WorldWideScience

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

    International Nuclear Information System (INIS)

    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 ?-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose ?-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy ?-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

  2. Low-Dose Radiation Induces Genes Promoting Cell Survival

    International Nuclear Information System (INIS)

    Apoptosis is an important process controlling homeostasis of the body. It is influenced by stimuli constantly arising from the external and internal environment of the organism. It is well known that radiation could induce apoptosis of cells in vitro and in vivo. However, the dose-effect relationship of apoptosis extending to the low-dose range has scarcely been studied. Here, the molecular basis of the phenomenon is explored by examining the changes in expression of some of the proapoptotic and antiapoptotic genes

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-15

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

  6. Mechanistic Basis for Nonlinear Dose-Response Relationships for Low-Dose Radiation-Induced Stochastic Effects

    OpenAIRE

    Scott, Bobby R.; Walker, Dale M.; Tesfaigzi, Yohannes; Schöllnberger, Helmut; Walker, Vernon

    2003-01-01

    The linear nonthreshold (LNT) model plays a central role in low-dose radiation risk assessment for humans. With the LNT model, any radiation exposure is assumed to increase one’s risk of cancer. Based on the LNT model, others have predicted tens of thousands of deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Here, we introduce a mechanism-based model for low-dose, radiation-induced, stochastic ...

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

    OpenAIRE

    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.

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

    International Nuclear Information System (INIS)

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

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

    CERN Document Server

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Gridley, Daila S.

    2008-10-31

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

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

    International Nuclear Information System (INIS)

    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

  12. Will Radiation-Induced Bystander Effects or Adaptive Responses Impact on the Shape of the Dose Response Relationships at Low Doses of Ionizing Radiation?

    OpenAIRE

    Morgan, William F.

    2006-01-01

    Radiation induced bystander effects and adaptive responses are two phenomena that modulate cellular responses to low doses of ionizing radiation. Bystander effects generally exaggerate the effects of low doses of radiation by eliciting detrimental effects in nonirradiated cells, thus making the target for radiation effects greater than the volume irradiated. Adaptive responses on the other hand indicate that low doses of radiation can reduce damage induced by a second challenging dose. The po...

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

    International Nuclear Information System (INIS)

    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 ?-rays-induced MNs to estimate the low dose radiation-exposed workers as a screening test

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

    International Nuclear Information System (INIS)

    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 excellent linear relations with total dose (<2.0 Gy) with little dose rate dependence. Experimental results show that the sensitivity (induced loss (dB) per meter fiber per Gy) of 5 mol% P-doped silica fiber is more than 30 times greater than that of a standard multi-mode (MM) communication fiber. The results suggest that P-doped silica fiber is a good candidate as a sensing component in fiber optic dosimetry, especially for radiation therapy applications

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

    Directory of Open Access Journals (Sweden)

    ?urovi? Branka 1

    2004-01-01

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

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

    International Nuclear Information System (INIS)

    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)

  17. [Low doses of ionizing radiation-induced apoptotic nature of erythrocyte hemolysis].

    Science.gov (United States)

    Krylov, V N; Deriugina, A V; Pleskova, S N; Kalinin, V A

    2015-01-01

    It is established that exposure of the red blood cells of the rats to low doses of ionizing radiation (0.04; 0.08; 0.16; 0.25 and 0.33 mGr) leads to non-linear changes in the processes of lipid peroxidation in the membrane of erythrocytes, their electrophoretic mobility, osmotic resistance. In a dose range from 0.08 to 0.16 mGr with ionizing radiation apoptosis that determines a temporary slowing of the process of hemolysis and stabilization of erythrocytes that is confirmed by morphological changes in erythrocytes is most likely triggered. PMID:25868347

  18. Low-dose ?-ray radiation induced seeds ultra-weak luminescence

    International Nuclear Information System (INIS)

    Cucumber seeds were irradiated with 60Co-? rays of 20 Gy, 30 Gy, 40 Gy, and tomato seeds were irradiated with 60Co-? rays of 10 Gy, 20 Gy, 40 Gy. Then ultra-weak luminescence intensity of dry seeds and sprout seeds were measured in 6, 12, 24, 48, 72 hours after irradiation. The results showed that ultra-weak luminescence intensity increased with the irradiation dose in the range of low-dose. Luminescence intensity at germination stage was stronger than that of dry seeds. Luminescence intensity of treated tomato seeds was higher than other dose treatments and CK

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Low-dose ionizing radiation induces mitochondrial fusion and increases expression of mitochondrial complexes I and III in hippocampal neurons.

    Science.gov (United States)

    Chien, Ling; Chen, Wun-Ke; Liu, Szu-Ting; Chang, Chuang-Rung; Kao, Mou-Chieh; Chen, Kuan-Wei; Chiu, Shih-Che; Hsu, Ming-Ling; Hsiang, I-Chou; Chen, Yu-Jen; Chen, Linyi

    2015-10-13

    High energy ionizing radiation can cause DNA damage and cell death. During clinical radiation therapy, the radiation dose could range from 15 to 60 Gy depending on targets. While 2 Gy radiation has been shown to cause cancer cell death, studies also suggest a protective potential by low dose radiation. In this study, we examined the effect of 0.2-2 Gy radiation on hippocampal neurons. Low dose 0.2 Gy radiation treatment increased the levels of MTT. Since hippocampal neurons are post-mitotic, this result reveals a possibility that 0.2 Gy irradiation may increase mitochondrial activity to cope with stimuli. Maintaining neural plasticity is an energy-demanding process that requires high efficient mitochondrial function. We thus hypothesized that low dose radiation may regulate mitochondrial dynamics and function to ensure survival of neurons. Our results showed that five days after 0.2 Gy irradiation, no obvious changes on neuronal survival, neuronal synapses, membrane potential of mitochondria, reactive oxygen species levels, and mitochondrial DNA copy numbers. Interestingly, 0.2 Gy irradiation promoted the mitochondria fusion, resulting in part from the increased level of a mitochondrial fusion protein, Mfn2, and inhibition of Drp1 fission protein trafficking to the mitochondria. Accompanying with the increased mitochondrial fusion, the expressions of complexes I and III of the electron transport chain were also increased. These findings suggest that, hippocampal neurons undergo increased mitochondrial fusion to modulate cellular activity as an adaptive mechanism in response to low dose radiation. PMID:26415228

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Commentary: ethical issues of current health-protection policies on low-dose ionizing radiation.

    Science.gov (United States)

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

    2014-05-01

    The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based on the assumption that every radiation dose increment constitutes increased cancer risk for humans. The risk is hypothesized to increase linearly as the total dose increases. While this model is the basis for radiation safety regulations, its scientific validity has been questioned and debated for many decades. The recent memorandum of the International Commission on Radiological Protection admits that the LNT-model predictions at low doses are "speculative, unproven, undetectable and 'phantom'." Moreover, numerous experimental, ecological, and epidemiological studies show that low doses of sparsely-ionizing or sparsely-ionizing plus highly-ionizing radiation may be beneficial to human health (hormesis/adaptive response). The present LNT-model-based regulations impose excessive costs on the society. For example, the median-cost medical program is 5000 times more cost-efficient in saving lives than controlling radiation emissions. There are also lives lost: e.g., following Fukushima accident, more than 1000 disaster-related yet non-radiogenic premature deaths were officially registered among the population evacuated due to radiation concerns. Additional negative impacts of LNT-model-inspired radiophobia include: refusal of some patients to undergo potentially life-saving medical imaging; discouragement of the study of low-dose radiation therapies; motivation for radiological terrorism and promotion of nuclear proliferation. PMID:24910586

  4. Low-dose Radiation-Induced Adaptive Response in Polychromatic Mice Erythrocyte as Measures by Acridine Orange Stained Micronucleus Assay

    International Nuclear Information System (INIS)

    The effect of conditioning pretreatment with 0.01Gy of gamma rays on micronucleated polychromatic erythrocyte (MN-PCE) induction by 2Gy of g-rays was determined in peripheral blood of C3H/He mice. The timing of their administration of challenge doses was 6 hr. The response was determined by scoring of Acridine orange due stained MN-PCEs. The results indicate that low dose gamma ray pretreatment does protect against MN-PCE induction by the challenge g-ray dose. Introduction: an adaptive response induced by low doses of ionizing radiation in vivo reported. Some research team reports that a reduction on MN-PCE of mice caused by the pretreatment was observed (1-4). However, there was variability in the amount of the response depending on the time and adaptive dose (3). This is important because the variation of MN-PCE frequency with time could lead to differences in the interpretation. In this study, differences in the biological effects within the priming dose ranges are discussed. (Author)

  5. Low-Dose Radiation-Induced Adaptive Response in Polychromatic Mice Erythrocyte as Measured by Acridine Orange Stained Micronuleus Assay

    International Nuclear Information System (INIS)

    The effect of conditioning pretreatment with 0.01Gy of gamma rays on micronucleated polychromatic erythrocyte (MN-PCE) induction by 2Gy of g-rays was determined in peripheral blood of C3H/He mice. The timing of their administration of challenge doses was 6hr. The response was determined by scoring of Acridine orange dye stained MN-PCEs. The results indicate that low dose gamma ray pretreatment does protect against MN-PCE induction by the challenge g-ray dose. Introduction: An adaptive response induced by low doses of ionizing radiation in vivo reported. Some research team reports that a reduction on MN-PCE of mice caused by the pretreatment was observed [1- 4]. However, there was variability in the amount of the response depending on the time and adaptive dose [3]. This is important because the variation of MN-PCE frequency with time could lead to differences in the interpretation. In this study, differences in the biological effects within the priming dose ranges are discussed. Materials and Methods: Specific pathogen free 5-week-old C3H/He mice, purchased from Shizuoka Laboratory Center (Japan), were kept in clean and conventional environment. When 6 weeks old, the animal were whole body irradiated using irradiator of IBL-437 (137Cs, 0.8Gy/min). After various time intervals, the two groups were administrated to adaptation dose and challenge dose of 0.01Gy and 2Gy, respectively. For experiments, sham-irradiated, only adaptive and challenge dose irradiated groups were run concurrently. Smears were stained and scored using Acridine orange dye method [2]. Statistically significant differences in MN-PCE frequency were determined by comparing tie individual values at each group with the respective control values (challenge dose irradiated group) by using the paired ttest. Results and Discussions: Induced MN by the challenge dose (2Gy) after the pretreatment with 0.01Gy is low to the one induced by the challenge dose alone. In the present study, this estimation for the experiment with a challenge dose of 2Gy suggests a response of nearly 15%. These results agree with some studies in which the induction of the adaptive response by g-rays was observed made in vivo in mice [1]. However, these results disagree with some studies using BALB/c mice. It is possible that genetic differences between C3H/He mice used in the present study and the BALB/c mice used in the previous one [3] could be explain the differential conditions. Moreover, the doses (0.025Gy) and the timing (2hr) of radiation exposures in previous study were different compared to presented here. These results indicate that low dose g-ray pretreatment doses protect against MN-PCE induction by the challenge g-ray dose depend on priming dose, adaptation time and mice strain. (Author)

  6. Estrogen Protects against Radiation-Induced Cataractogenesis

    OpenAIRE

    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-?-estradiol), when administered to ovariectomized rats commencing 1 week before ? 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...

  7. Halofuginone Mediated Protection against Radiation-Induced Leg Contracture

    OpenAIRE

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

    2009-01-01

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

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

    International Nuclear Information System (INIS)

    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.)

  9. Characterization of the adaptive response to ionizing radiation induced by low doses of X rays to human lymphocytes

    International Nuclear Information System (INIS)

    In previous studies we have shown that low doses of radiation from incorporated tritiated thymidine can make human lymphocytes less susceptible to the genetic damage manifested as chromatid breakage induced by a subsequent high dose of X rays. We have also shown that this adaptive response to ionizing radiation can be induced by very low doses of X rays (0.01 Gy; i.e., 1 rad) delivered during S phase of the cell cycle. To see if a low dose of X rays could induce this response in cells at other phases of the cell cycle, human lymphocytes were irradiated with 0.01 or 0.05 Gy before stimulation by phytohemagglutinin (G0) or with 0.01 Gy at various times after stimulation (G1), followed by 1.5 Gy (150 rad) at G2 phase. Although G0 lymphocytes failed to exhibit an adaptive response, G1 cells irradiated as early as 4 h after stimulation did show the response. Experiments were also carried out to determine how long the adaptive response induced by 0.01 Gy could persist. A 0.01-Gy dose was delivered to lymphocytes in the first S phase, followed by 1.5 Gy in the same or subsequent cell cycles. Lymphocytes receiving a 1.5-Gy dose at 40, 48, or 66 h after stimulation exhibited an adaptive response, whereas those receiving a 1.5-Gy dose at 90 or 114 h did not. Duplicate cultures containing bromodeoxyuridine showed that at 40 h all the lymphocytes were in their first cell cycle after stimulation, at 48 h half of the lymphocytes were in their first cell cycle and half in their second, and at 66 h 80% of the lymphocytes were in their third cell cycle. Thus, the adaptive response persists for at least three cell cycles after it is induced by 0.01 Gy of X rays

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

    Science.gov (United States)

    Azzam, Edouard

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

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

    Science.gov (United States)

    Nuth, Manunya; Kennedy, Ann R

    2013-07-01

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

  12. Characterization of the adaptive response to ionizing radiation induced by low doses of X-rays to Vibrio cholerae cells

    International Nuclear Information System (INIS)

    Pretreatment with sublethal doses of X-rays induced an adaptive response in Vibrio cholerae cells as indicated by their greater resistance to the subsequent challenging doses of X-irradiation. The adaptive response was maximum following a pre-exposure dose of 1.7 Gy X-rays and an optimum incubation period of 40 min at 37C. Pre-exposure to a sublethal dose of 1.7 Gy X-rays made the Vibrio cholerae cells 3.38-fold more resistant to the subsequent challenge by X-rays. Pretreatment with a sublethal dose of hydrogen peroxide offered a similar degree of protection to the bacterial cells against subsequent treatment with challenging doses of X-ray radiation. However, exposure of Vibrio cholerae cells to mild heat (42C for 10 min) before X-ray irradiation decreased their survival following X-irradiation

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

    Energy Technology Data Exchange (ETDEWEB)

    Fornace, Jr, A J

    2007-03-03

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

  14. Low Dose Radiation Adaptive Protection to Control Neurodegenerative Diseases

    OpenAIRE

    Doss, Mohan

    2013-01-01

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

  15. ROS/Autophagy/Nrf2 Pathway Mediated Low-Dose Radiation Induced Radio-Resistance in Human Lung Adenocarcinoma A549 Cell

    OpenAIRE

    Chen, Ni; Wu, Lijun; Yuan, Hang; Wang, Jun

    2015-01-01

    Low-dose ionizing radiation (LDIR) can induce radio-resistance to following high dose radiation in various mammalian cells. The protective role of LDIR has been thought to be associated with the overall outcomes of cancer radiotherapy. NF-E2 related factor 2 (Nrf2) is a transcription factor that plays pivotal roles in maintaining cellular oxidative equilibrium. Since oxidative stress has been indicated to be a mediator of LDIR induced radio-resistance, the role of Nrf2 in this process was inv...

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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 ?g). 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)

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

    OpenAIRE

    Scott, B. R.

    2008-01-01

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

  20. On the estimation of radiation-induced cancer risks from very low doses of radiation and how to communicate these risks

    International Nuclear Information System (INIS)

    The article is intended to give a short overview of epidemiological data on cancer risks associated with very low absorbed doses of ionising radiation. The linear no-threshold (LNT) approach to estimate cancer risks involves the use of epidemiological data at higher doses (>100 mSv), but is supported by data from lower exposure of more sensitive population groups like fetuses and children and the presence of rare types of cancer. The International Commission on Radiological Protection (ICRP) concludes that the LNT model, combined with a dose and dose-rate effectiveness (reduction) factor (DDREF) of 2 for extrapolation from high doses, should be used. The numerical value of the DDREF is challenged by the findings from some recent epidemiological studies demonstrating risks per unit dose compatible with the risks observed in the higher dose studies. In general there is very limited knowledge about the cancer risk after low absorbed doses (10 -100 mSv), as most of epidemiological studies have limitations in detecting small excess risks arising from low doses of radiation against fluctuations in the influence of background risk factors. Even if there may be significant deviations from linearity in the relevant dose range 0-100 mSv, one does not know the magnitude or even the direction of any such deviations. The risks could be lower than those predicted by a linear extrapolation, but they could also be higher. Until more results concerning the effects of low-dose exposure are available, a reasonable radiation protection approach is to consider the risk proportional to the dose. (authors)

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

    OpenAIRE

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

    2013-01-01

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

  2. Protection of liposomal lipids against radiation induced oxidative damage

    International Nuclear Information System (INIS)

    Liposomes were prepared from phospholipids extracted from biological membranes. A comparison was made between the peroxidation rate in handshake liposomes and in sonicated liposomes. The smaller sonicated liposomes were more vulnerable to peroxidation, probably because of the smaller radius of curvature, which results in a less dense packing of lipid molecules in the bilayer and a facilitated action of water radicals produced by the X-irradiation. High oxygen enhancement ratios were obtained, especially at low dose rates, suggesting the operation of slowly progressing chain reactions initiated by ionizing radiation. Three compounds were tested for their ability to protect the liposomal membranes against lipid peroxidation. The naturally occurring compounds reduced glutathione (GSH) and vitamin E (?-T) and the powerful radiation protector cysteamine (MEA). All three molecules could protect the liposomes against peroxidation. The membrane-soluble compound vitamin E was far the most powerful. About 50 per cent protection was achieved by using 5 x 10-6M ?-T, 10-4M GSH and 5 x 10-4M MEA. The fatty acid composition of the lipids altered drastically as a result of the irradiation. Arachidonic acid and docosahexanoic acid were the most vulnerable of the fatty acids. Very efficient protection of these polyunsaturated fatty acids could be obtained with relatively low concentrations of vitamin E built into the membranes. (author)

  3. Protection of liposomal lipids against radiation induced oxidative damage.

    Science.gov (United States)

    Konings, A W; Damen, J; Trieling, W B

    1979-04-01

    Liposomes were prepared from phospholipids extracted from biological membranes. A comparison was made between the peroxidation rate in handshake liposomes and in sonicated liposomes. The smaller sonicated liposomes were more vulnerable to peroxidation, probably because of the smaller radius of curvature, which results in a less dense packing of lipid molecules in the bilayer and a facilitated action of water radicals produced by the X-irradiation. High oxygen enhancement ratios were obtained, especially at low dose rates, suggesting the operation of slowly progressing chain reactions initiated by ionizing radiation. Three compounds were tested for their ability to protect the liposomal membranes against lipid peroxidation. The naturally occurring compounds reduced glutathione (GSH) and vitamin E(alpha-T) and the powerful radiation protector cysteamine (MEA). All three molecules could protect the liposomes against peroxidation. The membrane-soluble compound vitamin E was by far the most powerful. About 50 per cent protection was achieved by using 5 X 10(-6) M alpha-T, 10(-4) M GSH and 5 X 10(-4) M MEA. The fatty acid composition of the lipids altered drastically as a result of the irradiation. Arachidonic acid and docosahexanoic acid were the most vulnerable of the fatty acids. Very efficient protection of these polyunsaturated fatty acids could be obtained with relatively low concentrations of vitamin E built into the membranes. PMID:312791

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-31

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

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

    International Nuclear Information System (INIS)

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

  6. ROS/Autophagy/Nrf2 Pathway Mediated Low-Dose Radiation Induced Radio-Resistance in Human Lung Adenocarcinoma A549 Cell.

    Science.gov (United States)

    Chen, Ni; Wu, Lijun; Yuan, Hang; Wang, Jun

    2015-01-01

    Low-dose ionizing radiation (LDIR) can induce radio-resistance to following high dose radiation in various mammalian cells. The protective role of LDIR has been thought to be associated with the overall outcomes of cancer radiotherapy. NF-E2 related factor 2 (Nrf2) is a transcription factor that plays pivotal roles in maintaining cellular oxidative equilibrium. Since oxidative stress has been indicated to be a mediator of LDIR induced radio-resistance, the role of Nrf2 in this process was investigated in this research. Our results showed that in human lung adenocarcinoma A549 cell, 5cGy alpha particle induced radio-resistance to following 75cGy alpha particle radiation. The expression level of Nrf2 and its target Heme Oxygenase-1(HO-1) increased after 5cGy radiation. Both the shRNA of Nrf2 and the chemical inhibitor of HO-1 suppressed the induced radio-resistance, indicating the involvement of Nrf2 antioxidant pathway in this process. Further, we found 5cGy radiation stimulated autophagy process in A549. Inhibition of the autophagy process resulted in suppression of the radio-resistance and the induced expression of Nrf2 and HO-1. ROS scavenger N-acetyl-L-cysteine (NAC) blocked the autophagy process induced by 5cGy alpha particle, the upregulation of Nrf2 and HO-1, as well as the induced radio-resistance. In conclusion, ROS elevation caused by LDIR promoted Autophagy/Nrf2-HO-1 and conferred radio-resistance in A549. PMID:26078725

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

    Energy Technology Data Exchange (ETDEWEB)

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

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

    OpenAIRE

    Nuth, Manunya; Kennedy, Ann R.

    2013-01-01

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

  9. Linearity at low doses - fact or fiction?

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-15

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

  12. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2014-02-15

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

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

    International Nuclear Information System (INIS)

    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 ?-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 ?-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 ?-irradiating to medically relevant doses of 0.5, 1 and 2 Gy. The plasmid was recovered from the sham-irradiated and ?-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). ?-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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Lipotropes promote immunobiochemical plasticity and protect fish against low-dose pesticide-induced oxidative stress

    OpenAIRE

    Muthappa, N. A.; Gupta, Subodh; Yengkokpam, Sona; Debnath, Dipesh; Kumar, Neeraj; Pal, Asim Kumar; Jadhao, Sanjay B.

    2013-01-01

    An experiment was conducted to evaluate the role of different lipotropes in modulating immunity and biochemical plasticity under conditions of sublethal low-dose pesticide-induced stress in fish. Labeo rohita fish fingerlings were divided in two sets with one set of fish continuously exposed to low-dose endosulfan (1/10th of 96-h LC50) for 21 days, the other was unexposed, and both sets of fish were fed with practical diets supplemented with either 2 % lecithin, 0.5 % betaine, or 0.1 % cholin...

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

    OpenAIRE

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

    2007-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  3. Inactivation of Kupffer Cells by Gadolinium Chloride Protects Murine Liver From Radiation-Induced Apoptosis

    International Nuclear Information System (INIS)

    Purpose: To determine whether the inhibition of Kupffer cells before radiotherapy (RT) would protect hepatocytes from radiation-induced apoptosis. Materials and Methods: A single 30-Gy fraction was administered to the upper abdomen of Sprague-Dawley rats. The Kupffer cell inhibitor gadolinium chloride (GdCl3; 10 mg/kg body weight) was intravenously injected 24 h before RT. The rats were divided into four groups: group 1, sham RT plus saline (control group); group 2, sham RT plus GdCl3; group 3, RT plus saline; and group 4, RT plus GdCl3. Liver tissue was collected for measurement of apoptotic cytokine expression and evaluation of radiation-induced liver toxicity by analysis of liver enzyme activities, hepatocyte micronucleus formation, apoptosis, and histologic staining. Results: The expression of interleukin-1?, interleukin-6, and tumor necrosis factor-? was significantly attenuated in group 4 compared with group 3 at 2, 6, 24, and 48 h after injection (p <0.05). At early points after RT, the rats in group 4 exhibited significantly lower levels of liver enzyme activity, apoptotic response, and hepatocyte micronucleus formation compared with those in group 3. Conclusion: Selective inactivation of Kupffer cells with GdCl3 reduced radiation-induced cytokine production and protected the liver against acute radiation-induced damage.

