various antioxidants to mitigate the radiation-induced increase in expression of these markers. For the screen, 16-week old C57Bl6J mice were treated with a dietary antioxidant cocktail, injectable DHLA or a dried plum-enriched diet (DP). Mice were then exposed to 2Gy 137Cs radiation and one day later, marrow cells were collected and the relevant genes analyzed for expression levels. Among the candidate countermeasures tested, DP was most effective in reducing the expression of genes associated with bone loss. Furthermore, analysis of skeletal structure by microcomputed tomography (microCT) revealed that DP also prevents the radiation-induced deterioration in skeletal microarchitecture as indicated by parameters such as percent bone volume (BVTV), trabecular spacing and trabecular number. We also found that DP has similar protective effects on skeletal structure in a follow-up study using 1 Gy of sequential proton and iron, radiation species relevant to spaceflight. When cultured ex vivo under osteogenic conditions, bone marrow-derived cells from DP-fed animals exhibited increased colony numbers compared to control diet-fed animals. These findings suggest that DP exerts pro-osteogenic effects apart from its previously demonstrated anti-resorptive action, which may be one of the mechanisms underlying its radioprotective effect on bone. In conclusion, a diet enriched in certain types of antioxidants may be useful as an intervention for radiation-induced bone loss.

  4. The risk of radiation induced cancer - Whence? Whither?

    Current progress in molecular biology is rapid, and the identification of successive stages in cancer induction, the role of individual oncogenes and tumor supressor genes in specific organ cancers, and possible biomarkers for radiation-induced tumors, as well as for many others, are becoming commonplace. These will offer the prospect not only of understanding the whole process but also the possibility of preventing molecular changes from progressing to a tumor. This possibility may eventually reduce the importance of risk estimates. Risk estimates for radiation-induced cancer have dominated low-dose radiation protection for the last two decades at least. Their recent reevaluation has led to the first reduction in dose limits for radiation workers in 30 years. It behooves us to follow developments in these risk estimates carefully, as they seen likely to continue to be the most important element in the background science of radiation protection

  5. Nano-silymarin provides protection against γ-radiation-induced oxidative stress in cultured human embryonic kidney cells.

    Adhikari, Manish; Arora, Rajesh

    2015-10-01

    Radiation can produce biological damage, mainly oxidative stress, via production of free radicals, including reactive oxygen species (ROS). Nanoparticles are of interest as radioprotective agents, particularly due to their high solubility and bioavailability. Silymarin is a hepatoprotective agent but has poor oral bioavailability. Silymarin was formulated as a nanoemulsion with the aim of improving its bioavailability and therapeutic efficacy. In the present study, we evaluated self-nanoemulsifying drug delivery systems (SNEDDS) formulated with surfactants and co-surfactants. Nano-silymarin was characterized by estimating % transmittance, globule size, and polydispersity index, and by transmission electron microscopy (TEM). The nano-silymarin obtained was in the range of 3-8nm diameter. With regard to DNA damage, measured by a plasmid relaxation assay, maximum protection was obtained at 10μg/mL. Cytotoxicity of nano-silymarin to human embryonic kidney (HEK) cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Protective efficacy against γ-radiation was assessed by reduction in micronucleus frequency and ROS generation, using the 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assay. Radiation-induced apoptosis was estimated by microscopic analysis and cell-cycle estimation. Nano-silymarin was radioprotective, supporting the possibility of developing new approaches to radiation protection via nanotechnology. PMID:26433256

  6. Protective effect of ferulic acid on ?-radiation-induced micronuclei, dicentric aberration and lipid peroxidation in human lymphocytes

    Full text: In this study we examined radioprotective effect of ferulic acid (FA) on gamma radiation- induced micronuclei, dicentric aberration and lipid peroxidation with reference to alterations in cellular antioxidant status in cultured lymphocytes. To establish most effective protective support we used three different concentrations of FA (1, 5 and 10 ?g/ml) and three different doses of ?-radiation (1, 2 and 4 Gy). Treatment of lymphocytes with FA alone (at 10 ?g/ml) gave no significant change in micronuclei (MN), dicentric aberration (DC), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) or glutathione peroxidase (GPx) activities when compared with normal lymphocytes; irradiation at 1, 2 and 4Gy increased the MN and DC frequencies in a dose-dependent manner. Treatment with FA for 30 min before radiation exposure resulted in a significant decline of MN and DC yields as FA concentration increased. Compared to 1Gy exposure alone, the extent to which FA (1 ?g/ml) reduced the MN and DC yields was 75% and 50%, respectively. With 4Gy irradiation, FA (10 ?g/ml) decreased 45% MN and 25% DC frequencies. FA-pretreated lymphocytes (1, 5 and 10 ?g/ml) showed progressively decreased TBARS levels after irradiation. Irradiation (1, 2 and 4 Gy) significantly decreased GSH levels, SOD, CAT and GPx activities in a dose-dependent manner. Pretreatment with 10 ?g/ml of FA significantly (p < 0.05) prevented the decreases in the radiation-induced GSH, SOD, CAT and GPx activities. These findings suggest potential use and benefit of FA as a radioprotector

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

    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 γ-radiation through biochemical, histological, morphological abnormalities of sperms and DNA damage in the sperms induced by γ-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 luteinizing hormone (LH) which carried out for fertility assessment showed that whole body γ-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 γ-radiation induced DNA damage of sperms (tail moment values).

  8. The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity

    Murat Caloglu

    2012-01-01

    Full Text Available Background: The aim of the study was to compare the protective efficacy of l-carnitine (LC to amifostine on radiation-induced acute small intestine damage. Materials and Methods: Thirty, 4-week-old Wistar albino rats were randomly assigned to four groups - Group 1: control (CONT, n = 6, Group 2: irradiation alone (RT, n = 8, Group 3: amifostine plus irradiation (AMI+RT, n = 8, and Group 4: l-Carnitine plus irradiation (LC+RT, n = 8. The rats in all groups were irradiated individually with a single dose of 20 Gy to the total abdomen, except those in CONT. LC (300 mg/kg or amifostine (200 mg/kg was used 30 min before irradiation. Histopathological analysis of small intestine was carried out after euthanasia. Results: Pretreatment with amifostine reduced the radiation-induced acute degenerative damage (P = 0.009 compared to the RT group. Pretreatment with LC did not obtain any significant difference compared to the RT group. The vascular damage significantly reduced in both of the AMI+RT (P = 0.003 and LC+RT group (P = 0.029 compared to the RT group. The overall damage score was significantly lower in the AMI+RT group than the RT group (P = 0.009. There was not any significant difference between the LC+RT and RT group. Conclusions: Amifostine has a marked radioprotective effect against all histopathological changes on small intestinal tissue while LC has limited effects which are mainly on vascular structure.

  9. Protective role of Carica papaya (Linn.) in electron beam radiation induced hematological and cytogenetic damages in Swiss albino mice

    Carica papaya (Linn.) is known to possess various biomedical applications. It has remarkable antioxidant properties. The main objective of the study was to evaluate the leaf extracts of Carica papaya (Linn.) on hematologic and cytogenetic changes occurring due to irradiation of mice to sub-lethal doses of Electron Beam Radiation (EBR). Analysis of hematological changes occurring due to irradiation of mice to sub-lethal doses of EBR, and the effects of Carica papaya (Linn.) extract on the same. The Assessment of hematopoietic stress by spleen colony forming unit and spleen body weight index. The analysis of cell proliferation and immunomodulation with response to the effects of Carica papaya (Linn.) extract by estimation of IL-6. The estimation of serum total antioxidants, lipid peroxidation and analyzing the activities of enzymes like SOD, ALP, and AST. Male Swiss albino mice were fed orally with papaya aqueous leaf extract for 15 days. They were irradiated with a whole body dose of 6 Gy Electron Beam radiation. The mice were dissected for liver, kidney, bone marrow, spleen and brain. The hematological studies were done using blood cell count in an automated cell counter. The biochemical estimations like urea, creatinine, SGOT, SGPT, Total Protein, Albumin, Bilirubin were done using the serum and homogenates. The total antioxidant capacity, the antioxidant enzymes were estimated. The Interleukin-6 levels were estimated in serum to assess immune modulation. The results show a decrease in the hematological parameters in radiated animals. The papaya treated groups have shown modulation in the hematological parameters. The extract has also reduced the suppression of the bone marrow induced by radiation. The radiation induced liver damage is also reduced in papaya treated groups. The aqueous extract of Carica papaya (Linn.) has shown protective effects in electron beam radiation induced tissue damages in Swiss Albino mice (author)

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

    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.

  11. Protective immunity to UV radiation-induced skin tumours induced by skin grafts and epidermal cells

    There is little evidence that cutaneous dendritic cells (DC), including epidermal Langerhans cells (LC), can induce immunity to UV radiation (UVR)-induced skin tumours. Here, it is shown that cells within skin can induce protective antitumour immunity against a UVR-induced fibrosarcoma. Transplantation of the skin overlying subcutaneous tumours onto naive recipients could induce protective antitumour immunity, probably because the grafting stimulated the tumour Ag-loaded DC to migrate to local lymph nodes. This suggests that cutaneous APC can present tumour Ag to induce protective antitumour immunity. Previously, it has been shown that immunization of mice with MHC class II+ epidermal cells (EC) pulsed with tumour extracts could induce delayed-type hypersensitivity against tumour cells. Here, this same immunization protocol could induce protective immunity against a minimum tumorigenic dose of UVR-induced fibrosarcoma cells, but not higher doses. Epidermal cells obtained from semiallogeneic donors and pulsed with tumour extract could also induce protective immunity. However, presentation of BSA Ag from the culture medium was found to contribute to this result using semiallogeneic EC. The results suggest that LC overlying skin tumours may be able to induce protective immunity to UVR-induced tumours if stimulated to migrate from the skin. Copyright (2001) Australasian Society of Immunology Inc

  12. Radiation Leukemogenesis at Low Dose Rates

    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.

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

    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 μm 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 μm location on tissue section was pre-irradiated with 1-10 3He2+ particles (5 MeV; LET 75 keV/μm) 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)

  14. Protective effect of pioglitazone on cardiomyocyte apoptosis in low-dose streptozotocin & high-fat diet-induced type-2 diabetes in rats

    Uma Bhandari

    2015-01-01

    Full Text Available Background & objectives: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ combined with high fat diet (HFD in rats. Methods: Male Wistar rats (150-200 g were injected with low-dose STZ (45 mg/kg, i.v., single dose and orally fed with a HFD (20 g/day/rat for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o. for a period of 21 days (from 8 th day to 28 th day. On 29 th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination. Results: Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC and triglycerides (TGs, apoliproprotein-B glycosylated haemoglobin (HbA1c levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C and cardiac antioxidant enzymes. Interpretation & conclusions: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.

  15. Protection from radiation-induced damage to spermatogenesis by hormone treatment

    Infertility caused by killing of the spermatogonial stem cells occurs frequently in men treated for cancer with radiotherapy and chemotherapy. We investigated whether pretreatment of rats with testosterone plus estradiol, which reversibly inhibits the completion of spermatogenesis and protects spermatogonial stem cells from procarbazine-induced damage, would also protect these cells from radiation. Adult male LBNF rats were implanted for 6 weeks with capsules containing testosterone and estradiol and then irradiated with doses from 2.5-7.0 Gy. Controls were irradiated with 1.8-3.5 Gy. Implants were removed 1 day after irradiation, and all animals were killed 10 weeks later for assessment of stem cell survival by counting repopulating tubules in histological sections and by sperm head counts. At doses of 2.5 and 3.5 Gy the repopulation indices and sperm head counts were significantly higher (P < 0.001) in the rats treated with testosterone and estradiol than in the controls. Protection factors calculated from the dose-response curves were in the range of 1.5-2.2. Elucidation of the mechanism of protection is essential to apply it to clinical situations. The fact that the spermatogonia are protected against radiation as well as procarbazine indicates that the mechanism does not involve drug delivery or metabolism. 32 refs., 3 figs

  16. Protection from radiation-induced damage to spermatogenesis by hormone treatment

    Kurdoglu, B.; Wilson, G.; Parchuri, N.; Ye, W.; Meistrich, M.L. [Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States)

    1994-07-01

    Infertility caused by killing of the spermatogonial stem cells occurs frequently in men treated for cancer with radiotherapy and chemotherapy. We investigated whether pretreatment of rats with testosterone plus estradiol, which reversibly inhibits the completion of spermatogenesis and protects spermatogonial stem cells from procarbazine-induced damage, would also protect these cells from radiation. Adult male LBNF rats were implanted for 6 weeks with capsules containing testosterone and estradiol and then irradiated with doses from 2.5-7.0 Gy. Controls were irradiated with 1.8-3.5 Gy. Implants were removed 1 day after irradiation, and all animals were killed 10 weeks later for assessment of stem cell survival by counting repopulating tubules in histological sections and by sperm head counts. At doses of 2.5 and 3.5 Gy the repopulation indices and sperm head counts were significantly higher (P < 0.001) in the rats treated with testosterone and estradiol than in the controls. Protection factors calculated from the dose-response curves were in the range of 1.5-2.2. Elucidation of the mechanism of protection is essential to apply it to clinical situations. The fact that the spermatogonia are protected against radiation as well as procarbazine indicates that the mechanism does not involve drug delivery or metabolism. 32 refs., 3 figs.

  17. Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

    To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise unsafe doses of radiation in patients with CNS neoplasms

  18. Growth factors protect intestinal stem cells from radiation-induced apoptosis by suppressing PUMA through the PI3K/AKT/p53 axis

    QIU Wei; Leibowitz, Brian; Zhang, Lin; YU, JIAN

    2009-01-01

    Gastrointestinal toxicity is the primary limiting factor in abdominal and pelvic radiotherapy, but has no effective treatment currently. We recently showed a critical role of the BH3-only protein PUMA in acute radiation-induced GI damage and GI syndrome in mice. Growth factors such as IGF-1 and bFGF have been shown to protect against radiation-induced intestinal injury, although the underlying mechanisms remain to be identified. We report here the suppression of PUMA through the PI3K/AKT/p53 ...

  19. Protective role of grape seed extract against radiation induced oxidative stress in rats: Role of endogenous antioxidants

    The aim of this study was to investigate the protective role of grape seed extract against γ-irradiation induced oxidative stress in hepatic tissue. Animals were divided into four groups; Control group, Grape seed extract (GSE) group: animals were administered GSE for 14 consecutive days (100 mg/kg). Irradiated (IRR) group: rats were received dist. water for 7 days and then rats were irradiated with a single dose of 6 Gy and dist. water was maintained for 7 additional days. GSE-IRR group: rats were treated with GSE for 7 consecutive days, one hour later after the last dose of GSE, rats were irradiated with a single dose of 6 Gy and GSE was maintained for 7 additional days. Administration of GSE for 14 consecutive days resulted in a significant increase in the activities of both superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) and the level of reduced glutathione (GSH), in hepatic tissues which were reduced by radiation treatment. Also, GSE resulted in a significant decrease in total nitrate/nitrite (NO(x)) and malondialdehyde (MDA) levels in hepatic tissues and a significant decrease in Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and Gamma glutamyl transpeptidase (GGT) activities and NO(x) level compared to irradiated group. In conclusion, data obtained from this study indicate that GSE could increase the endogenous antioxidant defense mechanism in rat and thereby protect the animals from radiation-induced hepatotoxicity

  20. Protective effect of atorvastatin on radiation-induced vascular endothelial cell injury in vitro

    Vascular endothelial cells are very sensitive to ionizing radiation, and it is important to develop effective prevent agents and measures in radiation exposure protection. In the present study, the protective effects of atorvastatin on irradiated human umbilical vein endothelial cells (HUVEC) and the possible mechanisms were explored. Cultured HUVEC were treated by atorvastatin at a final concentration of 10 μmol/ml for 10 minutes, and then irradiated at a dose of 2 Gy or 25 Gy. Twenty-four hours after irradiation, apoptosis of HUVEC was monitored by flow cytometry, and the expression of thrombomodulin (TM) and protein C activation in HUVEC was respectively assessed by flow cytometry and spectrophotometry. After treatment with atorvastatin for 24 h, the rate of cell apoptosis decreased by 6% and 16% in cells irradiated with 2 Gy and 25 Gy, respectively. TM expression increased by 77%, 59%, and 61% in untreated cells, 2 Gy irradiation-treated cells, and 25 Gy irradiation-treated cells, respectively. The protein C levels in 2 Gy and 25 Gy irradiation-treated cells were reduced by 23% and 34% when compared with untreated cells, but up-regulated by 79% and 76% when compared with cells which were irradiated and treated with atorvastatin. In conclusion, these data indicate that atorvastatin exerts protective effects on irradiated HUVEC by reducing apoptosis by up-regulating TM expression and enhancing protein C activation in irradiated HUVEC. (author)

  1. Evolution of genetic damage in relation to cell-cycle control: a molecular analysis of mechanisms relevant for low dose effects. Final report. Reporting period: January 1997 - June 1999

    Goal of the project was to give a better understanding of the cellular mechanisms which determine the conversion of initial radiation induced DNA damage into genetic alterations. Knowledge of the effects and risks of low dose ionizing radiation is a key issue for radiation protection and requires an understanding of the molecular mechanisms leading to radiation damage and susceptibility. (orig./MG)

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

    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 μmol/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)

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

    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

  4. [Radiation-induced cancers].

    Dutrillaux, B

    1998-01-01

    The induction of malignant diseases is one of the most concerning late effects of ionising radiation. A large amount of information has been collected form atomic bomb survivors, patients after therapeutic irradiation, occupational follow-up and accidentally exposed populations. Major uncertainties persist in the (very) low dose range i.e., population and workers radioprotection. A review of the biological mechanisms leading to cancer strongly suggests that the vast majority of radiation-induced malignancies arise as a consequence of recessive mutations of tumour-suppressor genes. These mutations can be unveiled by ageing, this process being possibly furthered by constitutional or acquired genomic instability. The individual risk is likely to be very low, probably because of the usual dose level. However, the magnitude of medical exposure and the reliance of our societies on nuclear industry are so high that irreproachable decision-making processes and standards for practice are inescapable. PMID:9868399

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

    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)

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

    Ley, R.D. [The Lovelace Institutes, Albuqeurque, NM (United States). Photomdecine Program; Fourtanier, A. [L`Oreal, Advanced Research, Clichy (France)

    1997-06-01

    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).

  7. Effects of low doses

    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.)

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

    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 23±3 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 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)

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

    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

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

    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)

  11. Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity.

    Bin, Bum-Ho; Kim, Dae-Kyum; Kim, Nan-Hyung; Choi, Eun-Jeong; Bhin, Jinhyuk; Kim, Sung Tae; Gho, Yong Song; Lee, Ai-Young; Lee, Tae Ryong; Cho, Eun-Gyung

    2016-05-01

    Skin melanocytes are activated by exposure to UV radiation to secrete melanin-containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known. Here, we investigated the role of melanocyte-derived extracellular vesicles in melanocyte survival. Network analysis of the melanocyte extracellular vesicle proteome identified the extracellular matrix component fibronectin at a central node, and the release of fibronectin-containing extracellular vesicles was increased after exposure of melanocytes to UVB radiation. Using an anti-fibronectin neutralizing antibody and specific inhibitors of extracellular vesicle secretion, we demonstrated that extracellular vesicles enriched in fibronectin were involved in melanocyte survival after UVB radiation. Furthermore, we observed that in the hyperpigmented lesions of patients with melasma, the extracellular space around melanocytes contained more fibronectin compared with normal skin, suggesting that fibronectin is involved in maintaining melanocytes in pathological conditions. Collectively, our findings suggest that melanocytes secrete fibronectin-containing extracellular vesicles to increase their survival after UVB radiation. These data provide important insight into how constantly stimulated melanocytes can be maintained in pathological conditions such as melasma. PMID:26854492

  12. Protective role of green tea administration against radiation-induced biological changes in pregnant

    Green tea (Gt) derived from the leaves of camelia sinensis contains polyphenolic compounds also known as eipcatechins, which are anioxidant in nature. This study aims to evaluate the radioprotective, anioxidative potential of two concentrations of Gt extract in pregnant rats. Animals exposed to fractionated 3 Gy gamma radiation of 1 Gy installments at the 7th, 11th and 15th days of gestation were examined on the 20th day. Total protenis, uric acid, urea and creatinine, as well as ransmiase were measured. Irradiation of rats caused significant drop in serum total protein, which was significantly elevated specially with Gt 3%. Elevation in serum uric acid was dropped secially with Gt while, elevation in urea after irradiation dropped by Gt% only. Both concentrations of Gt did not signficantly change creatinine elevation exerted by irradiation. Results revealed sigbificat protection by both Gt concentrations against the elevation in serum glucose level. While was dropped approaching control by irradiation, which ASt dropped by irradiation was normalized attaining almost control level with Gt3%. While, AST dropped by irradiation was normalized attaining almost control level with Gt 3%. Histological damage to liver cells by irradiation was ameliorated by administration og Gt in both concentrations. This was indicated by restoration of the cellular integrity besides by nucleated cells and slight regenerative signs in the nuclei

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

    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

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

    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.

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

    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.

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

    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%, 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)

  17. Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage

    Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Yasuda, Takeshi [Department of Radiation Emergency Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Asada, Masahiro; Motomura, Kaori; Suzuki, Masashi [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Zakrzewska, Malgorzata [Faculty of Biotechnology, University of Wroclaw (Poland); Imamura, Toru [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

    2013-02-01

    Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with {gamma}-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal damage. Therefore, Q40P/S47I/H93G is pharmacologically one of the most promising candidates for clinical applications for radiation-induced gastrointestinal syndrome.