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

    Energy Technology Data Exchange (ETDEWEB)

    Jian Li

    2012-11-07

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

  5. Adaption By Low Dose Radiation Exposure

    Science.gov (United States)

    2015-01-01

    The procedures and dose limitations used for radiation protection in the nuclear industry are founded on the assumption that risk is directly proportional to dose, without a threshold. Based on this idea that any dose, no matter how small, will increase risk, radiation protection regulations generally attempt to reduce any exposure to “as low as reasonably achievable” (ALARA). We know however, that these regulatory assumptions are inconsistent with the known biological effects of low doses. Low doses induce protective effects, and these adaptive responses are part of a general response to low stress. Adaptive responses have been tightly conserved during evolution, from single celled organisms up to humans, indicating their importance. Here we examine cellular and animal studies that show the influence of radiation induced protective effects on diverse diseases, and examine the radiation dose range that is effective for different tissues in the same animal. The concept of a dose window, with upper and lower effective doses, as well as the effect of multiple stressors and the influence of genetics will also be examined. The effect of the biological variables on low dose responses will be considered from the point of view of the limitations they may impose on any revised radiation protection regulations.

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

    International Nuclear Information System (INIS)

    The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned 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.)

  7. Protective effect of prostaglandin E1 on radiation-induced proliferative inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in rats

    International Nuclear Information System (INIS)

    We examined the effects of prostaglandin E1 (PGE1) on radiation-induced proliferation inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in a rat model. PGE1 had a protective effect on radiation-induced growth inhibition in keratinocytes in vitro, but not in fibroblasts. Varying concentrations of PGE1 were subcutaneously administered into the posterior neck region. X-irradiation at a dose of 20 Gy was administrated to the lower part of the back using a lead sheet with two holes 30 min to 1 h before or after the administration of PGE1. Although X-irradiation induced epilation, minor erosions, or skin ulcers in almost all rats, PGE1 administration prior to irradiation reduced these irradiation injuries. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling showed that proportions of apoptotic keratinocytes in the X-irradiated skin of PGE1-administered rats were significantly lower than for those in the skin of rats which did not receive PGE1. Cutaneous full-thickness defective wounds were then formed in X-irradiated areas to examine the time course of wound healing. Wound healing was significantly delayed because of X-irradiation, but PGE1 administration prior to irradiation led to a significantly shorter delay in wound healing compared with controls. Decreasing delay in wound healing was correlated with concentration of PGE1 administrated. Thus, PGE1-administration may potentially alleviate the radiation-induced skin injury. (author)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase oneˇŻs 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 ˇÝ 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 ˇÝ 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low-LET radiation). Such phantom risks also may arise from risk assessments conducted for com

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

    International Nuclear Information System (INIS)

    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 (50?L/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)

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

    International Nuclear Information System (INIS)

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

  16. Extract of Xylopia aethiopica (Annonaceae) protects against gamma-radiation induced testicular damage in Wistar rats.

    Science.gov (United States)

    Adaramoye, Oluwatosin Adekunle; Adedara, Isaac Adegboyega; Popoola, Bosede; Farombi, Ebenezer Olatunde

    2010-01-01

    Ionizing radiation is an important environmental risk factor and, a major therapeutic agent for cancer treatment. This study was designed to evaluate the protective effect of extract of Xylopia aethiopica (XA) on gamma-radiation-induced testicular damage in rats. Vitamin C (VC) served as the reference antioxidant during the study. The study consists of 4 groups of 11 rats each. Group I received corn oil (vehicle), groups II and IV were pretreated with XA (250 mg/kg) and VC (250mg/kg) for 6 weeks before and 8 weeks after exposure to gamma-radiation; group III was exposed to a single dose of gamma-radiation (5 Gy). Biochemical analysis revealed that gamma-irradiation caused a significant increase (p Xylopia aethiopica has a protective effect by inhibiting oxidative damage in testes of irradiated rats. PMID:21305847

  17. Protection by dinitrophenol against radiation-induced hemolysis in hen erythrocytes

    International Nuclear Information System (INIS)

    Hen erythrocytes were ?-irradiated (up to 15 kR) and incubated at 370C for 20 hr in a slightly hypotonic saline solution (0.10 M NaCl buffered with 5 mM phosphate, pH 7.4) to which 2,4-dinitrophenol, glucose, NaF, or pyruvate were added in different combinations. Hemolysis was measured at the end of the incubation period. Dinitrophenol (2 x 10-4 M) reduced the radiation-induced hemolysis in both ATP-containing and ATP-depleted erythrocytes. Glucose (10 mM) and pyruvate (10 mM) antagonized the protective effect of dinitrophenol against radiation-hemolysis. NaF suppressed the antagonistic action of glucose on the protective effect of dinitrophenol

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    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

    2015-01-01

    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~5 × 11–88) or eight (Fla~8 × 11–88) 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 naďve 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

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

    Directory of Open Access Journals (Sweden)

    Raquel Pérez, María García-Fernández, Matías Díaz-Sánchez, Juan E Puche, Gloria Delgado, Marian Conchillo, Jordi Muntané, Inma Castilla-Cortázar

    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.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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

  6. Biology responses to low dose radiation

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-05-25

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

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Omaima Soliman Eissa* and Nehal Aly Moustafa

    2007-06-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  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

    OpenAIRE

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

    2014-01-01

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

  16. Protective Effects and Its Relative Mechanisms of Low Dose Ionizing Radiation on pancreatic cells of Male Diabetic Rat’s

    OpenAIRE

    Hanaa F. Waer, **Seham A. Helmy

    2012-01-01

    Back ground & Aim of the work: Diabetes mellitus (DM) is a chronic metabolic disorder brings great danger to human health. Low-dose-rate radiation modulates various biological responses including carcinogenesis, immunological responses and diabetes. This study examined the effect of low doses of irradiation on the pathological and ultrastructural progression of type I diabetes in rats inducted by Streptozotocin.Material and Methods: The present study was done on 80 healthy adult albino male...

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

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

  18. Recombinant human epidermal growth factor (rhEGF) protects radiation-induced intestine injury in murine system

    International Nuclear Information System (INIS)

    This study was to investigate whether rhEGF protects radiation induced intestine injury without compromising antitumor effect of radiation in murine system. A radiation induced intestinal injury model was established in mice by whole body irradiation. Using this model, 4 groups were set; control, rhEGF (100 ?g/kg intraperitoneally), radiation (10 Gy), and a combination (rhEGF and radiation). The level of apoptosis and proliferation were analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and proliferation cell nuclear antigen (PCNA) immunohistochemical staining, respectively, as well as observation of survival and body weight change. A tumor growth delay assay was performed using murine syngeneic tumors; one radioresistant tumor, HCa-I and one radiosensitive tumor, MCa-K. In the radiation induced intestinal injury model, the 10 Gy group had significantly more weight loss with less number of crypt cells and higher apoptosis than the 8 Gy group. Using 10 Gy model, radioprotective effect of rhEGF was tested. Addition of rhEGF improved not only the body weight loss but also survival following radiation. It also induced suppression of apoptosis as well as increase of PCNA expression and recovery of villi. rhEGF did not enhance the tumor growth after radiation exposure in the tested tumors. These findings suggest that combination of exogenous rhEGF and radiation can be a new anticancer strategy by protecting radiation-induced intestinal injury without alleviating antitumor effect of radiation. (author)

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

    Science.gov (United States)

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

    2015-08-01

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

  20. Protective effect of SH compounds on the radiation-induced mitotic delay, 3

    International Nuclear Information System (INIS)

    Effect of MEA on radiation-induced mitotic delay in cultured L-5 cells was studied by examination of changes in mitotic index after treatment with MEA (5, 10, 20, 30 and 40 mM) alone. With 5 mM MEA, no effect was found in the mitotic index but, with 20 mM MEA, mitotic index decreased 8 to 12 hr after the treatment, and with 30 or 40 mM MEA, strong inhibition on mitosis was observed. The cells treated with the agent (5, 10, 20 mM) during irradiation of 200 rads showed a faster recovery of the mitotic index than the control irradiated without the chemical treatment, and increase of their mitotic index began 2 hr after irradiation (shortening of mitotic delay time, viz., G2-block protection), but treatment with 40 mM of MEA showed no effect. MEA (5 mM) treatment was made 6 hr, 3 hr, and 30 min before and 30 min after irradiation with 200 rads. Post-treatment with the agent had no effect but pretreatment with MEA reulted in an enhancement of recovery rate of mitotic index, though there was no effect on the mitotic delay time induced by x-irradiation. On the basis of these data, the mechanisms of the radioprotective action of MEA were discussed. (author)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Objective: To investigate whether radiation-induced late injury of the brain can be ameliorated by traditional Chinese Medicine through blocking the primary events. Methods: This trial included five animal groups: sham irradiation, irradiation only, and three treatment groups. The whole brain of BALB/C mouse was irradiated with 22 Gy by using a 6 MV linear accelerator. Step down method was used to evaluate the study and memory abilities. Mouse weight was also recorded every week before and after irradiation. On D90, all mice alive were euthanized and Glee's silver dye method and Bielschousky silver dye method were used to detect the senile plaque and the neurofibrillary tangle. One-Way ANOVA was used to evaluate the differences among the groups in the various aspects of study and memory abilities as well as quality of life. Kaplan-Meier was used to evaluate the survival. Log-rank was used to detect the differences among the survival groups. Results: 1. There was no significant difference in survival among the treatment groups, even though Salvia Miltiorrhiza (SM) was able to improve the quality of life. As to the cognition function, it was shown that whole brain radiation would make a severe cognition damage with the learning and memorizing ability of the irradiated mice being worse than those of the sham irradiation group. The Traditional Chinese Medicine Salvia Miltiorrhiza possesses the role of a protective agent against cognition function damage induced by 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. Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome

    Science.gov (United States)

    Selinger, Christian; Strbo, Natasa; Gonzalez, Louis; Aicher, Lauri; Weiss, Jeffrey M.; Law, G. Lynn; Palermo, Robert E.; Vaccari, Monica; Franchini, Genoveffa; Podack, Eckhard R.

    2014-01-01

    Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with simian immunodeficiency virus (SIV) peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenges with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on postchallenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral loads 5 days after the first challenge but with unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant prechallenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling may enhance vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV. PMID:25274805

  4. Multiple low-dose challenges in a rhesus macaque AIDS vaccine trial result in an evolving host response that affects protective outcome.

    Science.gov (United States)

    Selinger, Christian; Strbo, Natasa; Gonzalez, Louis; Aicher, Lauri; Weiss, Jeffrey M; Law, G Lynn; Palermo, Robert E; Vaccari, Monica; Franchini, Genoveffa; Podack, Eckhard R; Katze, Michael G

    2014-12-01

    Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with simian immunodeficiency virus (SIV) peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenges with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on postchallenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral loads 5 days after the first challenge but with unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant prechallenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling may enhance vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV. PMID:25274805

  5. New risk estimates at low doses

    International Nuclear Information System (INIS)

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

  6. Protective Effects and Its Relative Mechanisms of Low Dose Ionizing Radiation on pancreatic cells of Male Diabetic Rat’s

    Directory of Open Access Journals (Sweden)

    Hanaa F. Waer, **Seham A. Helmy

    2012-10-01

    Full Text Available Back ground & Aim of the work: Diabetes mellitus (DM is a chronic metabolic disorder brings great danger to human health. Low-dose-rate radiation modulates various biological responses including carcinogenesis, immunological responses and diabetes. This study examined the effect of low doses of irradiation on the pathological and ultrastructural progression of type I diabetes in rats inducted by Streptozotocin.Material and Methods: The present study was done on 80 healthy adult albino male rats 9 weeks age, in the weight range from (150–200 gm. Rats were grouped to 4 groups they were cared according to the Guiding Principle in the Care and Use of Animals. Diabetes was induced by a single intraperitoneal injection of freshly prepared Streptozotocin (STZ- 45 mg/kg b.w.. Whole body gamma irradiation was performed using Caesium -137. Animals were exposed to fractionated dose levels of 0.5 Gy/week of ?-radiation for 3 and 6 weeks. The body weight, blood glucose and insulin levels were measured after 3 and 6 weeks. Small blocks of pancreatic tissues of different groups were removed and prepared for pathological and ultrastructure examination. Results: An elevated level of glucose and decreased level of insulin in blood were first detected at 3 and 6 weeks of age in the STZ treated rats. There was significant and remarkable tendency of gaining normal levels of both blood glucose and blood insulin by irradiation exposure especially after 6 weeks of irradiation. Both suppression of cell death and cellular injury induced by STZ were also observed by EM examination in 3 week and 6 weeks. Conclusion: The present results indicated that treatment with 0.5 Gy ? rays suppresses progression of type I diabetes in STZ rats

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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-?). 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)

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

    Science.gov (United States)

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

    2007-06-01

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

  10. Protection from Radiation-Induced Pulmonary Fibrosis by Peripheral Targeting of Cannabinoid Receptor-1.

    Science.gov (United States)

    Bronova, Irina; Smith, Brett; Aydogan, Bulent; Weichselbaum, Ralph R; Vemuri, Kiran; Erdelyi, Katalin; Makriyannis, Alex; Pacher, Pal; Berdyshev, Evgeny V

    2015-10-01

    Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic radiotherapy that limits its dose, intensity, and duration. The contribution of the endocannabinoid signaling system in pulmonary fibrogenesis is not known. Using a well-established mouse model of RIF, we assessed the involvement of cannabinoid receptor-1 (CB1) in the onset and progression of pulmonary fibrosis. Female C57BL/6 mice and CB1 knockout mice generated on C57BL/6 background received 20 Gy (2 Gy/min) single-dose thoracic irradiation that resulted in pulmonary fibrosis and animal death within 15 to 18 weeks. Some C57BL/6 animals received the CB1 peripherally restricted antagonist AM6545 at 1 mg/kg intraperitoneally three times per week. Animal survival and parameters of pulmonary inflammation and fibrosis were evaluated. Thoracic irradiation (20 Gy) was associated with marked pulmonary inflammation and fibrosis in mice and high mortality within 15 to 18 weeks after exposure. Genetic deletion or pharmacological inhibition of CB1 receptors with a peripheral CB1 antagonist AM6545 markedly attenuated or delayed the lung inflammation and fibrosis and increased animal survival. Our results show that CB1 signaling plays a key pathological role in the development of radiation-induced pulmonary inflammation and fibrosis, and peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating complication of radiotherapy/irradiation. PMID:26426981

  11. Comparison of the protective action of glutathione and cysteamine on radiation-induced mitotic delay in cultured L-5 cells

    International Nuclear Information System (INIS)

    The protective effect of glutathione (GSH) and cysteamine (MEA) on radiation-induced mitotic delay in cultured mammalian L-5 cells was studied. Cells treated with 20 mM of GSH during irradiation with 2 Gy (200 rad) showed faster recovery of the mitotic index than control cells irradiated without chemical treatment; however, GSH had no effect on mitotic delay time. Inhibition of mitosis was observed with 80, 100, and 120 mM of GSH. Cells treated with 5 mM of MEA during irradiation also showed faster recovery of the mitotic index than the controls, but in addition the delay time was shortened. Progression of G2-phase cells treated with 5-fluorouracil to mitosis after irradiation was protected by MEA but not by GSH. Progression of S-phase cells labeled with 3H-thymidine to mitosis was accelerated by both agents during irradiation

  12. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  13. Radiation induced bystander effects

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    Objective: To determine the Manganese (III) Tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP), a superoxide dismutase (SOD) mimic, protective effect against oxidative damage and tolerance enhancement to radiation-induced lung injury in the rat model. Methods: Female 150-160 g Fisher-344 rats were randomized into a RT + MnTE-2-PyP group and a RT group. The anesthetized rats were administrated with a single dose of 28 Gy of 4 MV photon to their right lung with MnTE-2-PyP (6 mg/kg) given intraperitoneally 15-30 min before irradiation in the former group. The breathing rate and plasma TGF-?1 level were assessed every two weeks after radiation. Once dyspnea appeared, the animals with severe respiratory distress were euthanized. Otherwise, they were sacrificed 6 months after irradiation. The irradiated lungs were revolved and processed for definitive analysis, including hydroxyproline content, immunohistochemical assay, histopathology and fibrosis scores. Results: The disparity of breathing frequency showed an ability of MnTE-2-PyP to reduce the severity of radiation-induced lung injury with evidently postponed and alleviated dyspnea in the RT+ MnTE-2-PyP group by 30% (P<0.01). Three rats died of respiratory distress with seven rats developed pleural effusion in the RT only group, while only one in the RT + MnTE-2-PyP group did so. There were significant reduction of the TGF-?1 level [(3.10±0.50) ng/ml vs (1.34±0.63) ng/ml; t=2.41, P=0.029)] and hydroxyproline content per gram of dry and wet lung in the RT + MnTE-2-PyP group compared with those in the RT alone group. The histopathological comparison also revealed the protective effect of MnTE-2-PyP. The lung fibrosis score was significantly lower in rats with MnTE-2-PyP administered (3.60±0.15 vs 5.82±0.34, P<0.05). TGF-?1 expression was also markedly reduced in RT+MnTE-2-PyP group, whereas intense immunoreactivity was found in the RT alone group. Conclusions: MnTE-2-PyP, a kind of novel SOD mimic demonstrating a significant protective effect from radiation-induced lung injury, may be a potential radio-protector

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

    International Nuclear Information System (INIS)

    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)

  16. Endoplasmic reticulum stress protects human thyroid carcinoma cell lines against ionizing radiation-induced apoptosis.

    Science.gov (United States)

    Wu, Xin-Yu; Fan, Rui-Tai; Yan, Xin-Hui; Cui, Jing; Xu, Jun-Ling; Gu, Hao; Gao, Yong-Ju

    2015-03-01

    Radiotherapy is one of the most effective forms of cancer treatment, used in the treatment of a number of malignant tumors. However, the resistance of tumor cells to ionizing radiation remains a major therapeutic problem and the critical mechanisms determining radiation resistance are poorly defined. In the present study, a cellular endoplasmic reticulum (ER) stress microenvironment was established through the pretreatment of cultured thyroid cancer cells with tunicamycin (TM) and thapsigargin (TG), in order to mimic the ER stress response in a tumor microenvironment. This microenviroment was confirmed through the X?box binding protein 1 splice process, glucose?regulated protein 78 kD and ER degradation?enhancing ??mannosidase?like mRNA expression. A clonogenic assay was used to measure cancer cell resistance to 60Co?? following TM pretreatment; in addition, human C/EBP homologous protein (CHOP) mRNA expression was determined and apoptosis assays were performed. The results showed that TM or TG pretreatment inhibited CHOP expression and reduced the apoptotic rate of cells. Furthermore, the results demonstrated that the induced ER stress response rendered cancer cells more resistant to ionizing radiation?induced apoptosis. Therefore, the ER stress pathway may be a potential therapeutic target in order to improve the clinical efficiency of radiotherapy. PMID:25405642

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

    Directory of Open Access Journals (Sweden)

    Can DEM?REL

    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.

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

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

  20. Radiation Leukemogenesis at Low Dose Rates

    Energy Technology Data Exchange (ETDEWEB)

    Weil, Michael; Ullrich, Robert

    2013-09-25

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

  1. Radiation Leukemogenesis at Low Dose Rates

    International Nuclear Information System (INIS)

    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

  2. Pretreatment by low-dose fibrates protects against acute free fatty acid-induced renal tubule toxicity by counteracting PPAR? deterioration

    International Nuclear Information System (INIS)

    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 (PPAR?), suggesting the benefit of PPAR? activation. However, an earlier study using a murine acute tubular injury model, FFA-overload nephropathy, demonstrated that high-dose treatment of PPAR? 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 PPAR? 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 PPAR? 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 NF?B activation. These effects are common to other fibrates and dependent on PPAR? function. Interestingly, however, clofibrate pretreatment also exerted PPAR?-independent tubular toxicities in PPAR?-null mice with FFA-overload nephropathy. The favorable properties of fibrates are evident when PPAR?-dependent tubular protective effects outweigh their PPAR?-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 PPAR? 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). PPAR? activationvia clofibrate pretreatment maintains fatty acid catabolism and attenuates oxidative stress, apoptosis, and NF?B activation, resulting in protection of PTECs. The favorable properties of fibrates are evident when PPAR?-dependent tubular protective effects outweigh their PPAR?-independent tubular toxicities. Display Omitted Highlights: ? Clofibrate pretreatment protects against acute FFA-induced tubular toxicity. ? PPAR? activation decreases FFA influx and maintains fatty acid catabolism. ? PPAR? activation attenuates oxidative stress, apoptosis, and NF?B activation. ? Protective effects must outweigh PPAR?-independent tubular toxicities of fibrates.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the protective role of grape seed extract against ?-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

  12. Low dose irradiation and biological defense mechanisms

    International Nuclear Information System (INIS)

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

  13. Low dose irradiation and biological defense mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Sugahara, Tsutomu (ed.) (Health Research Foundation, Kyoto (Japan)); Sagan, L.A. (ed.) (Electric Power Research Inst., Palo Alto, CA (United States)); Aoyama, Takashi (ed.) (Shiga Univ., Otsu (Japan))

    1992-01-01

    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.

  14. Relief with Rapamycin: mTOR inhibition protects against radiation-induced mucositis

    OpenAIRE

    Finkel, Toren

    2012-01-01

    In this issue of Cell Stem Cell, Iglesias-Bartolome et al (2012) show that mTOR inhibition with rapamycin protects against mucositis in mice, suggesting potential treatment strategies against this harmful side effect of anti-cancer therapies. In normal tissues, rapamycin prevents epithelial stem cell senescence by reducing oxidative stress through increased MnSOD.

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    Shuang-Qi Tian; Zhen-Yu Wang; Li-Li Zuo; Zi-Luan Fan

    2012-01-01

    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 e...