  18. Protective Role of Mint oil (MO) Against Radiation-Induced Oxidative Stress in Male Albino Rats

    The whole body exposure to high doses of gamma radiation resulted in alterations in the biological functions of vital organs in the body. This study is divided in two main parts: Part I - A preliminary study designed to determine the optimal dose of mint oil (MO) which delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the irradiated group. Male albino rats were assorted into two main groups. 1-Animals of this group were exposed to whole body (8 Gy) gamma irradiation. 2-Animals of this group were subdivided into 4 subgroups that received four different concentrations of mint essential oil (100, 150, 200, 250 μ1/animal/ day) for three consecutive days before irradiation. All animals were observed during 30 days for signs of radiation sickness, body weight change and mortality. The results revealed that pretreatment of rats with different doses of the MO prior to exposure to 8 Gy of gamma radiation resulted in a dose-dependent elevation in the survival time up to 200 μ1/kg b. wt., where the highest number of survival (80%) was observed 30 days post irradiation, when compared with the 8 Gy irradiated control (33.5%). The optimum protection against irradiation was observed at a dose 200 μ1/kg b. wt. and was used for the further investigations. The 2nd part intended to investigate the radio-protective effects of MO on some biochemical and haematological parameters. For this purpose, Swiss albino rats were selected and assorted into 4 groups. Animals in Group I control: animals without any treatment. Group II mint oil (MO): rats were administered orally MO once daily at a dose of 200 μ1for 3 consecutive days. Group III, Irradiated (IRR): animals were exposed to a single dose of 6 Gy gamma radiations. Group IV Rats were treated with MO (as in Group-II), and exposed to 6 Gy after half an hour of the last administration of MO. Animals of each group were sacrificed 1, 7 and 28 days post-irradiation for biochemical estimation in blood , liver, kidney and testis. Radiation exposure resulted in a significant decline in haemoglobin, hematocrite values, and erythrocytes and leucocytes counts. Significant decreases in serum EPO level, GSH content and ALP was observed in all specimens. Meanwhile, the values of MDA, serum acid phosphatase were significantly higher in irradiated rats as compared to control group. In MO pretreated irradiated animals, a significant increase was observed in blood constituents, EPO (erythropoietin) level, GSH content and ALP level in testes, liver and blood accompanied with remarkable decrease in the values of MDA, serum acid phosphatase. The results show that MO could exert a radioprotective effect by antioxidant activity, and might stimulate cellular regeneration, that may be attributed to the synergistic effects of its constituents.

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

    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

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

    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; α/β = 0 Gy) compared with cells transduced with the TAT peptide (D0 = 4.91 ± 1.0 Gy; α/β = 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 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.

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

    Sunavala-Dossabhoy, Gulshan, E-mail: gsunav@lsuhsc.edu [Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Palaniyandi, Senthilnathan; Richardson, Charles; De Benedetti, Arrigo [Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Schrott, Lisa [Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Caldito, Gloria [Department of Bioinformatics and Computational Biology, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2012-09-01

    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 (D{sub 0} = 4.13 {+-} 1.0 Gy; {alpha}/{beta} = 0 Gy) compared with cells transduced with the TAT peptide (D{sub 0} = 4.91 {+-} 1.0 Gy; {alpha}/{beta} = 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 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.

  2. Low dose irradiation and biological defense mechanisms

    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 radiation protection and the biological effects of low-dose irradiation

  3. Low Dose Effects: Testing the Assumptions

    Our work is to investigate the biological responses of cells and animals to low doses and low dose rates of low linear energy transfer radiation and to compare the results to the predictions of the Linear No-Threshold (LNT) hypothesis. These experiments indicate that at low dose, none of the assumptions of the LNT hypothesis were supported by the data, either in cells or in animals. If these results from human and rodent cells, and from other animals, are applicable to humans, the data further indicate that the use of the LNT hypothesis for radiation protection purposes is not conservative but may actually increase the overall risk of cancer

  4. Mentha piperita (Linn.) leaf extract provides protection against radiation induced chromosomal damage in bone marrow of mice

    Oral administration of M. piperita (1 g/kg body weight/day) before exposure to gamma radiation was found to be effective in protecting against the chromosomal damage in bone marrow of Swiss albino mice. Animals exposed to 8 Gy gamma radiation showed chromosomal aberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges and acentric fragments. There was a significant increase in the frequency of aberrant cells at 6 hr after irradiation. Maximum aberrant cells were observed at 12 hr post-irradiation autopsy time. Further the frequency of aberrant cells showed decline at late post-irradiation autopsy time. However in the animals pretreated with Mentha extract, there was a significant decrease in the frequency of aberrant cells as compared to the irradiated control. Also significant increase in percentage of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges, acentric fragments. total aberrations and aberrations/damaged cell was observed at 12 hr post-irradiation autopsy time in control animals, whereas Mentha pre-treated irradiated animals showed a significant decrease in percentage of such aberrations. A significant decrease in GSH content and increase in LPO level was observed in control animals, whereas Mentha pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPO level but the values remained below the normal. The radioprotective effect of Mentha was also demonstrated by determining the LD50/30 values (DRF=1.78). The results from the present study suggest that Mentha pretreatment provides protection against radiation induced chromosomal damage in bone marrow of Swiss albino mice. (author)

  5. Protective effects of Sipunculus nudus polysaccharides on rats injured by low-dose irradiation combined with carbon monoxide, benzene and noise

    Ying HE

    2012-10-01

    Full Text Available Objective To investigate the protective effects of Sipunculus nudus polysaccharides (SNPS on rats injured by low-dose irradiation combined with carbon monoxide, benzene and noise. Methods Fifty SD rats were randomly divided into normal control group, model control group, 70mg/(kg·d SNPS group (SNPS 70 group, 140mg/(kg·d SNPS group (SNPS 140 group and 280mg/(kg·d SNPS group (SNPS 280 group. SNPS was administrated intragastrically once a day before γ irradiation for 7 days. Model control group were given the same volume of 0.9% NaCl. Seven days later, all the rats were sacrificed. Peripheral blood cells were analyzed by auto blood cytometry. DNA in bone marrow cells was determined by ultraviolet spectrophotometry. The activities of superoxide dismutase (SOD and the contents of malondialdehyde (MDA in serum were detected by the reagent kits. The indexes of main organs (liver, spleen and thymus were also calculated. Results Compared with model control group, peripheral blood PLT, RBC, HCT and HGB increased significantly (P < 0.05 or P < 0.01, WBC increased a little, SOD activity and DNA in bone marrow increased significantly in SNPS groups, while the content of MDA decreased in SNPS groups compared with that in model control group (P < 0.05. No significant change was found of the main organs (liver, spleen and thymus indexes. Conclusion SNPS may take a protective effect on rats injured by deletion environment factors with increasing WBC and PLT in serum, improving antioxidant activity and promoting the repair of injured bone marrow.

  6. Systematic review and meta-analysis on the use of honey to protect from the effects of radiation-induced oral mucositis.

    Song, Jason J; Twumasi-Ankrah, Philip; Salcido, Richard

    2012-01-01

    Recently, 4 separate human controlled trials reported that honey appeared to protect from the effects of radiation-induced oral mucositis formation, a complication of radiation therapy that is responsible for pain and overall reduction in quality of life. In this systematic review and meta-analysis, the authors examined 3 of these controlled trials (n = 120) that met the inclusion and exclusion criteria to determine whether honey had protective effects against radiation-induced oral mucositis. The meta-analysis demonstrated an overall relative risk reduction of 80% in the honey treatment group compared with the control. Although favorable, the data must be approached with caution because of lack of description of the method of randomization and potential bias in all 3 of the individual studies included in the meta-analysis. The results are promising, and further studies are needed to strengthen the current evidence prior to a firm clinical recommendation being given. PMID:22218067

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

    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 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)

  8. Interest and limits of epidemiology for the evaluation of radiation induced cancer risks and the setting up of radiation protection standards

    Epidemiological studies allow to confirm that a risk does exist for some types of cancer following high-dose exposures often at high dose-rates. However, no conclusion can be drawn for low doses and low dose-rates. Therefore we have to extrapolate from known high-dose risks to low doses and low dose-rates by various dose-response patterns. Another difficulty in assessing radiation cancer risks comes from the long latency time, which explains that all excess cancers have not yet been observed in the irradiated population studied. Once more, mathematical models are used to project excess lifetime cancer mortality. The estimations of radiation cancer risks are therefore marked by a great number of uncertainties, since they change accordingly to the model used. Other uncertainties come from the data, especially the dose estimates and are heightened when extrapolating to other populations. In 1988, UNSCEAR assessed new estimates for excess lifetime cancer mortality in the range of 4 to 11% per gray. These values mean a revaluation of the previous estimates by a 1.6 to 4.4 factor, which is mainly consecutive to the use of different projection models. Besides, they are solely based on the Hiroshima and Nagasaki survivors, whereas patient studies assess a lower risk. Finally UNSCEAR does not precisely state what is the available reduction factor to modify risks for low doses and low dose rates which should lie between 2 and 10. Due to a number of persistent uncertainties, we should not consider it justified to revise protection standards presently. 9 tabs.; 45 refs

  9. Interests and limits of epidemiology for the evaluation of risks of radiation induced cancer and the establishing of radiation protection standards

    Epidemiological studies allow to confirm that a risk does exist for some types of cancer following high-dose exposures often at high dose-rates. However, no conclusion can be drawn for low doses and low dose-rates. Therefore we have to extrapolate from known high-dose risks to low doses and low dose-rates by various dose-response patterns. Another difficulty in assessing radiation cancer risks comes from the long latency time, which explains that all excess cancers have not yet been observed in the irradiated population studied. Once more, mathematical models are used to project excess lifetime cancer mortality. The estimations of radiation cancer risks are therefore marked by a great number of uncertainties, since they change accordingly to the model used. Other uncertainties come from the data, especially the dose estimates and are heightened when extrapolating to other populations. In 1988, UNSCEAR assessed new estimates for excess lifetime cancer mortality in the range of 4 to 11% per gray. These values mean a revaluation of the previous estimates by a 1.6 to 4.4 factor, which is mainly consecutive to the use of different projection models. Besides, they are solely based on the Hiroshima and Nagasaki survivors, whereas patient studies assess a lower risk. Finally UNSCEAR does not precisely state what is the available reduction factor to modify risks for low doses and low dose rates which should lie between 2 and 10. Due to a number of persistent uncertainties, we should not consider it justified to revise protection standards presently. (author)

  10. The Nigella Sativa seed extract protects γ-radiation induced GI damage in rats and PMA induced PKC inhibition in macrophages only in pretreated condition

    Bone marrow and gastro intestinal (GI) cells are more sensitive to radiation induced damages, due to presence of actively proliferating cell. The radiation induces apoptosis through generating oxidative stress. Here the protective effect of non-polar hexane fraction of seeds of Nigella sativa Linn. (NS) (NSH) has been explored on GI damage. The NSH was orally given to albino rats, in pre (90 min) and post treatment whole body irradiation (WBI) by 60Co gamma radiation for further 14 days. The NSH significantly raised the survival rate of animals. It further prevented the radiation (4 Gy) induced suppression in the activity of super oxide dismutase (SOD) and catalase and rise in Thio barbituric acid reactive substances (TBARS) on 7 days post-irradiation. Histo-pathological examinations revealed significant protection of ileum cells. It restored the radiation-induced reduction in villous height and crypt number and prevented the focal mucosal erosion, congestion and loss of villi. The response was dose dependent at lower concentrations only, suggesting its use as food supplement for the patients undergoing radiotherapy. At higher doses, opposite results were observed. The mechanism of action was proposed through its FR scavenging potential as it prevented the PMA induced PKC expression only when added in the pretreatment condition or within 2 min of PMA addition to macrophage culture. Late addition had no protective response. (author)

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

    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.

  12. Radiation-induced apoptosis

    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)

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

    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 SMP’s 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. Protection from radiation induced damages to biological system in mice exposed to whole body γ-radiation by phytophenol gallic acid

    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 γ-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 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)

  15. Inactivation of NADPH Oxidases NOX4 and NOX5 Protects Human Primary Fibroblasts from Ionizing Radiation-Induced DNA Damage

    Weyemi, Urbain; Redon, Christophe E.; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R.; Bonner, Michael Y.; ARBISER, JACK L.; Bonner, William M.

    2015-01-01

    Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sourc...

  16. Protective effect of inhalation of hydrogen gas on radiation-induced dermatitis and skin injury in rats

    The effect of inhalation of hydrogen-containing gas (1.3% hydrogen + 20.8% oxygen + 77.9% nitrogen) (HCG) on radiation-induced dermatitis and on the healing of healing-impaired skin wounds in rats was examined using a rat model of radiation-induced skin injury. An X-ray dose of 20 Gy was irradiated onto the lower part of the back through two holes in a lead shield. Irradiation was performed before or after inhalation of HCG for 2 h. Inhalation of HCG significantly reduced the severity of radiodermatitis and accelerated healing-impaired wound repair. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) showed that the proportion of apoptotic keratinocytes and the level of staining in the X-irradiated skin of rats that pre-inhaled HCG were significantly lower than that of rats which did not pre-inhale HCG. Cutaneous full-thickness wounds were then created in the X-irradiated area to examine the time-course of wound healing. X-irradiation significantly increased the time required for wound healing, but the inhalation of HCG prior to the irradiation significantly decreased the delay in wound healing compared with the control and post-inhalation of HCG groups. Therefore, radiation-induced skin injury can potentially be alleviated by the pre-inhalation of HCG. (author)

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

    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

  18. Low doses effects and gamma radiations low dose rates

    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.)

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

    Xin Yang; Jiaren Liu; Haitian Zhao; Zhenyu Wang; Cuilin Cheng; Lei Yao; Xiaoyi Fu

    2011-01-01

    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 SMP’s 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 radi...

  20. MELODI. The multidisciplinary European low dose initiative

    Weiss, Wolfgang [Bundesamt fuer Strahlenschutz, Oberschleissheim (Germany). Inst. fuer Strahlenschutz und Gesundheit

    2012-07-01

    The mission of MELODI is to coordinate and promote European research on the risks associated with low-dose exposure to ionizing radiation. There are a number of important scientific questions which require resolution in order to consolidate the European radiation protection knowledge in relation to low-dose exposure to ionizing radiation. Research on low-dose risk requires multidisciplinary approaches and long-term commitment. Several scientific and regulatory bodies set up MELODI in 2010 to address research requirements and joint approaches to the development of a coordinated research programme, including societal and public concerns related to radiation exposure. The research platform is open to any organization that shares the mission of developing and updating a joint research agenda. (orig.)

  1. The carcinogenic of low dose radiations

    The evaluation of the risks associated with low dose irradiations generally is a two-step process. The first is the assessment of the carcinogenic effects at doses higher than 500 mSv where data are available. The second is the extrapolation from these doses to low doses (below 200 mSv). In radiation protection, commissions, such as the ICRP have generally tended to adopt conservative hypotheses. This cautious approach might be legitimate for the purpose of health protection, however it should not be confused with a statement of scientific fact or a realistic estimate. The value of the cancer risk coefficient at low doses or dose rates has markedly increased during the past decade in the 1991 ICRP report the cancer risk coefficient was estimated equal to 8. 10-2 Sv-1 with a DRF equal to 2, hence at low dose its value was estimated 4. 10-2. Sv-1. It was entirely based on data concerning A-bomb survivors. The main cause of this three-fold increase was the introduction of risk projection models and to a much smaller extent the new assessment in 1986 of the doses received by the A-bomb survivors. The aim of this paper is not to question the new ICRP recommendations, it is to discuss firstly the critical importance of the data selected for the assessment of the carcinogenic risk and the other sources of inaccuracies, in particular that of projection models. Another point concerns persistent uncertainties about the dose reduction factor during extrapolations from high doses to low doses, and from high dose rates to low dose rates

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

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

    2015-05-01

    Outside the protection of earth’s 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 skin’s 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.

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

    Highlights: • Low doses of high LET radiation influence skin homeostasis. • Effects on proliferation and differentiation profiles are LET dependent. • Skin barrier function is not compromised following low dose exposure. - Abstract: Outside the protection of Earth's 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 skin's 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

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

    Neubeck, Claere von [German Cancer Consortium DKTK partner site Dresden, OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden (Germany); German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Geniza, Matthew J. [Molecular and Cellular Biology Program, Oregon State University, Corvallis OR 97331 (United States); Kauer, Paula M.; Robinson, R. Joe; Chrisler, William B. [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland WA 99352 (United States); Sowa, Marianne B., E-mail: marianne.sowa@pnnl.gov [Health Impacts and Exposure Science, Pacific Northwest National Laboratory, Richland WA 99352 (United States)

    2015-05-15

    Highlights: • Low doses of high LET radiation influence skin homeostasis. • Effects on proliferation and differentiation profiles are LET dependent. • Skin barrier function is not compromised following low dose exposure. - Abstract: Outside the protection of Earth's 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 skin's 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.

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

    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 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. Protective Effect of Diphlorethohydroxycarmalol against Ultraviolet B Radiation-Induced DNA Damage by Inducing the Nucleotide Excision Repair System in HaCaT Human Keratinocytes

    Mei Jing Piao

    2015-09-01

    Full Text Available We investigated the protective properties of diphlorethohydroxycarmalol (DPHC, a phlorotannin, against ultraviolet B (UVB radiation-induced cyclobutane pyrimidine dimers (CPDs in HaCaT human keratinocytes. The nucleotide excision repair (NER system is the pathway by which cells identify and repair bulky, helix-distorting DNA lesions such as ultraviolet (UV radiation-induced CPDs and 6-4 photoproducts. CPDs levels were elevated in UVB-exposed cells; however, this increase was reduced by DPHC. Expression levels of xeroderma pigmentosum complementation group C (XPC and excision repair cross-complementing 1 (ERCC1, which are essential components of the NER pathway, were induced in DPHC-treated cells. Expression of XPC and ERCC1 were reduced following UVB exposure, whereas DPHC treatment partially restored the levels of both proteins. DPHC also increased expression of transcription factor specificity protein 1 (SP1 and sirtuin 1, an up-regulator of XPC, in UVB-exposed cells. DPHC restored binding of the SP1 to the XPC promoter, which is reduced in UVB-exposed cells. These results indicate that DPHC can protect cells against UVB-induced DNA damage by inducing the NER system.

  7. Protective role of Tinospora cordifolia extract against radiation-induced qualitative, quantitative and biochemical alterations in testes

    In today's changing global scenario, ionizing radiation is considered as most potent cause of oxidative stress mediated by free radical flux which induces severe damage at various hierarchical levels in the organization in the living organisms. Testis is a highly prolific tissue with fast cellular renewal and poor antioxidant defense; therefore it becomes an easy target for the radiation-induced free radicals that have long been suggested as major cause of male infertility. Chemical radioprotection is an important strategy to countermeasure the deleterious effects of radiation. Several Indian medicinal plants are rich source of antioxidants and these have been used for the treatment of ailments. Tinospora cordifolia, commonly known as amrita, is one of the plants that have several pharmacological and therapeutic properties. Therefore, the present study was performed to evaluate the deleterious effects of semi lethal dose of gamma radiation on testicular tissue and their possible inhibition by Tinospora cordifolia root extract (TCE). For this purpose, healthy Swiss albino male mice were selected from an inbred colony and divided into four groups. Group I (normal) was administered double distilled water (DDW) volume equal to TCE (75 mg/kg.b.wt/animal) by oral gavage. Group II was orally supplemented TCE as 75 mg/kg. b.wt once daily for 5 consecutive days. Group III (irradiated control) received DDW orally equivalent to TCE for 5 days then exposed to 5 Gy gamma radiation. Group IV (experimental) was administered TCE as in Group II and exposed to radiation (as in Group III). Irradiation resulted into significant decrease in the frequency of different spermatogenic cell counts along with severe histo-pathological lesions up to 7th day of irradiation in testes of irradiated control animals, thereafter, recovery followed towards the normal architecture. TCE pretreatment effectively prevented radiation induced such alterations in cellular counts and testicular injuries by restoring almost normal structure at the end of experimentation. Furthermore, TCE administration inhibited radiation-induced elevation of lipid per-oxidation (LPO) and reduction of glutathione (GSH) and catalase (CAT) levels in testes. These observations signify that the Tinospora cordifolia root extract can be used as an efficient radio- protector against radiation mediated qualitative, quantitative and biochemical alterations in testes. (author)

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

    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.

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

    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

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

    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 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)

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

    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

  12. The protective action of O-(beta-hydroxyethyl) rutosides (HR) on radiation-induced brain oedema in rats

    The authors performed light and electron microscopy studies on rat brain to clarify whether or not O-(beta-hydroxyethyl) rutosides (HR) have a selective anti-oedematous action on the capillary endothelial cells of the brain thus suggesting it as a radioprotective substance suitable for future use in radiotherapy of CNS tumours. The following criteria were found to be most reliable for evaluation: 1) the number of capillaries and small vessels whose lumina were wide open, i.e. well perfused; 2) the incidence and extension of perivascular 'light areolas' without any light-optical structure as an expression of an intracellular oedema of the perivascular astrocyte processes; 3) the occurrence and quantity of hyperchromic, partially shrunk nerve cells. These findings confirm both a clearly anti-oedematous effect of HR on the radiation-induced cell oedema of the perivascular neuropile with a compression of capillary lumina, and the working hypothesis concerning the action mechanism of this substance as a 'membrane protector'. (orig./MG)

  13. Study on the protective effect of MgSO4 on the radiation-induced neural stem cell injury

    Objective: To explore the neuroprotective effect of magnesium sulfate on radiation induced neural stem cell injury. Methods: Brain tissue was obtained from new-born sprague-dawley rats within 24 hours, and the cerebral hemisphere was dissociated to culture the neural stem cells. After being identified by immunofluorescence method, the neural stem cells were randomly divided into 3 groups as blank control group, experimental control group and experimental group. The neural stem cells of experimental control group and experimental group were irradiated with 2 or 4 Gy of gamma rays. The proliferation and the cell cycle of neural stem cells were detected at different time-points ranging from 24 h,48 h, 72 h after irradiation with CCK-8 and FCM. Results: Compared with the blank control group, the proliferation rate of experimental control group was significantly reduced (t=5.33-8.44, P<0.05 ), and the G1 phase arrest of experimental control group was significantly enhanced (t=30.60-71.22, P<0.05).Compared with the experimental control group, the proliferation of experimental group significantly increased excluding that of 24 h (t=2.45-4.71, P<0.05), the apoptosis rate of experimental group significantly decreased (t=6.73-41.12, P<0.05), which was closer to the blank control group.Conclusion: Magnesium sulfate can alleviate the injury of proliferation and decrease the cell apoptosis in the early stage after irradiation. (authors)

  14. Biological effects of low-dose ionizing radiation exposure; Biologische Wirkungen niedriger Dosen ionisierender Strahlung

    Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst (comps.)

    2009-07-01

    The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

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

    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 γ-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 γ-radiation in cultured lymphocytes and hepatocytes. TBARS were increased significantly, whereas the levels of GSH and antioxidant enzymes were significantly decreased in γ-irradiated hepatocytes and lymphocytes. On pretreatment with curcumin and its analog (1, 5 and 10 μg/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 μg/ml curcumin and 5 μg/ml curcumin analog pretreatment. Thus, pretreatment with curcumin and its analog helps in protecting the normal hepatocytes and lymphocytes against γ-radiation induced cellular damage and can be developed as an effective radioprotector during radiotherapy in near future

  16. Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures.