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

    OpenAIRE

    Redpath, J. Leslie

    2005-01-01

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

  18. Reciprocal Paracrine Interactions Between Normal Human Epithelial and Mesenchymal Cells Protect Cellular DNA from Radiation-Induced Damage

    International Nuclear Information System (INIS)

    Purpose: To explore whether interactions between normal epithelial and mesenchymal cells can modulate the extent of radiation-induced DNA damage in one or both types of cells. Methods and Materials: Human primary thyrocytes (PT), diploid fibroblasts BJ, MRC-5, and WI-38, normal human mammary epithelial cells (HMEC), and endothelial human umbilical cord vein endothelial cells (HUV-EC-C), cultured either individually or in co-cultures or after conditioned medium transfer, were irradiated with 0.25 to 5 Gy of ?-rays and assayed for the extent of DNA damage. Results: The number of ?-H2AX foci in co-cultures of PT and BJ fibroblasts was approximately 25% lower than in individual cultures at 1 Gy in both types of cells. Reciprocal conditioned medium transfer to individual cultures before irradiation resulted in approximately a 35% reduction of the number ?-H2AX foci at 1 Gy in both types of cells, demonstrating the role of paracrine soluble factors. The DNA-protected state of cells was achieved within 15 min after conditioned medium transfer; it was reproducible and reciprocal in several lines of epithelial cells and fibroblasts, fibroblasts, and endothelial cells but not in epithelial and endothelial cells. Unlike normal cells, human epithelial cancer cells failed to establish DNA-protected states in fibroblasts and vice versa. Conclusions: The results imply the existence of a network of reciprocal interactions between normal epithelial and some types of mesenchymal cells mediated by soluble factors that act in a paracrine manner to protect DNA from genotoxic stress

  19. Effects of low doses

    International Nuclear Information System (INIS)

    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.)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    The radioprotective efficacy of methanolic extracts of leaves of Vernonia amygdalina (VA) and Hibiscus sabdariffa (HS), and vitamin C (VIT C) against gamma radiation (4 Gy) induced liver damage was studied in male Wistar albino rats. VIT C was administered at a dose of 250 mg/kg body weight, while VA and HS were administered at doses; 200, 400 and 800-mg/kg body weight, orally for 4 weeks prior to radiation and 5 weeks after irradiation. The rats were sacrificed at 24 hours and 5 weeks after irradiation. Treatment with VIT C and VA (800 mg/kg) significantly (p<0.05) decreased the gamma radiation-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at 24 hours after irradiation, whereas, HS (400 mg/kg) significantly (p<0.05) decreased the serum ALT activity only. Similarly, treatment with VIT C and VA (800 mg/kg) significantly (p<0.05) decreased the serum conjugated bilirubin levels by 56% and 29%, respectively at 24 hours. Furthermore, VIT C, VA and HS significantly (p<0.05) decreased the levels of serum lipid peroxidation (LPO) and increased the hepatic superoxide dismutase (SOD) activities at 24 hours. Treatment for 5 weeks after irradiation with VIT C, VA and HS significantly (p<0.05) decreased the levels of unconjugated bilirubin, while VIT C and VA alone decreased the levels of conjugated bilirubin. Furthermore, treatment with VA (400 and 800 mg/kg) decreased the serum ALT activities by 25% and 34%, 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)

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

    International Nuclear Information System (INIS)

    The development of effective non-toxic radioprotective agents is of considerable interest in the improvement of radio therapy of cancer and protection against unplanned exposures. The synthetic drugs developed in post-world war II have had serious constrains in clinical application due to their toxicity at the optimal protective dose level. Search for non toxic protectors from natural sources have indicated that some of the commonly used medicinal plants and the polyherbal formulation could prove to be valuable sources of the clinically used radioprotector as their ratio of effective dose to toxic dose is very high. A worldwide hunt is on for the development of non-toxic/less toxic radioprotectors. Keeping this view, the present study has been undertaken to find out the possible radioprotective potential of the Rosemarinus officinalis extract (ROE) in the liver of Swiss albino mice as its leaves have various medicinal properties like analgesic, anti-epileptic, antioxidant, hepatoprotactive and anti-cancer etc. Adult male Swiss albino mice, 6-8 weeks old with an average weight of 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)

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

    Directory of Open Access Journals (Sweden)

    Shuang-Qi Tian

    2012-12-01

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

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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 ?1/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 ?1/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 ?1/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 ?1for 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.

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

    International Nuclear Information System (INIS)

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

  8. Melatonin blunts the mitochondrial/NLRP3 connection and protects against radiation-induced oral mucositis.

    Science.gov (United States)

    Ortiz, Francisco; Acuńa-Castroviejo, Darío; Doerrier, Carolina; Dayoub, José C; López, Luis C; Venegas, Carmen; García, José A; López, Ana; Volt, Huayqui; Luna-Sánchez, Marta; Escames, Germaine

    2015-01-01

    Mucositis is a common and distressing side effect of chemotherapy or radiotherapy that has potentially severe consequences, and no treatment is available. The purpose of this study was to analyze the molecular pathways involved in the development of oral mucositis and to evaluate whether melatonin can prevent this pathology. The tongue of male Wistar rats was subjected to irradiation (X-ray YXLON Y.Tu 320-D03 irradiator; the animals received a dose of 7.5 Gy/day for 5 days). Rats were treated with 45 mg/day melatonin or vehicle for 21 days postirradiation, either by local application into their mouths (melatonin gel) or by subcutaneous injection. A connection between reactive oxygen species, generating mitochondria and the NLRP3 (NLR-related protein 3 nucleotide-binding domain leucine-rich repeat containing receptor-related protein 3) inflammasome, has been reported in mucositis. Here, we show that mitochondrial oxidative stress, bioenergetic impairment and subsequent NLRP3 inflammasome activation are involved in the development of oral mucositis after irradiation and that melatonin synthesized in the rat tongue is depleted after irradiation. The application of melatonin gel restores physiological melatonin levels in the tongue and prevents mucosal disruption and ulcer formation. Melatonin gel protects the mitochondria from radiation damage and blunts the NF-?B/NLRP3 inflammasome signaling activation in the tongue. Our results suggest new molecular pathways involved in radiotherapy-induced mucositis that are inhibited by topical melatonin application, suggesting a potential preventive therapy for mucositis in patients with cancer. PMID:25388914

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

    Directory of Open Access Journals (Sweden)

    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 ? 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.

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

    International Nuclear Information System (INIS)

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Repussard, J.; Weiss, W.; Quintana Trias, O.; Rosario Perez, M. del; Andersen, M.; Rudiger Trott, K.; Ottolenghi, A.; Smyth, V.; Graw, J.; Little, M.P.; Yonai, S.; Barcellos-Hoff, M.H.; Bouffler, S.; Chevillard, S.; Jeggo, P.; Sabatier, L.; Baatout, S.; Niwa, O.; Oesch, F.; Atkinson, M.; Averbeck, D.; Lloyd, D.; O' Neill, P.

    2011-07-01

    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

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

    International Nuclear Information System (INIS)

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

  14. Effect of low dose ionizing irradiation on rat metabolism

    International Nuclear Information System (INIS)

    The biological effect of low dose radiation is little known. In the current study male Wistar rats were exposed monthly to a 60Co-source low dose whole body irradiation (0.25 Gy, per 18 months; total dose: 4.5 Gy). The glutathione disulphide (GSSH): total glutathione (GSH) ratio, the concentration of thiobarbituric acid-reactive substances and the activities of glutathione peroxidase and glutathione transferase in: small intestine, spleen, kidney, soleus muscle, and liver were analysed. Low dose irradiation is accompanied by distinct peroxidative changes in organs, observed in the small intestine, the spleen and in the kidneys. The current study suggests that the measurement of glutathione status and thiobarbituric acid-reactive substances can be proposed as sensitive parameters for low dose radiation induced changes. (author)

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

    International Nuclear Information System (INIS)

    Objective: To understand the expression of acute brain injury induced by radiation and the protective effect of traditional Chinese Medicine in BALB/C mouse. Methods: The whole brain of BALB/C mouse was irradiated to a dose of 25 Gy using a 6 MV X linear accelerator. Ten hours later, the brain tissue and blood sample were taken. Thiobarbituric acid reaction was used to detect the malonaldehyde substitute for the lipid peroxide. Immunohistochemical method was used to detect the expression of ICAM-1 on D1, 2, 3, and 10 after having received radiation. One-Way ANOVA was used to evaluate the differences in the values of LPO in the brain tissue and plasma between the groups. The difference of expression of ICAM-1 between the groups was compared by ?2 method. Results: Two hundred and twelve female BALB/C mice were divided into five groups: Control group, Radiation alone group (R), R + dexamethasone group, R + 654-2 group and R + Salvia Miltiorrhiza group. The contents of LPO in the mouse brain tissue 10 hours after 25 Gy of whole brain irradiation were as follows (mean ± standard error): Control group (1975.5±94.2) nmol/g, Radiation alone group (R) (3417.3±109.7) nmol/g, R + dexamethasone group (3113.6±178.1) nmol/g, R + 654-2 group (3406.4±159.1) nmol/g, R + Salvia Miltiorrhiza group (2981.5±140.1) nmol/g. Salvia Miltiorrhiza significantly reduced the LPO increase induced by irradiation (P<0.05). There were no significant differences between the other groups in the change of LPO in the plasma 10 hours after whole brain irradiation. The expression of ICAM-1 after whole brain irradiation was time-dependent . There was an increase of expression of ICAM-1 24 hours after irradiation, reaching the peak at 48 hours. Salvia Miltiorrhiza and dexamethasone strongly inhibited the expression of ICAM-1 when compared with radiation only, with the difference significant (P<0.01). Conclusions: The change of LPO content in the BALB/C mouse brain tissue and the increase in expression of ICAM-1 on the brain vascular endothelial cell can act as indexes of acute brain injury induced by radiation. Traditional Chinese medicine Salvia Miltiorrhiza has a protective effect on radiation-induced acute brain injury

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

    Science.gov (United States)

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

    2011-12-01

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

    Outside the protection of 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.

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

    International Nuclear Information System (INIS)

    Recently, accumulating evidences have reported non-targeted effects, which are not a direct effect of the initial damage produced in cellular DNA. Radiation-induced bystander responses (RIBR) are the most important non-targeted effect, which are defined as cellular responses which have not been directly induced by radiation but are induced in the neighborhood cells of the directly irradiated. Here the importance and current issues of RIBR in the low dose radiation risk assessment were reported through the summary of present topics of RIBR and microbeam probes of radiation responses. Non-targeted effects include adaptive responses, low dose hypersensitivity, genomic instability, gene expression, inverse dose rate effect and bystander responses, which have common features that saturate with increasing dose. The accumulating evidence of the results obtained using alpha-particles suggests that a linear extrapolation of risks from high to low doses would underestimate the risks at low doses. However, in the 2007 recommendations of the International Commission of Radiological Protection (ICRP), it has been concluded that knowledge of the roles of bystander cell signaling in the genesis of radiation-induced health effects is insufficiently well developed for radiological protection purposes. Now the study of RIBR is considered that one of the most important study to clear the mechanisms of the effect of low dose radiation. RIBR is mainly mediated by cell-to-cell 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)

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

    OpenAIRE

    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...

  1. Low doses effects and gamma radiations low dose rates

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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)

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

    Scientific Electronic Library Online (English)

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

    2013-09-27

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

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

    DEFF Research Database (Denmark)

    Börjesson, A; Rřnn, S G; Karlsen, A E; Billestrup, Nils; Sandler, S

    2011-01-01

    We investigated the impact of ß-cell specific overexpression of suppressor of cytokine signalling-3 (SOCS-3) on the development of multiple low dose streptozotocin (MLDSTZ) induced Type 1 diabetes and the possible mechanisms involved. MLDSTZ treatment was administered to RIP-SOCS-3 transgenic and wild-type (wt) mice and progression of hyperglycemia monitored. Isolated islets from both strains were exposed to human IL-1ß (25U/ml) or a combination of human IL-1ß (25U/ml) and murine IFN-ż (1000U/ml...

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

    International Nuclear Information System (INIS)

    1,4-Naphthoquinone (NQ) is the parent molecule of many clinically approved anticancer, anti-infective, and antiparasitic drugs such as anthracycline, mitomycin, daunorubicin, doxorubicin, diospyrin, and malarone. Presence of NQ during a-irradiation (4Gy) significantly reduced the death of irradiated murine splenic lymphocytes in a dose dependent manner (0.05-liM), with complete protection at liM as assessed by PI staining. Radioprotection by NQ was further confirmed by inhibition of caspase activation, decrease in cell size, DNA-fragmentation, nuclear-blebbing and clonogenic assay. All trans retinoic acid which is inhibitor of Nrf-2 pathway, completely abrogated the radioprotective effect of NQ, suggesting that radioprotective activity of NQ may be due to activation of Nrf-2 signaling pathways. Further, addition of NQ to lymphocytes activated Nrf-2 in time dependent manner as shown by confocal microscopy, electrophoretic mobility shift assay and quantitative real time PCR. It also increased the expression of Nrf-2 dependent cytoprotective genes like hemeoxygenase-1, MnSOD, catalse as demonstrated by real time PCR and flowcytometry. NQ protected lymphocytes significantly against radiation-induced cell death even when added after irradiation. Complete protection was observed by addition of NQ up to 2 h after irradiation. However, percentage protection decreased with increasing time interval. These results suggested that NQ may offer protection to lymphocytes activating 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

    Science.gov (United States)

    Piao, Mei Jing; Madduma Hewage, Susara Ruwan Kumara; Han, Xia; Kang, Kyoung Ah; Kang, Hee Kyoung; Lee, Nam Ho; Hyun, Jin Won

    2015-01-01

    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. PMID:26404324

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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)

  10. Protective role of perillic acid against radiation-induced oxidative stress, cytokine profile, DNA damage, and intestinal toxicity in mice.

    Science.gov (United States)

    Pratheeshkumar, P; Raphael, T J; Kuttan, Girija

    2010-01-01

    The radioprotective effect of perillic acid was studied using an in vivo mouse model. Whole-body exposure of Swiss albino mice to ?-rays (6 Gy) reduced the total white blood cell count to 1035 ± 378 cells/mm3 on the 9th day, which was significantly elevated to 2196 ± 382 cells/mm3 by the administration of perillic acid (50 ?moles/kg body weight, intraperitoneally) on the same day. The number of bone marrow cells and ?-esterase positive cells in control animals after 11 days of irradiation was reduced to 12.5 ± 0.8 × 106 cells/femur and 674 ± 45.2/4000 cells, respectively. In perillic acid treated animals, bone marrow cellularity was increased to 14.8 ± 1.8 × 106 cells/femur and ?-esterase positive cells were 941 ± 56.5 /4000 cells, similar to normal level (935 ± 51.4/4000 cells). Administration of perillic acid could reduce the radiation-induced elevated levels of alkaline phosphatase (ALP), glutathione-pyruvate transferase (GPT) and lipid peroxidation (LPO) in both serum and liver of irradiated animals. Perillic acid could significantly enhance the glutathione (GSH) content in liver and intestinal mucosa of irradiated animals. Histopathological analysis of small intestine also suggests that perillic acid could reduce the radiation-induced intestinal damage. The level of proinflammatory cytokines such as IL-1?, TNF-? and CRP, which were elevated during irradiation, was significantly reduced by the Perillic acid administration. Perillic acid treatment could also stimulate the production of other cytokines such as GM-CSF and IFN-? in animals exposed to whole-body gamma irradiation. Agarose gel electrophoresis of DNA isolated from bone marrow of mice exposed to gamma radiation showed heavy damage that was reduced by treatment with perillic acid. PMID:21303327

  11. The Protective Role of Combined Administration of Daidzein and Genistein in Modulating Radiation-Induced Damage in the Mitochondria of Some Tissues in Rats

    International Nuclear Information System (INIS)

    The objective of this study was to evaluate the role of combined administration of isoflavones daidzein and genistein in the modulation of mitochondrial oxidative damage and cellular energy metabolism in the liver, heart and lung tissues of irradiated rats. Animals were supplemented with isoflavones by gavage 4.5 mg/ kg body wt/ day, for 7 successive days before whole body exposure to 8 Gy of gamma-radiation (delivered as 2 Gy every other day up to a total dose of 8 Gy); supplementation was extended during the period of radiation exposure. Experimental investigations performed 7 days after the last dose of irradiation revealed that combined administration of daidzein and genistein has significantly minimized the radiation-induced increase of xanthine oxidase (XO) activity and lipid peroxides content measured as thiobarbituric acid reactive substances (TBARS) in the mitochondria of liver, heart and lung tissues accompanied by significant elevation in the activities of manganese superoxide dismutase (Mn-SOD), catalase (CAT), glutamate dehydrogenase (GDH), and creatine kinase (Mi-CKs). According to the results obtained, it could be concluded that combined administration of daidzein and genistein at optimized dosages might protect mitochondria from radiation induced oxidative stress and would play a role in regulating cellular energy metabolism

  12. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

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

  13. Radiation-induced adaptive response in fish cell lines

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    This study aimed to analyze whether Ulinastatin, a urinary trypsin inhibitor (UTI), inhibits the transforming growth factor (TGF)-? signaling pathway and lung fibrosis induced by thoracic irradiation in a lung injury mouse model. The thoraces of 9-week-old female fibrosis-sensitive C57BL/6 mice were irradiated with a single X-ray dose of 12 Gy or 24 Gy. UTI was administrated intraperitoneally at a dose of 200,000 units/kg concurrently with radiation (concurrent UTI) or daily during the post-irradiation period for 8-14 days (post-RT UTI). Mice were sacrificed at 16 weeks after irradiation to assess the histological grade of lung fibrosis and immunohistochemical TGF-? expression. Survival rates of mice given 24 Gy to the whole lung ±UTI were also compared. Post-RT UTI reduced the score of lung fibrosis in mice, but concurrent UTI had no beneficial effects in irradiated mice. The fibrosis score in post-RT UTI mice was 3.2±1.0, which was significantly smaller than that of irradiated mice without UTI treatment (RT alone; 6.0±1.3; p2=0.26, p<0.01). The survival rate at 30 weeks for post-RT UTI mice was significantly better than that of RT alone mice (33% vs. 10%, p<0.05). The administration of post-RT UTI suppressed TGF- expression and radiation-induced lung fibrosis, which resulted in significant survival prolongation of the irradiated mice. (author)

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

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

  18. Radiation induced effects in the developing central nervous system

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2014-10-01

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

  20. Experimental Quantification of Delayed Radiation-Induced Organ Damage in Highly Irradiated Rats With Bone Marrow Protection: Effect of Radiation Dose and Organ Sensitivity.

    Science.gov (United States)

    Boittin, François-Xavier; Martigne, Patrick; Mayol, Jean-François; Denis, Josiane; Raffin, Florent; Coulon, David; Grenier, Nancy; Drouet, Michel; Hérodin, Francis

    2015-08-01

    The evolution of organ damage following extensive high-dose irradiation remains largely unexplored and needs further investigation. Wistar rats [with or without partial bone marrow protection (?20%)] were irradiated at lethal gamma-ray doses (12, 14, and 16 Gy) and received antibiotic support. While total-body-irradiated rats did not survive, bone marrow protection (achieved by protecting hind limbs behind a lead wall) combined with antibiotic support allowed survival of 12-Gy and 14-Gy irradiated rats for more than 3 mo, with a late phase of body weight loss and altered clinical status. Histological analysis of radiation-induced damages in visceral organs (liver, kidney, and ileum), performed 64 and 104 d after high-dose body irradiation, indicates that the extent and the evolution of damage depend on both the irradiation dose and organ. A dose-related aggravation of lesions was observed in the liver and kidney but not in the ileum. In contrast to the liver, alterations in the kidney and ileum aggravate with time, emphasizing the need to develop new efficient countermeasures to protect both the gastrointestinal tract and kidney from late-occurring radiation effects. Specifically, the complex evolution of organ damage presented in this paper offers the possibility to explore and then validate specific therapeutic windows using candidate drugs targeted to each injured visceral organ. PMID:26107434

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-09-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-05-10

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Zhi-Min [Harvard School of Public Health

    2013-04-28

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

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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)

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

    Directory of Open Access Journals (Sweden)

    Bertrand P. Tseng

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-12-11

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

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

    International Nuclear Information System (INIS)

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

  11. Ferulic acid protects human umbilical vein endothelial cells from radiation induced oxidative stress by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways

    International Nuclear Information System (INIS)

    Ferulic acid (FA) has been demonstrated to have a remarkable antioxidant activity, the mechanism of FA of protecting human umbilical vein endothelial cells (HUVECs) from radiation induced oxidative stress was investigated in the present study. The oxidative protection of FA was assessed by cellular glutathione (GSH) content, nicotinamide adenine dinucleotide phosphate (NADPH) levels, and reactive oxygen species (ROS) analysis. Nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation was detected using Western blotting. The upstream signaling pathway involved in FA mediated Nrf2 activation was determined by signaling inhibitors. FA significantly increased the transcription of antioxidant related genes such as GCLC (glutamate-cysteine ligase catalytic subunit), GCLM (glutamate-cysteine ligase regulatory subunit), NQO1 (NADPH quinone oxidoreductase-1) and heme oxygenase-1 (HO-1) mRNA in radiated cells, and these changes involved in a significant increase of the intracellular GSH content and the expression of NAPDH. FA evidently promoted NrfT2 translocation into nuclei and increased the intracellular GSH and NADPH levels in radiated cells. Phosphatidylinositol 3-kinase (PI3K) and extracellular signal regulated kinase (ERK) pathways were associated with FA-induced Nrf2 activation. The results suggested that FA-induced Nrf2 activation play key role in cytoprotective effect of FA against oxidative stress via PI3K and ERK signaling pathways. (author)

  12. Protective effect of various thiol compounds on radiation-induced mitotic delay in cultured mammalian cells (L-5)

    International Nuclear Information System (INIS)

    A comparison of the effects of 2-aminoethanthiol (MEA), 2-aminoethylisothiouronium bromide hydrobromide (AET), glutathione (GSH), 2-mercaptopropionylglycine (MPG), thiourea and cysteine has shown that their action is related to the cell cycle. They can be classified into two groups according to the mode of radioprotective action in mitotic delay. The compounds all had a protective effect on mitotic delay of S-phase cells at X-irradiation. MEA, AET and cysteine protected G2 phase, but GSH,MPG and thiourea had a lesser effect. (U.K.)

  13. 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

    International Nuclear Information System (INIS)

    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)

  14. The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes

    OpenAIRE

    MABLEY, JON G.; PACHER, PAL; Murthy, Kanneganti G K; Williams, William; Southan, Garry J.; Salzman, Andrew L.; Szabo, Csaba

    2008-01-01

    Endogenous purines including inosine have been shown to exert immunomodulatory and anti-inflammatory effects in a variety of disease models. The dosage of inosine required for protection is very high because of the rapid metabolism of inosine in vivo. The aim of this study was to determine whether a metabolic-resistant purine analogue, INO-2002, exerts anti-inflammatory effects in two animal models of type I diabetes. Type I diabetes was induced chemically with streptozotocin or genetically u...

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

    International Nuclear Information System (INIS)

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

  16. Ionizing radiation induced cataract

    International Nuclear Information System (INIS)

    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.)

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

    Science.gov (United States)

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

    2009-12-01

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

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

    International Nuclear Information System (INIS)

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

  19. 1,2,3,4,6-penta-?-galloyl-?-D-glucose protects splenocytes against radiation-induced apoptosis in murine splenocytes

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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

  3. The risk to health from low doses of ionising radiation

    International Nuclear Information System (INIS)

    Controversy continues over the shape of the dose-response curve describing the risk of stochastic health effects (cancer and hereditary disorders) following exposure to low doses of ionizing radiation. Radiological protection is currently based upon the assumption that the dose-response curve has no threshold and is linear in the low dose region. This position is challenged by groups suggesting either that this approach seriously underestimates the true risk at low doses or that low-level exposure results in no risk (a threshold dose exists) or even a beneficial effect ('radiation hormesis'). In this paper, the epidemiological and radiobiological bases of the linear no-threshold model and some of the alternatives that have been proposed, are discussed. It is concluded that the evidence for a material deviation from a linear no-threshold dose-response relationship at low doses is not persuasive and that the standard model provides the most parsimonious description of the available scientific evidence. (author)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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

  6. A randomized controlled trial of green tea catechins in protection against ultraviolet radiation–induced cutaneous inflammation12

    Science.gov (United States)

    Farrar, Mark D; Nicolaou, Anna; Clarke, Kayleigh A; Mason, Sarah; Massey, Karen A; Dew, Tristan P; Watson, Rachel EB; Williamson, Gary; Rhodes, Lesley E

    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-controlled trial to examine whether GTCs protect against clinical, histologic, and biochemical indicators of UVR-induced inflammation. Design: Healthy adults (aged 18–65 y, phototypes I–II) were randomly allocated to 1350 mg encapsulated green tea extract (540 mg GTC) with 50 mg vitamin C or placebo twice daily for 3 mo. Impact on skin erythema, dermal leukocytic infiltration, and concentrations of proinflammatory eicosanoids was assessed after solar-simulated UVR challenge, and subject compliance was determined through assay of urinary GTC metabolite epigallocatechin glucuronide. Results: Volunteers were assigned to the active (n = 25) or the placebo (n = 25) group. After supplementation, median (IQR) sunburn threshold (minimal erythema dose) was 28 (20–28) and 20 (20–28) mJ/cm2 in the active and placebo groups, respectively (nonsignificant), with no difference in AUC analysis for measured erythema index after a geometric series of 10 UVR doses. Skin immunohistochemistry showed increased neutrophil and CD3+ T-lymphocyte numbers post-UVR in both groups (P < 0.01) with no statistically significant differences between groups after supplementation. Cyclooxygenase and lipoxygenase metabolites prostaglandin E2 (vasodilator) and 12-hydroxyeicosatetraenoicacid (chemoattractant), respectively, increased after UVR (P < 0.05), with no differences between supplementation groups. Conclusion: Oral GTC (1080 mg/d) with vitamin C over 3 mo did not significantly reduce skin erythema, leukocyte infiltration, or eicosanoid response to UVR inflammatory challenge. This trial was registered at clinicaltrials.gov as NCT01032031. PMID:26178731

  7. Statistical and low dose response

    International Nuclear Information System (INIS)

    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

  8. Protective effect of topically applied polypeptide from Chlamys farreri against ultraviolet radiation-induced chronic skin damage in guinea pig

    Science.gov (United States)

    Chi, Mingliang; Cao, Pengli; Yu, Guoying; Zhu, Li; Wang, Yuejun; Wang, Chunbo

    2003-12-01

    Polypeptide from Chlamys farreri (PCF), a topical polypeptide isolated from Chlamys farreri, was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation. The chronic ultraviolet-irradiated guinea pig model was established, and visible changes in the skin including wrinkling, sagging and erythema were observed. Malondialdehyde (MDA) and antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in the dorsal skin were determined using biochemical methods. The results showed: (1) PCF (5 % and 20%) could greatly protect the dorsal skin of guinea pig against wrinkling, sagging and erythema induced by UV radiation in a concentration-dependent manner. (2) PCF could reduce MDA formation in the dorsal skin caused by UV irradiation, while increasing the activities of SOD and GSH-px. (3) The differences among the PCF groups and UV model group were significant ( P<0.05, P<0.01). These results indicated that topical application, of PCF provided broad solar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-06-15

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  13. Reduction in malformations by low dose pre-irradiation. The early beginning of adaptive response story in fetal mice

    International Nuclear Information System (INIS)

    Radiation-induced adaptive response is defined as the phenomenon of priming low-dose-induced resistance to subsequent irradiation at higher doses. Research on adaptive response, which provides important scientific basis for radiation risk estimates and offer significant insight into the defense mechanisms regarding radiation protection, is of great concern for both public health and academic research. In the in vitro examinations, diminished detrimental effects such as chromosome aberrations, mutations, transformation and cell death are documented. In the in vivo investigations, adaptive response is recorded mainly as a rescuing effect resulting in an improved survival. In a series of studies using an in utero model with fetal mice, we demonstrated the existence of adaptive response and characterized the experimental conditions for its successful induction. (author)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  17. Biological Effects of Low-Dose Exposure

    CERN Document Server

    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...

  18. Global DNA methylation responses to low dose radiation exposure

    International Nuclear Information System (INIS)

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

  19. Radiation Induced Fermion Resonance

    OpenAIRE

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

    1998-01-01

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

  20. A Paradigm Shift in Low Dose Radiation Biology

    Directory of Open Access Journals (Sweden)

    Z. Alatas

    2015-08-01

    Full Text Available When ionizing radiation traverses biological material, some energy depositions occur and ionize directly deoxyribonucleic acid (DNA molecules, the critical target. A classical paradigm in radiobiology is that the deposition of energy in the cell nucleus and the resulting damage to DNA are responsible for the detrimental biological effects of radiation. It is presumed that no radiation effect would be expected in cells that receive no direct radiation exposure through nucleus. The risks of exposure to low dose ionizing radiation are estimated by extrapolating from data obtained after exposure to high dose radiation. However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose radiation than they do to high dose radiation. Moreover, recent experimental evidences from many laboratories reveal the fact that radiation effects also occur in cells that were not exposed to radiation and in the progeny of irradiated cells at delayed times after radiation exposure where cells do not encounter direct DNA damage. Recently, the classical paradigm in radiobiology has been shifted from the nucleus, specifically the DNA, as the principal target for the biological effects of radiation to cells. The universality of target theory has been challenged by phenomena of radiation-induced genomic instability, bystander effect and adaptive response. The new radiation biology paradigm would cover both targeted and non-targeted effects of ionizing radiation. The mechanisms underlying these responses involve biochemical/molecular signals that respond to targeted and non-targeted events. These results brought in understanding that the biological response to low dose radiation at tissue or organism level is a complex process of integrated response of cellular targets as well as extra-cellular factors. Biological understanding of the effects of radiation can be used to improve the assessment of low dose radiation risk. In this article, the mechanisms of targeted and non-targeted responses, and interrelation between the phenomena on cellular injury after exposure to low doses of radiation as they relate to low dose radiation effects will be reviewed.

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

    Science.gov (United States)

    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.

  2. Risks to health from radiation at low dose rates

    International Nuclear Information System (INIS)

    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)

  3. The researches on the effects of low doses irradiation

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    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

  5. Radiation-induced nondisjunction

    International Nuclear Information System (INIS)

    The methodology and results of epidemiological studies of the effects of preconception diagnostic x-rays of the abdomen on chromosome segregation in humans are described. The vast majority of studies show the same positive, though not significant, trend to increased nondisjunction among the offspring of irradiated women. The results of the various studies, however, cannot be pooled because of differing methodologies used. Abnormal chromosome segregation during mitotic division has been inducted experimentally by the in vitro exposure of human lymphocytes to a low dose of 50 R gamma irradiation. First meiotic nondisjunction has been successfully induced by whole body exposure of female mice to a low dose of radiation. The question of time-related repair of the mechanism involved in chromosome segregation is raised

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

    Science.gov (United States)

    Hegyesi, Hargita; Sándor, Nikolett; Schilling, Boglárka; Kis, Enik?; 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 ?-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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-31

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

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

    International Nuclear Information System (INIS)

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

  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). WR-33278 and spermine protect against mutation induction

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Cheryl G. Burrell, Ph.D.

    2012-05-14

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

  12. Consequences for general practice: exposure with low doses

    International Nuclear Information System (INIS)

    New radiobiological findings like genomic instability and genetic predisposition did not only give an impetus to research activities but prompted also the assumption that radiation protection has to be revised. This paper outlines possible consequences for the practically relevant area of low doses. It begins with a discussion of damage distributions after low dose exposure including a critical evaluation of the applicability of this quantity. The radiobiological findings which started the present discussion are briefly summarised as well as the results of new studies in genetics. Possible consequences might be envisaged for the evaluation of epidemiological investigations, both with regard to radiation related cancer risk as well as to the possible occurrence of radiation-related non-cancer diseases. In conclusion it is stated that the new findings will not lead to an upward revision of present risk factors and hence there is no need for fundamental changes of the current system of radiation protection. (orig.)

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Radiation induced pesticidal microbes

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-01-01

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

  16. Radiation induced pesticidal microbes

    International Nuclear Information System (INIS)

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

  17. Radiation Induced Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F.

    2011-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

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

    International Nuclear Information System (INIS)

    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.)

  20. Organ Specific Gene Expression by Low Dose Radiation

    International Nuclear Information System (INIS)

    Whole gene expression profiling has become one of the most widely used approaches identify genes and their functions in the context of specific biological questions. There is growing acknowledgement of the usefulness of determining expression patterns to identify and categorize genes, be it to use as disease markers, to discover drug targets, to map specific pathways, or to find markers of drug toxicity in early drug testing. Cellular and tissue sensitivity against ionizing radiation depends on many endogenous gene expression patterns. It is well known that various stimuli such as ionizing radiation produce genetic alteration and an important factor seems to be whether the cell dies, repair all the damage, undergoes defective repair or responds in a way which leads to transformation. The decision whether the damage is dealt with apoptosis, rescue or repair is critical. Death of the individual cell removes the problem from the tissue, however, if the cell does not die, it may acquire genomic instability and lead to a population of cells with abnormally high susceptibility to chromosomal instability mutation and other delayed effects. Studies using inbred strains of rodents have clearly shown genotype-dependent differences in response to radiation exposure, including susceptibility to radiation-induced cellular transformation and tumor formation, as well as differences in susceptibility to radiation-induced chromosomal instability. In this study, we analyzed the genes which have previously been reported to be overexpressed in human peripheral blood lymphocytes, in brain, heart, spleen, intestine, and lung which have been shown to have different intrinsic radiosensitivity, especially after low dose radiation exposure (0.2Gy), and examined the correlation between gene expression patterns and organ sensitivity and attempted to identify genes which are possibly responsible for radiation sensitivity

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

    Energy Technology Data Exchange (ETDEWEB)

    Kleiman, Norman Jay [Columbia University

    2013-11-30

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

  2. RIS - radiation induced superheroes

    International Nuclear Information System (INIS)

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

  3. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    Science.gov (United States)

    Jiang, Erkang; Wu, Lijun

    2009-04-01

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

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

    International Nuclear Information System (INIS)

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

  5. Biological influence from low dose and low-dose rate radiation

    International Nuclear Information System (INIS)

    Although living organisms have defense mechanisms for radioadaptive response, the influence is considered to vary qualitatively and quantitatively for low dose and high dose, as well as for low-dose rate and high-dose rate. This article describes the bioresponse to low dose and low-dose rate. Among various biomolecules, DNA is the most sensitive to radiation, and accurate replication of DNA is an essential requirement for the survival of living organisms. Also, the influence of active enzymes resulted from the effect of radiation on enzymes in the body is larger than the direct influence of radiation on the body. After this, the article describes the carcinogenic risk by low-dose radiation, and then so-called Hormesis effect to create cancer inhibition effect by stimulating active physiology. (S.K.)

  6. The biological effects of low doses of radiation: medical, biological and ecological aspects

    International Nuclear Information System (INIS)

    Full text: The results of recent studies show that low doses of radiation make many different structural and functional changes in a cell and these changes are preserved for a long time. This phenomenon is called as effects of low doses of radiation in biophysics, radiation biology and radiation medicine. The structural and functional changes depend on doses and this dependence has non-linear and bimodal behaviour. More detail, the radiation effect goes up and reaches its maximum (Low doses maximum) in low doses region, then it goes down and takes its stationary means (there is a negative effect in a few cases). With increases in doses and with further increases it goes up. It is established that low dose's maximum depends on physiological state of a biological object, radiation quality and dose rate. During the experiments another special date was established. This specialty is that many different physical and chemical factors are mutually connected and have synergetic behaviour. At present, researches are concentrating their attention on the following three directions: 1. Direct and indirect interaction of radiation's low doses: 2. Interpretation of its molecular mechanism, regulation of the positive effects and elaboration of ways o removing negative effects: 3. Application of the objective research results into practice. In conclusion the authors mention the current concepts on interpretation of low doses effect mechanism, forward their own views and emphasize the importance of considering low doses effects in researches of environmental radiation pollution, radiation medicine and radiation protection. (author)

  7. Long-term effects of monthly low dose whole-body irradiation on the glutathione status and thiobarbituric acid reactive substances of different organs of male Wistar rats

    International Nuclear Information System (INIS)

    Male Wistar-H rats were exposed monthly to a 60Co low dose whole-body irradiation (0.25 Gy, total dose: 4.5 Gy). The glutathione disulphide total glutathione ratio, the concentration of thiobarbituric acid reactive substances and the activities of glutathione peroxidase and glutathione transferase in eight different organs and blood were analyzed. The low dose irradiation is accompanied by distinct peroxidative changes in organs. These oxidative loadings occur in the small intestine, spleen and kidneys. The measurements of glutathione status and of thiobarbituric acid reactive substances are proposed as sensitive parameters for low dose radiation-induced changes. (author)

  8. Long term effects of monthly low dose whole body irradiation on the glutathione status and thiobarbituric acid-reactive substances in different organs of male Wistar rats

    International Nuclear Information System (INIS)

    Male Wistar-H rats were exposed monthly to a 60Co source low dose whole-body irradiation (0.25 Gy, total dose 4.5 Gy). The glutathione disulphide: total glutathione ratio, the concentration of thiobarbituric acid-reactive substances and the activities of glutathione peroxidase and glutathione transferase in eight different organs and blood were analysed. The low dose irradiation is accompanied by distinct peroxidative changes in organs. These oxidative loadings occur in the small intestine, the spleen and the kidneys. The measurements of glutathione status and of thiobarbituric acid-reactive substances are proposed as sensitive parameters for low dose radiation-induced changes. (author)

  9. Stimulation of seeds by low dose irradiation

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  11. 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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  12. MELODI: the 'Multidisciplinary European Low-Dose Initiative'.

    Science.gov (United States)

    Belli, M; Salomaa, S; Ottolenghi, A

    2011-02-01

    The importance of research to reduce uncertainties in risk assessment of low and protracted exposures is now recognised globally. In Europe a new initiative, called 'Multidisciplinary European LOw Dose Initiative' (MELODI), has been proposed by a 'European High Level and Expert Group on low-dose risk research' (www.hleg.de), aimed at integrating national and EC (Euratom) efforts. Five national organisations: BfS (DE), CEA (FR), IRSN (FR), ISS (IT) and STUK (FI), with the support of the EC, have initiated the creation of MELODI by signing a letter of intent. In the forthcoming years, MELODI will integrate in a step-by-step approach EU institutions with significant programmes in the field and will be open to other scientific organisations and stakeholders. A key role of MELODI is to develop and maintain over time a strategic research agenda (SRA) and a road map of scientific priorities within a multidisciplinary approach, and to transfer the results for the radiation protection system. Under the coordination of STUK a network has been proposed in the 2009 Euratom Programme, called DoReMi (Low-Dose Research towards Mutidisciplinary Integration), which can help the integration process within the MELODI platform. DoReMi and the First MELODI Open Workshop, organised by BfS in September 2009, are now important inputs for the European SRA. PMID:21106638

  13. Low dose effects detected by micronucleus assay in lymphocytes

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  16. Radiation-induced detriment in the population

    International Nuclear Information System (INIS)

    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)

  17. Radiation-induced cancers in man

    International Nuclear Information System (INIS)

    Radiation-induced cancers in man were divided into three groups, a group in which cancers occurred after atomic bomb exposure, a group in which cancers occurred in radiologists and other medical specialists, and a group in which cancers occurred after exposure to diagnostic radiation, and they were summarized. In atomic bomb survivors leukemia, thyroid cancer, salivary gland cancer, lung cancer, and breast cancer occurred so frequently. In addition to them, mortality ratios by malignant lymphoma, stomach cancer, esophageal cancer, and by cancer of urinary tract were increased. The incidence of leukemia was decreased in those who treated radiation owing to the development of the protection of occupational exposure, and the incidence of radiation-induced cancers was decreased in patients owing to the improvement of therapy. However, a new problem has arisen as to the occurrence of cancers after medical exposure, such as various histological types of cancers after the treatment of skin diseases on the head, and breast cancer after the treatment of pneumothorax. Dose-to-effect relation, hereditary factors, effect of age, immunological influences and endocrine actions were also studied in each radiation-induced cancer. (Ichikawa, K.)

  18. Low dose irradiation reduces cancer mortality rates

    International Nuclear Information System (INIS)

    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)

  19. 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)

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

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

  1. Ionizing radiation: effects of low doses

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  3. Low-Dose Computed Tomography Protocols

    International Nuclear Information System (INIS)

    Complementary diagnostic means, namely CT, contribute decisively to the quality of modern health care. However, the eventual deleterious effects caused by radiation must be taken into account. It is essential to implement measures aiming to reduce the irradiation dose, according to the ALARA (as low as reasonable achievable) policy. Image quality must not be chosen over potential irradiation consequences. The authors intend to demonstrate the feasibility of obtaining images with clinical diagnostic quality while using low dose radiation protocols. (author)

  4. Tardive dyskinesia with low dose amisulpride

    OpenAIRE

    Tharoor, Hema; Padmavati, R

    2013-01-01

    In recent years, there has been an increasing trend to use amisulpride in the treatment of dysthymia and also as an adjunct treatment in patients with major depression. At low doses (50 mg), amisulpride preferentially blocks presynaptic auto receptors, enhances dopamine release, and therefore acts as a dopaminergic compound able to resolve the dopaminergic hypo activity that characterizes depression. Based on experimental data, amisulpride is the drug of choice for dopaminergic transmission d...

  5. Estimation of radiation risks at low dose

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  7. Global DNA methylation responses to low dose radiation exposure

    International Nuclear Information System (INIS)

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

  8. Ionizing radiation induces myofibroblast differentiation via lactate dehydrogenase.

    Science.gov (United States)

    Judge, J L; Owens, K M; Pollock, S J; Woeller, C F; Thatcher, T H; Williams, J P; Phipps, R P; Sime, P J; Kottmann, R M

    2015-10-15

    Pulmonary fibrosis is a common and dose-limiting side-effect of ionizing radiation used to treat cancers of the thoracic region. Few effective therapies are available for this disease. Pulmonary fibrosis is characterized by an accumulation of myofibroblasts and excess deposition of extracellular matrix proteins. Although prior studies have reported that ionizing radiation induces fibroblast to myofibroblast differentiation and collagen production, the mechanism remains unclear. Transforming growth factor-? (TGF-?) is a key profibrotic cytokine that drives myofibroblast differentiation and extracellular matrix production. However, its activation and precise role in radiation-induced fibrosis are poorly understood. Recently, we reported that lactate activates latent TGF-? through a pH-dependent mechanism. Here, we wanted to test the hypothesis that ionizing radiation leads to excessive lactate production via expression of the enzyme lactate dehydrogenase-A (LDHA) to promote myofibroblast differentiation. We found that LDHA expression is increased in human and animal lung tissue exposed to ionizing radiation. We demonstrate that ionizing radiation induces LDHA, lactate production, and extracellular acidification in primary human lung fibroblasts in a dose-dependent manner. We also demonstrate that genetic and pharmacologic inhibition of LDHA protects against radiation-induced myofibroblast differentiation. Furthermore, LDHA inhibition protects from radiation-induced activation of TGF-?. We propose a profibrotic feed forward loop, in which radiation induces LDHA expression and lactate production, which can lead to further activation of TGF-? to drive the fibrotic process. These studies support the concept of LDHA as an important therapeutic target in radiation-induced pulmonary fibrosis. PMID:26254422

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-29

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Leenhouts, H P [Bennekom (Netherlands); Chadwick, K H, E-mail: kennethhchadwick@aol.com [Cowan Head, Kendal (United Kingdom)

    2011-03-01

    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.

  11. Food preservation by irradiation at low doses

    Energy Technology Data Exchange (ETDEWEB)

    Freita, Renildes Matos de; Gavazza, Sergio; Morales, Rudnei Karam [Instituto Militar de Engenharia IME, Rio de Janeiro, RJ (Brazil). Secao de Engenharia Nuclear]. E-mail: renildes@gmail.com; gavazza@ime.eb.br; d7karam@ime.eb.br; Vital, Helio de Carvalho [Centro Tecnologico do Exercito CTEx, Rio de Janeiro, RJ (Brazil)]. E-mail: vital@ctex.eb.br

    2007-07-01

    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)

  12. Low doses: myth or true danger

    International Nuclear Information System (INIS)

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

  13. Low-dose oral iron absorption test

    DEFF Research Database (Denmark)

    Jensen, N M; Brandsborg, M; Boesen, A M; Yde, H; Dahlerup, Jens Frederik

    1998-01-01

    The low-dose oral iron absorption test (OIAT), a possible test for iron deficiency, is based on the fact that intestinal iron absorption is higher in iron-deficient subjects than in those with normal or increased iron stores. The aims of this study were to establish a reference interval for the OIAT, to evaluate five different ways of presenting the results, and to advocate for the use of one of these methods. OIAT was performed in 122 healthy volunteers, 3 of whom were excluded as a result of t...

  14. Food preservation by irradiation at low doses

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    We have tested the hypothesis that the alcoholic and phenolic components of wine are protective against the DNA damaging and cytotoxic effects of hydrogen peroxide and gamma radiation in vitro. The components of wine tested were ethanol, glycerol, a mixture of the phenolic compounds catechin and caffeic acid, and tartaric acid, all at concentrations that were 2.5% or 10.0% of the concentration in a typical Australian white wine Riesling. These components were tested individually or combined as a mixture and compared to a white wine stripped of polyphenols as well as a Hanks balanced salt solution control which was the diluent for the wine components. The effect of the components was tested in lymphocytes, using the cytokinesis-block micronucleus assay, after 30 minutes incubation in plasma or whole blood for the hydrogen peroxide or gamma-radiation challenge respectively. The results obtained showed that ethanol, glycerol, the catechin-caffeic acid mixture, the mixture of all components, and the stripped white wine significantly reduced the DNA damaging effects of hydrogen peroxide and gamma radiation (ANOVA P = 0.043 - 0.001). The strongest protective effect against DNA damage by gamma irradiation was observed for the catechin-caffeic acid mixture and mixture of all components (30% and 32% reduction respectively). These two treatments as well as ethanol produced the strongest protective effects against DNA damage by hydrogen peroxide (24%, 25% and 18% respectively) . 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

  17. Exposure to low dose radiation and its effect

    International Nuclear Information System (INIS)

    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.)

  18. Radiation-induced cataract

    International Nuclear Information System (INIS)

    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)

  19. Genes activated by low dose radiation

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    A model for carcinogenesis (the TSCE model) was applied in order to examine the effects of ''Low-dose hypersensitivity (LDH)'' and the ''Bystander effect (BE)'' on the derivation of radiation related cancer mortality risks. LDH has been discovered to occur in the inactivation of cells after acute exposure to low LET radiation. A corresponding version of the TSCE model was applied to the mortality data on the Abomb survivors from Hiroshima and Nagasaki. The BE has been mainly observed in cells after exposure to high LET radiation. A Version of the TSCE model which included the BE was applied to the data on lung cancer mortality from the workers at the Mayak nuclear facilities who were exposed to Plutonium. In general an equally good description of the A-bomb survivor mortality data (for all solid, stomach and lung tumours) was found for the TSCE model and the (conventional) empirical models but fewer parameters were necessary for the TSCE model. The TSCE model which included the effects of radiation induced cell killing resulted in non-linear dose response curves with excess relative risks after exposure at young ages that were generally lower than in the models without cell killing. The main results from TSCE models which included cell killing described by either conventional survival curves or LDH were very similar. A sub multiplicative effect from the interaction of smoking and exposure to plutonium was found to result from the analysis of the Mayak lung cancer 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.)