    Honar, H; Riazi, K; Homayoun, H; Sadeghipour, H; Rashidi, N; Ebrahimkhani, M R; Mirazi, N; Dehpour, A R

    2004-01-01

    Significant potentiation of analgesic effects of opioids can be achieved through selective blockade of their stimulatory effects on intracellular signaling pathways by ultra-low doses of opioid receptor antagonists. However, the generality and specificity of this interaction is not well understood. The bimodal modulation of pentylenetetrazole-induced seizure threshold by opioids provide a model to assess the potential usefulness of this approach in seizure disorders and to examine the differential mechanisms involved in opioid anti- (morphine at 0.5-3 mg/kg) versus pro-convulsant (20-100 mg/kg) effects. Systemic administration of ultra-low doses of naltrexone (100 fg/kg-10 ng/kg) significantly potentiated the anticonvulsant effect of morphine at 0.5 mg/kg while higher degrees of opioid receptor antagonism blocked this effect. Moreover, inhibition of opioid-induced excitatory signaling by naltrexone (1 ng/kg) unmasked a strong anticonvulsant effect for very low doses of morphine (1 ng/kg-100 microg/kg), suggesting that a presumed inhibitory component of opioid receptor signaling can exert strong seizure-protective effects even at very low levels of opioid receptor activation. However, ultra-low dose naltrexone could not increase the maximal anticonvulsant effect of morphine (1-3 mg/kg), possibly due to a ceiling effect. The proconvulsant effects of morphine on seizure threshold were minimally altered by ultra-low doses of naltrexone while being completely blocked by a higher dose (1 mg/kg) of the antagonist. The present data suggest that ultra-low doses of opioid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of opioids. PMID:15541894

  17. Low dose gamma knife surgery for small cerebral arteriovenous malformations

    We respectively evaluated the effectiveness of low-dose gamma knife surgery (GKS) for small cerebral arteriovenous malformations (AVMs) in Chiba Cardiovascular Center. One-hundred consecutive cases with small (<10 cc) AVM treated with ≤20 Gy at the periphery were analyzed. The survival curves for angiographical complete occlusion, radiation-induced edema and latency period bleeding were calculated by the Kaplan-Meier method, and the prognostic values of 9 covariates were obtained. The complete obliteration rate at 4 years was 91.6%. On multivariate analysis, the only significant prognostic factor was peripheral dose (p=0.0101). Radiation-induced edema was observed in 62.7%. Seven cases (12.5%) developed minor transient symptoms. The only permanent delayed radiation injury was cyst formation in 1 case. The significant prognostic factors for radiation-induced edema were peripheral dose (p=0.0387) and nidus volume (p=0.0161). Bleeding during the latency period was relatively rare (2.0%). In conclusion, our low-dose GKS using ≤20 Gy at the periphery provides excellent results for small AVMs. (author)

  18. Response of Biological Systems to Low Doses of Ionizing Radiation.

    Hei, Tom K

    2016-03-01

    Radiation is ubiquitous in the environment. Biological effects of exposure to low doses of ionizing radiation are subjected to several modulating factors. Two of these, bystander response and adaptive protections, are discussed briefly. PMID:26808883

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

    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 α-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.

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

    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.

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

    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 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

  2. A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced suppression of contact hypersensitivity

    Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semi purified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control-fed mice, a dose-responsive protection was observed in the garlic-fed mice; contact hypersensitivity in the UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations of cis-urocanic acid, a dose-responsive suppression of contact hypersensitivity was demonstrated in control-fed mice (urocanic acid at 25, 50, 100 and 200 micrograms per mouse resulting in 22-46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected from cis-urocanic acid-induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB-induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of the cis-urocanic acid mediation of this form of immunosuppression

  3. Radiological protection effect on vanillin derivative VND3207 radiation-induced cytogenetic damage in mouse bone marrow cells

    Objective: To study the protection of vanillin derivative VND3207 on the cytogenetic damage of mouse bone marrow cell induced by ionizing radiation. Methods: BALB/c mice were randomly divided into five groups: normal control group, 2 Gy dose irradiation group, and three groups of 2 Gy irradiation with VND3207 protection at doses of 10, 50 and 100 mg/kg, respectively. VND3207 was given by intragastric administration once a day for five days. Two hours after the last drug administration, the mice were irradiated with 2 Gy ?-rays. The changes of polychromatophilic erythroblasts micronuclei (MN), chromosome aberration (CA) and mitosis index (MI) of mouse bone marrow cells were observed at 24 and 48 h after irradiation. Results: Under the protection of VND3207 at the dosages 10, 50, 100 ?mg/kg, the yields of poly-chromatophilic erythroblasts MN and CA of bone marrow cells were significantly decreased (t=2.36-4.26, P<0.05), and the marrow cells MI remained much higher level compared with the irradiated mice without drug protection (t=2.58, 2.01, P<0.05). The radiological protection effect was drug dose-dependent, and the administration of VND3207 at the dosage of 100 mg/kg resulted in reduction by 50 % and 65% in the yields of MN and CA, respectively. Conclusions: VND3207 had a good protection effect of on ?-ray induced cytogentic damage of mouse bone marrow cells. (authors)

  4. Cancer Control Related to Stimulation of Immunity by Low-Dose Radiation

    Liu, Shu-Zheng

    2006-01-01

    Previous studies showed that low dose radiation (LDR) could stimulate the immune system in both animal and human populations. This paper reviews the present status of relevant research as support to the use of LDR in clinical practice for cancer prevention and treatment. It has been demonstrated that radiation-induced changes in immune activity follows an inverse J-shaped curve, i.e., low dose stimulation and high dose suppression. The stimulation of immunity by LDR concerns most anticancer p...

  5. Universal character of the cytogenetic damage induction regularities at low doses and the problem of genetic risk estimation

    The analysis of contemporary state of the problem in quantitative estimation of cytogenetic effects within the low dose range is given. Basing on the experimental data the universal (concerning test-objects) and principally non-linear character of relationship between radiation induced cytogenetic damage and dose within the low dose range is shown. Consequences of the results obtained for biological dosimetry and estimation of genetic and carcinogenic risk of low dose exposure are discussed

  6. Modification of radiation-induced apoptosis in radiation- or hyperthermia-adapted human lymphocytes

    We have investigated the influence of the cellular adaptive response to ionizing radiation on radiation-induced apoptosis in human cells. The adaptive response is believed to be a protective mechanism that confers resistance to the detrimental effects of ionizing radiation and that can be induced by different agents, including hyperthermia and radiation. We have used fluorescence analysis of DNA unwinding (FADU) to assay the induction of apoptosis in human peripheral blood lymphocytes by ionizing radiation. Using the FADU assay, we have observed the initial radiation-induced DNA damage, its subsequent disappearance due to enzymatic repair, and its time- and dose-dependent reappearance. We believe this reappearance of DNA damage to be indicative of the DNA fragmentation event associated with apoptosis. This interpretation has been supported at the individual cell level using an in situ terminal deoxynucleotidyl transferase (TDT) assay (Apoptag, Oncor Inc.), which detects the 3'-hydroxyl ends of fragmented DNA, and by fluorescence analysis of nuclear morphology in Hoechst 33258 stained cells. Pretreatment of cells with low-dose ?-radiation (0.1 Gy) or mild hyperthermia (40oC for 30 min) altered the extent of radiation-induced (3 Gy) apoptosis. Both pretreatments sensitized lymphocytes to become apoptotic after the 3-Gy radiation exposure. This sensitization may represent an adaptive response mechanism that reduces the risk that genetically damaged cells will proliferate. The ability to modify the probability of radiation-induced apoptosis may lower the cancer risk from a radiation exposure. (author)

  7. Radiation induced effects in the developing central nervous system

    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

  8. 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

    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/μm, respectively) protects the irradiated cells (P < 0.0001) against chromosomal damage induced by a subsequent exposure to a mean absorbed dose of 50 cGy from 1 GeV/u iron ions (LET ∼ 151 keV/μm). Surprisingly, unirradiated (i.e. bystander) cells with which the 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. (author)

  9. Low doses effects of ionizing radiation on Saccharomyces cerevisiae

    The exposure of living cells to low doses of ionizing radiation induce in response the activation of cellular protection mechanisms against subsequent larger doses of radiation. This cellular adaptive response may vary depending on radiation intensity and time of exposure, and also on the testing probes used whether they were mammalian cells, yeast, bacteria and other organisms or cell types. The mechanisms involved are the genome activation, followed by DNA repair enzymes synthesis. Due to the prompt cell response, the cell cycle can be delayed, and the secondary detoxification of free radicals and/or activation of membrane bound receptors may proceed. All these phenomena are submitted to intense scientific research nowadays, and their elucidation will depend on the complexity of the organism under study. In the present work, the effects of low doses of ionizing radiation (gamma rays) over a suspension of the yeast Saccharomyces cerevisiae (Baker's yeast) was studied, mainly in respect to survival rate and radio-adaptive response. At first, the yeast surviving curve was assessed towards increasing doses, and an estimation of Lethal Dose 50 (LD50) was made. The irradiation tests were performed at LINAC (electrons Linear Accelerator) where electron energy reached approximately 2.65 MeV, and gamma-radiation was produced for bremsstrahlung process over an aluminium screen target. A series of experiments of conditioning doses was performed and an increment surviving fraction was observed when the dose was 2.3 Gy and a interval time between this and a higher dose (challenging dose) of 27 Gy was 90 minutes. A value of 58 ± 4 Gy was estimated for LD50, at a dose rate of 0.44 ± 0.03 Gy/min These quantities must be optimized. Besides data obtained over yeast survival, an unusual increasing amount of tiny yeast colonies appeared on the agar plates after incubation, and this number increased as increasing the time exposure. Preliminary results indicate these colonies as 'petite' (mutants with mt DNA damage). (author)

  10. Protective effect of vitamins C and E on Gamma radiation induced Genetic injuries in male mice germ cells

    The effects of vitamins C and E on meiotic chromosomal metaphase-8 at diakinesis of the mouse to 3 Gy of whole body gamma- irradiation were studied. These vitamins were injected intraperitoneally as acute doses 2 hr before irradiation. Both vitamins significantly reduced the frequencies of chromosomal aberration in spermatic germ cells. The protective effect of vitamin E was greater than that afforded by vitamin C. A combined treatment of both vitamins resulted in additional protection over that offered by each vitamine alone. In all animal groups the most frequent aberration found was translocation in the from of either ring four (R IV) or chain four (C IV). The percentage of each or them was significantly increased in male mice sacrificed after 15 days post-irradiation. Other types of aberrations as autosomal univalent, X-Gamma univalent and polyploidy were rarely present

  11. A randomized controlled trial of green tea catechins in protection against ultraviolet radiation-induced cutaneous inflammation.

    Farrar, Mark D; Nicolaou, Anna; Clarke, Kayleigh A; Mason, Sarah,; Massey, Karen A.; Dew, Tristan P; Watson, Rachel EB; Williamson, Gary; Rhodes, Lesley E; Farrar MD, Nicolaou A, Clarke KA, Mason S, Massey KA, Dew TP, Watson REB, Williamson G, Rhodes LE

    2015-01-01

    BACKGROUND: Safe systemic protection from the health hazards of ultraviolet radiation (UVR) in sunlight is desirable. Green tea is consumed globally and is reported to have anti-inflammatory properties, which may be mediated through the impact on cyclooxygenase and lipoxygenase pathways. Recent data suggest that green tea catechins (GTCs) reduce acute UVR effects, but human trials examining their photoprotective potential are scarce. OBJECTIVE: We performed a double-blind, randomized, placebo...

  12. Effect of low dose radiation on the immune system

    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)

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

    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.

  14. 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

    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

  15. 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

    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.

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

    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)

  17. Protection from radiation-induced damage of spermatogenesis in the rhesus monkey (Macaca mulatta) by follicle-stimulating hormone

    In adult rhesus monkeys a two- to threefold increase in the number of spermatogonia was found at Day 75 after 1 Gy of X-irradiation when the animals were pretreated with two intramuscular injections of follicle-stimulating hormone (FSH) each day. Also the percentage of cross-sections of seminiferous tubules showing spermatogonia (repopulation index) was much higher when FSH was given before irradiation. At 75 days postirradiation the repopulation index was 39 +/- 10% after irradiation alone and 81 +/- 11% when FSH pretreatment was applied. The pretreatment with two injections of FSH each day during 16 days caused an increase in the number of proliferating A spermatogonia. In view of earlier results in the mouse, where proliferating spermatogonial stem cells appeared more radioresistant than quiescent ones, it is suggested that the protective effects of FSH treatment are caused by the increase in the proliferative activity of the A spermatogonia and consequently of the spermatogonial stem cells. The results indicate that in the rhesus monkey the maximal protective effect of FSH is reached after a period of treatment between 7 and 16 days

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

    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

  19. Protection from radiation-induced damage of spermatogenesis in the rhesus monkey (Macaca mulatta) by follicle-stimulating hormone

    van Alphen, M.M.; van de Kant, H.J.; de Rooij, D.G.

    1989-02-01

    In adult rhesus monkeys a two- to threefold increase in the number of spermatogonia was found at Day 75 after 1 Gy of X-irradiation when the animals were pretreated with two intramuscular injections of follicle-stimulating hormone (FSH) each day. Also the percentage of cross-sections of seminiferous tubules showing spermatogonia (repopulation index) was much higher when FSH was given before irradiation. At 75 days postirradiation the repopulation index was 39 +/- 10% after irradiation alone and 81 +/- 11% when FSH pretreatment was applied. The pretreatment with two injections of FSH each day during 16 days caused an increase in the number of proliferating A spermatogonia. In view of earlier results in the mouse, where proliferating spermatogonial stem cells appeared more radioresistant than quiescent ones, it is suggested that the protective effects of FSH treatment are caused by the increase in the proliferative activity of the A spermatogonia and consequently of the spermatogonial stem cells. The results indicate that in the rhesus monkey the maximal protective effect of FSH is reached after a period of treatment between 7 and 16 days.

  20. Radiation-induced cataracts: the Health Protection Agency’s response to the ICRP statement on tissue reactions and recommendation on the dose limit for the eye lens

    This paper presents the response of the Health Protection Agency (HPA) to the 2011 statement from the International Commission on Radiological Protection (ICRP) on tissue reactions and recommendation of a reduced dose limit for the lens of the eye. The response takes the form of a brief review of the most recent epidemiological and mechanistic evidence. This is presented together with a discussion of dose limits in the context of the related risk and the current status of eye dosimetry, which is relevant for implementation of the limits. It is concluded that although further work is desirable to quantify better the risk at low doses and following protracted exposures, along with research into the mechanistic basis for radiation cataractogenesis to inform selection of risk projection models, the HPA endorses the conclusion reached by the ICRP in their 2011 statement that the equivalent dose limit for the lens of the eye should be reduced from 150 to 20 mSv per year, averaged over a five year period, with no year’s dose exceeding 50 mSv. (memorandum)

  1. Again about low doses of ionizing radiation

    Radiation hormesis, i.e., the positive stimulation by and positive biological effect of low doses of ionizing radiation is discussed. Various views of this phenomenon are given: some studies are in favour, others have not been able to prove its value. In radiation protection practice the principle of linearity and threshold-free nature of radiation effects is still being applied. The demand is voiced that the exposure of individuals and of the whole population should be as low as is possible with regard to economic and social aspects (ALARA principle). Hormesis has not as yet been unambiguously proved. (M.D.). 1 fig

  2. Protection and latent and patent sensitization by nucleotides of radiation-induced transformations of glycyl tryptophan and serum albumin

    A study was made of the influence of nucleotides (AMP, GMP, UMP and CMP) on roentgenochemiluminescence of glycyl tryptophan and serum albumin solutions in humans. The coefficient of modification of radiation transformations of peptide (10-4 M) and protein (1.47x10-4 M) was shown to be a function of nucleotide concentration representing smooth curves with a plateau at the nucleotide concentration of above 2x10-3 M. The extreme values of the modification coefficient vary from 0.35 to 2.18 and from 1 to 2 for peptide and protein respectively. The experimental data follow the kinetic mechanism suggesting that the protective effect is implemented by the nucleotide reactions with hydroxyl radicals whereas sensitization is implemented by the reactions of free radical nucleotides with peptide and protein molecules

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

    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

  4. Review of European research trends of low dose radiation risk

    Large research projects on low dose radiation effects in Europe and US over the past decade have provided limited scientific knowledge which could underpin the validation of radiation protection systems. Recently in Europe, there have been repeated discussions and dialogues to improve the situation, and as the consequence, the circumstances surrounding low dose radiation risks are changing. In 2009, Multidisciplinary European Low Dose Initiative (MELODI) was established as a trans-national organization capable of ensuring appropriate governance of research in the pursuit of a long term shared vision, and Low Dose Research towards Multidisciplinary Integration (DoReMi) network was launched in 2010 to achieve fairly short term results in order to prove the validity of the MELODI approach. It is expected to be very effective and powerful activities to facilitate the reduction of uncertainties in the understanding of low dose risks, but the regulatory requests rushing the reinforcement of radiological protection regulations based on the precautional principles are more increasing. To develop reasonable radiological protection systems based on scientific evidences, we need to accelerate to collect scientific evidences which could directly underpin more appropriate radiation protection systems even in Japan. For the purpose, we Japan need to develop from an independent standpoint and share as a multidisciplinary vision a long term and holistic research strategy which enables to enhance Japanese advantages such as low dose rate facilities and animal facilities, as soon as possible. (author)

  5. Protective Role of Hsp27 Protein Against Gamma Radiation-Induced Apoptosis and Radiosensitization Effects of Hsp27 Gene Silencing in Different Human Tumor Cells

    Purpose: The ability of heat shock protein 27 (Hsp27) to protect cells from stressful stimuli and its increased levels in tumors resistant to anticancer therapeutics suggest that it may represent a target for sensitization to radiotherapy. In this study, we investigate the protective role of Hsp27 against radiation-induced apoptosis and the effect of its attenuation in highly expressing radioresistant cancer cell lines. Methods and Materials: We examined clonogenic death and the kinetics of apoptotic events in different tumor cell lines overexpressing or underexpressing Hsp27 protein irradiated with photons. The radiosensitive Jurkat cell line, which does not express Hsp27 constitutively or in response to γ-rays, was stably transfected with Hsp27 complementary DNA. Attenuation of Hsp27 expression was accomplished by antisense or RNAi (interfering RNA) strategies in SQ20B head-and-neck squamous carcinoma, PC3 prostate cancer, and U87 glioblastoma radioresistant cells. Results: We measured concentration-dependent protection against the cytotoxic effects of radiation in Jurkat-Hsp27 cells, which led to a 50% decrease in apoptotic cells at 48 hours in the highest expressing cells. Underlying mechanisms leading to radiation resistance involved a significant increase in glutathione levels associated with detoxification of reactive oxygen species, a delay in mitochondrial collapse, and caspase activation. Conversely, attenuation of Hsp27 in SQ20B cells, characterized by their resistance to apoptosis, sensitizes cells to irradiation. This was emphasized by increased apoptosis, decreased glutathione basal level, and clonogenic cell death. Sensitization to irradiation was confirmed in PC3 and U87 radioresistant cells. Conclusion: Hsp27 gene therapy offers a potential adjuvant to radiation-based therapy of resistant tumors

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

    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

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

    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]-α, and lymphotoxin-β) or fibrogenic cytokines (transforming growth factor [TGF]-β) 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-α, and lymphotoxin-β) and the fibrogenic cytokine, TGF-β, 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 therapy

  8. Solar ultraviolet radiation induces biological alterations in human skin in vitro: Relevance of a well-balanced UVA/UVB protection

    Françoise Bernerd

    2012-01-01

    Full Text Available Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

  9. Soluble TGF-? type II receptor gene therapy reduces TGF-? activity in irradiated lung tissue and protects lungs from radiation-induced injury

    Full text: The objective was to determine whether administration of recombinant human adenoviral vector carrying soluble TGF-?1 type II receptor (T?R-II) gene reduces availability of active TGF?1 and protects lung from radiation-induced injury. Female Fisher-344 rats were randomized into four groups to receive: 1) Control 2) Adenoviral green fluorescent protein vector (AdGFP) alone 3) Radiation (RT) + Adenoviral vector with TGF-?1 type II receptor gene (AdexT?R-II-Fc) 4) RT alone. Animals were irradiated to right hemithorax using a single dose of 30 Gy. The packaging and production of a recombinant adenovirus carrying the fused human T?R-II-IgG1 Fc gene was achieved by use of the AdEasy system. The treatment vector AdexTbR-II-Fc (1.5*1010 PFU) and control vector AdGFP (1*109 PFU) were injected i.v. 24 hrs after RT. Respiratory rate was measured as an index of pulmonary function weekly for 5 weeks post RT. Structural damage was scored histologically. Immunohistochemistry was performed to identify activated macrophages. ELISA was used to quantify active TGF-?1 in tissue homogenate. Western blot was used to determine T?R-II expression in plasma and lung tissue. Animals receiving treatment vector AdexTbR-II-Fc have elevated plasma levels of soluble T?R-II at 24 and 48 hours after injection. In the RT+AdexTbR-II-Fc group, there was a significant reduction in respiratory rate (p = 0.002) at four weeks after treatment compared to RT alone group. Histology revealed a significant reduction in lung structural damage in animals receiving gene therapy after RT vs RT alone (p=0.0013). There was also a decrease in the number of activated macrophage (p= 0.02) in RT+AdexTbR-II-Fc group vs RT alone. The tissue protein expression of active TGF-?1 was significantly reduced in rats receiving RT+AdexTbR-II-Fc treatment (p<0.05). This study shows the ability of adenovirus mediated soluble T?R-II gene therapy to reduce tissue levels of active TGF-?1 and ameliorate radiation-induced lung injury in rats 4 weeks after irradiation

  10. Statistical and low dose response

    The low dose response and the lower limit of detection of the Hanford dosimeter depend upon may factors, including the energy of the radiation, whether the exposure is to be a single radiation or mixed fields, annealing cycles, environmental factors, and how well various batches of TLD materials are matched in the system. A careful statistical study and sensitivity analysis were performed to determine how these factors influence the response of the dosimeter system. Estimates have been included in this study of the standard deviation of calculated dose for various mixed field exposures from 0 to 1000 mrem

  11. Ionizing radiation induced cataract

    Until recently it was believed that the cataract (opacity of the eye lens) is a deterministic effect with a dose threshold of several Gray in dependence on the exposure conditions. Studies in Hiroshima and Nagasaki, in the vicinity of Chernobyl, of American radiologic technologists, astronauts, and patients after having received several computer tomographies of the head region, however, have shown that this assumption is not correct. It had been overlooked in the past that with decreasing dose the latency period is increasing. Therefore, the originally available studies were terminated too early. The more recent studies show that, in the case of a threshold existing at all, it is definitely below 0.8 Gy independently of an acute or a chronic exposure. All studies, however, include 0 Gy in the confidence interval, so that the absence of a dose threshold cannot be excluded. The German Commission on Radiological Protection (Strahlenschutzkommission, SSK) suggested therefore among others: targeted recording of the lens dose during activities which are known to be associated with possible significant lens exposure, examination of the lens should be included as appropriate in the medical monitoring of people occupationally exposed to radiation, if there is potentially high lens exposure, adoption of research strategies to develop a basic understanding of the mechanisms underlying radiation induced cataracts. The International Commission on Radiological Protection (ICRP) actually assumes a threshold dose of 0.5 Gy and, based on this assumption, has recommended in 2011 to reduce the dose limit for the eye lens from 150 mSv in a year to 20 mSv in a year for people occupationally exposed to ionising radiation. (orig.)

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

    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 γ-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 μg/ml), 1 h before irradiation, with 1 Gy of γ 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)

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

    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-cysteine can serve as a protective agent against the side effects of radiotherapy. (J.P.N.)

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

    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)

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

    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 γ-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.

  16. 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

    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).

  17. An integrated model for radiation induced cancer

    Risk estimates for radiation induced cancer are based on epidemiological data, principally the Japanese A bomb survivors. These estimates for radiation are better known than for any other environmental pollutant, but they do not relate directly to exposure to low doses and low dose rate. Recent rapid advances in molecular genetics, coupled with steady gains in cellular biology, radiation physics and chemistry led to the notion that the time may not be far off when it may be possible to arrive at human cancer risk estimates entirely from laboratory data. Whether risk estimates based on laboratory data will ever replace estimates based on epidemiological studies is an open question. What is clear is that laboratory data can supplement the present risk estimates by providing information on the relative effectiveness of high LET radiations, the importance of dose rate and dose protraction, and by identifying subpopulations which are unusually sensitive or resistant to radiation carcinogenesis. (author)

  18. Characteristics of repair following very low doses

    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

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

    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.)

  20. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the results from single 0.13 or 0.26 Gy acute titanium exposures. Theoretical modeling of the data show that a nontargeted effect model provides a better fit than the targeted effect model, providing important information at space-relevant doses of heavy ions. PMID:27092765

  1. Radiologic low-dose pelvimetry

    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.)

  2. A two-mutation model of radiation-induced acute myeloid leukemia using historical mouse data.

    Dekkers, Fieke; Bijwaard, Harmen; Bouffler, Simon; Ellender, Michele; Huiskamp, Ren; Kowalczuk, Christine; Meijne, Emmy; Sutmuller, Marjolein

    2011-03-01

    From studies of the atomic bomb survivors, it is well known that ionizing radiation causes several forms of leukemia. However, since the specific mechanism behind this process remains largely unknown, it is difficult to extrapolate carcinogenic effects at acute high-dose exposures to risk estimates for the chronic low-dose exposures that are important for radiation protection purposes. Recently, it has become clear that the induction of acute myeloid leukemia (AML) in CBA/H mice takes place through two key steps, both involving the Sfpi1 gene. A similar mechanism may play a role in human radiation-induced AML. In the present paper, a two-mutation carcinogenesis model is applied to model AML in several data sets of X-ray- and neutron-exposed CBA/H mice. The models obtained provide good fits to the data. A comparison between the predictions for neutron-induced and X-ray-induced AML yields an RBE for neutrons of approximately 3. The model used is considered to be a first step toward a model for human radiation-induced AML, which could be used to estimate risks of exposure to low doses. PMID:20842369

  3. Steam generators: low dose mark Duke's first SG replacement

    Duke Power claimed a US record in radiation protection this summer in its first ever steam generator replacement. The very low doses achieved for the Catawba 1 campaign was a welcome reward for management's strong commitment made early in the project to keep exposures to an absolute minimum. Radiation protection was considered throughout the planning process, alongside engineering and scheduling demands. (author)

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

    Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocytes, and resultant apoptosis of β-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect β-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)

  5. Radiation- induced aneuploidy in mammalian germ cells

    The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

  6. Radiation-induced apoptosis

    This review concerns the apoptosis which is a kind of cell death defined in 1972 and differs from the necrosis in the morphology and function. Apoptosis occurs in the order of pycnosis, cell atrophy, blebbing and cell fragmentation into apoptotic bodies and is an active process while necrosis is a passive one. The molecular mechanism involves the signal reception for apoptosis; its transduction and gene expression; protein degradation by caspases and DNA fragmentation by endonucleases; and removal of apoptotic bodies. Radiation-induced cell death involves the interphase and reproductive (or mitotic) death, the former of which, the authors found, was a typical apoptosis in thymocytes and is important in radiation therapy. A part of the latter death is also considered to be apoptosis. In the radiation-induced apoptosis, there are processes through p53 and interferon regulatory factor-1, and through membrane ceramide formation. Radiation-induced apoptosis has such means as the cause of radiation damage, the mechanism for the damage removal and the therapy of cancer. Research of the radiation-induced apoptosis was concluded important in the future. (K.H.)

  7. Radiation Induced Fermion Resonance

    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. Biological Effects of Low-Dose Exposure

    Komochkov, M M

    2000-01-01

    On the basis of the two-protection reaction model an analysis of stochastic radiobiological effects of low-dose exposure of different biological objects has been carried out. The stochastic effects are the results published in the last decade: epidemiological studies of human cancer mortality, the yield of thymocyte apoptosis of mice and different types of chromosomal aberrations. The results of the analysis show that as dependent upon the nature of biological object, spontanous effect, exposure conditions and radiation type one or another form dose - effect relationship is realized: downwards concave, near to linear and upwards concave with the effect of hormesis included. This result testifies to the incomplete conformity of studied effects of 1990 ICRP recomendations based on the linear no-threshold hypothesis about dose - effect relationship. Because of this the methodology of radiation risk estimation recomended by ICRP needs more precisian and such quantity as collective dose ought to be classified into...

  9. Biological effects of low-dose exposure

    On the basis of the two-protection reaction model an analysis of stochastic radiobiological effects of low-dose exposure of different biological objects has been carried out. The stochastic effects are the results published in the last decade: epidemiological studies of human cancer mortality, the yield of thymocyte apoptosis of mice and different types of chromosomal aberrations. The results of the analysis show that dependent upon the nature of biological object, spontaneous effect, exposure conditions and radiation type one or another form of a dose - effect relationship is realized: downward concave, near to linear and upward concave with the effect of hormesis included. This result testifies to the incomplete conformity of the studied effects of 1990 ICRP recommendations based on the linear no-threshold hypothesis about dose - effect relationship. Because of this the methodology of radiation risk estimation recommended by ICRP needs more precision and such quantity as collective dose ought to be classified into the category of nonsense. (author)

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

    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.

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

    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

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

    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

  13. Regulatory aspects of low doses control in Albania

    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)

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

    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)

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

    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)

  16. Global DNA methylation responses to low dose radiation exposure

    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/BHP Dose Radiation Research Scholarship.

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

    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 irradiation and a series of low dose rate irradiation. (Serizawa, K.)

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

    Objective: To clone and identify radiation-induced genes from 0.5 Gy γ-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 γ-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 radiation

  19. Some remarks on the significance of low doses

    The criteria of the present system of individual dose limitation are considered as well as the evolution of the limiting values. The assumption of the linearity of the dose-effect relationship without any threshold is probably the best approach to adopt for recommendations in radiation protection and for accounting the doses acquired by exposure to ionizing radiation. On the other hand the present evaluation of the natural background could imply a different dose-effect relationship in the low doses region and perhaps the existence of a threshold. Therefore the extrapolations which are usually made after exposures of different groups of people to low doses cannot be considered as scientifically sound. (author)

  20. Low Dose Risk, Decisions, and Risk Communication

    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

  1. Risks to health from radiation at low dose rates

    Our focus is on whether, using a balance-of-evidence approach, it is possible to say that at a low enough dose, or at a sufficiently low dose rate, radiation risk reduces to zero in a population. We conclude that insufficient evidence exists at present to support such a conclusion. In part this reflects statistical limitations at low doses, and in part (although mechanisms unquestionably exist to protect us against much of the damage induced by ionizing radiation) the biological heterogeneity of human populations, which means these mechanisms do not act in all members of the population at all times. If it is going to be possible to demonstrate that low doses are less dangerous than we presently assume, the evidence, paradoxically, will likely come from studies of higher dose and dose rate scenarios than are encountered occupationally. (author)

  2. Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

    Ionizing radiation induces clusters of DNA damages-oxidized bases, abasic sites and strand breaks-on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster).We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, double strand breaks (DSB) are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responsesfor cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation. (author)

  3. Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

    Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

    2002-01-01

    Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

  4. Transcriptional regulation of the low dose ionizing radiation induced protein clusterin

    Full text: Radiation therapy using ionizing radiation (IR), along with chemotherapy, are common treatments for many different cancers. Therefore, it is vital to understand the cellular responses to these treatments in malignant cells, as well as the surrounding normal tissues for optimizing the efficacy of these treatments. Clusterin (CLU) has been implicated in many normal and pathological disease processes, although the function of clusterin still remains to be elucidated. Additionally, a correlation between increased CLU expression and increased tumor malignancy has been noted. It has been suggested that secretory clusterin (sCLU), the fully processed and glycosylated form of CLU, plays a role in cytoprotection after cellular stress, possibly due to its ability to act as a chaperone and clear cell debris after damage. Our laboratory identified clusterin as an x-ray inducible protein/transcript. We have shown that doses of IR as low as 2 cGy, which do not cause DNA damage, induce sCLU transcript and protein suggesting a potential role for sCLU in adaptive survival responses and bystander effects. The regulatory mechanisms underlying sCLU expression following IR are unknown. Recent data generated by our laboratory suggest that the tumor suppressor protein, p53, may play a major role in the regulation of this protein. p53 is found mutated in over 50% of all human cancers. MCF-7 human breast cancer cells containing the HPV-16 E6 protein have high basal levels of sCLU as compared to parental MCF-7 cells. Additionally, p53 null HCT116 human colon cancer cells show a greatly enhanced induction of sCLU after IR, compared to parental HCT116 cells containing wild-type p53. Current work is focused on better understanding the mechanisms underlying p53 suppression of this gene, as well as transcription factors needed for IR induction

  5. 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

    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

  6. 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

    Grdina, D.J.; Shigematsu, N.; Schwartz, J.L.

    1994-08-01

    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.

  7. Differentially Expressed Genes Associated with Low-Dose Gamma Radiation

    Hegyesi, Hargita; Sándor, Nikolett; Schilling, Boglárka; Kis, Enikő; Lumniczky, Katalin; Sáfrány, Géza

    We have studied low dose radiation induced gene expression alterations in a primary human fibroblast cell line using Agilent's whole human genome microarray. Cells were irradiated with 60Co γ-rays (0; 0.1; 0.5 Gy) and 2 hours later total cellular RNA was isolated. We observed differential regulation of approximately 300-500 genes represented on the microarray. Of these, 126 were differentially expressed at both doses, among them significant elevation of GDF-15 and KITLG was confirmed by qRT-PCR. Based on the transcriptional studies we selected GDF-15 to assess its role in radiation response, since GDF-15 is one of the p53 gene targets and is believed to participate in mediating p53 activities. First we confirmed gamma-radiation induced dose-dependent changes in GDF-15 expression by qRT-PCR. Next we determined the effect of GDF-15 silencing on radiosensitivity. Four GDF-15 targeting shRNA expressing lentiviral vectors were transfected into immortalized human fibroblast cells. We obtained efficient GDF-15 silencing in one of the four constructs. RNA interference inhibited GDF-15 gene expression and enhanced the radiosensitivity of the cells. Our studies proved that GDF-15 plays an essential role in radiation response and may serve as a promising target in radiation therapy.

  8. Low-dose radiation epidemiology studies: status and issues.

    Shore, Roy E

    2009-11-01

    Although the Japanese atomic bomb study and radiotherapy studies have clearly documented cancer risks from high-dose radiation exposures, radiation risk assessment groups have long recognized that protracted or low exposures to low-linear energy transfer radiations are key radiation protection concerns because these are far more common than high-exposure scenarios. Epidemiologic studies of human populations with low-dose or low dose-rate exposures are one approach to addressing those concerns. A number of large studies of radiation workers (Chernobyl clean-up workers, U.S. and Chinese radiological technologists, and the 15-country worker study) or of persons exposed to environmental radiation at moderate to low levels (residents near Techa River, Semipalatinsk, Chernobyl, or nuclear facilities) have been conducted. A variety of studies of medical radiation exposures (multiple-fluoroscopy, diagnostic (131)I, scatter radiation doses from radiotherapy, etc.) also are of interest. Key results from these studies are summarized and compared with risk estimates from the Japanese atomic bomb study. Ideally, one would like the low-dose and low dose-rate studies to guide radiation risk estimation regarding the shape of the dose-response curve, DDREF (dose and dose-rate effectiveness factor), and risk at low doses. However, the degree to which low-dose studies can do so is subject to various limitations, especially those pertaining to dosimetric uncertainties and limited statistical power. The identification of individuals who are particularly susceptible to radiation cancer induction also is of high interest in terms of occupational and medical radiation protection. Several examples of studies of radiation-related cancer susceptibility are discussed, but none thus far have clearly identified radiation-susceptible genotypes. PMID:19820457

  9. The researches on the effects of low doses irradiation

    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.)

  10. Molecular targets for radioprotection by low dose radiation exposure

    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 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

  11. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm

  12. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E., E-mail: claudia.ruebe@uks.eu

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  13. Radiation induced bladder carcinoma

    In recent years many authors had been concerned with malignancy which was followed by irradiation for malignant diseases and it was suggested that cancers developing in the organ or tissues adjacent to these irradiation were increasing in number. Authors reported a case of radiation induced bladder carcinoma and reviewed some published literature. A 68 year-old Japanese female who had been operated on and irradiated for cervical carcinoma of the uterus in 1964, was admitted to our hospital in Jan. 15, 1978 for evaluation of one month history of hematuria. The dose of prior irradiation was 4,500 rads. On physical examination, moderate late radiation changes of the skin and an operated scar were found in lower abdominal wall. A sessile, infiltrating tumor was observed in left lateral wall on the cystoscopic examination. IVP films revealed nonvisual left kidney with normal right kidney. The right upper urinary tract was normal in shape. The laboratory tests showed no abnormal value without slight anemia. Under a clinical diagnosis of radiation induced bladder carcinoma, the segmental cystectomy with left total nephro-ureterectomy was carried out and the removed specimens were offered for pathologic examinations. It made a diagnosis of transitional cell carcinoma with marked mucous forming adenomatous metaplasia, grade III, stage C. There was no malignant change in upper urinary tract and kidney. (author)

  14. Compelling Issues Compounding the Understanding of Low Dose Radiation Effects: But Do They Matter?

    Morgan, William F

    2016-03-01

    Recent advances in low dose radiation research have raised a number of compelling issues that have compounded the understanding of low dose radiation effects. Here some of them are outlined: the linear no-threshold model for predicting effects at low radiation doses, dose rate effectiveness factor, attributability, and public perception of low dose radiation effects. The impact of changes in any of these hotly debated issues on radiation protection is considered. PMID:26808886

  15. Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods

    Vuslat Yurut-Caloglu

    2015-01-01

    Full Text Available Purpose: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC and amifostine against radiation-induced acute ovarian damage. Materials and Methods: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7; irradiation alone RT: radiation therapy (RT, n = 8; amifostine plus irradiation (AMI + RT, n = 8; LC plus irradiation (LC + RT, n = 8; LC and sham irradiation (LC, n = 7; and amifostine and sham irradiation (AMI, n = 7. The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg and amifostine (200 mg/kg was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA and advanced oxidation protein product (AOPP were measured. Results: Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P 0.05. The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P 0.005. The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005. Conclusions: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.

  16. Radiation-induced lung injury

    This paper reviewed concerning the recent development about mechanism, diagnoses, probability of prevention and care of radiation-induced lung injury. Section items of this review are as follows: Pathomorphdogic lesion; Injury and functional change of alveolus; Change of lung stroma matrix; Bronchoalveolar lavage cell and its functional change; Lung injury outside of radiation field; Imaging diagnosis of radiation-induced lung injury; Probability of prevention and care of radiation-induced lung injury. (K.H.). 55 refs

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

    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.

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

    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

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

    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.

  20. NRH:Quinone Oxidoreductase 2 (NQO2) Protein Competes with the 20 S Proteasome to Stabilize Transcription Factor CCAAT Enhancer-binding Protein α (C/EBPα), Leading to Protection against γ Radiation-induced Myeloproliferative Disease*

    Xu, Junkang; Patrick, Brad Allen; Jaiswal, Anil K.

    2013-01-01

    NRH:quinone oxidoreductase 2 (NQO2) is a flavoprotein that protects cells against radiation and chemical-induced oxidative stress. Disruption of the NQO2 gene in mice leads to γ radiation-induced myeloproliferative diseases. In this report, we showed that the 20 S proteasome and NQO2 both interact with myeloid differentiation factor CCAAT-enhancer-binding protein α (C/EBPα). The interaction of the 20 S proteasome with C/EBPα led to the degradation of C/EBPα. NQO2, in the presence of its cofactor NRH, protected C/EBPα against 20 S degradation. Deletion and site-directed mutagenesis demonstrated that NQO2 and 20 S competed for the same binding region of S(268)GAGAGKAKKSV(279) in C/EBPα. Exposure of mice and HL-60 cells to γ radiation enhanced the levels of NQO2, which led to an increased NQO2 interaction with C/EBPα and decreased 20 S interaction with C/EBPα. NQO2 stabilization of C/EBPα was independent of NQO1, even though both interacted with the same C/EBPα domain. NQO2−/− mice, deficient in NQO2, failed to stabilize C/EBPα. This contributed to the development of γ radiation-induced myeloproliferative disease in NQO2−/− mice. PMID:24142791

  1. Radiation induced pesticidal microbes

    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.

  2. Radiation induced pesticidal microbes

    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

  3. Radiation-induced cancer

    The induction of malignant diseases is one of the most concerning late effects of ionising radiation. A large amount of information has been collected form atomic bomb survivors, patients after therapeutic irradiation, occupational follow-up and accidentally exposed populations. Major uncertainties persist in the (very) low range i.e, population and workers radioprotection. A review of the biological mechanisms leading to cancer strongly suggests that the vast majority of radiation-induced malignancies arise as a consequence of recessive mutations can be unveiled by ageing, this process being possibly furthered by constitutional or acquired genomic instability. The individual risk is likely to be very low, probably because of the usual dose level. However, the magnitude of medical exposure and the reliance of our societies on nuclear industry are so high that irreproachable decision-making processes and standards for practice are inescapable. (author)

  4. Radiation Induced Genomic Instability

    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.

  5. LOW DOSE MAGNESIUM SULPHATE REGIME FOR ECLAMPSIA

    Bangal V

    2009-09-01

    Full Text Available Pre- eclampsia is one of the commonest medical complications seen during pregnancy. It contributes significantly to maternal and perinatal morbidity and mortality. Dr.J.A.Pritchard in 1955, introduced magnesium sulphate for control of convulsions in eclampsia and is used worldwide. Considering the low body mass index of indian women, a low dose magnesium sulphate regime has been introduced by some authors. Present study was carried out at tertiary care centre in rural area. Fifty cases of eclampsia were randomly selected to find out the efficacy of low dose magnesium sulphate regime to control eclamptic convulsions. Maternal and perinatal outcome and magnesium toxicity were analyzed. It was observed that 86% cases responded to initial intravenous dose of 4 grams of 20% magnesium sulphate . Eight percent cases, who got recurrence of convulsion, were controlled by additional 2 grams of 20% magnesium sulphate. Six percent cases required shifting to standard Pritchard regime, as they did not respond to low dose magnesium sulphate regime. The average total dose of magnesium sulphate required for control of convulsions was 20 grams ie. 54.4% less than that of standard Pritchard regime. The maternal and perinatal morbidity and mortality in the present study werecomparable to those of standard Pritchard regime. The study did not find a single case of magnesium related toxicity with low dose magnesium sulphate regime. Low dose magnesium sulphate regime was found to be safe and effective in eclampsia.

  6. RIS - radiation induced superheroes

    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!

  7. LOW DOSE RISK, DECISIONS, and RISK COMMUNICATION

    The objective of this project is 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. 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

  8. Evaluation of the detriment associated with exposure at low doses and low dose rates in the radiation protection system; Evaluation du detriment associe a l'exposition aux faibles doses et faibles debits de dose dans le systeme de radioprotection

    Vaillant, Ludovic; Schneider, Thierry [CEPN, 28, rue de la Redoute, 92260 Fontenay-aux-Roses (France)

    2012-03-15

    Questions about quantifying the radiological risk associated with exposure to ionising radiation have been debated repeatedly for a variety of exposure situations, including, among others, medical irradiation, discharges from nuclear facilities, transportation of radioactive waste, and potential nuclear accidents. This paper aims to shed light on the link between exposure and risk, focusing on the items that constitute the detriment associated with this exposure. The management of the risk associated with it relies on a cautious hypothesis of a linear no-threshold relation between exposure and risk of death or detriment. The International Commission on Radiological Protection (ICRP) published General Recommendations in 1966 that recognised this relation, but did not publish a quantification of the risk until 1977. The Commission introduced the concept of effective dose as a risk indicator that makes it possible to determine dose limits according to the risk associated with them. In 1990, the Commission proposed a revision of the quantification and construction of detriment. New limits, based on risk quantification and, for the first time, risk tolerability, were proposed. The optimisation of radiation protection - keeping radiation exposure as low as reasonably achievable in light of the economic and social context - became the key principle of the radiation protection system. The use of detriment makes it possible to use economic tools to guide the decision process for this optimisation - by assessing the monetary value of human life. This concept, widely used in health economics during the 1980's, has been criticised by many and must be used cautiously. ICRP published the latest quantifications of detriment in 2007. Detriment is thus an indicator that assesses the risk of death associated with exposure to ionising radiation for an average individual. Its construction relies on simplifying assumptions that are needed to implement a robust and effective radiation protection system. (authors)

  9. Radiation induced emulsion polymerization

    High energy radiation is particularly favored for the initiation of emulsion polymerization. The yield of free radicals, for example, from the radiolysis of the aqueous phase, is high; G(radical) values of 5-7. In addition, the rather special kinetics associated with emulsion polymerization lead, in general, to very large kinetic chain lengths, even with 'non-ideal' monomers such as vinyl acetate. Together, high polymerization rates at low doses become possible. There are some important advantages of radiation polymerization compared with chemical initiators, such as potassium persulfate. Perhaps the most important among them is the temperature independence of the initiation step. This makes low temperature polymerization very accessible. With monomers such as vinyl acetate, where chain termination to monomer is predominant, low temperatures lead to often highly desirable higher molecular weights. With styrene, the classical ideally behaved monomer, there are the advantages such as, for example, the feasibility of using cationic monomers. These and some attendant disadvantages are discussed in detail, including pilot plant studies

  10. Exposure to low doses of ionizing radiations

    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

  11. [Epidemiology of digestive complications associated with use of low-dose aspirin].