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

    International Nuclear Information System (INIS)

    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 ?g/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 ?g/ mL of alcoholic Cassia fistula extracts which showed a protection against irradiated groups. (author)

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

    International Nuclear Information System (INIS)

    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)

  4. [Extrapolation of dose-effect relationships for cytogenetic aberrations from high to low doses].

    Science.gov (United States)

    Eidus, L Kh

    1999-01-01

    It is known, that extrapolation of dose response curve for cytogenic lesions, based on the linear non-threshold concept is not correct due to anomalies in the low dose region, among them the dose intervals of the so-called "low dose effects" (LDE) and "plato"-effect. As a rule they are attributed to assumed heterogeneity of cell populations or to existence of several repair systems. Analysing the data on modification the cytogenetic lesions we concluded, that in the whole low-dose range functions one on the same repair system, but it "switches on" only at sufficient reorganization of chromatin (accompanied by expression of before "silent" genes), caused by radiation-induced increase of the membranes permeability. In the dose interval of LDE this occurs only in vary narrow diapason of dose rate (approximately(1-30) cGy/min for many cell kinds); in the "plato" dose interval--in its beginning. By the assessment of cancerogenic risk the linear non threshold concept can be used only for dose dependence, obtained when repair is absent or inhibited. PMID:10347611

  5. Adaptive response to mutagenesis and its molecular basis in a human T-cell leukemia line primed with a low dose of ?-rays

    International Nuclear Information System (INIS)

    The effect was studied of a low dose of ?-ray preexposure on the frequency and molecular spectrum of radiation-induced mutations at the hprt locus in a human T-cell leukemia line. When the cells were preexposed to 0.01 Gy of ?-rays, the yield of mutations induced by a subsequent 2-Gy challenge dose was reduced by 60%, compared with the 2 Gy of irradiation alone. The data of Southern blot analysis showed that 47% of the mutants induced by 2 Gy in the cells without low-dose preexposure were of the deletion or rearranged mutations type. In contrast, in the low-dose radioadapted cells the proportion of this type of 2-Gy-induced mutations decreased to 28%. This is close to the control level (22%) of spontaneous mutations. Our results confirm that a low dose of ?-ray preexposure leads to a decreased susceptibility to gene deletions and rearrangements after high-dose irradiation. (orig.)

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

    International Nuclear Information System (INIS)

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

  7. Health effects of low dose radiation

    International Nuclear Information System (INIS)

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

  8. How to understand low dose risks

    International Nuclear Information System (INIS)

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

  9. 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

    International Nuclear Information System (INIS)

    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)

  10. Radiation induced crosslinking of polytetrafluoroethylene

    International Nuclear Information System (INIS)

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

  11. Low dose irradiation creep of pure nickel

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Simon Bouffler

    2010-07-28

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

  13. Radiation-induced heart injury

    International Nuclear Information System (INIS)

    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.)

  14. Radiation-induced brain injury

    International Nuclear Information System (INIS)

    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)

  15. Radiation-induced chromosomal instability

    International Nuclear Information System (INIS)

    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/?m) 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.)

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Spitz, Douglas R.

    2009-11-09

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

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

    International Nuclear Information System (INIS)

    Complete text of publication follows. Objective: The objective of this study is to detect the noble proteins that were functionally regulated by change of arginine methylation through irradiation of the low dose. The increase of the arginine methylation which is induced by low dose gamma-ray will have meaningful Introduction: Exposure of cells to low doses of radiation has well documented biological effect, but the underlying regulatory mechanisms are still poorly understood. Arginine methylation is a post translational modification that results in the formation of asymmetrical and symmetrical dimethylated arginines. Post-translational methylation of arginine residues of proteins involved in a growing number of cellular processes, including transcriptional regulation, cell signaling, RNA processing and DNA repair, biological influence. Methods: Human normal cell line Chang-liver was irradiation by gamma-ray of 0.02Gy, 0.2Gy. After irradiation, cells were incubated for 4h, 8h, 24h, and then harvested to prepare protein extracts. ASYM24(anti-dimethyl-Arginine, asymmetric) antibody was used to Western blot and immunoprecipitation. Proteins that show different degrees of intensity between the two samples were analyzed by Mass spectrometry. Results: We detected increased asymmetric arginine methylation of two proteins at 24h after a dose of 0.2Gy irradiation. The mass spectrometry identified that it is 27kDa and 73kDa proteins. The 27kDa is hypothetical protein that 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.

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Jansen-van der Weide, Marijke C. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands); Greuter, Marcel J.W.; Pijnappel, Ruud M. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); Jansen, Liesbeth [University Medical Center Groningen, University of Groningen, Department of Surgery, Groningen (Netherlands); Oosterwijk, Jan C. [University Medical Center Groningen, University of Groningen, Department of Clinical Genetics, Groningen (Netherlands); Bock, Geertruida H. de [University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands)

    2010-11-15

    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.)

  1. Factors that modify risks of radiation-induced cancer

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Tomita, Masanori; Maeda, Munetoshi

    2014-01-01

    Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology....

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

    Directory of Open Access Journals (Sweden)

    Mayado Andrea

    2011-11-01

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

  4. low dose irradiation growth in zirconium

    International Nuclear Information System (INIS)

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

  5. Contraception. Low-dose pill launched.

    Science.gov (United States)

    1993-01-01

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

  6. Effects of low doses: Proof and inferences

    International Nuclear Information System (INIS)

    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)

  7. Prevention of radiation induced taste aversion in rats

    International Nuclear Information System (INIS)

    Diltiazem, a calcium channel blocker, and a cardiovascular therapeutic agent offers significant protection to mice against lethal dose of ionizing radiation. Considering the potential efficacy of diltiazem as a radioprotector for human use, it was deemed necessary to investigate its influence on radiation-induced behavioural changes like nausea, vomiting, learning, memory and performance. In the present studies, conditioned taste aversion (CTA) test based on consumption of saccharin solution, was used as a marker of behavioural changes. Significant CTA (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)

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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

  11. The line-threshold effects after low doses gamma-irradiation

    International Nuclear Information System (INIS)

    The dose-independent effects in the low-dose diapason after ?-irradiation the invertebrate hydrobiontes in a broad variety of doses had been observed. Then a threshold transition to the new functional level below control took place. The mechanism of non line effects in the low doses irradiation has been connecting with the epigenetic processes in the cells and the elimination of genetic damages. It's necessary to underline the significance of the discovered data in view of the radiation protection problem. It follows from the experiments, that already the low levels of radiation contamination of the reservoirs is dangerous for investigating species. (authors)

  12. Radiation-induced cardiovascular effects

    Science.gov (United States)

    Tapio, Soile

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

  13. Particle radiation-induced genetic damage in vivo

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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).

  15. Effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

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

  16. Biological effects of low-dose irradiation

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Low dose and the adaptation process in human lymphocytes

    International Nuclear Information System (INIS)

    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)

  2. Radiation-induced thermoacoustic imaging

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

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

  4. Advances in study of biological effects with low-dose rate irradiation

    International Nuclear Information System (INIS)

    The dose rate with which radiation is delivered significantly affects the biological response to radiation and reducing the dose rate decreases the biological effect. However, DNA damage introduced at a reduced rate does not activate the DNA damage sensor ATM and that failure to activate ATM-associated repair pathways contributes to the increased lethality of continuous radiation exposures, which has been termed the 'inverse dose rate effect'. Under continuous low dose rate irradiation, there are two major pathways by which DSB's can be repaired, nonhomologous end joining (NHEJ), and homologous recombination (HR), which play an important role in sublethal damage repair and the generation of dose-rate effect. A change in sensitivity is modified if DNA damage can be repaired with high fidelity. The cells will lead to apoptosis if the cell DNA damage is not sufficiently repaired. The p53 gene is a key factor in he radiation-induced the cell cycle arrest and the activation of apoptosis after exposure to low dose-rate irradiation. (authors)

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

    International Nuclear Information System (INIS)

    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.)

  6. Significance of low dose hypersensitivity in fractionated radiotherapy

    International Nuclear Information System (INIS)

    Objective: To analyze the influences of the low radiation dose hypersensitivity (LDH) to the dose-effect relationship of fractionated radiotherapy. Methods: Collect data of LDH from literature and do curve fit for cell survival curve. Condition to join the data set: the lowest dose and dose increment in the experiment were less than 0.1 and 0.2 Gy, respectively. Based on parameters of the fit curve and fraction-effect relationship curve of fractionated irradiation were to be simulated. Result:(1) Four modes were classified according to cell's capacity of LDH and resistance to higher dose radiation. Mode A: LDH was not marked and radiation resistance could be seen in higher dose irradiation in these cells. Mode B: LDH was marked but radiation resistance could be seen in higher dose irradiation. Mode C: LDH was not marked but radiation sensitivity could be seen in higher dose irradiation. Mode D: LDH was marked and radiation sensitivity could be seen in higher dose irradiation. (2) The fraction-effect relationship curve was a multiphase curve: in very low fraction size (less than 0.3 Gy in V79), the curve came down rapidly with high dose efficiency. Subsequently, the speed of curve drop became so slow as to become negative in some cell lines with high LDH and the fraction dose efficiency declined comparing with low dose irradiation. After the above radiation resistant scope, which was about 0.5 to 1.0 Gy, the curve started to drop monotonically with the increment of dose according to the LQ Model. (3) According to the above fraction-effect curve, the sense of fraction modes that had been used in current radiotherapy should be reconsidered. Ultrafractionation: the dose efficiency of the radiation in low dose could be used adequately in this mode, so it may be a effective fractionation for cells with marked LDH such as in B or D cell. Hyperfractionation : this fractionation was designed to improve the total effect through increased total dose by upping of fraction number with downing of fraction size. As downing of fraction size would decrease the dose efficiency, whether the total effect being improved was not ensured. Routine mode with 1.5-2.5 Gy per fraction was a compromise between fraction efficiency and normal tissue protection. Hypofractionation with > 2.5 Gy per fraction was satisfactory in fraction efficiency, but special technology such as conformal radiation or heavy iron would have to be used to protect the normal tissue. Conclusions: The fraction-effect curve from 0.1 to several Gy of fraction size is a multiphase but not a monotonic fall curve that has been prefigured in LQ model. If the low dose hypersensitivity is considered, the small change of dose efficiency will lead to magnitude difference in total effect after multi-fractions radiotherapy for the role of exponentially enlarging fractionation. This multiphase fraction-effect curve is significant in the evaluation and determination of fractionation mode and protection of normal tissue in clinical practice of radiotherapy

  7. Radiation-induced apoptosis in microvascular endothelial cells.

    OpenAIRE

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

    1997-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Eric Y. Chuang

    2006-08-31

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

  9. Radiation induced lipid peroxidation: role for Ca2+

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Kathy Held; Kevin Prise; Barry Michael; Melvyn Folkard

    2002-12-14

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

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

    International Nuclear Information System (INIS)

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

  12. Risk of cancer subsequent to low-dose radiation.

    Science.gov (United States)

    Warren, S

    1980-10-01

    Prominent among media items related to the Three Mile Island episode were prophecies of future cancers. The credibility of some of these estimates are discussed. The average person has been exposed by the age of 50 to 2.5 rad (0.025 Gy) from natural background. We define low doses as under 25 rad (0.25 Gy). The most heavily exposed members of the general population during the Three Mile Island event received 83 mrad (0.83 mGy). Those exposed to 2500 mrad (25 mGy) would show no pathologically recognizable effects of radiation though there is evidence that chromosomal damage may occur with doses about 1 rad (0.01 Gy). An official stated among the consequences of the Three Mile Island accident that two additional cancer deaths would result. No epidemiologist could detect such an increase in the population at risk. It has been generally agreed that the linear hypothesis is useful for determining protection standards, not prognosis. Objective criteria for pathologic diagnosis of cause-effect relations are presented. PMID:7430985

  13. Radiation induced sulfur dioxide removal

    International Nuclear Information System (INIS)

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

  14. Radiation-induced heat diseases

    International Nuclear Information System (INIS)

    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

  15. Radiation induced osteogenic sarcoma of the maxilla

    Directory of Open Access Journals (Sweden)

    Ramchandran Krishnankutty

    2005-07-01

    Full Text Available Abstract Background Radiation induced sarcoma arise as a long term complication of radiation treatment for other benign or malignant conditions. They are of very rare occurrence in jaw bones and are even rarer in maxilla. Case presentation Here we report a case of radiation induced sarcoma in a patient treated for squamous cell carcinoma of buccal mucosa with radiation who developed osteosarcoma of maxillary bone after six years. The patient was treated successfully with surgery. Conclusion What should be the best treatment of radiation induced sarcoma is still debatable; however, surgery offers the best chance of cure. Role of reradiation and adjuvant chemotherapy needs to be further evaluated.

  16. Risk of cancer subsequent to low-dose radiation

    International Nuclear Information System (INIS)

    The author puts low dose irradiation risks in perspective using average background radiation doses for standards. He assailed irresponsible media coverage during the height of public interest in the Three-Mile Island Reactor incident

  17. Topics on study of low dose-effect relationship

    International Nuclear Information System (INIS)

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

  18. Low Dose Rate (LDR) Ir-192 Wire Source for Brachytherapy

    International Nuclear Information System (INIS)

    This article reviews several aspects of overloading brachytherapy using low dose rate radioactive sources especially Ir-192 wire sources. The rationale for low dose rate is referred and the advantages of Ir-192 were also considered. The importance of accurate radioactivity calibration is stresses and the radiocalorimetric method is suggested as a new quality control technique. The present status of the low dose rate Ir-192 brachytherapy in Japan is briefly described along and this example of clinical practices in this technique. The status in Indonesia is also quoted by introducing the recent commencement of cooperation between the Batan and the Hasan Sadikin Hospital, Bandung. As a summary of author appeals the importance of low dose rate brachytherapy using Ir-192 source with has a potential of development and dissemination with a number of advantageous characteristics for both production and utilization sectors

  19. Applicability of heminal mechanism to description of radiation-induced conductivity of polymers

    International Nuclear Information System (INIS)

    Numerical calculations of radiation-induced conductivity transitional process under homogeneous and Nable generation of separated ion pairs are carried out for a model dielectric simulating high-pressure polyethylene (HPPE) or polytetrafluoroethylene (PTPE) at the absence of pair overlapping (irradiation low dose). The obtained results are compared with the available experimental data. Additional factor explaining kinetic braking of the pair recombination and the ensuing discription of Langevia mechanism of charge carrier volume recombination is required to correlate the experimental results with the theory of heminal conductivity in HPPE, PTFE and polyprolyelene type polymers. 20 refs., 3 figs., 3 tabs

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

    Energy Technology Data Exchange (ETDEWEB)

    Barry D. Michael; Kathryn Held; Kevin Prise

    2002-12-19

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

  1. Low Dose Combination Steroids Control Autoimmune Mouse Hearing Loss

    OpenAIRE

    Trune, Dennis R; Kempton, J Beth

    2010-01-01

    The severe side effects of glucocorticoids prevent long term management of hearing loss. Alternative steroid treatments that minimize or eliminate these effects would significantly benefit therapeutic control of hearing disorders. A steroid treatment study of mouse autoimmune hearing loss was conducted to determine the efficacy of combining aldosterone and prednisolone at low doses. An assessment also was made of low dose fludrocortisone, a synthetic mineralocorticoid that also has a slight g...

  2. Development of Plant Application Technique of Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-07-15

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

  3. Development of Plant Application Technique of Low Dose Radiation

    International Nuclear Information System (INIS)

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

  4. The effect of caffeine on radiation-induced division delay

    International Nuclear Information System (INIS)

    Caffeine (100 ?g/ml) was added to monolayer cultures of Chinese hamster ovary cells coincident with 60Co ?-irradiation (75 to 300 rad). The results indicated that caffeine (at concentrations that did not perturb cell-cycle progression as monitored by the mitotic selection technique) exerted a protective effect against radiation-induced division delay. This protection consisted of an increase in the number of cells that were refractory to the radiation insult, as well as a decrease in the average time that non-refractory cells were delayed before they recovered their ability to progress through the cell cycle. (U.K.)

  5. Radiation-induced moyamoya syndrome

    International Nuclear Information System (INIS)

    Purpose: The moyamoya syndrome is an uncommon late complication after radiotherapy (RT). Methods and Materials: A PubMed search of English-language articles, with radiation, radiotherapy, and moyamoya syndrome used as search key words, yielded 33 articles from 1967 to 2002. Results: The series included 54 patients with a median age at initial RT of 3.8 years (range, 0.4 to 47). Age at RT was less than 5 years in 56.3%, 5 to 10 years in 22.9%, 11 to 20 years in 8.3%, 21 to 30 years in 6.3%, 31 to 40 years in 2.1%, and 41 to 50 years in 4.2%. Fourteen of 54 patients (25.9%) were diagnosed with neurofibromatosis type 1 (NF-1). The most common tumor treated with RT was low-grade glioma in 37 tumors (68.5%) of which 29 were optic-pathway glioma. The average RT dose was 46.5 Gy (range, 22-120 Gy). For NF-1-positive patients, the average RT dose was 46.5 Gy, and for NF-1-negative patients, it was 58.1 Gy. The median latent period for development of moyamoya syndrome was 40 months after RT (range, 4-240). Radiation-induced moyamoya syndrome occurred in 27.7% of patients by 2 years, 53.2% of patients by 4 years, 74.5% of patients by 6 years, and 95.7% of patients by 12 years after RT. Conclusions: Patients who received RT to the parasellar region at a young age (<5 years) are the most susceptible to moyamoya syndrome. The incidence for moyamoya syndrome continues to increase with time, with half of cases occurring within 4 years of RT and 95% of cases occurring within 12 years. Patients with NF-1 have a lower radiation-dose threshold for development of moyamoya syndrome

  6. Genomic alterations in radiation-induced murine acute myeloid leukemias

    International Nuclear Information System (INIS)

    High-dose radiation induces acute myeloid leukemia (AML) in C3H mice, most of which have a high frequent hemizygous deletion around the D2Mit15 marker on the interstitially deleted region of chromosome 2. This region involves PU.1 (Sfpi-1), which is a critical candidate gene for initiation of mouse leukemogenesis. To identify other genes contributing to leukemogenesis with PU.1, we analyzed chromosomal aberrations and changes of expression in 18 AML-related genes in 39 AMLs. Array CGH analysis revealed that 35 out of 39 AMLs had hemizygous deletions of chromosome 2, and recurrent aberrations on chromosomes 4, 6, 8, 10, 11, 12, 15, and 18. Expressions of 18 AML-related genes, within the altered chromosome regions detected by array CGH were analyzed by using RT-PCR and/or real-time PCR. Although Wnt5b, Wnt16, G-CSFR, M-CSFR, SCL/Tal-1 and GATA1 genes were down-regulated, the c-myc gene was, on the contrary, up-regulated. Expression levels of two genes, Rasgrp1 and Wt1, within the deleted region of chromosome 2 correlated with the loss of one of two alleles, although the expression of PU.1 showed an inverse correlation. In addition, the expression level of PU.1 appeared to be higher with a coincidental missense point mutation in DNA-binding domain of PU.1 in the remaining allele, suggesting a feedback transcription control on PU.1. Such an autoregulation might be relevant to the fact that PU.1 haploinsufficiency per se triggers radiation-induced AML. Together with the detection of chromosomal aberrations, these findings provide useful clues to identify cooperative genes that are responsible for molecular pathogenesis of AMLs induced by low-dose-rate radiation exposure. (author)

  7. Radiation-induced carcinoma of the penis

    International Nuclear Information System (INIS)

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

  8. Effects of low doses of Tat-PIM2 protein against hippocampal neuronal cell survival.

    Science.gov (United States)

    Woo, Su Jung; Shin, Min Jea; Kim, Dae Won; Jo, Hyo Sang; In Yong, Ji; Ryu, Eun Ji; Cha, Hyun Ju; Kim, Sang Jin; Yeo, Hyeon Ji; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Park, Sungyeon; Im, Seung Kwon; Kim, Duk-Soo; Kwon, Oh-Shin; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-11-15

    Oxidative stress is considered a major factor in various neuronal diseases including ischemia-reperfusion injury. Proviral Integration Moloney 2 (PIM2) proteins, one of the families of PIM kinases, play crucial roles in cell survival. However, the functions of PIM2 protein against ischemia are not understood. Therefore, the protective effects of PIM2 against oxidative stress-induced hippocampal HT22 cell death and brain ischemic injury were evaluated using Tat-PIM2, a cell permeable fusion protein. Tat-PIM2 protein transduced into hippocampal HT22 cells. Low doses of transduced Tat-PIM2 protein protected against oxidative stress-induced cell death including DNA damage and markedly inhibited the activation of mitogen activated protein kinase (MAPKs), NF-?B and the expression levels of Bax protein. Furthermore, Tat-PIM2 protein transduced into the CA1 region of the hippocampus and significantly prevented neuronal cell death in an ischemic insult animal model. These results indicated that low doses of Tat-PIM2 protein protects against oxidative stress-induced neuronal cell death, suggesting low doses of Tat-PIM2 protein provides a potential therapeutic agent against oxidative stress-induced neuronal diseases including ischemia. PMID:26365288

  9. Radiation induced osteogenic sarcoma of the maxilla

    OpenAIRE

    Ramchandran Krishnankutty; Nayak Nileema; Mathews Anita; Varghese Bipin T; Prakash Om; Pandey Manoj

    2005-01-01

    Abstract Background Radiation induced sarcoma arise as a long term complication of radiation treatment for other benign or malignant conditions. They are of very rare occurrence in jaw bones and are even rarer in maxilla. Case presentation Here we report a case of radiation induced sarcoma in a patient treated for squamous cell carcinoma of buccal mucosa with radiation who developed osteosarcoma of maxillary bone after six years. The patient was treated successfully with surgery. Conclusion W...