    Czernichow, Pierre; Merle, Véronique

    2004-04-01

    Low-dose aspirin (myocardial infarction or ischemic stroke. Six to 12% of the general population is exposed to low-dose aspirin. The most frequently studied digestive complications are bleeding peptic ulcers, whose risk is increased twofold by low-dose aspirin treatment, and non-complicated peptic ulcers. History of bleeding or non-complicated peptic ulcer, alcohol intake, concomitant treatment with NSAID or calcic inhibitors are demonstrated risk factors of bleeding ulcer associated with low-dose aspirin. The role of enteric coating, of low-dose aspirin dose, of delay since low-dose aspirin treatment onset, and of Helicobacter pylori infection, remains controversial. Antisecretory drugs (H2 inhibitors, proton pump inhibitors), and nitroglycerin are associated with a decreased risk of bleeding ulcer. The protective effect of COX-2 inhibitors on the risk of bleeding ulcer is suppressed by concomitant treatment with low-dose aspirin. The risk of no- complicated peptic ulcer was increased by low-dose aspirin intake by a factor 2.9 in one study. Low-dose aspirin dose, infection by Helicobacter pylori, NSAID intake, and absence of enteric coating, are possible risk factors for non-complicated peptic ulcer. No association was retrieved with alcohol intake and peptic ulcer history. PMID:15366673

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

    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.

  13. Problems linked to effects of ionizing radiations low doses

    The question of exposure to ionizing radiations low doses and risks existing for professional and populations has been asked again, with the recommendations of the International Commission of Radiation Protection (ICRP) to lower the previous standards and agreed as guides to organize radiation protection, by concerned countries and big international organisms. The sciences academy presents an analysis which concerned on epidemiological and dosimetric aspects in risk estimation, on cellular and molecular aspects of response mechanism to irradiation. The observation of absence of carcinogen effects for doses inferior to 200 milli-sieverts and a re-evaluation of data coming from Nagasaki and Hiroshima, lead to revise the methodology of studies to pursue, to appreciate more exactly the effects of low doses, in taking in part, particularly, the dose rate. The progress of molecular and cellular biology showed that the extrapolation from high doses to low doses is not in accordance with actual data. The acknowledge of DNA repair and carcinogenesis should make clearer the debate. (N.C.). 61 refs., 9 annexes

  14. Possible implications of non-linear radiobiological effects for the estimation of radiation risk at low doses.

    Prokic, V; Jacob, P; Heidenreich, W

    2002-01-01

    Possible implications of the effects of low LET radiation on the induction of cancer at low doses are studied. Low dose hypersensitivity and adaptive response were identified as candidates which may give a non-linear dose effect curve for acute exposures, whereas adaptive response may influence protracted exposures. In this paper acute exposures are studied. Several radiobiological reports on studies with mammalian cell lines have indicated the presence of a hypersensitive region in the radiation survival response at low doses followed by an increase in radioresistance. The two step clonal expansion (TSCE) model for the process of carcinogenesis was adapted in such a way that cell killing after acute radiation induces increased clonal expansion for some time and thus gives a promoting effect of radiation. As a first step, the Radiation Effects Research Foundation (RERF) data on the lung cancer incidence are fitted to study how such a model would influence the assessment of the cancer risk at low doses. PMID:12194306

  15. Possible implications of non-linear radiobiological effects for the estimation of radiation risk at low doses

    Prokic, V.; Jacob, P.; Heidenreich, W

    2002-07-01

    Possible implications of the effects of low LET radiation on the induction of cancer at low doses are studied. Low dose hypersensitivity and adaptive response were identified as candidates which may give a non-linear dose effect curve for acute exposures, whereas adaptive response may influence protracted exposures. In this paper acute exposures are studied. Several radiobiological reports on studies with mammalian cell lines have indicated the presence of a hypersensitive region in the radiation survival response at low doses followed by an increase in radioresistance. The two step clonal expansion (TSCE) model for the process of carcinogenesis was adapted in such a way that cell killing after acute radiation induces increased clonal expansion for some time and thus gives a promoting effect of radiation. As a first step, the Radiation Effects Research Foundation data on the lung cancer incidence are fitted to study how such a model would influence the assessment of the cancer risk at low doses. (author)

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

    Rithidech, Kanokporn; Simon, Sanford, R.; Whorton, Elbert, B.

    2006-01-06

    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-{kappa}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-{kappa}B) activation were also determined in cells at 1 and 4 hrs following irradiation (indicative of early responses).

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

    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-κB), 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-κB) activation were also determined in cells at 1 and 4 hrs following irradiation (indicative of early responses)

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

    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 μM 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 β and DNA ligase I. At higher concentrations (> 10 μM), 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 one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues

  19. Low dose effects of ionizing radiation on normal tissue stem cells.

    Manda, Katrin; Kavanagh, Joy N; Buttler, Dajana; Prise, Kevin M; Hildebrandt, Guido

    2014-02-22

    In recent years, there has been growing evidence for the involvement of stem cells in cancer initiation. As a result of their long life span, stem cells may have an increased propensity to accumulate genetic damage relative to differentiated cells. Therefore, stem cells of normal tissues may be important targets for radiation-induced carcinogenesis. Knowledge of the effects of ionizing radiation (IR) on normal stem cells and on the processes involved in carcinogenesis is very limited. The influence of high doses of IR (>5Gy) on proliferation, cell cycle and induction of senescence has been demonstrated in stem cells. There have been limited studies of the effects of moderate (0.5-5Gy) and low doses (<0.5Gy) of IR on stem cells however, the effect of low dose IR (LD-IR) on normal stem cells as possible targets for radiation-induced carcinogenesis has not been studied in any depth. There may also be important parallels between stem cell responses and those of cancer stem cells, which may highlight potential key common mechanisms of their response and radiosensitivity. This review will provide an overview of the current knowledge of radiation-induced effects on normal stem cells, with particular focus on low and moderate doses of IR. PMID:24566131

  20. The OER at low-dose rates

    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 γ 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.)

  1. Stimulation of seeds by low dose irradiation

    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)

  2. What physicians think about the need for informed consent for communicating the risk of cancer from low-dose radiation

    The National Institute of Environmental Health Sciences, a subsidiary of the Food and Drug Administration, has declared that X-ray radiation at low doses is a human carcinogen. The purpose of our study was to determine if informed consent should be obtained for communicating the risk of radiation-induced cancer from radiation-based imaging. Institutional review board approval was obtained for the prospective survey of 456 physicians affiliated with three tertiary hospitals by means of a written questionnaire. Physicians were asked to state their subspecialty, number of years in practice, frequency of referral for CT scanning, level of awareness about the risk of radiation-induced cancer associated with CT, knowledge of whether such information is provided to patients undergoing CT, and opinions about the need for obtaining informed consent as well as who should provide information about the radiation-induced cancer risk to patients. Physicians were also asked to specify their preference among different formats of informed consent for communicating the potential risk of radiation-induced cancer. Statistical analyses were performed using the chi-squared test. Most physicians stated that informed consent should be obtained from patients undergoing radiation-based imaging (71.3%, 325/456) and the radiology department should provide information about the risk of radiation-induced cancer to these patients (54.6%, 249/456). The informed consent format that most physicians agreed with included modifications to the National Institute of Environmental Health Services report on cancer risk from low-dose radiation (20.2%, 92/456) or included information on the risk of cancer from background radiation compared to that from low-dose radiation (39.5%, 180/456). Most physicians do not know if patients are informed about cancer risk from radiation-based imaging in their institutions. However, they believe that informed consent for communicating the risk of radiation-induced cancer should be obtained from patients undergoing radiation-based imaging. (orig.)

  3. Radiation induced diarrhoea - literature review

    Radiation-induced diarrhoea is an acute side effect of radiotherapy treatment to the pelvic area, experienced by nearly all patients. This paper will explore the patho-physiological rationale of diarrhoea, the causes of radiation-induced diarrhoea, the factors that influence the severity and occurrence, and the treatment of diarrhoea in relation to the radiotherapy setting, by analysing the current literature and will conclude by outlining future directions in this field. Copyright (2004) Australian Institute of Radiography

  4. Low dose irradiation reduces cancer mortality rates

    Low doses of ionizing radiation stimulate development, growth, memory, sensual acuity, fecundity, and immunity (Luckey, T.D., ''Radiation Hormesis'', CRC Press, 1991). Increased immune competence reduces cancer mortality rates and provides increased average lifespan in animals. Decreased cancer mortality rates in atom bomb victims who received low dose irradiation makes it desirable to examine populations exposed to low dose irradiation. Studies with over 300,000 workers and 7 million person-years provide a valid comparison of radiation exposed and control unclear workers (Luckey, T.D., Nurture with Ionizing Radiation, Nutrition and Cancer, 34:1-11, 1999). Careful selection of controls eliminated any ''healthy worker effect''. The person-year corrected average indicated the cancer mortality rate of exposed workers was only 51% that of control workers. Lung cancer mortality rates showed a highly significant negative correlation with radon concentrations in 272,000 U.S. homes (Cohen, B.L., Health Physics 68:157-174, 1995). In contrast, radon concentrations showed no effect on lung cancer rates in miners from different countries (Lubin, J.H. Am. J. Epidemiology 140:323-332, 1994). This provides evidence that excessive lung cancer in miners is caused by particulates (the major factor) or toxic gases. The relative risk for cancer mortality was 3.7% in 10,000 Taiwanese exposed to low level of radiation from 60Co in their steel supported homes (Luan, Y.C. et al., Am. Nuclear Soc. Trans. Boston, 1999). This remarkable finding needs further study. A major mechanism for reduced cancer mortality rates is increased immune competence; this includes both cell and humoral components. Low dose irradiation increases circulating lymphocytes. Macrophage and ''natural killer'' cells can destroy altered (cancer) cells before the mass becomes too large. Low dose irradiation also kills suppressor T-cells; this allows helper T-cells to activate killer cells and antibody producing cells. Increased production of many molecules (interleukins, interferons, leukotrienes, chemotactic agents, and mitogens) related to immunity are found in mice exposed to low dose irradiation (Lim, S.-Z., Biologic Effects of Low Level Exposures to Radiation and Related Agents, pp.15-16, 1993). Those plus many enzymes and cofactors are inter- and intra-cellular agents involved in gene expression, T-cell maturation, phagocytosis, signal transduction, antigen reception and antibody production. This basic science information has been utilized for cancer therapy in Japanese and United States clinics. With the usual radio-, chemo- and surgical therapy, the 10 year survival of non-Hodgkin's lymphoma was 59%; when this was augmented by low dose irradiation, survival was 80% (Sakamoto, K., ICONE-7 Abstracts, p 50-51, 1999). Low dose irradiation of the mid-section of the body was effective. This area includes many elements of the immune system: the spleen with its germinal centers and lymphoid follicles, the liver with its phagocytosing Kupffer cells, kidney phagocytes, and the lamina propria and Peyer's patches of the intestinal wall. Irradiation of either the head and chest or the groin-legs area was unresponsive. Chronic low dose irradiation redness premature cancer mortality 51%. Standards should be revised with health, not risks, as the goal. Safe supplementation with ionizing radiation would provide a new plateau of health for people and wealth for nations. (author)

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

    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.)

  6. Low dose effects detected by micronucleus assay in lymphocytes

    The effects of low doses of X-rays between 0.01 and 1 Gy were studied on whole blood samples of various individuals using the cytokinesis-blocked lymphocyte micronucleus assay as an endpoint. The adaptive response could be induced in G0 cells by 0.01 Gy followed by 1 Gy challenging dose within a time period of 8 hours, in vitro. The probability distribution of micronucleus increments in those samples which had received very low doses in the range 0.01-0.05 Gy proved to be of asymmetrical type (i.e. lognormal) -very likely to the same shape which has been verified for unirradiated (control) population - while the variable turned to be normally distributed at or above 1 Gy. Profound changes have been experienced in the main characteristics of the linear dose - response relationship and in regression parameters, as well, when successively lessened dose ranges were studied toward 0.01 Gy. In the range below ∼ 0.2 Gy the response were found to be unrelated to the absorbed dose. These findings suggest that in (very) low dose range a higher attention should be needed to biological parameters like repair, protective mechanisms and antioxidant capacities, rather than to the absorbed radiation energy only. (author)

  7. Health risks associated with low doses of radiation. Final report

    With its review of possible human health effects from exposure to low doses of ionization radiation, this report offers an important reference source for nuclear utility workers. An overview of general knowledge in this area defines how ionizing radiation can cause biological damage and the basic units in which radiation exposure is expressed. Included is a summary of radiation protection standards as well as estimates of annual and life-time exposures among the nuclear utility workforce. A key area of the report is its explanation of epidemiologic studies that form the basis for the current understanding of radiation health effects, following by a description of various risk models. In its discussion of the most important radiation health studies undertaken to date, the report includes those that form the foundation of current risk estimates as well as ones that have yielded inconclusive, sometimes controversial data. Finally, the report describes the basic scientific method for estimating health risks from low-dose, low-dose-rate exposures. Overall, this report will help utility personnel evaluate the potential health risks associated with exposure to low-level ionizing radiation and place these risks in perspective

  8. 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)

    Grdina, D.J.; Schwartz, J.L. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology]|[Argonne National Lab., IL (United States); Shigematsu, N. [Argonne National Lab., IL (United States)

    1993-06-01

    The polyamine spermine and the disulfide NN{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 (WR-2721). Because of their structural 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 VM-33278 into cells and the direct comparison between the protective properties of WR-33278 and spermine, these agents were electroporated into cells. Electroporation alone reduced cell survival to 75% but had no effect on hprt mutation frequency. The electroporation of either spermine or WR-33278 at concentrations greater than 0.01 mM was extremely toxic. The exposure of cells to both electroporation and irradiation gave rise to enhanced cell killing and mutation induction. Cell survival values at a radiation dose of 750 cGy were enhanced by factors of 1.3 and 1.8 following electroporation of 0.01 mM of spermine and WR-33278, respectively, 30 min prior to irradiation. 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.

  9. 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)

    The polyamine spermine and the disulfide NN 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 (WR-2721). Because of their structural 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 VM-33278 into cells and the direct comparison between the protective properties of WR-33278 and spermine, these agents were electroporated into cells. Electroporation alone reduced cell survival to 75% but had no effect on hprt mutation frequency. The electroporation of either spermine or WR-33278 at concentrations greater than 0.01 mM was extremely toxic. The exposure of cells to both electroporation and irradiation gave rise to enhanced cell killing and mutation induction. Cell survival values at a radiation dose of 750 cGy were enhanced by factors of 1.3 and 1.8 following electroporation of 0.01 mM of spermine and WR-33278, respectively, 30 min prior to irradiation. 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

  10. Radiation-induced detriment in the population

    A variety of quantities can be introduced to describe 'Detriment' induced by ionizing radiation, which are related to the estimate of the probability rate of occurrence of subsequent undesirable health effects. The estimate is evaluated from mathematical models which describe the probability of events (risk model) and the characteristics of subject population. Exposures are usually categorized into 1) exposure in the population, 2) occupational exposure and 3) medical exposure in the frame of radiation protection. It should be noted, however, that there is no essential difference in radiation-induced detriment itself among the three categories, except differences in the mode of exposure, the quality of radiation and the age structure of subjects. So far, the excess cancer death (probability) has been one of main detriment indicators in the exposed population. This reflects that risk model of ionizing radiation has been derived mainly from the data-base on the surveys of cancer mortality such as life span study (LSS) in Hiroshima-Nagasaki A-bomb survivors. In this paper are briefly discussed some radiation-induced detriment indicators in the population, including unconditional quantities 1) excess cancer death probability and 2) loss of life expectancy, together with 3) excess cancer incidence probability based on risk models newly reported for radiation-induced cancer incidence. As an example of conditional probability, is also discussed the simulation on the probability of causation (PC) of leukemias. (author)

  11. Cytogenetic effects of low-dose radiation

    The effects of ionizing radiation on chromosomes have been known for several decades and dose-effect relationships are also fairly well established in the mid- and high-dose and dose-rate range for chromosomes of mammalian cells. In the range of low doses and dose rates of different types of radiation few data are available for direct analysis of the dose-effect relationships, and extrapolation from high to low doses is still the unavoidable approach in many cases of interest for risk assessment. A review is presented of the data actually available and of the attempts that have been made to obtain possible generalizations. Attention is focused on some specific chromosomal anomalies experimentally induced by radiation (such as reciprocal translocations and aneuploidies in germinal cells) and on their relevance for the human situation. (author)

  12. The OER at low dose-rates

    The author comments on a letter (Kal, H.B., and Barendsen, G.W., 1976, Br. J. Radiol., vol. 49, 1049) reviewing published values of the OER for low dose-rate γ-rays. Artefacts of the system may have been responsible for one very low OER value taken from work carried out in the early 1960s, but later work in which these problems were eliminated still yielded OER values significantly lower than for acute X- or γ-ray exposures. Consideration is given to significance of this reduction in OER for γ-rays at the low dose-rates characteristic of interstitial implants. The performance of these interstitial implants may be comparable with the most sophisticated and expensive pion or heavy ion treatments. (U.K.)

  13. Ionizing radiation: effects of low doses

    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

  14. Epigenomic Adaptation to Low Dose Radiation

    Gould, Michael N. [Univ. of Wisconsin, Madison, WI (United States)

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  15. Estimation of radiation risks at low dose

    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

  16. Genomic Instability Induced by Low Dose Irradiation

    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.

  17. Experimental observation of lens damage after low doses of γ-ray irradiation to rabbit eyes

    Objective: To investigate and evaluate low dose γ-ray radiation induced lens damage. Methods: Both eyes of each rabbit were exposed to a single dose of 25 or 50 cGy γ-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 γ-ray (25 and 50 cGy) irradiation can markedly damage lens of rabbits

  18. Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease

    Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. In this series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy. (author)

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

    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

  20. Complex damage, low doses and Bystander effects

    Ionizing radiations of all types can produce a wide array of biological effects that overlap with those produced by many other genotoxic agents. Ionizing radiation, however, has unique features that sets it apart and these features are likely to dominate its modes of action and consequences, especially at low doses. Radiation insult is always in the form of highly structured 'tracks' along the paths of moving charged particles. This feature largely determines the spectrum of initial DNA damage produced in cells or people, the repairability of the damage by cellular processes, and its spatial and temporal distribution in the irradiated material. At the DNA level a substantial proportion of the initial damage is clustered over a few base pairs within a few nanometres of the track, thereby forming local complex damage consisting of several strand breaks and/or damaged bases. Simple double-strand breaks are in the minority compared to more complex combinations, even from so-called sparsely-ionizing (or low-LET) radiations. At low doses, the nature of the radiation tracks determines also the distributions of the primary complex lesions over the larger subcellular, cellular and tissue scales. At exposure levels of natural background radiation and also in most situations of occupational or diagnostic medical exposure, cells are traversed by single isolated individual tracks, so it is the biological capabilities of these single tracks that must determine the probability of harmful effects, if any. Thus, questions relating to the linear no-threshold hypothesis versus thresholds, hormesis, hypersensitivity, and so on, reduce at the low-dose end to understanding the capabilities and consequences of a single track, or a small number, and the persistence and range of its influence in tissue. Much is now understood about the nature and consequences of immediate 'targeted' radiation damage in cells from radiation tracks in them and near their DNA. However, over the last decade, there has been a wealth of new data showing that there are also 'untargeted' intracellular and extracellular processes that can be observed as high frequencies of delayed cellular effects (eg genomic instability) or effects in cells that have not themselves been irradiated ('bystander' effects). In considering risks from low doses and/or low dose rates of radiation, what are the relative contributions from untargeted mechanisms and how should this balance be applied to guide extrapolations of robust epidemiological data to the low exposure levels of practical relevance?

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

    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 γ-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 γ-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 γ-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.

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

    Reliene, Ramune [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Department of Medicine, Center for Human Nutrition, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Pollard, Julianne M. [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Biomedical Physics Interdepartmental Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Sobol, Zhanna; Trouiller, Benedicte [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Gatti, Richard A. [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Schiestl, Robert H., E-mail: rschiestl@mednet.ucla.edu [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Biomedical Physics Interdepartmental Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095 (United States); Department of Environmental Health Sciences, School of Public Health, University of California Los Angeles, Los Angeles, CA 90095 (United States)

    2009-06-01

    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 {gamma}-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 {gamma}-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 {gamma}-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.

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

    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

  4. Radiation-induced oxidation of plastics

    Radiation-induced oxidation of polymers is reviewed, focusing on fundamental free radical aspects, degradation, along with changes in molecular structure and mechanical properties. Postirradiation oxidation involving carbon-centered free radicals, as well as kinetics, have been investigated by electron spin resonance methods. Oxygen diffusion into plastics plays an important role in the oxidation process. The relation between the polymer radical reactions and molecular motion has been determined by studying the peroxy radicals trapped in polypropylene. Oxygen uptake, analyses of oxidation products, effects of irradiation conditions, and the protection offered by antioxidants and antirad agents are also reviewed. (orig.)

  5. The protective effect of amifostine on radiation-induced acute pulmonary toxicity: Detection by 99mTc-DTPA transalveolar clearances

    Purpose: The purpose of this study was to determine by using 99mTc-diethylenetriaminepentaacetic acid (DTPA) lung scintigraphy whether amifostine given before irradiation protects alveolocapillary integrity in a rabbit model. Methods and materials: Twenty white New Zealand rabbits were randomly divided into 4 groups: (1) control (CONT), (2) amifostine alone (AMF), (3) radiation (RAD), and (4) radiation plus amifostine (RAD+AMF). The AMF and RAD+AMF groups received amifostine. The RAD and RAD+AMF groups were irradiated to the right hemithorax with a single dose of 20 Gy using a 60Co treatment unit. Amifostine (200 mg/kg) was given i.p. 30 min before irradiation. The 99mTc-DTPA radioaerosol study was performed 14 day after irradiation. Results: The mean clearance rate of 99mTc-DTPA in control subjects was 140 21 min. The highest t1/2 value was noted in the RAD group (603 105 min, p = 0.001). There were no significant differences between the 99mTc-DTPA lung clearance rates of the CONT, RAD+AMF (238 24 min), and AMF groups (227 54 min). The mean penetration index values of CONT, RAD, AMF, and RAD+AMF are 63% 1.6%, 63% 2.5%, 60% 2.9%, and 63% 2%, respectively. Conclusions: We concluded that amifostine treatment before the lung irradiation protects the lung alveolocapillary integrity. This study confirms the protective effect of amifostine in an acute phase of radiation lung injury

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

    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) . 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

  7. Low dose TL characteristics of Nigerian fluorite

    Nigerian fluorite has been characterized by ?-irradiation for thermoluminescence in the low dose range (40 ?Gy72 mGy). The glow curves exhibit 3 peaks recorded at 111 11 C, 196 2 C and 282 4 C at the heating rate of 5 C s?1. The two high temperature peaks exhibit a linear response over the range of study. The minimum detectable dose for each of the observed peaks has been determined and the lowest detection limit of fluorite was also determined. A complex fading pattern was observed for the phosphor and the possible source of the TL buildup has been discussed.

  8. Low doses: myth or true danger

    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.)

  9. Food preservation by irradiation at low doses

    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)

  10. Global DNA methylation responses to low dose radiation exposure

    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.

  11. Radiation-inducible gene therapy

    The radiation-inducible chimeric genetic construct Egr-TNF? introduced into human xenografts produces cytotoxicity of infected tumor cells resulting in tumor growth inhibition. The interaction between Egr-TNF and radiation is selectively cytotoxic for the tumor microvasculature resulting in vascular thrombosis and tumor necrosis. Gene therapy combined with radiation therapy offers great potential for the treatment of localized human cancers. (author)

  12. Radiation-induced cataract

    Dose assessments for cataract threshold doses are available based on epidemiological studies of radiotherapy patients, survivors of the nuclear bombing of Hiroshima and Nagasaki, and of persons with occupational exposure to radiation. According to these, short-term application of low-level LET radiation of a dose ranging between 0.5 and 2.0 Gy may suffice to cause a cataract in the course of a few months or years which results in inpairment of vision (UNSCEAR, 1982). In fractionated irradiation, cataractogenic threshold dose increases to 4 Sv at treatment times between 3 weeks and 3 months, and to more than 5 Sv at more than 3 months (ICRP 41). Densely ionizing radiation must be assumed to have threshold doses between 2 and 20 Sv. An ICRP assessment (ICRP Publ. No. 41, 1984) gives a threshold dose of more than 8 Sv for a vision-impairing cataract if these was protracted irradiation at a low-level dose rate. Concerning radiation protection, a maximum lens dose of 150 mSv per annum was recommended which should not be exceeded. This indicates a maximum of 7.5 Sv of exposure throughout a period of 50 years of working life. (orig./HP)

  13. Uncertainty, low-dose extrapolation and the threshold hypothesis

    Risk-based radiation protection policy is influenced by estimated risk and by the uncertainty of that estimate. Thus, if the upper limit, at (say) 95% probability, of risk associated with a given radiation dose is at an 'acceptable' level, it is unlikely (or not credible) that the true level of risk associated with the dose is at an unacceptable level. Central estimates presented alone, in the absence of probability limits, lack this safety factor. Estimating cancer risks from low doses of ionising radiation involves extrapolation of risk estimates based on high-dose data to the much lower dose levels that characterize the vast majority of exposures of regulatory concern. Proof of a universal low-dose threshold, below which there is no radiation-related risk, would revolutionise radiation protection. Available data fail to provide such proof and, in fact, leave considerable room for the possibility that DNA damage from a single photon can contribute to the carcinogenic process. Allowing for the possibility of a threshold would, however, remove very little of the regulatory burden associated with the so-called linear, no-threshold hypothesis, unless that possibility were a virtual certainty. (author)

  14. In vitro studies to evaluate the protective effects of Cassia fistula on electron beam radiation induced damages in human dermal fibroblasts

    Radiation is increasingly used for medical and occupational purposes and is an established weapon in the diagnosis and the therapy of cancer. Cassia fistula, a member of the Leguminosae family, it is used as a traditional medicine specially to treat the skin diseases. The main objective of the study was to evaluate the changes induced by different doses of Electron Beam radiation on Human Dermal Fibroblasts (HDF) and protective effects of Cassia fistula on the same. Aqueous, methanolic and ethonolic extracts of Cassia fistula were prepared. In vitro biochemical assays like DPPH radical scavenging assay, Ferric Anion Reducing Potential using TPTZ, Nitric Oxide scavenging assay. Total antioxidant determination assay, Super Anion Radical Scavenging assays were carried out to study the antioxidant properties. HDF cells were standardized and treated with the Cassia fistula MTT assay was performed. Cells were irradiated and MTT, Micronucleus (MN) assays were performed then compared with control and non-irradiated cells. Cells were treated with Cassia fistula and irradiated; MTT and MN were performed. On comparison with the standard Ascorbic acid, ethanolic extract of Cassia fistula was showing 90% activity. The ethanolic extract of Cassia fistula is having high EC50 value. On comparison to the standard the alcoholic extracts of Cassia fistula has shown a higher FRAP value. Aqueous extract of Cassia fistula has minimum Nitric oxide scavenging property compared to alcoholic extracts. Methanolic and ethanolic extracts of Cassia fistula has shown 38-40% of Superoxide Radical Scavenging property in 500 μg/mL concentration. Also ethanolic and methanolic extracts of Cassia fistula has remarkable antioxidant property. Hence these concentrations were selected for further studies. Human Dermal Fibroblast cells were treated with the 500 μg/ mL of alcoholic Cassia fistula extracts which showed a protection against irradiated groups. (author)

  15. Semiquinone glucoside derivative isolated from Bacillus sp. INM-1 offers protection to male reproductive system of mice against γ-radiation induced toxicity

    Ionizing radiation causes reversible/irreversible damages to the testis by inducing oxidative stress through reactive oxygen species lead to impotency in young cancer patients undergoing lower abdomen radiotherapy. Therefore, protection of testicular cells against gamma radiation is of utmost significance. Present study was focused to evaluate radioprotective efficacy of a semiquinone rich fraction isolated from radioresistant bacterium Bacillus sp. INM-1. In the present study, mice were pre-treated with semiquinone glucoside derivative (SQGD; 50 mg/ kg.b.wt. i.p.) 2h before irradiation (5Gy) and various radioprotective cellular parameters including histology, quantitative analysis of spermatids, spermatocytes, sperm counts, sperm abnormalities, structural and morphological analysis of seminiferous tubules were observed for complete two cycles (70 days) of spermatogenesis and compared with irradiated (5 Gy) control group. Results of the study demonstrated that untreated control and SQGD treated groups showed no significant difference in sperm counts even after 70 days post treatment time. However, whole body irradiation reduced the sperm count significantly (p<0.05%) from the day 1st to day 70th. SQGD treatment to irradiated mice significantly increased the sperm count, reduced morphological abnormality in the sperms as compared to irradiated group. Untreated control mice showed a higher seminiferous tubular area compared to irradiation control at 35th and 70th day post irradiation time. SQGD pretreatment to irradiated mice led to significant increase in seminiferous tubule area compared to irradiated control. Concomitantly, seminiferous lumen size increases in radiation control mice compared to SQGD pre-treated mice at 35th and 70th day due to germ cells depletion. Qualitative histological study of testis at all tested time points suggests that drug treatment protects the spermatogenesis by enhancing the spermatogonial proliferation, enhancing the stem cell survival and reducing sperm abnormalities. Though, cellular level study clearly demonstrated radioprotective potential of SQGD, however, further study to verify the finding at molecular level is underway. (author)

  16. Risk of low-doses in radiodiagnosis

    The effect of low doses of X-rays is inferred from the indubitable effects of high doses in human carcinogenesis, Genetic and teratogenic effects are mainly inferred from animal experimentation because clinical surveys of irradiated pregnant women have failed to demonstrate such consequences in the children, except for mental retardation after Japanese atomic bombing. Since no evidence of carcinogenic effect has been produced by epidemiological studies for doses lower than 500 mSv. the estimation of the risk due to low doses has been extrapolated from the linear relation between dose and cancers at high doses. Such an extrapolation gives a maximal risk which is falsely used as a probability of cancer. The actual risk lies between zero and this maximal number, and many epidemiologic surveys in people receiving doses much higher than the mean level of background irradiation failed to demonstrate higher rate of cancer. The explanation of this fact, which is supported by the most recent biological data, is the efficacy of the DNA repair system at low level of exposure to ionizing radiations. We expose the principles of regulation of radioprotection for workers, and give estimations of the doses delivered to the patients and the personnel by diagnostic investigations, by comparing these doses with those of natural irradiation. Practical aspect for conventional and computed radiology are exposed for patients and workers. (authors)

  17. Genes activated by low dose radiation

    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.)

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

    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 γ- 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.

  19. A schedule to demonstrate radiation-induced sister chromatid exchanges in human lymphocytes

    The reciprocal interchange between the chromatids of a chromosome, termed sister chromatid exchange (SCE), is considered to be one of the most sensitive and accurate cytogenetic parameters and respond to toxic chemicals at very low doses. But the response of SCE to ionizing radiation is very poor. Human lymphocytes fail to give SCE response when irradiated at G0. Probably the primary lesions induced at G0 do not remain available long enough to find expression as SCEs. Based on this assumption a schedule was developed using caffeine to demonstrate radiation induced SCEs. Following this schedule a dose-dependent increase in the frequency of radiation induced SCEs has been observed. (orig.)

  20. Increased radioresistance, modelling of carcinogenesis and low-dose risk estimation

    Jacob, Peter; Prokic, Vesna [GSF-Institute of Radiation Protection, Neuherberg (Germany)

    2002-09-01

    Increased radioresistance for exposures to low-LET radiation with doses exceeding a few hundred milligray is a well established fact for cell inactivation in vitro and in vivo. Cell inactivation and the subsequent replacement by intermediate cells is a possible mechanism for a radiation-induced increase of the number of intermediate cells in carcinogenesis in an irradiated organ. In the present work this mechanism has been implemented in the two-step clonal expansion model for carcinogenesis in the lung in addition to the conventionally assumed radiation-induced initiation. Compared with the original TSCE model, the new model has the same number of parameters and fits the lung cancer incidence data for the atomic bomb survivors slightly better. The resulting estimate of the lung cancer risk after low-dose exposures of persons with an age of 20 or 40 years is similar in the two models; however, it is higher by about an order of magnitude in the new model for an age-at-exposure of 60 years. Age-at-exposure dependence and risk estimates at low dose turn out to be closer to best estimates obtained with a constant-excess-relative-risk model for different age-at-exposure subgroups. (author)

  1. Increased radioresistance, modelling of carcinogenesis and low-dose risk estimation.

    Jacob, Peter; Prokic, Vesna

    2002-09-01

    Increased radioresistance for exposures to low-LET radiation with doses exceeding a few hundred milligray is a well established fact for cell inactivation in vitro and in vivo. Cell inactivation and the subsequent replacement by intermediate cells is a possible mechanism for a radiation-induced increase of the number of intermediate cells in carcinogenesis in an irradiated organ. In the present work this mechanism has been implemented in the two-step clonal expansion model for carcinogenesis in the lung in addition to the conventionally assumed radiation-induced initiation. Compared with the original TSCE model, the new model has the same number of parameters and fits the lung cancer incidence data for the atomic bomb survivors slightly better. The resulting estimate of the lung cancer risk after low-dose exposures of persons with an age of 20 or 40 years is similar in the two models; however, it is higher by about an order of magnitude in the new model for an age-at-exposure of 60 years. Age-at-exposure dependence and risk estimates at low dose turn out to be closer to best estimates obtained with a constant-excess-relative-risk model for different age-at-exposure subgroups. PMID:12400947

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

    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

  3. In vitro studies to evaluate the antioxidant property of salidroside and rosavin and protective effects of electron beam radiation induced damages in human dermal fibroblasts

    Rosavin and Salidroside are active component of Rhodiola rosea, it is a phenylpropanoid derivative of plant. Rhodiola rosea, also known as 'golden root' or 'roseroot' belongs to the plant family Crassulaceae. Rhodiola grows primarily in dry sandy ground at high altitudes in the arctic areas of Europe and Asia. Plant is rich with phenolic compounds, known to have a strong antioxidant property. Studies have shown that Rhodiola rosea has a capacity to decrease toxicity of Adriamycin (anti-cancer drugs), while it enhances their anti-carcinogenic effects. Enhanced antioxidant activity of Rhodiola rosea play role in the prevention of both chronic disease and aging. Present study is aimed to determine the antioxidant property of Rosavin and Salidroside and dose determination on human dermal fibroblast against dermal fibroblast. Rosavin and Salidroside were dissolved in 10% DMSO. Invitro biochemical assays like DPPH radical scavenging assay, Ferric Anion Reducing Potential using TPTZ, Nitric Oxide scavenging assay, Total antioxidant determination assay, Super Anion Radical Scavenging assays were carried out to know property of the extract. Extracts were then treated on monolayer dermal fibroblast cells survival assay was performed. Salidroside has shown 80% total antioxidant property compare to Rosavin with respect Ascorbic acid as a standard. 100'R concentration of Salidroside and Rosavin has quite equal potential to scavenging DPPH similar like Ascorbic acid. Ferric Anion Reducing Potential using TPTZ, Nitric Oxide scavenging assays have also shown both Salidroside and Rosavin has a good antioxidant property. Invitro studies on dermal fibroblast have shown remarkable protective effect on normal and irradiated groups. (author)

  4. Effects at low doses: do we know enough

    The brief editorial discusses the limitations of the understanding of effects which will be induced at the low doses and dose-rates that are relevant to the radiological protection of workers and the general public. The possible link between childhood leukemia in Cumbria and exposure to Sellafield radiation, cell transformation system studies in cell cultures, and epidemiological studies which form the basis of standards to protect against unacceptable incidences of malignant disease following radiation exposure are mentioned, the latter with particular reference to the suggestion that breast cancer of young women is independent of dose-rates down to those only a few times those that might be experienced in the occupational context. (U.K.)

  5. Exposure to low dose radiation and its effect

    The title subjects are easily explained. As an introduction, the concept of the ICRP Recommendation (2007) is explained briefly on its use of radiation protection and management. Natural radiation dose to ordinary Japanese is said to be the average 1.5 mSv/y in contrast to the whole world people, 2.4. Medical radiation dose to Japanese is estimated to amount to 2.3 mSv/y, to American, 3.0, and to people of medically advanced nations, 1.92. There are areas always exposed to the natural high dose radiation like Ramsar 10.2 mSv/y (Iran). The effect of such natural low dose has been shown to be all insignificant on cancer mortality in Yangjian area (3.3 mSv/y) in China, on lung cancer risk due to radon in Japan Misasa spa area (>10 mSv/y), and on cancer mortality among 176 thousands nuclear industry workers in Japan (average accumulated dose 12 mSv), etc. There have been such reports as increased bladder cancer in Chernobyl, increased leukemic relative risk of infants whose fathers worked in Sellafield nuclear facility, and acute death/health-injury of residents in the past Lou-Lan area where Chinese nuclear bombs were tested. Fallout data from 1955 to 2011 shows the process of radioactive materials fallen and peaks were due to nuclear tests and Chernobyl/Fukushima Accidents. Basic studies on low dose effect involve those of the radioadoptive response, radiation hormesis, bystander effect and cluster injury of DNA. In low dose-carcinogenesis relationship, presented are models of linear non-threhold (LNT), those estimating lower risk than LNT like linear quadratic (LQ) model, and higher risk like supra-linear model. Risks leading to cancer formation include the occupation and others like medical doctors, tobacco smoking and various anxieties/stresses. (T.T.)

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

    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 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.)

  7. Dose-effect relationships, epidemiological analysis and the derivation of low dose risk

    This paper expands on our recent comments in a letter to this journal about the analysis of epidemiological studies and the determination of low dose RBE of low LET radiation (Chadwick and Leenhouts 2009 J. Radiol. Prot. 29 445-7). Using the assumption that radiation induced cancer arises from a somatic mutation (Chadwick and Leenhouts 2011 J. Radiol. Prot. 31 41-8) a model equation is derived to describe cancer induction as a function of dose. The model is described briefly, evidence is provided in support of it, and it is applied to a set of experimental animal data. The results are compared with a linear fit to the data as has often been done in epidemiological studies. The article presents arguments to support several related messages which are relevant to epidemiological analysis, the derivation of low dose risk and the weighting factor of sparsely ionising radiations. The messages are: (a) cancer incidence following acute exposure should, in principle, be fitted to a linear-quadratic curve with cell killing using all the data available; (b) the acute data are dominated by the quadratic component of dose; (c) the linear fit of any acute data will essentially be dependent on the quadratic component and will be unrelated to the effectiveness of the radiation at low doses; consequently, (d) the method used by ICRP to derive low dose risk from the atomic bomb survivor data means that it is unrelated to the effectiveness of the hard gamma radiation at low radiation doses; (e) the low dose risk value should, therefore, not be used as if it were representative for hard gamma rays to argue for an increased weighting factor for tritium and soft x-rays even though there are mechanistic reasons to expect this; (f) epidemiological studies of chronically exposed populations supported by appropriate cellular radiobiological studies have the best chance of revealing different RBE values for different sparsely ionising radiations.

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

    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.

  9. How to understand low dose risks

    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)

  10. Health effects of low dose radiation

    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)

  11. Disturbances of the cell at low doses

    Blood samples have been irradiated at 6 radiation doses ranging from 5 and 500 mGy in order to study the impact of gamma radiation on T CD4 genes of humane lymphocytes. These lymphocytes are key players of the immune response. The results show that among the 17000 genes that are effectively expressed in the cells in question, 2745 have an expression modulated by the irradiation. Among these genes the statistic analysis puts aside 370 genes that can be parted into 2 groups: a group of 68 genes for which their expression increases with the radiation doses and a group of 302 genes for which their expression increases significantly as soon as 5 mGy and stays at that level whatever the radiation dose. This fact is new and shows a disturbance at the scale of the cell even at very low doses. (A.C.)

  12. 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

    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

  13. Low Dose Ionizing Radiation Modulates Immune Function

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a 'Th2 polarized' immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the dose range of 5 to 50 cGy.

  14. Low Dose Ionizing Radiation Modulates Immune Function

    Nelson, Gregory A. [Loma Linda Univ., CA (United States)

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the dose range of 5 to 50 cGy.

  15. Low dose irradiation creep of pure nickel

    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

  16. Genome instability induced by extreme low dose/low dose rate heavy ion radiation

    We irradiated normal human fibroblasts (HFL III) with carbon ions (290 MeV/u, 70 keV/um) at very low dose (1 mGy total dose) and low dose rate (1 mGy/6 h) and observed the growth kinetics for several months by continuous culturing. The growth of carbon irradiated cells started to slow down much earlier than that of non-irradiated control cells before reaching senescence. On the other hand, HFL III cells irradiated at the same dose and the dose rate of gamma-rays were slightly accelerated their growth. Our measurements on DNA double strand break (DSB) such as gamma-H2AX foci revealed a higher number of foci in carbon irradiated cells than in gamma-irradiated cells at a cell passage near senescence. Taken together, our results suggest that high linear energy transfer (LET) radiation causes different effects than low LET radiation even at very low doses and that the effect of single low dose irradiation can affect the stability of genome many generations after irradiation. (author)

  17. Radiation induced crosslinking of polytetrafluoroethylene

    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)

  18. NIRS programme on low dose radiation as IAEA CC

    The year 2006 was the first year for the National Institute of Radiological Sciences (NIRS) as an International Atomic Energy Agency (IAEA) Collaborating Center on Biological Effects of Low Dose Radiation; NIRS was designated as one of the IAEA Collaborating Centers on January 18, 2006. The ceremony for the designation was held on February 8 with the presence of Professor Pedro Andreo, Director, Division of Human Health, Department of Nuclear Sciences and Applications, IAEA. In April 2006, NIRS initiated the second 5-year plan. The aim of the plan is to pursue comprehensive research and development on radiation and human health. The missions include the research on the effects of radiation on human bodies, medical countermeasures against radiation, diagnosis and treatment of diseases using radiation and radioisotopes, dissemination of research, and promotion of their uses. Among the missions of Research Center for Radiation Protection, both an understanding of the biological effects of low dose radiation and training of the skills of researchers and radiation workers have been the most important aspects. (author)

  19. Radiation-induced heart injury

    In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the internal between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue. (Evans, G.)

  20. Radiation-induced brain injury

    Radiation-induced brain injury is a life-threatening or at least quality of life (QOL)-compromising pathological entity induced by therapeutic irradiation to malignant brain tumors. Although life-threatening late delayed radiation necrosis and radiation-induced leukoencephalopathy had been assumed to be major complications of radiation therapy to the brain classically, these complications seem to be less frequently seen in therapeutic irradiation to the brain recently because in many treatment protocols to brain tumors, irradiation field is now confined to tumors and their margins and adjuvant chemotherapy consisting of methotrexate etc. has been avoided as much as possible. Instead, less aggressive but still QOL-compromising encephalopathy has been recognized for the past 20 years. This encephalopathy occurs in senior adults several months after the extended field irradiation with even less amount of irradiation dose such as 40 Gy whole brain irradiation. This encephalopathy is characterized by cognitive impairment and brain atrophy which attenuates QOL of the patients. In this article, these radiation-induced brain injuries are reviewed clinically, etiologically and histopathologically based on reports in the literature. (author)

  1. Radiation-induced chromosomal instability

    Recent studies on radiation-induced chromosomal instability in the progeny of exposed mammalian cells were briefly described as well as other related studies. For the analysis of chromosomal damage in clones, cells were seeded directly after exposure in cell well-dish to form single cell clones and post-irradiation chromosome aberrations were scored. Both exposure to isoeffective doses of X-ray or 270 MeV/u C-ions (13 keV/μm) increased the number of clones with abnormal karyotype and the increase was similar for X-ray and for C-ions. Meanwhile, in the progeny of cells for mass cultures, there was no indication of a delayed expression of chromosomal damage up to 40 population doublings after the exposure. A high number of aberrant cells were only observed directly after exposure to 10.7 MeV/u O-ions, i.e. in the first cycle cells and decreased with subsequent cell divisions. The reason for these differences in the radiation-induced chromosomal instability between clonal isolates and mass culture has not been clarified. Recent studies indicated that genomic instability occurs at a high frequency in the progeny of cells irradiated with both sparsely and densely ionizing radiation. Such genomic instability is thought likely to increase the risk of carcinogenesis, but more data are required for a well understanding of the health risks resulting from radiation-induced delayed instability. (M.N.)