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

    International Nuclear Information System (INIS)

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

  11. Radiation-induced apoptosis: relevance to radiotherapy

    International Nuclear Information System (INIS)

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

  12. Chromosome damage in liver cells from low dose rate alpha, beta, and gamma irradiation: derivation of RBE

    International Nuclear Information System (INIS)

    Relative biological effectiveness (RBE) for chromosome damage in liver cells was determined after low dose rate exposures to alpha, beta, or gamma irradiation. Protracted exposures to beta and gamma irradiation were equally effective, whereas low dose rate exposures to alpha emitters were 15 to 20 times more damaging than exposures to beta or gamma irradiation. These data support the use of the quality factor of 10 recommended by the International Commission on Radiological Protection and the National Council on Radiation Protection for estimating the biological hazard from internally deposited alpha emitters. When the dose rates were low, all types of chromosome damage observed were produced by single-hit processes

  13. Radioresponsiveness at low doses. Hyper-radiosensitivity and increased radioresistance in mammalian cells

    International Nuclear Information System (INIS)

    The rationale for and importance of research on effects after radiation at 'low doses' are outlined. Such basic radiobiological studies on induction of repair enzymes, protective mechanisms, priming, and hypersensitivity are certainly all relevant to treatment of cancer (see Section 1, Studies at low doses - relevance to cancer treatment). Included are examples from many groups, using various endpoints to address the possibility of an induced resistance, which has been compared to the adaptive response [M.C. Joiner, P. Lambin, E.P. Malaise, T. Robson, J.E. Arrand, K.A. Skov, B. Marples, Hypersensitivity to very low single radiation doses: its relationship to the adaptive response and induced radioresistance, Mutat. Res. 358 (1996) 171-183.]. This is not intended to be an exhaustive review - rather a re-introduction of concepts such as priming and a short survey of molecular approaches to understanding induced resistance. New data on the response of HT29 cells after treatment (priming) with co-cultured activated neutrophils are included, with protection against X-rays (S1). Analysis of previously published results in various cells lines in terms of increased radioresistance (IRR)/intrinsic sensitivity are presented which complement a study on human tumour lines [P. Lambin, E.P. Malaise, M.C. Joiner, Might intrinsic radioresistance of human tumour cells be induced by radiation?, Int. Radiat. Biol. 69 (1996) 279-290]. It is not feasible to extrapolate to low doses from studies at high doses. The biological responses probably vary with dose, LET, and have variable time frames. The above approaches may lead to new types of treatment, or additional means to assess radioresponsiveness of tumours. Studies in many areas of biology would benefit from considerations of different dose regions, as the biological responses vary with dose. There may also be some implications in the fields of radiation protection and carcinogenesis, and the extensions of concepts of hyper-radiosensitivity (HRS)/IRR extended to radiation exposure are considered in Section 2, Possible relevance of IRR concepts to radiation exposure (space). More knowledge on inducible responses could open new approaches for protection and means to assess genetic predisposition. Many endpoints are used currently - clonogenic survival, mutagenesis, chromosome aberrations and more direct - proteins/genes/functions/repair/signals, as well as different biological systems. Because of scant knowledge of the relevant aspects at low doses, such as inducible/protective mechanisms, threshold, priming, dose-rate effects, LET within one system, it is still too early to draw conclusions in the area of radiation exposure. Technological advances may permit much needed studies at low doses in the areas of both treatment and protection

  14. Low-dose risk, hormesis, analogical and logical thinking.

    Science.gov (United States)

    Zapponi, Giovanni A; Marcello, Ida

    2006-09-01

    The hormesis theory proposes the low-dose beneficial and high-dose detrimental pattern, existing for specific conditions, as a "general default assumption" for toxicology and carcinogenicity. Crump and Kitchin and Drane underline that in a post hoc retrospective scientific literature searching for hormetic dose-response patterns, the consideration of the whole available relevant studies is necessary and, for statistical testing purposes, for instance at a 0.05 standard level, a P value obtained from 1 - (1 - P)(n) = 0.05 (i.e., P = 0.0005 for 100 examined cases) should be used (otherwise, by definition, 5 "positive" results are expected by chance over 100 cases). The hypothesis, based on some experimental data on rodents, by Calabrese and Baldwin, of an hormetic effect of 2,3,7,8-TCDD at the 1-10 ng/kgbw/day dose, of Na-saccharine in the < or = 1% of diet exposure range, of Cadmium Chloride in the 0-5 micromol/kg dose range, single injection, and of neutrons in the 0- to 2-rad dose range, are not confirmed, and, rather, are contradicted, when the whole relevant data presented by international and national agencies are considered. As far as the radiation risk is in particular concerned, a recently published epidemiological study on more than 400,000 nuclear plant workers, co-ordinated by the IARC has indicated a small, but significant risk, at the current exposure limits, and possibly below them. Therefore, the hormesis theory-based criticism of current radiation protection criteria, assumed to be excessively conservative, is not justified. Also not justified is the assumption that "by dismissing hormesis, regulatory agencies such as U.S. EPA deny the public the opportunity for optimal health and avoidance of diseases;" rather, the contrary is here considered true. Analogical considerations are not necessarily logical ones and the single result should be considered in its whole context. PMID:17119261

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

    International Nuclear Information System (INIS)

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

  16. Induction of chromosomal instability in human lymphoblasts by low doses of ?-radiation

    International Nuclear Information System (INIS)

    Full text: Genomic instability is a hallmark of tumorigenic progression, and a similar phenotype is also observed in a high fraction (10 - 50%) of cells that survive exposure to ionizing radiation. In both cases unstable clones are characterized by non-clonal chromosomal rearrangements, which are indicative of a high rate of genetic change during the outgrowth of an unstable parental cell. We postulate that the remarkably high frequency of radiation-induced genomic instability is incompatible with a mutational mechanism for a specific gene, or even a large family of genes. Rather, we hypothesize that a major portion of instability is attributable to the formation of chromosomal rearrangement junction sequences that act as de novo chromosomal breakage hotspots. We further suggest that critical target sequences, which represent at least 10% of the genome and include repetitive DNA sequences such as those found in centromeric heterochromatin, can be involved in breakage and rearrangement hotspots that drive persistent genomic instability and karyotypic heterogeneity. Since chromosomal damage is induced even by low dose radiation exposure, we hypothesize that this phenotype can be efficiently induced at doses that are relevant to environmental, occupational, or medical exposure. In the present study, TK6 human B-lymphoblastoid cells were irradiated with 0, 10, 20 and 200cGy, in order to provide a set of data points for single, low dose exposures. Independent clones were analyzed karyotypically approximately 40 generations after radiation exposure. Preliminary results suggest that the fraction of clones exhibiting genomic instability after 20 cGy (0.16) is similar to and statistically indistinguishable from the fraction of unstable clones following 200 cGy (0.2) exposure. These findings support the hypothesis that instability following radiation, and perhaps also in cancer, primarily reflects non-mutational mechanisms

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

    International Nuclear Information System (INIS)

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

  18. Dose-effect relationship of chromosome aberrations induced by different LET rays at low doses

    International Nuclear Information System (INIS)

    Objective: To establish the dose-effect curves of chromosome aberrations in human peripheral blood lymphocytes induced by different LET rays,including 60Co ?-rays, 252Cf neutrons, 14 MeV neutrons and 12C heavy ions at low doses, respectively, in order to assess radiation-induced damages after occupational and accidental exposure. Methods: Heparinized whole blood samples were irradiated with the various radiation devices and doses ranged from 0 to 1 Gy with the interval of 0.25 Gy. Conventional chromosome culture method was applied with adding colchicines at the beginning and chromosome specimens were prepared after 48 h incubation. The Metafer scanning system was used for automatical finder of chromosome metaphases. The mathematic models were fitted according to aberration data obtained. Results: At the dose range of 0-1 Gy, the math models of dic + r were linear for 60Co ?rays and linear-quadratics for 252Cf neutrons, 14 MeV neutrons and 12C heavy ions. The models of ace were linear-quadratic for 60Co ?-rays and 12C heavy ion beams, and linear for 252Cf and 14 MeV neutrons. The models of total aberrations were linear-quadratic for all types of radiation. Conclusions: High LET rays have higher biological effects in inducing chromosome aberrations yields compared with low LET rays. Moreover, the severity of damage is 252Cf > 14 MeV neutrons > 12C heavy ions > 60Co ?-rays in turn. Therefore, in the range of low doses, the dic + r may be a better target of radiation damage for high LET radiation. (authors)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

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

    International Nuclear Information System (INIS)

    The present study aimed to investigate the protective effect of chronic low level of melatonin against an acute radiation induced oxidative stress in the cerebellum of Swiss mice, with special reference to Purkinje cells

  1. Inconsistencies and open questions regarding low-dose health effects of ionizing radiation

    International Nuclear Information System (INIS)

    The state of knowledge of health effects from low-dose exposures to ionizing radiation has recently been reviewed in extensive reports by three prestigious national and international commissions of scientific and medical experts with partially overlapping membership, known by their acronyms UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation), BEIR V (Biological Effects of Ionizing Radiation), and ICRP (International Commission on Radiological Protection). Publication of these reports was followed by a number of summaries in scientific journals, authored by recognized radiation experts, that purport to present a scientific consensus of low-dose effects in a more accessible format for health professionals. A critical comparison between various presentations of accepted views, however, reveals inconsistencies regarding open-quotes establishedclose quotes facts and unsettled questions

  2. Implication of prostaglandins and histamine h1 and h2 receptors in radiation-induced temperature responses of rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A.; Mickley, G.A .

    1988-01-01

    Exposure of rats to 1-15 Gy cobalt 60 gamma radiation induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxgenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H(1) and H(2) receptors may be involved in radiation-induced hypothermia since both the H(1) receptor antagonist, mepyramine, and H(2) receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggested that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations.

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

    International Nuclear Information System (INIS)

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

  4. Effects of low dose radiation and epigenetic regulation

    International Nuclear Information System (INIS)

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

  5. Achieving a low dose commitment to nuclear power station employees

    International Nuclear Information System (INIS)

    The author argues that a low dose policy is not only a requirement of ICRP 26 but also aids the efficiency of the nuclear establishment. It gives employees (and the general public) confidence in the management's desire to ensure that they will not be put at risk. This confidence is essential for an official industry. The author supports this claim by quoting performance and radiation exposure data at his own nuclear power station (Sizewell) and then outlines how this 'low dose' policy has been achieved by the Central Electricity Generating Board in general and Sizewell in particular. (author)

  6. The 20th L H Gray Conference - Radiation Cancer Analysis and Low Dose Risk Assessment: New Developments and Perspectives (Ede, the Netherlands, February 2002)

    International Nuclear Information System (INIS)

    There are few international venues where scientists in vastly different fields working on a common problem, or on a number of closely related problems, can get together in an intimate setting to present the results of their research and to discuss their approaches and views in a collegial atmosphere, and without the trappings of a huge convention with its conflicting parallel sessions and distracting events. Over the years, the L H Gray Conferences have provided an ideal setting for such intimate gatherings. This year the 20th L H Gray Conference, held in Ede, the Netherlands, was no exception. Convened for the first time outside the United Kingdom and hosted by the Dutch National Institute for Public Health and the Environment (RIVM). Paramount in all the participants' minds was the emerging information from molecular radiation biology on the recently recognised 'new' processes such as genomic instability, bystander effects, hypersensitivity, and the adaptive response. A novel aspect this year was the introduction of the opportunity, both at the beginning and at the end of the meeting, to participate in a 'vote' on controversial subjects by answering electronically such questions as: 'does radiation hormesis occur at low doses?' and 'should an age-dependence of radiological risk be incorporated into recommendations for radiation protectionThere appears to be no evidence for radiation-induced genomic instability, at least in this tumour. If this model holds for other tumour types, it would suggest that there is no 'radiation fingerprint' and that no special mechanism lies behind radiation-induced cancer. The major social event of the meeting was an afternoon devoted to a delightful excursion to the renowned Kroeller-Mueller Museum in the nearby national park (De Hoge Veluwe). Our Dutch hosts were even able to order up some sunshine for the day. After an afternoon of strolling through the museum and surrounding park, we were bussed to a hotel on the precipitous cliffs of a Dutch mountainside, and found ourselves enjoying a banquet overlooking the Rhine valley several thousand centimetres below. The banquet itself turned into a retirement dinner of sorts, honouring Henk Leenhouts of RIVM, who, after a distinguished career, will soon be seeking the serenity of a well-deserved retirement. Several colleagues and friends took the opportunity to say some kind words about Henk between banquet courses. Overall the meeting was an enjoyable experience, well-organised and efficiently run with provocative presentations, and reflected well the intent of the instigators of the L H Gray Conference series. (meeting report)

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

    Energy Technology Data Exchange (ETDEWEB)

    Green, Lora M

    2006-05-25

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

  8. Radiation-induced solution chlorination of PVC

    International Nuclear Information System (INIS)

    The high solubility in the usual solvents makes the chlorinated PVC most suitable for lacquers, adhesives and fibres. For this reason, the radiation-induced solution chlorination of PVC in methylene chloride was studied. The results of many experiments show that during the reaction between chlorine and PVC the solvent (methylene chloride) is chlorinated only in a small percentage to chloroform (9.5%) and finally to tetrachloromethane (0.1%). It was found that the radiation-induced chlorinated PVC has the same structure as the thermally chlorinated polymer, while the thermal stability and the rate of degradation of the radiation products show the better data for application purposes. (author)

  9. Radiation-induced electric conductivity of polymers

    International Nuclear Information System (INIS)

    Radiation-induced electric conductivity of polystyrene, polyethylene and polypropylene, excited by pulses of accelerated (60 keV) electrons of 1 ms to 10 s duration with a change in electric field to prebreak down voltage (? 2x108 V/m) in vacuum at room temperature was studied. Specific features of recombination effects at increased dose rate were considered. General theoretic problems of radiation-induced electric conductivity of the polymers, especially of heminal mechanism realized in polypropylene, and for pulses of radiation shorter than 0.1 s in polyethylene, as well, are discussed

  10. Hazard of the radiation induced thyroid cancer

    International Nuclear Information System (INIS)

    The level of thyroid cancer in Belarus before Chernobyl accident was low and made in different age and sex groups 0,03-2,5 (male) and 0,1-3,9 (female) per 100000 correspondingly. Different risk factors, which can influence the thyroid cancer development, are being taken into account. They are the factors of environment (strong external irradiation, long-time irradiation for medical purposes or in result of disaster), endo gen factors (hormonal, reproductive, genetic predisposition), some medicinal preparations and other. The protective effect of vegetable and fish consumption was found out. Among the factors of thyroid cancer development one of the most important is radiation. There is a point of view, which assumes that one of the reasons of thyroid cancer cases increase among the population of developed countries is increase of radiation induced thyroid cancer. The results of first research testify the influence of radiation factor on thyroid cancer development. During the period 1920 -1960 in the USA X-ray therapy was applied for the treatment of different good-quality diseases. Thyroid got in the zone of irradiation during the complex treatment with using of radiation. The results of the research of 1970 revealed that 70% of children with thyroid cancer were exposed to radiation in children's age. The subsequent researches of by-effects from the side of a thyroid at beam therapy of various diseases alongside with the results of the estimation of consequences of inhabitants of Hiroshima and Nagasaki irradiation owing to nuclear bombardment have shown the influence of irradiation of a thyroid on cancer development. High quantity of radio-epidemiological researches was directed to the studying of the consequences of thyroid external irradiation at young age. In all carried out researches the quantity of observed thyroid cancer cases among irradiated people has exceeded number of expected. The influence of thyroid internal irradiation by I-131 at young age was investigate on the groups, exposed to the diagnostic procedures with the using of I-131 in the USA and Sweden, on the population of irradiated owing to nuclear tests people in the state of Utah. The data received pointed on lower I-131 efficiency in the induction of radiation cancer in comparison with external irradiation. The quantitative expression of probability of the radiating factor influence on the induction of thyroid cancer is the concept of risk (absolute and relative). Risk coefficients received in separate research to the certain extend expressed the specificity of population irradiated and irradiation conditions (kind and duration of irradiation, dose capacity). The consequences of the Chernobyl accident are the precondition of the research of the role of radiation factor expansion, and especially of I-131, in the induction of thyroid cancer. The population of Belarus has suffered from the Chernobyl accident in the greatest extends. Meteorological conditions of the air masses spreading during the first weeks after disaster have determined the radioactive fall outs formation in north-west and north-east directions. Consequently, the main territory of Belarus was contaminated by iodine. The population of areas suffered got various dose loading on thyroid. Formed irradiation doses of thyroid created preconditions of radiation induced cancer development. Ecological investigation in the area of radiation epidemiology includes the comparative analysis of the level diseases of population from different areas and time periods. The research by a method 'case-control' assumes comparison of groups of people observing who have and do not have thyroid gland cancer. It allows revealing the influence of radiation factor. In the result of ecological researches can be received detail information that quantitatively describes the level of extra diseases during an early period after irradiation as such researches operate by all the cancer cases registered. During the post Chernobyl accident period numerous data were received. They bring significant contribution in radiat

  11. Low-dose ionizing radiation – is it harmful to health?

    International Nuclear Information System (INIS)

    A conference on the health effects of low-dose ionizing radiation organized in London earlier this year by the British Nuclear Energy Society brought together epidemiologists who have been investigating the mortality of workers from the nuclear industry in an attempt to put low-level radiation risk estimates on a scientific basis

  12. Topics on study of low dose-effect relationship

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Takeshi [Toho Univ., School of Medicine, Tokyo (Japan); Ohyama, Harumi

    1999-09-01

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

  13. Glyphosate Applied at Low Doses Can Stimulate Plant Growth

    Science.gov (United States)

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

  14. Concept of biological effect of low dose radiation on cells

    International Nuclear Information System (INIS)

    A concept biological cellular effect of ionizing radiation at small doses was suggested on the basis of analysis of physical interactions of ionizing radiation with substance as well as of experimentally observed cell reactions to low dose radiation. Probable molecular-cellular mechanisms of cell response at low level irradiation were considered. 34 refs

  15. Malignant melanoma of the tongue following low-dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  16. LOW-DOSE RISK, DECISIONS, AND RISK COMMUNICATION

    Science.gov (United States)

    This grant application seeks funding for a program of basic research in the areas of risk perception and decision making as applied to the role of communication of biological research results on low-dose radiation exposure. Widespread adverse views about radiation exposure makes...

  17. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    Energy Technology Data Exchange (ETDEWEB)

    Engelward, Bevin P

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy iron particle radiation on large scale sequence rearrangements and we have discovered tissue specific differences in sensitivity to homologous recombination. DOE support has given rise to critical new knowledge about the biological impact of low dose rate radiation and about the underlying mechanisms that govern genomic stability in response to radiation exposure. This work has spurred interest in radiation among MIT scientists, and has fostered ongoing research projects that will continue to contribute toward our understanding of the biological effects of low dose radiation exposure.

  18. Low-dose radiation enhances survivin-mediated virotherapy against malignant glioma stem cells.

    Science.gov (United States)

    Nandi, Suvobroto; Ulasov, Ilya V; Tyler, Matthew A; Sugihara, Adam Quasar; Molinero, Luciana; Han, Yu; Zhu, Zeng B; Lesniak, Maciej S

    2008-07-15

    To improve the efficacy and selectivity of virotherapy for malignant glioma, we designed a strategy to amplify adenoviral replication in conjunction with radiotherapy using a radioinducible promoter. First, we compared the radiation-inducible activity of FLT-1, vascular endothelial growth factor, DR5, Cox2, and survivin. We then examined the capacity of the optimal promoter to modulate transgene expression followed by E1A activity in vitro and in vivo in a glioma stem cell model. In the presence of radiation, survivin mRNA activity increased 10-fold. Luciferase transgene expression was dose dependent and optimal at 2 Gy. A novel oncolytic adenovirus, CRAd-Survivin-pk7, showed significant toxicity and replication against a panel of passaged and primary CD133(+) glioma stem cells. On delivery of radiation, the toxicity associated with CRAd-Survivin-pk7 increased by 20% to 50% (P E1A activity increased 3- to 10-fold. In vivo, treatment of U373MG CD133(+) stem cells with CRAd-Survivin-pk7 and radiation significantly inhibited tumor growth (P E1A activity was 100-fold increased versus CRAd-Survivin-pk7 alone. Selected genes linked to radioinducible promoters whose expression can be regulated by ionizing radiation may improve the therapeutic ratio of virotherapy. In this study, we have identified a new radioinducible promoter, survivin, which greatly enhances the activity of an oncolytic adenovirus in the presence of low-dose radiotherapy. PMID:18632631

  19. Experimental study of preventive effect of Anduolin (ADL) on radiation-induced lung injury in mice

    International Nuclear Information System (INIS)

    Objective: To observe the preventive effect of Anduolin (ADL) on radiation-induced lung injury in mice. Methods: Totally 180 of Kunming mice were randomly classified into six groups:normal control group (N), irradiation control group (R), irradiation plus low dose ADL group (L), irradiation plus middle dose ADL group (M), irradiation plus high dose ADL group (H), and irradiation plus Dexamethasone group (D). The mice except group N were irradiated with 20 Gy of 6 MV X-rays on whole lung. The mice in group L, M and H were given with ADL 1 d before irradiation and continued for 6 weeks after irradiation. At 2, 4 and 6 weeks after irradiation, the general situation and the lung pathological changes of mice were observed. The lung wet weight, collagen contents of the whole lung tissue, hydroxyproline concentration, and TGF-?1 expression in the lung were also detected. Results: Compared to the group R, the mice breathing rate, hydroxyproline concentration, and TGF-?1 expression in the group L were not significantly changed. While in the groups M, H and D, the breathing rate, the generation of hydroxyproline and the expression of TGF-?1 were decreased significantly (F=2.668-161.646, P<0.05). In addition, ADL alleviated the pathological changes on radiation-induced lung injury in mice. Conclusions: ADL might have the preventive effect on radiation-induced lung injury in mice. (authors)

  20. p53-dependent apoptosis suppresses radiation-induced teratogenesis

    International Nuclear Information System (INIS)

    About half of human conceptions are estimated not to be implanted in the uterus, resulting in unrecognizable spontaneous abortions. Experimental studies with mice have established that irradiation during the preimplantation period of the embryo induces a high incidence of prenatal deaths but virtually no malformations. This suggests that some mechanism is screening out the damaged fetuses. In order to elucidate the mechanisms of tissue repair of radiation-induced teratogenic injury, we compared the incidences of radiation-induced malformations and abortions in p53 null (p53-/-) and wild-type (p53+/+) mice. After X-irradiation with 2 Gy on day 9.5 of gestation, p53-/- mice showed a 70% incidence of anomalies and a 7% incidence of deaths, whereas p53+/+ mice had a 20% incidence of anomalies and a 60% incidence of deaths. Similar results were obtained after irradiation on day 3.5 of gestation. This reciprocal relationship of radiosensitivity to anomalies and to embryonic or fetal lethality supports the notion that the p53 gene protects embryos and fetuses against the teratogenic effects of radiation by eliminating cells that have been badly damaged. In fact, after X-irradiation, the frequency of dying cells by apoptosis was greatly increased in tissues of the p53+/+ fetuses but not at all in those of the p53-/- fetuses. Mammals are protected from radiation-induced injury by two mechanisms, p53-dependent apoptotic tissue repair in addition to well known DNA repair. Therefore, there are threshold doses below which there is no induction of teratogenic and carcinogenic effects after exposure to low-level radiation. (author)

  1. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin.