  2. Final Report - Epigenetics of low dose radiation effects in an animal model

    Kovalchuk, Olga

    2014-10-22

    This project sought mechanistic understanding of the epigenetic response of tissues as well as the consequences of those responses, when induced by low dose irradiation in a well-established model system (mouse). Based on solid and extensive preliminary data we investigated the molecular epigenetic mechanisms of in vivo radiation responses, particularly – effects of low, occupationally relevant radiation exposures on the genome stability and adaptive response in mammalian tissues and organisms. We accumulated evidence that low dose irradiation altered epigenetic profiles and impacted radiation target organs of the exposed animals. The main long-term goal was to dissect the epigenetic basis of induction of the low dose radiation-induced genome instability and adaptive response and the specific fundamental roles of epigenetic changes (i.e. DNA methylation, histone modifications and miRNAs) in their generation. We hypothesized that changes in global and regional DNA methylation, global histone modifications and regulatory microRNAs played pivotal roles in the generation and maintenance low-dose radiation-induced genome instability and adaptive response. We predicted that epigenetic changes influenced the levels of genetic rearrangements (transposone reactivation). We hypothesized that epigenetic responses from low dose irradiation were dependent on exposure regimes, and would be greatest when organisms are exposed in a protracted/fractionated manner: fractionated exposures > acute exposures. We anticipated that the epigenetic responses were correlated with the gene expression levels. Our immediate objectives were: • To investigate the exact nature of the global and locus-specific DNA methylation changes in the LDR exposed cells and tissues and dissect their roles in adaptive response • To investigate the roles of histone modifications in the low dose radiation effects and adaptive response • To dissect the roles of regulatory microRNAs and their targets in low dose radiation effects and adaptive response • To correlate the levels of epigenetic changes with genetic rearrangement levels and gene expression patterns. In sum, we determined the precise global and locus-specific DNA methylation patterns in the LDR-exposed cells and tissues of mice, and to correlated DNA methylation changes with the gene expression patterns and manifestations of genome instability. We also determined the alterations of global histone modification pattern in the LDR exposed tissues. Additionally, we established the nature of microRNAome changes in the LDR exposed tissue. In this study we for the first time found that LDR exposure caused profound tissue-specific epigenetic changes in the exposed tissues. We established that LDR exposure affect methylation of repetitive elements in the murine genome, causes changes in histone methylation, acetylation and phosphorylation. Importantly, we found that LDR causes profound and persistent effects on small RNA profiles and gene expression, and that miRNAs are excellent biomarkers of LDR exposure. Furthermore, we extended our analysis and studied LDR effects in rat tissues and human tissues and cell lines. There we also analyzed LDR-induced gene expression, DNA methylation and miRNA changes. Our datasets laid foundation for several new research projects aimed to understand molecular underpinnings of low dose radiation responses, and biological repercussions of low dose radiation effects and radiation carcinogenesis.

  3. Melatonin ameliorates radiation induced mutilation of learning in mice

    Brain is highly susceptible to oxidative damage due to its high utilization of oxygen and rather poorly developed anti oxidative defense mechanism. Present study is aimed at investigating the protective effect of melatonin against radiation-induced impairment in the learning ability of mice

  4. Mitochondrial DNA deletion and aging induced by low dose rate of radiation in mice

    Mitochondrial DNA (mtDNA) is a closed circular DNA molecule and more than 100 copies are present in a cell. Deletion mutation of mtDNA accumulates with aging and can be a suitable marker for estimating biological effects on radiation-induced mutation in mice. The mice life span study in the Institute for Environmental Sciences suggests that low dose rate of radiation might accelerate aging in mice prolongly irradiated by 137Cs γ-rays (20 mGy/day for 400 days). To know the relationships between low dose rate irradiation, aging and mutation, we observed deletion mutations of mtDNA from mice irradiated by 137Cs γ-rays (20 mGy/day) for different dates. The real-time fluorescence PCR method was sensitive enough to determine the relative amount of deletion in several tissues. Age-dependent accumulations of deletion mutations were observed in aged mice (250-700 days). However, a significant increase of deletion mutation related to accumulated dose was not detected in 137Cs γ-ray irradiated mice for 4-12 Gy. These data suggest that the effect of the low dose rate irradiation on mtDNA is within a background level. (author)

  5. A single, low dose of a current Good Manufacturing Practice (cGMP recombinant BCG vaccine confers protection against human respiratory syncytial virus (hRSV infection and lung pathology in mice

    Pablo Francisco Cspedes

    2015-04-01

    Full Text Available Human respiratory syncytial virus (hRSV is a major health burden worldwide, causing most of the hospitalizations due to bronchiolitis and pneumonia in children below the age of two years. HRSV causes year-to-year outbreaks of disease, which also affects the elderly and immunocompromised individuals. Furthermore, both hRSV morbidity and epidemics are explained by a consistently high rate of re-infections that could be established throughout the host life. Importantly, currently there are no licensed vaccines for the prophylaxis of this important human pathogen. Here, we describe a novel, recombinant Bacillus Calmette-Guerin (BCG vaccine expressing the nucleoprotein (N of hRSV (herein rBCG-N and its protective capacity in the BALB/cJ model of infection. A single dose of 3 x 105 colony forming units (cfu of the rBCG-N vaccine protected mice against infection with 1 x 107 plaque forming units (pfu of the 13018-8 hRSV A2 strain. Compared to infected controls, vaccinated mice displayed reduced weight loss and infiltration of neutrophils within the airways, as well as reduced viral loads in bronchoalveolar lavages. Interestingly, vaccinated mice displayed increased activation of T cells within the airways and no significant antiviral antibodies at the time of sacrifice, which suggested that the rBCG-N vaccine induced a strong antiviral T cell immunity. Indeed, ex vivo re-stimulation of splenic T cells at 28 days post-vaccination activated a repertoire of T cells secreting IFN-gamma and IL-17, which further suggest that the rBCG-N vaccine induced a mixed, CD8+ and CD4+ T cell response capable of both restrain viral spread in the lungs and prevent the pulmonary pathology.

  6. Radiation induced cancer following radiation therapy

    Radiation induced cancer following radiation therapy for various organ sites as well as our recent data of radiation-induced cancer following radiation therapy for cervical cancer were summarized and analyzed. Radiation induced cancers were apparent in radiation therapy for various cancers. However, the benefit of radiation therapy is not weaken by the demerit of second cancer. The potential diagnostic impact of differentiation between late recurrence with same histology and radiation-induced cancer was discussed. From analysis, late recurrence of about 10 years following radiation therapy seems to be radiation induced cancer. (author)

  7. Investigation of the Cellular and Molecular Mechanisms of Radiation-induced Bystander Effects

    Furlong, Hayley

    2014-01-01

    The overall aim of this study was to investigate the cellular and molecular mechanisms involved in radiation-induced bystander effects in HaCaT cells, predominantly at low-doses of irradiation. They do not follow the original dose-response theory and exhibit a unique cascade of signalling events, which are under intense investigation for radiation risk purposes. An in vitro system was first used to observe the bystander effect, comparing two cell viability assays while measuring apoptotic cel...

  8. Ultraviolet radiation-induced non-melanoma skin cancer in the Crl:SKH1:hr-BR hairless mouse: augmentation of tumor multiplicity by chlorophyllin and protection by indole-3-carbinol.

    Cope, R B; Loehr, C; Dashwood, R; Kerkvliet, N I

    2006-05-01

    Over 1 million new cases of ultraviolet radiation-induced non-melanoma skin cancers (NMSC) per year now occur in the USA and the incidence of these diseases continues to increase. New preventative strategies are required. The hypothesis tested was that dietary administration of the putative cancer chemopreventatives sodium-copper-chlorophyllin (Chlor) or indole-3-carbinol (I3C) would inhibit UV-induced skin carcinogenesis in the Crl:SKH1:hr-BR hairless mouse. Groups of 20 mice were pre-fed isocaloric/isonutritive 20% corn-oil AIN-76a based diets that contained either Chlor (1.52 g%), I3C (5.08 g%) or no chemopreventative (control) for 2 weeks followed by exposure of their dorsal skin to a 10 week incremental, sub-erythemal, carcinogenic simulated solar UV exposure regime. Feeding was continued for the duration of the experiment. Matched non-UV exposed dietary groups were also included in the experimental design. The diets had no significant (p > 0.05) effect on body weight, feed consumption, cutaneous methanol-extractable UV photoprotective substances or on cutaneous UV-reflective characteristics. By day 180, UV-irradiated mice fed the Chlor had a significantly (p 0.05) affect UV-induced systemic suppression of contact hypersensitivity responses. These results demonstrate augmentation of the UV-induced cutaneous carcinogenic process by dietary chlorophyllin and protection from this carcinogenic process by indole-3-carbinol via mechanisms that do not involve changes in skin optical properties, modulation of photoimmunosuppression or caloric/nutrient effects. PMID:16685328

  9. Effects of low doses: Proof and inferences

    It is essential to discuss the plausibility of 'low-dose' effects from environmental exposures. The question, nonetheless, is wrongly labelled, for it is not the magnitude of the dose that matters, but rather the effect. The question thus concerns 'doses with low effects'. More precisely, because the low effects on large populations are not that small, even when epidemiological tools fail to detect them, it would be more accurate to talk about 'doses with undetectable or barely detectable effects'. Hereafter, we describe this 'low-effect dose' concept from the viewpoint of toxicology and epidemiology and discuss the fragile boundary line for these low-effect doses. Next, we review the different types of inference from observed situations (i.e., with high effects) to situations relevant to public health, to characterize the level of confidence to be accorded them. The first type is extrapolation - from higher to lower doses or from higher to lower dose rates. The second type is transposition - from humans to other humans or from animals to humans. The third type can be called 'analogy' as in 'read across' approaches, where QSAR (Quantitative Structure Activity Relationship) methodology can be used. These three types of inferences can be based on an estimate of the 'distance' between observed and predicted areas, but can also rely on knowledge and theories of the relevant mechanisms. The new tools of predictive toxicology are helpful both in deriving quantitative estimates and grounding inferences on sound bases. (author)

  10. low dose irradiation growth in zirconium

    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.)

  11. The genetic risk at low doses

    How are we to assess the genetic risk to man resulting from exposure to low doses of irradiation from the environment of nuclear power plants. The team of Brewen and Preston showed that there was a decrease by a factor of four in the rate of chromosomal aberrations existing in germinal cell line as compared with somatic cell (leukocyte) line. They subsequently demonstrated the importance of the selection process taking place at the time of gametogenesis. However, their study went only as far as a 50-rem dose. Applying fractionation of a 275-rem dose (55 daily sessions of 5 rem each), Sheridan was unable to induce in mice either dominant or recessive mutations in quantities greater than in the controls; the recessives would appear to have been fewer, but the difference was not significant. Nor did experiments by various teams involving systematic irradiation (either chronic or acute) of several tens of generations of mice and rats succeed in producing mutants over the different generations. In order to affect fertility and also mortality before weaning, it is necessary to achieve single doses of the order of 500 rem. Results of this kind, which show the existence of both repair and selection, are reassuring, although they are obtained at dose rates that have nothing in common with those which are relevant to the environment. They support the assumption that no deleterious effect is present in the latter case. (author)

  12. Assessment of the expected harm from prenatal irradiation with low doses and low dose rates

    The validity of the coefficients, suggested by ICRP (Publication 45) for assessment of the risk from prenatal irradiation with low doses and low dose rates is discussed. This includes: development of lethal and curable cancer, severe genetic defects, death before implantation and retarded mental development. Summarizing the individual assessment, the total harm from prenatal irradiation with 1 mvSv have been estimated at 4,9.104 lost years. The expected harm from the additional irradiation of the Bulgarian population during the first year after the Chernobyl accident is evaluated on that basis, taking into account the number of expected pregnancies among Bulgarian women in reproductive age and the individual effective equivalent doses. 15 refs

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

    Zhang, Xin, E-mail: xinzhang@gmail.com [Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, School of Medicine, West Wenhua Road No. 107, Ji' nan, Shandong 250012 (China); Li, Xiaoyan, E-mail: xiaoyanli1219@gmail.com [Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, West Wenhua Road No. 107, Ji' nan, Shandong 250012 (China); Zhang, Ning, E-mail: zhangning0816@gmail.com [Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, West Wenhua Road No. 107, Ji' nan, Shandong 250012 (China); Yang, Qifeng, E-mail: qifengy@gmail.com [Department of Breast Surgery, Qilu Hospital, Shandong University, School of Medicine, West Wenhua Road No. 107, Ji' nan, Shandong 250012 (China); Moran, Meena S., E-mail: meena.moran@yale.edu [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States)

    2011-08-19

    Highlights: {yields} Low doses ionizing irradiation would enhance the invasiveness of breast cancer cells by inducing EMT. {yields} Low doses ionizing radiation induced morphologic changes in breast cancer cells. {yields} Low doses ionizing radiation led to upregulation of mesenchymal markers and down-regulation of epithelial markers. {yields} 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.

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

    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.

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

    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.

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

    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 No.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 No.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.

  17. Microdosimetric approach to the anlysis of cell responses at low dose and low dose rate

    An approach to the problem of radiation response is proposed and described by which effects produced at low doses and dose rates can be understood as the consequences of radiation absorption events in the nucleus of a single relevant cell and in its DNA. Radiation quality appears as the consequence of two related probabilities, that of energy deposition in the cell nucleus and that of energy deposition in DNA. The starting point is a ''gross sensitive volume'', GSV, identified with an average mammalian cell nucleus and composed of smaller sensitive volumes, identified with some critical parts of the DNA genome. The GSV leads to the definitions of an ''elemental dose'', the ''integral probability of responses of the GSV population'', and the smaller volumes lead to a ''relative local efficiency''. This approach is applied to various biological endpoints illustrating its merits. The level of dose below which the fraction of hit cells depends linearly on absorbed dose and is independent of dose rate, is delineated. Finally, guide lines for designing low dose and low dose rate experiments are proposed. (author)

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

    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.)

  19. Radiation induced corrosion of copper

    Björkbacka, Åsa

    2015-01-01

    The process of radiation induced corrosion of copper is not well understood. The most obvious situation where the knowledge of this process is crucial is in a deep repository for high level spent nuclear fuel where the fuel will be sealed inside copper canisters. The radiation will penetrate the canisters and be absorbed by the surrounding environment. In this study gamma irradiations of polished and pre-oxidized copper cubes in anoxic pure water, air of 60-100 % RH and in humid argon were pe...

  20. Oxidative stress, radiation-induced damage and

    Sevil KILÇIKSIZ

    2008-01-01

    Full Text Available Many of the regulatory changes in cells after irradiation may be mediated through the production and interaction of classical signal transduction, free radicals, and DNA damage. The protection of normal tissues may provide an increase in tumor control by providing an increase in the radiation dose. N-acetylcysteine (NAC is a potent free radical scavenger and may be beneficial in conditions of glutathione (GSH depletion and free radical formation during oxidative stress. NAC has been shown to prevent radiation-induced DNA breaks and to have a place in cancer prevention. It may be suggested that NAC decreases irradiation-induced genocytotoxicity. NAC has not yet been widely used clinically for this purpose; further experimental studies are needed for determining its radioprotector effect. In the current review, we aimed to discuss the radioprotective potential of NAC.

  1. Effects of low doses of ionizing radiation

    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.)

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

    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 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.

  3. Induction of nuclear factor kB after low-dose ionizing radiation involves a reactive oxygen intermediate signaling pathway

    Reactive oxygen intermediates (ROIs) have been found to be the messengers in the activation of the kB transcription regulator in mitogen- or cytokine-stimulated cells, operating in conjunction with or independently of various other mechanisms; these include Ca++-dependent and PKC-dependent cytoplasmic signaling pathways. We have recently reported that low-dose ionizing radiation induces NF-kB in human lymphoblastoid 244B cells. Since ionizing radiation generates free radicals in cells, we have investigated whether the ROIs generated by ionizing radiation induce NF-kB activity, and also whether they do so by a similar mechanism as in cells treated with PMA or H2O2. The results not only confirm a previous observation from our laboratory that low-dose ionizing radiation (0.1-2.0 Gy) activates kB transcription factor transiently with a maximal induction at 0.5 Gy exposure, but also demonstrate mechanistically that the activation of NF-kB by low-dose ionizing radiation can be inhibited considerably by the antioxidant N-acetyl-L-cysteine, indicating that at least the major part of the activation process is mediated by ROIs. These findings support the idea that ROIs can regulate the kB elements which in turn can serve as response elements for oxidant stress. 37 refs., 4 figs., 1 tab

  4. Theoretical epidemiology applied to health physics: estimation of the risk of radiation-induced breast cancer

    Indirect estimation of low-dose radiation hazards is possible using the multihit model of carcinogenesis. This model is based on cancer incidence data collected over many decades on tens of millions of people. Available data on human radiation effects can be introduced into the modeling process without the requirement that these data precisely define the model to be used. This reduction in the information demanded from the limited data on human radiation effects allows a more rational approach to estimation of low-dose radiation hazards and helps to focus attention on research directed towards understanding the process of carcinogenesis, rather than on repeating human or animal experiments that cannot provide sufficient data to resolve the low-dose estimation problem. Assessment of the risk of radiation-induced breast cancer provides an excellent example of the utility of multihit modeling procedures

  5. Factors that modify risks of radiation-induced cancer

    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)

  6. Factors that modify risks of radiation-induced cancer

    Fabrikant, J.I.

    1988-11-01

    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).

  7. Radiation-induced cardiovascular effects

    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.

  8. How relevant to radiation protection is the adaptive response mechanism?

    There is evidence that the phenomenon of adaptive response (AR) which results from a low dose exposure could modify the risk of a subsequent radiation exposure, and conceivably could even provide a net benefit rather than the putative radiation detriment at low doses. The AR has been widely observed in human and other mammalian cells exposed to low doses and low-dose rates. The phenomenon has been demonstrated at the level of one track per cell, the lowest insult a cell can receive. The AR to radiation has been shown to: (i) protect against the DNA damaging effects of radiation and many chemical carcinogens; (ii) increase the probability that improperly repaired cells will die by apoptosis, thereby reducing risk to the whole organism; (iii) suppress both spontaneous- and radiation-induced neoplastic transformation in vitro; and (iv) reduce life-shortening in mice that develop myeloid leukemia as a result of a radiation exposure. It remains unclear, however, if the AR will be relevant to either risk assessment or radiation protection. There is currently no evidence of AR's influence on the incidence of radiogenic cancer in vivo although recent data indicate that adapting doses could lead to reduced risk in animal or human populations. Currently the existing dose control and dose management programs attempt to limit or eliminate even very low exposures, without evidence that such an approach has economic and societal benefits. Indeed, if adaptation from exposure to low doses provides the same responses in vivo as have been shown in vitro, then the current approach to protection against low doses may be counterproductive However, the demonstrated principles of the adaptive response to radiation in vitro will not likely influence the long held current formulation of radiation protection practices until the biological action of accumulated low doses of radiation in vivo and its impact on the modulation of radiation carcinogenesis are better understood. (author)

  9. Prevention of radiation induced taste aversion in rats

    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 (97±2%) 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 (62±3%). 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)

  10. Low dose mercury toxicity and human health.

    Zahir, Farhana; Rizwi, Shamim J; Haq, Soghra K; Khan, Rizwan H

    2005-09-01

    Post Minamata incident there has been awareness about mercury toxicity even among the general public. Previous researches contributed a vast amount of data regarding acute mercury exposure, but gradually information about the low dose [Ninomiya, T., Ohmori, H., Hashimoto, K., Tsuruta, K., Ekino, S., 1995. Expansion of methylmercury poisoning outside minamata: an epidemiological study on chronic methylmercury poisoninig outside of Minamata. Environ. Res. 70 (1) 47-50; Lebel, J., Mergler, D., Lucotte, M., Amorim, M., Dolbec, J., Miranda, D., Arantes, G., Rheault, I., Pichet, P., 1996. Evidence of early nervous system dysfunction in Amazonian populations exposed to low-levels of methylmercury. Neurotoxicology 17 (1) 157-167] of mercury toxicity has been trickling in. With mercury contaminating rain-, ground- and sea-water no one is safe. Polluted water leads to mercury laced fish, meat and vegetable. In aquatic environments, inorganic mercury is microbiologically transformed into lipophilic organic compound 'methylmercury'. This transformation makes mercury more prone to biomagnification in food chains. Consequently, populations with traditionally high dietary intake of food originating from fresh or marine environment have highest dietary exposure to mercury. Extensive research done on locals across the globe have already established this, persons who routinely consume fish or a particular species of fish are at an increased risk of methylmercury poisoning. The easy access of the toxicant to man through multiple pathways air, water, food, cosmetic products and even vaccines increase the exposure. Foetus and children are more susceptible towards mercury toxicity. Mothers consuming diet containing mercury pass the toxicant to foetus and to infants through breast milk. Decreased performance in areas of motor function and memory has been reported among children exposed to presumably safe mercury levels. Similarly, disruption of attention, fine motor function and verbal memory was also found in adults on exposure to low mercury levels. It is an occupational hazard for dental staff, chloralkali factory workers and goldminers, etc. Mercury has been found to be a causative agent of various sorts of disorders, including neurological, nephrological, immunological, cardiac, motor, reproductive and even genetic. Recently heavy metal mediated toxicity has been linked to diseases like Alzeihemer's, Parkinson's, Autism, Lupus, Amyotrophic lateral sclerosis, etc. Besides this, it poses danger to wildlife. Therefore, it becomes imperative to spread the information regarding the threat of mercury exposure amongst the scientists and masses. PMID:21783611

  11. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of ≥5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. (orig.)

  12. Low-dose radiation response of the p21WAF1/CIP1 gene promoter transduced by adeno-associated virus vector.

    Nenoi, Mitsuru; Daino, Kazuhiro; Ichimura, Sachiko; Takahash, Shin-ichiro; Akuta, Teruo

    2006-10-31

    In cancer gene therapy, restriction of antitumor transgene expression in a radiation field by use of ionizing radiation-inducible promoters is one of the promising approaches for tumor-specific gene delivery. Although tumor suppressor protein p53 is induced by low doses (p53-target gene promoter, such as that of the p21 gene. This is mainly because the transiently transfected promoter of p53-target genes is not much sensitive to radiation. We examined the response of the p21 gene promoter to low-dose radiation when transduced into a human breast cancer cell line MCF-7 by use of recombinant adeno-associated virus (rAAV) vectors. It was shown that the p21 gene promoter transduced by rAAV vectors was more highly radiation-responsive than that transiently transfected by electroporation. A significant induction of the p21 gene promoter by radiation of low doses down to 0.2 Gy was observed. When cells were transduced with the p21 gene promoter-driven HSVtk gene by rAAV vector, they were significantly sensitized to repetitive treatment with low dose radiation (1 Gy) in the presence of the prodrug ganciclovir. It was therefore considered that the p21 gene promoter in combination with a rAAV vector is potentially usable for the development of a low-dose radiation-inducible vector for cancer gene therapy. PMID:17079872

  13. Theory and data for estimating the risk at low doses and dose rates

    Radiological protection bases the Linear Non-Threshold (LNT) model for estimating the risk at low doses and dose rates. Incorporation of risk concept into radiological protection brought the LNT model that implies that there is no wholly ''safe'' dose of radiation. Epidemiological studies have provided statistically reasonable basis for the LNT model for radiological protection. In estimating the cancer risk at low dose and dose rate using the atomic bomb survivor data, the dose and dose rate effectiveness factor (DDREF) is estimated. Theoretical and methodological issues on the DDREF emerged from the biological points of view. The International Commission of Radiological Protection (ICRP) indicated that uncertainty analysis of the risk suggests that the LNT model is more reasonable than the threshold model with uncertain threshold doses. The latest epidemiological studies at low dose rates support LNT models. The gap between biology and epidemiology is increasing although some issues already exist in risk estimation at low doses. To get more scientifically reliable risk estimate, the dialogue between biology and epidemiology is needed to construct the framework of risk estimation such as biologically-based carcinogenesis models. (author)

  14. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R., E-mail: akennedy@mail.med.upenn.edu

    2014-03-15

    Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2Gy of whole-body proton or gamma radiation and monitored for 30days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ?1.5Gy, with 100% mortality at 2Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.

  15. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD50) of the ferrets was established at ∼1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals

  16. Research on enhanced low dose rate sensitivity effect for PMOSFET used in space dosimeter

    In this paper, the ionizing damage effects and annealing behavior of foreign manufacturer production PMOSFET in 4007 circuit under different dose rates and bias conditions were investigated. The experiment results show that the PMOSFETs threshold voltage negative shift is more obvious with the dose rate reduction. It is thought that the PMOSFET of this kind of type has enhanced low dose rate sensitivity (ELDRS) effect. The PMOSFETs threshold voltage does not recover at room annealing after high dose rate exposure and continues the negative drifting, which is due to the radiation-induced interface traps buildup. The annealing temperature is higher, the threshold voltage return drift is more obvious. Zero bias is the worst bias condition. (authors)

  17. The redox homeostasis system in radiation-induced genome instability

    The participation of the redox homeostasis system in the formation of the radiation-induced genome instability and new data of literature, that give a direct evidence the presence of this instability in vivo, is considered. The O2- radical, H2O2 and NO radical role as signal molecules, that trigger the cascade of active responses to change of redox status of the cells, are discussed. The reactive oxygen species (ROS) reorganize the membrane physico-chemical system of cell metabolism regulation. The data about changes in ROS generation system, including NO, that lead to genome instability after ionizing irradiation even in low doses, are analyzed. It is noted, that the radiation-induced genome instability and ROS production increase may be observed both in direct irradiated cells and their progeny and in the cells, that are not find oneself in ionization tracks, and their progeny. There evidences that the genome instability of irradiated cell progeny is maintained by the increases ROS production

  18. New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies

    Noriyuki Yanagida

    2016-04-01

    With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods.

  19. A reasonable price to prevent death caused by radiation induced neoplasms

    This paper discusses the risk based prioritization of radiation protection procedures versus the reduction of radiation induced neoplasms. An economic valuation of death reduction is necessary in many situations

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

    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-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, 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-1β 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-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β 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 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (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-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  1. Radiation-induced clastogenic plasma factors

    Ionizing irradiation induces chromosomal aberrations in directly exposed cells and is known to have mutagenic and carcinogenic potential for the exposed host. Under controlled conditions, we examined whether such clastogenic effects of irradiation might be due in part to radiation-induced plasma factors. Irradiated cells and sera from CF-Nelson rats were used at 15 min, and 1, 7, 14, and 56-70 days after total body irradiation (250 R, n . 67 or 400 R, n . 39). Control rats (n . 44) served as donors of nonirradiated sera and cells. In addition, sera from six rats were irradiated (250 R or 400 R) in vitro. On the average, 298 metaphases from six rats were studied at each time-point. Cytogenetic abnormalities observed included chromatid- and chromosome-type lesions and hyperdiploidy. The frequency of abnormalities was comparable at both radiation doses. Nonirradiated cells exposed in vitro to irradiated serum (15 min postirradiation) exhibited a 36- to 48-fold increment in hyperdiploidy (p . 0.0001) and a 2.- to 2.2-fold rise in chromatid gaps and breaks (p less than 0.01), but none of the chromosome-type aberrations seen in cells exposed to radiation. The clastogenic activity of irradiated plasma persisted in circulation for the 10-wk duration of the study and was not abrogated by dilution with nonirradiated serum. Serum irradiated in vitro was not clastogenic. This study shows that irradiation of rats results in the prompt appearance of clastogenic activity in their plasma. This activity is not due to radiation-induced depletion of protective factors nor to chemical-physical changes of normal plasma components, but results from circulating factors released by irradiated cells

  2. Radiation-induced thermoacoustic imaging

    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

  3. The struggle in the USA over low doses and risks. Forerunner of a discussion in Europe?

    In the USA hot-tempered discussions are going on on the subject of radiation protection. In particular, a recommendation (position statement) of the Health Physics Society on the risks of low dose radiation and dose-response relationships (referred to as the so-called linear non-threshold model or LNT). It is argued that the LNT is an oversimplification of the dose-response relationship and results in an overestimation of health risks in the low dose range. However, the ICRP insists on following the point of view regarding the LNT model. 2 figs., 7 refs

  4. International Conference on Low Doses of Ionising Radiation

    Is there a threshold? and is a little radiation good for you? were two questions raised at the International Conference on Low Doses of Ionising Radiation : Biological Effects and Regulatory Control, jointly organised by the IAEA and WHO, and convened in Seville, Spain, over 17-21 November 1997. The answer to both these questions appears to be 'Maybe', but the answer has no present implications for radiation protection practice and regulation. The conference which had over 500 participants from 65 countries, was organised around ten fora which explored basic molecular mechanisms of radiation effects, through to radiation protection principles and implementation in practices and interventions. Each forum was introduced by an overview presentation by an invited keynote speaker. Brief presentations of a few of the proffered papers followed, and then open discussion. There was opportunity for all proffered papers to be presented as posters. The fora, which occupied 3 full days, were preceded by reports on biological effects of radiation from international orgnaisations, and on related international conferences held in the recent past. The fora were followed by round table presentations of regulatory control and scientiFic research, and a summary session drawing together conclusions on the topic areas of the conference. (author)

  5. Final report of the group research. Studies on the low dose radiation risk and carcinogenesis. (Research Group of NIRS)

    This report concerns investigations on the title conducted by 3 subgroups of National Institute of Radiological Sciences (NIRS) during the period of April 1996-March 2001. The report involves summary reports from the subgroups for Experimental study on long-term effects of low dose radiation as a basis of risk assessment, Effects of genetic factors on radiation carcinogenesis and Studies on molecular mechanisms of radiation carcinogenesis. Significant results are as follows: Life-span risk analysis of low dose radiation in juvenile mice; Finding that Ikaros gene mutation is highly specific for radiation carcinogenesis as revealed by loss of heterozygosity (LOH) analysis in radiation-induced T-cell lymphoma and presentation of the dose-effect relationship in the lymphoma development in Scid mice; and Findings that Noch1 gene plays an important role in the lymphoma development and partial deletion of the gene occurs in relation to Scid mutation. (N.I.)

  6. Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease

    Littley, M.D.; Shalet, S.M.; Beardwell, C.G.; Ahmed, S.R.; Sutton, M.L. (Christie Hospital, Manchester (UK))

    1990-10-01

    Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. In this series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy. (author).

  7. Radiation Induced Degradation of Galactomannan Polysaccharides

    Galactomannans are neutral polysaccharides that occur in substantial amounts in the endosperm of the seeds of some leguminous plants. Structurally they consist of a β(1-4)-D-mannose backbone to which galactose units are attached α(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, γ-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

  8. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    Simon, James; Nachtigall, Lila; Ulrich, Lian G; Eugster-Hausmann, Michaela; Gut, Robert

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  9. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    Simon, James; Nachtigall, Lila; Ulrich, Lian G; Eugster-Hausmann, Michaela; Gut, Robert

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  10. Low dose and the adaptation process in human lymphocytes

    Low doses of ionizing radiation, which normally lead to a decrease in damage caused by subsequent exposure, may also interact synergistically with mutagenic treatment. The adaptive response of human lymphocytes to low doses of ionizing radiation has been studied in two donors, using blood drawn at 9 a.m and 5 p.m to test possible circadian variations. (UK)

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

    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)

  12. Radiation-induced breast cancer

    Concern is expressed over a recent U.K. newspaper report (The Times, 21 January 1977, 5) on the possible hazards of mammography, as women may over-react to the extent of refusing mammography. The problems of radiation risk estimates, particularly at low dose levels, are very briefly reviewed. Recent improvements in mammography techniques have minimised the radiation hazard. Conflicting reports of the mortality rates following mammography screening programmes are discussed. In England and Wales, breast cancer is the commonest cause of death in women aged 35 to 54, and it would be unfortunate if the possible benefits of screening were denied to this age group before the latest mammographic techniques have been fully evaluated. (U.K.)

  13. [Indications for low-dose CT in the emergency setting].

    Poletti, Pierre-Alexandre; Andereggen, Elisabeth; Rutschmann, Olivier; de Perrot, Thomas; Caviezel, Alessandro; Platon, Alexandra

    2009-08-19

    CT delivers a large dose of radiation, especially in abdominal imaging. Recently, a low-dose abdominal CT protocol (low-dose CT) has been set-up in our institution. "Low-dose CT" is almost equivalent to a single standard abdominal radiograph in term of dose of radiation (about one sixth of those delivered by a standard CT). "Low-dose CT" is now used routinely in our emergency service in two main indications: patients with a suspicion of renal colic and those with right lower quadrant pain. It is obtained without intravenous contrast media. Oral contrast is given to patients with suspicion of appendicitis. "Low-dose CT" is used in the frame of well defined clinical algorithms, and does only replace standard CT when it can reach a comparable diagnostic quality. PMID:19754008

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

    Shawna M. Hengel

    2014-07-01

    Full Text Available To assess responses to low-dose ionizing radiation (LD-IR exposures potentially encountered during medical diagnostic procedures, nuclear accidents or terrorist acts, a quantitative proteomic approach was used to identify changes in protein abundance in a reconstituted human skin tissue model treated with 0.1 Gy of ionizing radiation. To improve the dynamic range of the assay, subcellular fractionation was employed to remove highly abundant structural proteins and to provide insight into radiation-induced alterations in protein localization. Relative peptide quantification across cellular fractions, control and irradiated samples was performing using 8-plex iTRAQ labeling followed by online two-dimensional nano-scale liquid chromatography and high resolution MS/MS analysis. A total of 107 proteins were detected with statistically significant radiation-induced change in abundance (>1.5 fold and/or subcellular localization compared to controls. The top biological pathways identified using bioinformatics include organ development, anatomical structure formation and the regulation of actin cytoskeleton. From the proteomic data, a change in proteolytic processing and subcellular localization of the skin barrier protein, filaggrin, was identified, and the results were confirmed by western blotting. This data indicate post-transcriptional regulation of protein abundance, localization and proteolytic processing playing an important role in regulating radiation response in human tissues.

  15. The effect of low dose-rate irradiation on the microstructure of 304 stainless steel

    Changes in mechanical and corrosion properties caused by the development of radiation-induced microstructure have relevance to the aging and lifetime extension of light water reactors (LWR's). However, much of the current data related to microstructural development in irradiated metals are generated from studies carried out at much higher dose-rates than encountered in LWR's. An opportunity exists to study the influence of low dose-rate irradiation on microstructural development for a variety of structural and surveillance materials extracted from the experimental breeder reactor EBR-II. In this study, irradiated 304 stainless steel hexagonal ''hex'' duct material is examined in order to compare microstructure in the dose-rate range of 10-7-10-9 dpakec. The samples, taken from the reflector locations in EBR-II, experienced a total dose between 10 and 12 dpa at a temperature of ∼375 C. Transmission electron microscopy (TEM) results reveal that there is a moderate dose-rate effect on microstructural development for samples irradiated in the range of 2 x 10-8 to 4 x 10-8 dpa/sec, however a substantial dose rate-effect exists between dose-rates of 2 x 10-8 and 1 x 10-9 dpa/sec Transmission electron microscopy (TEM) results will detail the development of the microstructure in terms of radiation-induced cavities, dislocations, and precipitates

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

    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)

  17. Injury to the blood-testis barrier after low-dose-rate chronic radiation exposure in mice

    Exposure to ionising radiation induces male infertility, accompanied by increasing permeability of the blood-testis barrier. However, the effect on male fertility by low-dose-rate chronic radiation has not been investigated. In this study, the effects of low-dose-rate chronic radiation on male mice were investigated by measuring the levels of tight-junction-associated proteins (ZO-1 and occludin-1), Niemann-Pick disease type 2 protein (NPC-2) and anti-sperm antibody (AsAb) in serum. BALB/c mice were exposed to low-dose-rate radiation (3.49 mGy h-1) for total exposures of 0.02 (6 h), 0.17 (2 d) and 1.7 Gy (21 d). Based on histological examination, the diameter and epithelial depth of seminiferous tubules were significantly decreased in 1.7-Gy-irradiated mice. Compared with those of the non-irradiated group, 1.7-Gy-irradiated mice showed significantly decreased ZO-1, occludin-1 and NPC-2 protein levels, accompanied with increased serum AsAb levels. These results suggest potential blood-testis barrier injury and immune infertility in male mice exposed to low-dose-rate chronic radiation. (authors)

  18. Spatial charge in low density polyethylene irradiated with low dose gamma-ray

    The research on the effect that radiation exerts on polymer insulation materials is indispensable for the improvement of safety in nuclear power generation, future nuclear fusion power generation and the expansion of space utilization, and it is important also as the technique for examining the electrical properties of polymer insulation materials themselves. However, in the case of carrying out irradiation at relatively low dose, the example of the research on the initial state of deterioration is few. Therefore, in this study, through the measurements of thermal pulse current, residual voltage, thermal stimulation currents, radiation-induced electrical conduction and other experiment, the behavior of spatial charges in the low density polyethylene irradiated with low dose gamma-ray was investigated. Gamma ray was irradiated at room temperature in the atmosphere at the dose rate of 200 Gy/h. The samples and the experimental method and the results are reported. In the irradiated samples, at a relatively low electric field of 0.1 MV/cm, hetero spatial charges were formed near both electrodes. In the irradiation of 0.2 - 5 kGy, either many carriers are generated or the mobility of carriers increases, which is one of the causes of initial deterioration. (K.I.)

  19. Human health effects of low doses of ionizing radiation: the BEIR III controversy

    Controversy in the BEIR III Subcommittee on Somatic Effects concerning human health effects of low doses of low-LET radiation has centered on (a) the appropriate dose-response relationship by which extrapolation to low doses of data obtained at relatively high doses should be governed, and (b) the appropriate human evidence which should be the basis of estimation of lifetime cancer risk from radiation exposure. It is shown that the use of the linear no-threshold dose-response relationship for extrapolation purposes is an excellent approximation that is in agreement with widely accepted fundamental radiobiological principles. The appropriate human data for derivation of cancer risks are the composite age-specific risks derived from all epidemiologic studies of human cancer resulting from partial-body and whole-body radiation exposure; this composite is in good agreement with the currently available cancer incidence dose-response data obtained from the Nagasaki Tumor Registry. The current version of BEIR III significantly underestimates the radiation-induced cancer risk because it ignores the effect of high-dose-rate, low-LET radiation on cell survival in relation to cancer induction probability, and because it emphasizes cancer mortality rather than cancer incidence. The controversy and the way in which it was resolved raises important questions about how the public and its representatives can in the future obtain objective scientific evaluations of issues that may have significant economic, social, and political implications

  20. Modification in the Expression of Mre11/Rad50/Nbs1 Complex in Low Dose Irradiated Human Lymphocytes

    Singh, Sompal; Bala, Madhu; Kumar, Raj; Kumar, Anil; Dhiman, SC

    2009-01-01

    Despite the fact that high doses of radiation are detrimental, low dose radiation (LDR) often protects the organism against a subsequent exposure of lethal doses of radiation. Present study was undertaken to understand the role of Mre11, Rad50 and Nbs1 genes in the low dose radio-adapted human peripheral blood mononuclear cells (PBMCs). Optimum time interval between low dose (0.07 Gy) and high dose (5.0 Gy) of 60Co-γ-radiation was observed to be 5.0 hours, at which PBMCs showed maximum LDR in...

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

    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 μM 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 (0,5-1μM) reduced the cytotoxicity of alpha particles, depending on the compound, incubation time, cell line treated and 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.

  2. Suppressive effect of low dose rate radiation on tumorigenesis in mice

    Irradiation with low dose/dose rate irradiation is known to stimulate a number of biological functions in vitro and in vivo, including anti-oxidative capacity, DNA damage repair, the process of apoptosis, and immune responses. Each of these functions may work in a suppressive manner in the process of tumorigenesis. To examine this possibility we have looked into the effects of low dose rate irradiation on the process of chemically induced or radiation-induced tumorigenesis in mice, using our long-term low dose rate irradiation facility, which is equipped with a 370 GBq 137 Cs source built in a clean room to allow chronic irradiation of mice under a clean conventional condition. A group of 5-week-old female ICR mice, 35 in each group, were irradiated at 2.6, 0.95, or 0.30 mGy/hr for 35 days. The mice were then injected in the groin with 0.5 mg of 20-methylcholanthrene dissolved in olive oil and irradiation was continued. A statistically significant suppression of cumulative tumor incidences up to 216 days after MC injection was observed in the group irradiated with 0.95 mGy/hr. The suppression of tumor incidence or the delay in tumor appearance was also observed in B6C3F1 and C57BL/6N strain. Thymic lymphomas were induced in 10-week-old C57BL/6N female mice by 4 weekly X-irradiations (1.8 Gy at 2.0 Gy/min). The continuous irradiation, from 5th week of age to 13th, at 0.95 mGy/hr delayed the timing of the appearance of the thymic lymphomas. These results indicate the suppressive effect of the low dose rate irradiation on the process of tumor induction initiated by at least two types of agents: methylcholanthrene and high dose radiation. This work has been performed in collaboration with T. Iwasaki, Y. Hoshi, T. Nomura, Y. Ina, T. Yamada, and H. Tanooka, Low Dose Radiation Research Center, Central Research Institute of Electric Power Industry

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

    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 γ-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.

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

    Kovačević 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.

  5. Mechanisms and biological importance of photon-induced bystander responses. Do they have an impact on low-dose radiation responses

    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 γ-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 by-stander 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. (author)

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

    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 γ-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.

  7. Pre-irradiation at a low dose-rate blunted p53 response

    Full text: We have studied whether the p53-centered signal transduction pathway induced by acute radiation is interfered with chronic pre-irradiation at a low dose-rate in human cultured cells and whole body of mice. In squamous cell carcinoma cells, we found that a challenge irradiation with X-ray immediately after chronic irradiation resulted in lower levels of p53 than those observed after the challenge irradiation alone. In addition, the induction of p53-centered apoptosis and the accumulation of its related proteins after the challenge irradiation were strongly correlated with the above-mentioned phenomena. In mouse spleen, the induction of apoptosis and the accumulation of p53 and Bax were observed dose-dependently at 12 h after a challenge irradiation. In contrast, we found significant suppression of them induced by challenge irradiation at a high dose-rate when mice were pre-irradiated with chronic irradiation at a low dose-rate. These findings suggest that chronic pre-irradiation suppressed the p53 function through radiation-induced p53-dependent signal transduction processes. There are numerous papers about p53 functions in apoptosis, radiosensitivity, genomic instability and cancer incidence in cultured cells or animals. According to our data and other findings, since p53 can prevent carcinogenesis, pre-irradiation at a low dose-rate might enhance the predisposition to cancer. Therefore, it is possible that different maximal permissible dose equivalents for the public populations are appropriate. Furthermore, concerning health of human beings, studies of the adaptive responses to radiation are quite important, because the radiation response strongly depends on experience of prior exposure to radiation

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

    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 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)

  9. Radiation-induced heat diseases

    Pericardial lesions are the most frequent complications of thoracic radiotherapy; they occur in 2% to 30% of the cases depending on the publications. Acute pericarditis, which is the most common form, develops early or late and usually has a favourable course. Chronic pericarditis is divided into chronic pericardial effusion, the incidence of which is underestimated as it produces few or no symptoms, and chronic constrictive pericarditis, itself divided into 2 subgroups of different prognosis depending on the presence (pure fibrous pericarditis) or absence (constrictive sero-fibrous pericarditis) of underlying myocardial lesions. The incidence of myocardial lesions (''myocarditis'') varies from 4% to 13% in the literature. They have a minor clinical form characterized by arrhythmias or disorders of conduction and a major form as restrictive or congestive cardiomyopathy with or without cardiac failure. Lesions of the coronary vessels are probably underestimated in view of the results of recent necropsies. Radiation-induced vascular lesions and hyperlipidaemia seem to act synergetically in the genesis of atherosclerosis. Cardiac valve lesions are even less frequent, but here again their incidence seems to be underestimated by conventional diagnostic methods. Echocardiography, radionucleide angiography and exercise tests appear to be useful for the long-term monitoring of patients who had their chest irradiated