    Science.gov (United States)

    Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2013-05-01

    Nicotinamide (vitamin B3) protects from ultraviolet (UV) radiation-induced carcinogenesis in mice and from UV-induced immunosuppression in mice and humans. Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD(+)), an essential coenzyme in adenosine triphosphate (ATP) production. Previously, we showed that nicotinamide prevents UV-induced ATP decline in HaCaT keratinocytes. Energy-dependent DNA repair is a key determinant of cellular survival after exposure to DNA-damaging agents such as UV radiation. Hence, in this study we investigated whether nicotinamide protection from cellular energy loss influences DNA repair. We treated HaCaT keratinocytes with nicotinamide and exposed them to low-dose solar-simulated UV (ssUV). Excision repair was quantified using an assay of unscheduled DNA synthesis. Nicotinamide increased both the proportion of cells undergoing excision repair and the repair rate in each cell. We then investigated ssUV-induced cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxoG) formation and repair by comet assay in keratinocytes and with immunohistochemistry in human skin. Nicotinamide reduced CPDs and 8oxoG in both models and the reduction appeared to be due to enhancement of DNA repair. These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention. PMID:23349012

  2. The European initiative on low-dose risk research: from the HLEG to MELODI.

    Science.gov (United States)

    Belli, Mauro; Tabocchini, Maria Antonella; Jourdain, Jean-René; Salomaa, Sisko; Repussard, Jacques

    2015-09-01

    The importance of low-dose risk research for radiation protection is now widely recognised. The European Commission (EC) and five European Union (EU) Member States involved in the Euratom Programme set up in 2008 a 'High Level and Expert Group on European Low Dose Risk Research' (HLEG) aimed at identifying research needs and proposing a better integration of European efforts in the field. The HLEG revised the research challenges and proposed a European research strategy based on a 'Multidisciplinary European LOw Dose Initiative' (MELODI). In April 2009, five national organisations, with the support of the EC, created the initial core of MELODI (http://www.melodi-online.eu) with a view to integrate the EU institutions with significant programmes in the field, while being open to other scientific organisations and stakeholders, and to develop an agreed strategic research agenda (SRA) and roadmap. Since then, open workshops have been organised yearly, exploring ideas for SRA implementation. As of October 2014, 31 institutions have been included as members of MELODI. HLEG recommendations and MELODI SRA have become important reference points in the radiation protection part of the Euratom Research Programme. MELODI has established close interactions through Memorandum of Understanding with other European platforms involved in radiation protection (Alliance, NERIS and EURADOS) and, together with EURADOS, with the relevant medical European Associations. The role of Joint Programming in priority setting, foreseen in the forthcoming EU Horizon 2020, calls for keeping MELODI an open, inclusive and transparent initiative, able to avoid redundancies and possible conflicts of interest, while promoting common initiatives in radiation protection research. An important issue is the establishment of a proper methodology for managing these initiatives, and this includes the set-up of an independent MELODI Scientific Committee recently extended to Alliance, NERIS and EURADOS, with the aim of identifying research priorities to suggest for the forthcoming Euratom research calls. PMID:25862536

  3. Can results from animal studies be used to estimate dose or low dose effects in humans

    International Nuclear Information System (INIS)

    A method has been devised to extrapolate biological equilibrium levels between animal species and subsequently to humans. Our initial premise was based on the observation that radionuclide retention is normally a function of metabolism so that direct or indirect measures could be described by a power law based on body weights of test animal species. However, we found that such interspecies comparisons ought to be based on the coefficient of the power equation rather than on the exponential parameter. The method is illustrated using retention data obtained from five non-ruminant species (including humans) that were fed radionuclides with different properties. It appears that biological equilibrium level for radionuclides in man can be estimated using data from mice, rats, and dogs. The need to extrapolate low-dose effects data obtained from small animals (usually rodents) to humans is not unique to radiation dosimetry or radiation protection problems. Therefore, some quantitative problems connected with estimating low-dose effects from other disciplines have been reviewed, both because of the concern about effects induced by the radionuclide moiety of a radiopharmaceutical and those of the nonradioactive component. The possibility of extrapolating low-dose effects calculated from animal studies to human is discussed

  4. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

    International Nuclear Information System (INIS)

    The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16INKa and DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16INKa promoter methylation upon LDR exposure. In male liver tissue, p16INKa promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16INKa promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16INKa and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure

  5. Role of extracellular DNA oxidative modification in radiation induced bystander effects in human endotheliocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kostyuk, Svetlana V. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Ermakov, Aleksei V., E-mail: avePlato@mail.ru [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Alekseeva, Anna Yu.; Smirnova, Tatiana D.; Glebova, Kristina V.; Efremova, Liudmila V. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Baranova, Ancha [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); School of System Biology, George Mason University, Fairfax, VA 22030 (United States); Veiko, Natalya N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation)

    2012-01-03

    The development of the bystander effect induced by low doses of irradiation in human umbilical vein endothelial cells (HUVECs) depends on extracellular DNA (ecDNA) signaling pathway. We found that the changes in the levels of ROS and NO production by human endothelial cells are components of the radiation induced bystander effect that can be registered at a low dose. We exposed HUVECs to X-ray radiation and studied effects of ecDNA{sup R} isolated from the culture media conditioned by the short-term incubation of irradiated cells on intact HUVECs. Effects of ecDNA{sup R} produced by irradiated cells on ROS and NO production in non-irradiated HUVECs are similar to bystander effect. These effects at least partially depend on TLR9 signaling. We compared the production of the nitric oxide and the ROS in human endothelial cells that were (1) irradiated at a low dose; (2) exposed to the ecDNA{sup R} extracted from the media conditioned by irradiated cells; and (3) exposed to human DNA oxidized in vitro. We found that the cellular responses to all three stimuli described above are essentially similar. We conclude that irradiation-related oxidation of the ecDNA is an important component of the ecDNA-mediated bystander effect.

  6. Effect of low dose radiation on somatic intrachromosomal recombination in vivo and in vitro

    International Nuclear Information System (INIS)

    Full text: High doses of ionising radiation are mutagenic in a wide range of mutation assays. The majority of radiation exposure studies in in vivo mouse mutation assays have been performed at high doses, eg greater than 1 Gy. However, these doses are not relevant to the low doses of ionising radiation that the majority of the population might likely come into contact with. Radiation protection levels tend to be based on a simple linear no-threshold model which suggests that any radiation above zero is potentially harmful. The pKZ1 recombination mutagenesis mouse model has proven to be a sensitive assay for the detection of mutations caused by low doses of chemical agents. In pKZ1 mice, somatic intrachromosomal recombination (SICR) inversion events can be detected in cells using histochemistry for the E. coli LacZ transgene. We exposed pKZ1 mice to a single radiation dose ranging from 0.001 to 2 Gy. A significant increase in SICR was observed in spleen at the two highest doses of 0.1 and 2 Gy and a significant reduction in SICR below the endogenous frequency was observed at the two lowest doses of 0.01 and 0.001 Gy. After exposing a pKZ1 cell line to the same dose range, a similar J curve response was observed with significant increases in SICR observed at the 3 highest doses and a significant decrease below the endogenous frequency at the lowest dose (0.001 Gy). The next experiments will be to determine the dose where the SICR frequency returns to the endogenous level. The important question posed by these results is 'Is a reduction below the endogenous SICR level caused by low doses of ionising radiation anti-mutagenic?' Studies now need to be performed to investigate the effect of low doses of radiation on other mutation end-points, and the mechanism for the reduction in SICR

  7. Cohort studies on cancer mortality among nuclear workers exposed to low-dose ionizing radiation: a meta-analysis

    International Nuclear Information System (INIS)

    To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for low-dose ionising radiation exposure. Published papers referring to 20 low-dose ionising radiation-exposed cohorts among nuclear industry workers with Standardized Mortality Ratios (SMR) were recta-analyzed in fixed and random effect models. The significantly deficient Meta-SMRs for all deaths (0.73; 95% CI: 0.66-0.80), all cancers (0.83; 95% CI: 0.77- 0.91), lung cancer (0.93; 95% CI: 0.90-0.95), non-Hodgkin lymphoma (0.88; 95% CI: 0.78- 0.99), esophagus cancer (0.83; 95% CI:0.76-0.91), colorectal cancer (0.88; 95% CI: 0.83-0.94), stomach cancer (0.81; 95% CI: 0.76-0.86) were observed. The Meta-SMRs for leukemia, multiple myeloma, Hodgkin's disease were found to be no significant difference with normal populations. There was no excessive risk of cancers among nuclear workers exposed to low-doses and low-dose rates ionizing radiation. (authors)

  8. Comparison of hyperuricemia in type 2 diabetics on low dose aspirin and not on low dose aspirin

    International Nuclear Information System (INIS)

    Objective: To compare the frequency of hyperuricemia in type 2 diabetes patients who are taking low dose aspirin with those patients who are not taking low dose aspirin. Study design: Quasi experimental study. Place and duration of study: This study was carried out at Military Hospital Rawalpindi for a period of two years (June 2006-May 2008). Patients and Methods: Sixty diabetic patients were selected who were taking low dose aspirin comparing group A and sixty diabetic patients who were not taking aspirin were placed in group B. These patients were selected from the OPD through non probability convenience sampling. All these patients were being followed up in medical outpatient quite regularly on fort-nightly basis. Data had been collected through a carefully designed questionnaire. Results: In group A, 90% of the patients had uric acid less than 445 micro mol/l and 10% of the patients had uric acid more than 445micro mol/l. Whereas in group B 100% of the patients had uric acid less than 445umol/l, there was a statistically significant difference between the two groups (p< 0.05). Conclusion: Aspirin in low doses cause hyperuricemia and regular monitoring of uric acid is mandatory to prevent its adverse effects. (author)

  9. Radiation-induced neuropathy in cancer survivors

    International Nuclear Information System (INIS)

    Radiation-induced peripheral neuropathy is a chronic handicap, frightening because progressive and usually irreversible, usually appearing several years after radiotherapy. Its occurrence is rare but increasing with improved long-term cancer survival. The pathophysiological mechanisms are not yet fully understood. Nerve compression by indirect extensive radiation-induced fibrosis plays a central role, in addition to direct injury to nerves through axonal damage and demyelination and injury to blood vessels by ischaemia following capillary network failure. There is great clinical heterogeneity in neurological presentation since various anatomic sites are irradiated. The well-known frequent form is radiation-induced brachial plexopathy (RIBP) following breast cancer irradiation, while tumour recurrence is easier to discount today with the help of magnetic resonance imaging and positron emission tomography. RIBP incidence is in accordance with the irradiation technique, and ranges from 66% RIBP with 60 Gy in 5 Gy fractions in the 1960s to less than 1% with 50 Gy in 2 Gy fractions today. Whereas a link with previous radiotherapy is forgotten or difficult to establish, this has recently been facilitated by a posteriori conformal radiotherapy with 3D-dosimetric reconstitution: lumbosacral radiculo-plexopathy following testicular seminoma or Hodgkin’s disease misdiagnosed as amyotrophic lateral sclerosis. Promising treatments via the antioxidant pathway for radiation-induced fibrosis suggest a way to improve the everyday quality of life of these long-term cancer survivors.

  10. Marked depression of time interval between fertilization period and hatching period following exposure to low-dose X-rays in zebrafish

    International Nuclear Information System (INIS)

    In recent years there has been growing concern over the stimulating effects of very low-dose X -rays. Our laboratory had observed that zebrafish irradiated with low-dose X-rays tended to emerge earlier than sham controls. This observation led us to quantitatively examine the effects of low-dose X irradiation on a series of stages of development in the zebrafish. The embryos were fertilized simultaneously in vitro and incubated at an optimal temperature without crowding. Following exposure of the cleavage period (1.5 h after fertilization) to 0.025-Gy X-rays, the duration to hatching was slightly shorter than that of the sham controls. This tendency was increased when the X-ray exposure occurred during the blastula period (3.5 h). In these embryos, the duration to hatching decreased significantly by an average of 6 h sooner than for sham controls. No differences in duration to hatching were seen when irradiation was given during either the zygote period (45 min) or the segmentation period (12 h). On the contrary, upon exposure to 0.5-Gy X-rays during the blastula period, the duration to hatching increased significantly relative to that of sham controls. These results suggest that the radiation-induced early hatching effect is observed for low doses of X-rays

  11. Influence of low-dose and low-dose-rate ionizing radiation on mutation induction in human cells

    Science.gov (United States)

    Yatagai, F.; Umebayashi, Y.; Suzuki, M.; Abe, T.; Suzuki, H.; Shimazu, T.; Ishioka, N.; Iwaki, M.; Honma, M.

    This is a review paper to introduce our recent studies on the genetic effects of low-dose and low-dose-rate ionizing radiation (IR). Human lymphoblastoid TK6 cells were exposed to ?-rays at a dose-rate of 1.2 mGy/h (total 30 mGy). The frequency of early mutations (EMs) in the thymidine kinase ( TK) gene locus was determined to be 1.7 × 10 -6, or 1.9-fold higher than the level seen in unirradated controls [Umebayashi, Y., Honma, M., Suzuki, M., Suzuki, H., Shimazu, T., Ishioka, N., Iwaki, M., Yatagai, F., Mutation induction in cultured human cells after low-dose and low-dose-rate ?-ray irradiation: detection by LOH analysis. J. Radiat. Res., 48, 7-11, 2007]. These mutants were then analyzed for loss of heterozygosity (LOH) events. Small interstitial-deletion events were restricted to the TK gene locus and were not observed in EMs in unirradated controls, but they comprised about half of the EMs (8/15) after IR exposure. Because of the low level of exposure to IR, this specific type of event cannot be considered to be the direct result of an IR-induced DNA double strand break (DSB). To better understand the effects of low-level IR exposure, the repair efficiency of site-specific chromosomal DSBs was also examined. The pre ?-irradiation under the same condition did not largely influence the efficiency of DSB repair via end-joining, but enhanced such efficiency via homologous recombination to an about 40% higher level (unpublished data). All these results suggest that DNA repair and mutagenesis can be indirectly influenced by low-dose/dose-rate IR.

  12. Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

    Science.gov (United States)

    Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

    2000-01-01

    Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

  13. Radiation-induced liver damage

    International Nuclear Information System (INIS)

    Due to the recent increase in the use of radiation therapy in the treatment of cancer with or without chemotherapy, the risk of liver radiation damage has become a significant concern for the radiotherapist when the treated tumour is located in the upper abdomen or lower thorax. Clinically evident radiation liver damage may result in significant mortality, but at times patients recover without sequelae. The dose of 3000 rads in 3 weeks to the entire liver with 5 fractions per week of 200 rads each, seems to be tolerated well clinically by adult humans. Lower doses may lead to damage when used in children, when chemotherapy is added, as in recent hepatectomy cases, and in the presence of pre-existent liver damage. Reduced fractionation may lead to increased damage. Increased fractionation, limitation of the dose delivered to the entire liver, and restriction of the high dose irradiation volume may afford protection. With the aim of studying the problems of hepatic radiation injury in humans, a project of liver irradiation in the dog is being conducted. Mongrel dogs are being conditioned, submitted to pre-irradiation studies (haemogram, blood chemistry, liver scan and biopsy), irradiated under conditions resembling human cancer therapy, and submitted to post-irradiation evaluation of the liver. Twenty-two dogs have been entered in the study but only four qualify for the evaluation of all the study parameters. It has been found that dogs are susceptible to liver irradiation damage similar to humans. The initial mortality has been high mainly due to non-radiation factors which are being kept under control at the present phase of the study. After the initial experiences, the study will involve variations in total dose and fractionation, and the addition of anticoagulant therapy for possible prevention of radiation liver injury. (author)

  14. Effect of low-dose radiation on ocular circulation

    International Nuclear Information System (INIS)

    We treated 6 eyes of unilateral age-related macular degeneration by low-dose radiation. Each eye received daily dose of 2 Gy by 4MV lineac totalling 20 Gy over 2 weeks. Color doppler flowmetry was used to determine the mean blood flow velocity (Vmean) and vascular resistive index (RI) in the short posterior ciliary artery, central retinal artery and ophthalmic artery in the treated and fellow eyes before and up to 6 months of treatment. There were no significant differences in Vmean and RI before and after treatment. The findings show the absence of apparent influence of low-dose radiation on the ocular circulation in age-related macular degeneration. (author)

  15. Effect of low-dose radiation on ocular circulation

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Keiko; Hiroishi, Goro; Honda, Masae; Yoshikawa, Hiroshi; Fujisawa, Kimihiko; Ishibashi, Tatsuro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1999-05-01

    We treated 6 eyes of unilateral age-related macular degeneration by low-dose radiation. Each eye received daily dose of 2 Gy by 4MV lineac totalling 20 Gy over 2 weeks. Color doppler flowmetry was used to determine the mean blood flow velocity (Vmean) and vascular resistive index (RI) in the short posterior ciliary artery, central retinal artery and ophthalmic artery in the treated and fellow eyes before and up to 6 months of treatment. There were no significant differences in Vmean and RI before and after treatment. The findings show the absence of apparent influence of low-dose radiation on the ocular circulation in age-related macular degeneration. (author)

  16. Enhanced low dose rate sensitivity (ELDRS) in bipolar linear circuits

    International Nuclear Information System (INIS)

    Enhanced Low Dose Rate Sensitivity (ELDRS) in bipolar linear transistors was first identified in bipolar microcircuit transistors in 1991 and demonstrated in bipolar linear circuits in 1994. Since then it has been a major topic of research, characterization and analysis. Data compendia of low dose rate enhancement factors were presented in 1996, 2001 and 2008, identifying 30 unique widely used circuit types as susceptible to ELDRS. A space experiment has verified the phenomenon for ELDRS parts in space. Early work on ELDRS was directed toward identifying mechanisms, characterizing circuits and developing hardness assurance methods, concentrating on accelerated testing techniques. More recently the research has focused on the effects of pre-irradiation elevated temperature stress (PETS), final passivation layers and molecular hydrogen in the package on the ELDRS response, providing a basis for developing ELDRS-free parts. In this review paper the phenomena of ELDRS, its characteristics, the most recent modeling results and the latest hardness assurance techniques are discussed. (author)

  17. Gamma regularization based reconstruction for low dose CT.

    Science.gov (United States)

    Zhang, Junfeng; Chen, Yang; Hu, Yining; Luo, Limin; Shu, Huazhong; Li, Bicao; Liu, Jin; Coatrieux, Jean-Louis

    2015-09-01

    Reducing the radiation in computerized tomography is today a major concern in radiology. Low dose computerized tomography (LDCT) offers a sound way to deal with this problem. However, more severe noise in the reconstructed CT images is observed under low dose scan protocols (e.g. lowered tube current or voltage values). In this paper we propose a Gamma regularization based algorithm for LDCT image reconstruction. This solution is flexible and provides a good balance between the regularizations based on l0-norm and l1-norm. We evaluate the proposed approach using the projection data from simulated phantoms and scanned Catphan phantoms. Qualitative and quantitative results show that the Gamma regularization based reconstruction can perform better in both edge-preserving and noise suppression when compared with other norms. PMID:26305538

  18. A Case of Lichen Amyloidosis Treated with Low Dose Acitretin

    Directory of Open Access Journals (Sweden)

    Fatma Pelin Cengiz

    2014-12-01

    Full Text Available Primary localized cutaneous amyloidosis (PCA is a rare disorder characterized by amyloid deposition in dermis without systemic involvement. There are three different types of primary localized cutaneous amyloidosis: Lichen amyloidosis, macular amyloidosis and nodular amyloidosis. The lesions of lichen amyloidosis are characterized by pruritic papules. Although, topical or intralesional treatment with corticosteroids, topical dimethyl sulfoxide, ultraviolet B, oral psoralen plus ultraviolet A, retinoic acid derivatives are the recommended treatment for lichen amyloidosis, the results are often unsatisfactory. In the literature, there have been only a few reports evaluating the efficacy of low dose acitretin in the treatment of lichen amiloidosis. In this article, we report a case of lichen amyloidosis with pruritic hyperkeratotic papules on the back and chest of 5 years’ duration, successfully treated with low dose acitretin.

  19. Radiation-induced processes of adaptation research by statistical modelling

    CERN Document Server

    Korogodina, Victoria L; Osipova, Ludmila P

    2013-01-01

    This book examines radiation-induced adaptation as processes produced in cells, tissues, and populations. It demonstrates the radiation-induced adaptation processes that continue even when the radiation itself is no longer at a critical background level.

  20. Radioprotective effects of melatonin on radiation-induced cataract

    International Nuclear Information System (INIS)

    One of the mechanisms proposed to explain lens opacification is the oxidation of crystallins, either by radiation or reactive oxygen species (ROS). It has been shown that melatonin has both an anti-peroxidative effect on several tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant role of melatonin (5 mg/kg/day) against radiation-induced cataract in the lens after total-cranium irradiation of rats with a single dose of 5 Gy. Sprague-Dawley rats were divided into four groups. Control group received neither melatonin nor irradiation. Irradiated rats (IR) and melatonin+irradiated rats (IR+Mel) groups were exposed to total cranium irradiation of 5 Gy in a single dose by using a cobalt-60 teletherapy unit. IR+Mel and melatonin (Mel) groups were administered 5 mg/kg melatonin daily by intraperitoneal injections during ten days. Chylack's cataract classification was used in this study. At the end of the 10th day, the rats were killed and their eyes were enucleated to measure the antioxidant enzymes i.e. the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and lipid peroxidation level (malondialdehyde (MDA)). Irradiation significantly increased the MDA level, as an end product of lipid peroxidation, and also significantly decreased SOD and GSH-Px activity, emphasizing the generation of increased oxidative stress. Rats injected with melatonin only did not cause cataract formation. Melatonin supplementation with irradiation significantly increased the activity of SOD and GSH-Px enzymes and significantly decreased the MDA level. Total cranium irradiation of 5 Gy in a single dose enhanced cataract formation, and melatonin supplementation protected the lenses from radiation-induced cataract formation. Our results suggest that supplementing cancer patients with adjuvant therapy of melatonin may reduce patients suffering from toxic therapeutic regimens such as chemotherapy and/or radiotherapy and may provide an alleviation of the symptoms due to radiation-induced organ injuries. (author)

  1. A model-free approach to low-dose extrapolation.

    OpenAIRE

    Krewski, D; Gaylor, D; Szyszkowicz, M

    1991-01-01

    Estimates of risk associated with exposure to low levels of carcinogenic substances present in the environment are generally obtained by linear extrapolation from higher exposure levels at which risks can be estimated directly. In this paper, we examine the scientific basis for the assumption of low-dose linearity in carcinogenic risk assessment and the different statistical methods that have been proposed for linear extrapolation. A model-free approach to linear extrapolation is described an...

  2. Transcriptome profiling of mice testes following low dose irradiation

    DEFF Research Database (Denmark)

    Belling, Kirstine Christensen; Nielsen, H.B.; Brunak, S.; Tanaka, M.; Dalgaard, M.D.; Nielsen, J.E.; Almstrup, K.; Leffers, H.

    2013-01-01

    Background: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types in the adult testis.Methods: Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression cha...

  3. Transcriptome profiling of mice testes following low dose irradiation

    DEFF Research Database (Denmark)

    Belling, Kirstine C.; Tanaka, Masami; Dalgaard, Marlene Danner; Nielsen, John Erik; Nielsen, Henrik Bjřrn; Brunak, Sřren; Almstrup, Kristian; Leffers, Henrik

    2013-01-01

    ABSTRACT: BACKGROUND: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types in the adult testis. METHODS: Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall exp...

  4. Image noise and artifact in chest low-dose CT

    International Nuclear Information System (INIS)

    Objective: To analyze the image noise and artifact of low-dose chest CT scanning and the distribution pattern. Methods: A chest phantom equivalent to human tissue was scanned by 64 slices spiral scanner at standard dose (250 mAs) and low-dose (50, 30, and 21 mAs) respectively, HU in sites of the phantom and SD of which was recorded. 200 patients with pulmonary nodules were scanned at 30 or 21 mAs for minimal length. The relationship between severity of noise and artifact in chest low-dose CT scanning and gender or body mass index (BMI) of the patients, as well as the distribution of noise and artifact was evaluated. Results: There was no statistical difference between the HU in sites of the phantom: lung (-777.3- -758.2 HU, F=0.992, P0.05), vertebra (835.6-875.3 HU, F=1.453, P>0.05), while the SD of which was of statistical signification: lung (9.5-29.0 HU, F=108.7, P2=2.294, P>0.05), and significant difference between groups of different BMI(in BMI2=128.274, P2=18.918, P2=6.760, P<0.05). Conclusions: The image noise and artifact was significant in low-dose CT, especially in the dorsal and upper field of the lung, which might be attributed to the distribution of skeleton in the chest. It was recommended that scanning protocol (mAs value) be individualized adjusted in according to the patients BMI. (authors)

  5. Early Outcomes Following Low Dose Naltrexone Enhancement of Opioid Detoxification

    OpenAIRE

    Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen; Gottheil, Edward; Wu, Li-Tzy; Gorelick, David A

    2009-01-01

    Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) o...

  6. Effects of low doses; Effet des faibles doses

    Energy Technology Data Exchange (ETDEWEB)

    Le Guen, B. [Electricite de France (EDF-LAM-SCAST), 93 - Saint-Denis (France)

    2001-07-01

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  7. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    OpenAIRE

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2012-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsycholog...

  8. Low-Dose Naltrexone for Pruritus in Systemic Sclerosis

    OpenAIRE

    Tracy Frech; Kirsten Novak; Revelo, Monica P; Maureen Murtaugh; Boaz Markewitz; Nathan Hatton; Mary Beth Scholand; Edward Frech; David Markewitz; Allen D. Sawitzke

    2011-01-01

    Pruritus is a common symptom in systemic sclerosis (SSc), an autoimmune disease which causes fibrosis and vasculopathy in skin, lung, and gastrointestinal tract (GIT). Unfortunately, pruritus has limited treatment options in this disease. Pilot trials of low-dose naltrexone hydrochloride (LDN) for pruritus, pain, and quality of life (QOL) in other GIT diseases have been successful. In this case series we report three patients that had significant improvement in pruritus and total GIT symptoms...

  9. Biological effects of low doses of ionising radiation

    International Nuclear Information System (INIS)

    A study was performed with the aim to examine whether the progeny of cells that had been repeatedly irradiated with low doses of gamma rays will change their sensitivity to cytotoxic agents. Four mammalian cell lines were used in the experiment. It was found that the progeny of cells irradiated in this way do not change their sensitivity to gamma rays but would change their sensitivity to various cytostatics drugs. (A.K.)

  10. Exercise and Sport Performance with Low Doses of Caffeine

    OpenAIRE

    Lawrence L. Spriet

    2014-01-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5–13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (

  11. Ageing effects of polymers at very low dose-rates

    International Nuclear Information System (INIS)

    The equipment irradiation dose-rate into the containment is variable from 10-6 to 10-4 gray per second for the most exposed materials. During qualification, safety equipments are submitted in France to dose-rates around 0.28 gray per second. This study purpose is to now if a so large irradiation dose-rate increase is reasonable. Three elastomeric materials used in electrical cables, o'rings seals and connectors, are exposed to a very large dose-rates scale between 2.1.10-4 and 1.4 gray per second, to 49 KGy dose. This work was carried out during 3.5 years. Oxygen consumption measurement of the air in contact with polymer materials, as mechanical properties measurement show that: - at very low dose-rate, oxygen consumption is maximum at the same time (1.4 year) for the three elastomeric samples. Also, mechanical properties simultaneously change with oxygen consumption. At very low dose-rate, for the low irradiation doses, oxygen consumption is at least 10 times more important that it is showed when irradiation is carried out with usual material qualification dose-rate. At very low dose-rate, oxygen consumption decreases when absorbed irradiation dose by samples increases. The polymer samples irradiation dose is not still sufficient (49 KGy) to certainly determine, for the three chosen polymer materials, the reasonable irradiation acceleration boundary during nuclear qualification tests

  12. Effects of continuous low dose-rate irradiation: computer simulations.

    Science.gov (United States)

    King, C R; Nath, R; Rockwell, S

    1988-09-01

    The effects of continuous low dose-rate irradiation are studied with a computer model that incorporates cell kinetics and the accumulation and repair of radiation damage. This theoretical approach independently explores the effects on survival curves of a phase block, inherited damage and proliferation by dying cells. The computer model is a Monte Carlo simulation which follows the evolution in time of the family trees of a growing cell population under continuous irradiation. The model uses as input the measured phase-specific survival curves for acute exposures and the cell kinetic parameters to generate survival curves for continuous low dose-rate irradiations. Cell survival curves for Chinese hamster lung cells (V79) for dose rates ranging from 15 to 500 cGy/h have been generated using various model assumptions. The model shows that for these cells a G2 block will maximize cell killing for an optimum dose rate near 75 cGy/h. The effect on survival curves of inherited damage, as well as that of the proliferation by dying cells, is shown to increase monotonically with decreasing dose rates, and to be quite large at low dose rates. PMID:3245956

  13. Radiation induced membrane effects at the apoptotic cell death

    International Nuclear Information System (INIS)

    Lymphocytes are rather sensitive towards radiation induced apoptosis. The hypothesis can be tried that the cellular membrane (or intracellular membranes) be the primary target for the radiation induced apoptosis. Chemically induced and radiation induced apoptosis follow, at least partially, common mechanistic patterns. It involves a fluidisation of the cellular membrane. Rigidisation of the membrane by incorporation of cholesterol interferes with the radiation induced apoptosis. (orig.)

  14. Modification of radiation induced lipid peroxidation by calmodulin antagonists

    International Nuclear Information System (INIS)

    It has been shown that calmodulin antagonists provide radio-protection in euoxic and sensitization in hypoxic conditions. This differential protection in euoxic conditions might have arisen from the interaction of calmodulin antagonists with oxygen free radicals. This possibility has been tested in the present communication. Radiation induced lipid peroxidation process in liposomes has been used for this purpose. Liposomes prepared from L-?-lecithin were irradiated with or without calmodulin antagonists. Calmodulin antagonists inhibited lipid peroxidation significantly. The inhibition was found to increase with increase in concentration of the drugs. These observations suggest that calmodulin antagonists have a capacity to scavenge oxygen free radicals involved in initiation and/or propagation of lipid peroxidation process. This may be the reasons for their differential radioprotection in euoxic conditions in biological systems. (author). 5 figs., 1 tab., 23 refs

  15. Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females

    International Nuclear Information System (INIS)

    Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5 Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes

  16. Effect of low-dose gamma-radiation upon hatchability and weight of chickens

    Energy Technology Data Exchange (ETDEWEB)

    Vilic, M.; Kraljevic, P.; Simpraga, M. [Zagreb Univ., Veterinary faculty (Croatia); Miljanic, S. [Ruder Boskovic Institute, Zagreb (Croatia)

    2006-07-01

    Full text of publication follows: Although any dose of ionizing radiation has generally been recognized to be detrimental to living being, low dose ionizing radiation seems to invoke primary stimulative effects. Stimulatory effects of low dose ionizing radiation include many aspects such as growth, fecundity and longevity stimulation, accelerated development, enhance biological responses for immune systems, enzymatic repair, physiological functions, and the removal of cellular damage, including prevention and removal of cancers and other diseases. Low dose ionizing radiation might also cause changes in the concentration of some biochemical parameters in blood plasma of chickens such as changes in the concentration of total proteins, glucose and cholesterol. The objective of this study was to determine the effect of low doses of gamma irradiation before incubation and on the seventh day of incubation on hatchability of eggs and body weight of chickens. This study includes three independent experiments. In the first experiment, six-hundred eggs produced by a commercial flock of Avian-line 34, were irradiated by a dose of 0.15 Gy gamma radiation (60 Co) before incubation. In the second experiments also involving six-hundred-line 34 eggs were irradiated by dose of 0.15 Gy gamma radiation on the seventh day of incubation. In the third experiment three-hundred eggs produced by a commercial flock of Ross 308 were irradiated by dose 0.30 Gy gamma irradiation before incubation. Along with the chickens which were hatched from irradiated eggs, there was a control group of chickens hatched from nonirradiated eggs. All other conditions were the same for both groups. Hatchability was calculated in terms of all eggs divided with fertile eggs which hatched. The individual weights of the chickens were determined on the first and on the forty second day. Growth data were analyzed statistically by t-test. Irradiation of chicken eggs and embryos at rates o f 0.15 Gy increases hatchability. Namely, hatchability of eggs of Avian-line 34 was improved by 0.83% over that of control eggs by the dose of 0.15 Gy before incubation (1 st experiment) and 1.37% by the same dose on seventh day of incubation. The hatchability of commercial broiler Ross 308 eggs was reduced by 2.5% by exposing the eggs to 0.30 Gy of gamma radiation before incubation. The weight of chickens was increased in all three experiments on the first day, however it was not significantly different when compared to control chickens. Treatment with 0.15 Gy gamma irradiation before incubation significantly increases body mass on the forty second day (P<0.05) when compared to the control group. Chickens that received 0.15 Gy on the seventh day of incubation did not differ in the weight from the controls at the end of fattening period (1 -42 days) while chickens that received 0.30 Gy before incubation had a significant reduction (P<0.01) in body weight on the 42. day of the(P<0.05). These results suggest that the stimulatory radiation effect is limited to the dose such as a 0.15 Gy. However, increasing the dose to 0.30 Gy eliminated the radiation-induced effect. The fact that only chickens irradiated with 0.15 Gy obtained a higher weight on first day may be due to stimulatory effects on embryonal development processes. (authors)

  17. Micronuclei: sensitivity for the detection of radiation induced damage

    International Nuclear Information System (INIS)

    The in vitro cytokinesis-block (CB) micronucleus (MN) assay for human peripheral blood has been used extensively for the assessment of chromosomal damage induced by ionizing radiation and chemicals and considered a suitable biological dosimeter for estimating in vivo whole body exposures, particularly in the case of large scale radiation accidents. One of the major drawbacks of the MN assay is its reduced sensitivity for the detection of damage induced by low doses of low LET radiation, due to the high variability among the spontaneous MN frequencies. It is suggested that age, smoking habit and sex are the main confounding factors that contribute to the observed variability. Previous work in our laboratory, shows a significant positive correlation of the spontaneous and radiation induced MN frequencies with age and smoking habit, the latter being the strongest confounder. These findings led to in vitro studies of the dose-response relationships for smoking and non smoking donors evaluated separately, using 60Co ? rays. The objectives of the present work are: 1-To increase the amount of data of the dose-response relationships, using ? rays from a 60Co source, for smoking and non smoking donors, in order to find, if applicable, a correction factor for the calibration curve that takes into account the smoking habit of the individual in the case of accidental overexposure dose assessment, particularly in the low dose range. 2-To establish general conclusions on the current state of the technique. The sample for smoking and non smoking calibration curves was enlarged in the range of 0Gy to 2Gy. The fitting of both curves, performed up to the 2Gy dose, resulted in a linear quadratic model. MN distribution among bi nucleated cells was found to be over dispersed with respect to Poisson distribution, the average ratio of variance to mean being 1.13 for non smokers and 1.17 for smokers. Each fitted calibration curve, for smoking and non smoking donors, fell within the 95% confidence curves of the other, with the exception of the spontaneous frequency values of both calibration curves. Thus, for the accidental overexposure dose assessment it seems to be appropriate to use a pooled data (smokers + non smokers) calibration curve and in the case of dose assessment up to 0.5Gy, it is convenient to use the corresponding spontaneous term in the yield equation; associated to the individual smoking habit condition. General conclusions: 1-The high and variable spontaneous MN frequency prevents an adequate dose estimation below 0.2-0.3Gy of low LET radiation. 2-At high doses, of low LET radiation, the sensitivity of the MN test is lower than the conventional aberration methods (dicentrics) due to the smaller squared term in the yield equation. 3-Radiation induced MN tend to be over dispersed with respect to Poisson distribution. Over dispersion increases the standard error on the observed yield and thus the uncertainties on the dose estimation. (author)

  18. Amelioration of Radiation-induced Skin Injury by HIV-TAT-Mediated Protein Transduction of RP-1 from Rana pleurade

    OpenAIRE

    ZHANG, SHUYU; Wang, Wenjie; Peng, Ying; GU, QING; Luo, Judong; Zhou, Jundong; Wu, Jinchang; Hou, Yinglong; Cao, Jianping

    2013-01-01

    Radiation-induced reactive oxygen species (ROS) can damage DNA and most other biological macromolecules in skin and radiation-induced skin injury is a serious concern for radiation therapy. Skin possesses an extremely efficient antioxidant system, which is conferred by two systems: antioxidant enzymes and small molecules that can scavenge ROS by donating electrons. Amphibian skin is a multifunctional organ, which protects against dangers of various oxidative stresses. Recently, a small peptid...

  19. Plants as warning signal for exposure to low dose radiation

    International Nuclear Information System (INIS)

    The stamen-hair system of Tradescantia for flower colour has proven to be one of the most suitable materials to study the frequency of mutations induced by low doses of various ionizing radiations and chemical mutagens. The system has also been used successfully for detecting mutagenic synergisms among chemical mutagens and ionizing radiations as well as for studying the variations of spontaneous mutation frequency. In this study of radiobiology, the main objective is to observe somatic mutation (occurrence of pink cells from blue cells) induced on stamen hairs of five Tradescantia sp. available in Malaysia after exposure to low doses of chronic gamma irradiation using Gamma Green House. Pink cells appeared only on Tradescantia Pallida Purpurea stamen hairs after 13 days of exposure to irradiation with different doses of gamma rays. The highest number of stamens with pink cells was recorded from flowers irradiated with the highest dose of 6.37 Gy with 0.07 Gy/ h of dose rate. The lowest number of stamens with pink cells was recorded with an average of 0.57, irradiated with the lowest dose of 0.91 Gy with 0.01 Gy/ h of dose rate. There were no pink cells observed on Tradescantia Spathaceae Discolor after exposure to different doses of gamma rays. Similar negative results were observed for the control experiments. The principal cells in this assay are the mitotic stamen hair cells developing in the young flower buds. After exposure to radiation, the heterozygous dominant blue character of the stamen hair cell is prevented, resulting in the appearance of the recessive pink color. Furthermore, no pink cell appears on all species of Tradescantia spathaceae after irradiated with different doses of gamma rays. The sensitivity of the Tradescantia has been used widely and has demonstrated the relation between radiation dose and frequency of mutation observed at low doses which can contribute to the effects of low doses and their consequences for human health. This system carries the advantage of observing meaningful data in a short period of time, being able to meditate effects on human health and to prevent possible accidents, when adopted as periodical monitoring. Tradescantia Pallida Purpurea can be regarded as a biosensor plant or a biological warning signal for exposure to low dose radiation which exhibits a noticeable quantity of cell alteration in a short time following exposure to radiation. Hence, the effects caused on the environment might be anticipated, and by extension on the human being, as a result of its occupation exposition level. The use of this method can be recommended for radiation monitoring, therefore into the environment acclimatization, and may be used, in addition, in the prevention of radiological accidents. (author)

  20. Implication of prostaglandins and histamine H1 and H2 receptors in radiation-induced temperature responses of rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, S.B.; Hunt, W.A.; Mickley, G.A.

    1988-04-01

    Exposure of rats to 1-15 Gy gamma radiation (/sup 60/Co) induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxygenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu-receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H1 and H2 receptors may be involved in radiation-induced hypothermia, since both the H1 receptor antagonist, mepyramine, and H2 receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggest that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations.

  1. Multiple factors participating in radiation-induced adaptive response

    International Nuclear Information System (INIS)

    Radiation-induced adaptive response (RAR) is essentially the acquisition of radiation resistance by pre-exposed low dose radiation (priming). In this paper, in vitro findings on RAR-related factors are reviewed and authors' studies of RAR-related gene analysis in lethality and malformation of mouse fetus are described for future view. Studies on in vitro RAR have involved such participating factors as signal transduction, response appearance and bystander effect, and gene expression profiling. In RAR, DNA double strand break (DSB) by priming is conceivably the initial stimulation. In various cell systems including p53-knockout cells and in enzyme inhibition studies, intracellular signaling factors like protein kinase C, p38 MAPK, phospholipase C have been shown to participate. Increased activities of antioxidant and of damaged DNA repairing system, modulation of cell cycle, heat-shock reactions and apoptosis are suggested to concern to RAR appearance. Relationship between RAR and bystander effect is conceived to be important based on findings of cell lethality, mutagenesis, gap junction and NO radical. Genes relating to DSB repair, stress response, cell cycle and apoptosis have been shown to be specifically changed in RAR by their expression profile. Authors have conducted in vivo studies on RAR using embryogenetic system in the mouse. They have shown by gene profiling that signaling evoked by priming is important when the fetal lethality and malformation are used as RAR measures, and that in the subsequent process to RAR appearance, many signaling factors, particularly the transcription factor like p53, play a role. Database construction according to measures employed in individual studies, classification of living systems studied, radiation factors like linear energy transfer (LET), dose and dose rate, and functional genes concerned is thought useful for understanding the ultimate molecular mechanisms involved in ARA. (K.T.)

  2. Intracranial germinomas: a case for low dose radiation therapy alone

    International Nuclear Information System (INIS)

    Purpose: To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma. Materials and Methods: Between 1975 and 1995, 39 patients with a diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All but one pt received whole brain (WB) RT, (median dose: 3240 cGy range: 1500-4437 cGy) and a boost to the tumor volume (median total tumor volume dose: 5200 cGy, range: 3960-5950 cGy). Thirty-one pts received RT to the spine (median dose: 2500, range: 1875-3750). Eleven pts were treated with low dose RT and a tumor volume boost, (WB dose ? 2550 cGy, and spine dose ? 2160 cGy). Five pts were treated with cisplatin-based chemotherapy and low dose WB RT. Fifteen pts were biopsy-proven and 18 presented with multiple midline germinomas (MMG). Among all pts, 33% had serum or CSF positive for low levels of HCG and none of 19 (9 biopsy-proven) germinomas measured positive for AFP tumor marker. Six of 22 (27%) pts who had spine imaging or CSF cytology had evidence of tumor seeding. The male-to female-ratio was 1.4. Median age at diagnosis was 14 yrs for male pts and 9.5 yrs for females (p=.02, overall age range: 1-31 yrs). Median follow-up for survivors is 64 months (range: 1-226 months). Toxicity of treatment relative to dose was assessed. Results: The 5-yr. actuarial rate of disease-free survival (DFS) and overall survival for presumed germinomas was 97%. No pts died of germinoma. One pt died of a shunt infection who had received concurrent chemotherapy and low dose whole brain RT. Among the low dose RT alone group 6 pts received whole brain RT of ? 2550 cGy and 9 pts were treated with spinal RT of ? 2160 cGy without chemotherapy. Two of these pts had CSF cytology positive for tumor seeding. Additionally, 8 pts received a total dose to the tumor volume of ? 4800 cGy without chemotherapy. The 5-yr DFS was 100%. Five pts were treated with cisplatin-based chemotherapy followed by low dose RT. There were 2 CRs and 1 PR after 3 cycles, and 2 PRs after 1 cycle (chemotherapy was discontinued after 1 cycle due to ototoxicity). Among 18 pts treated with ? 3060 cGy WB RT (median follow-up: 35 mos), the most striking toxicity was in (4(5)) pts treated with chemotherapy who developed ototoxicity prior to RT. One pt had worsening of neuropsychological function which was present at diagnosis and 5 pts developed endocrinopathies. Among 20 pts treated with > 3060 cGy WB RT (median follow-up: 72 mos) there were 7 new or worsened neuropsychological outcomes. There were 10 pts who developed endocrinopathies. One female pt who received high dose WB RT was diagnosed with a glioblastoma multiforme within the treatment field 6 yrs after CSI. Conclusions: 1) Germinomas are highly curable with RT alone. 2.) These results suggest that low dose RT alone to the craniospinal axis (2000 cGy) and a boost to the tumor volume (4500 cGy) is effective and associated with few treatment complications. This may be more clearly indicated for pts with MMG or evidence of spinal seeding. Further experience is necessary to confirm this. 3.) The toxicity associated with high dose RT or chemotherapy and low dose RT argues against its use in germinomas

  3. Divalent cations and radiation induced lipid peroxidation

    International Nuclear Information System (INIS)

    Response of Co2+, Cu2+, Fe2+, Ni2+ and Mn2+ against radiation induced lipid peroxidation has been examined. Liposomes prepared from L-?-lecithin were irradiated with or without divalent cations, Co2+ and Cu2+ inhibited lipid peroxidation in concentration dependent manner. On the other hand Fe2+, Ni2+ and Mn2+ enhanced the peroxidation. The enhancement of peroxidation due to Ni2+ was biphasic in nature. Higher concentration of Mn2+ decreased the peroxidation. Except Cu2+ no other cations studied could change the non-linear pattern of radiation induced lipid peroxidation. The pro- or antioxidant effect of divalent cations may be due to their reactivity towards oxygen and oxygen free radicals, and at least in part to their hard/soft acid character. (author). 29 refs., 3 figs

  4. Calculation of radiation-induced stress relaxation

    Science.gov (United States)

    Nagakawa, Johsei

    1994-09-01

    A numerical calculation based on point defect kinetics under stress was carried out to evaluate radiation-induced stress relaxation in a solution-annealed 316 stainless steel at low and medium temperatures (60 and 300°C). The calculation shows that the stress relaxation relative to the initial stress is almost independent of the initial stress under irradiation. At 1 × 10 -6 dpa/s, stress relaxation at 60°C is greater than that at 300°C and the stress almost disappears in a month of continuous irradiation. Even with a low damage rate of 1 × 10 -8 dpa/s, the stress relaxation at 60°C is considerable and exceeding that at 300°C and 1 × 10 -6 dpa/s during the first several months of irradiation. The results indicate the importance of the radiation-induced stress relaxation in experimental fusion reactors.

  5. European low-dose radiation risk research strategy: future of research on biological effects at low doses

    International Nuclear Information System (INIS)

    In 2009, the European High Level and Expert Group identified key policy and scientific questions to be addressed through a strategic research agenda for low-dose radiation risk. This initiated the establishment of a European Research Platform, called MELODI (Multidisciplinary European Low Dose Research Initiative). In 2010, the DoReMi Network of Excellence was launched in the Euratom 7. Framework Programme. DoReMi has acted as an operational tool for the sustained development of the MELODI platform during its early years. A long-term Strategic Research Agenda for European low-dose radiation risk research has been developed by MELODI. Strategic planning of DoReMi research activities is carried out in close collaboration with MELODI. The research priorities for DoReMi are designed to focus on objectives that are achievable within the 6-y lifetime of the project and that are in areas where stimulus and support can help progress towards the longer-term strategic objectives. (authors)

  6. Radiation-induced brain injury: A review

    OpenAIRE

    MichaelRobbins

    2012-01-01

    Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and ex...

  7. Study of chemical and radiation induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chmura, A.

    1995-11-01

    The study of chemical and radiation induced carcinogenesis has up to now based many of its results on the detection of genetic aberrations using the fluorescent in situ hybridization (FISH) technique. FISH is time consuming and this tends to hinder its use for looking at large numbers of samples. We are currently developing new technological advances which will increase the speed, clarity and functionality of the FISH technique. These advances include multi-labeled probes, amplification techniques, and separation techniques.

  8. International Activities in Radiation-Induced Carcinogenesis. Survey Paper

    International Nuclear Information System (INIS)

    During the past 10 years special attention has been paid to the problem of late effects of radiation and in particular to radiation-induced carcinogenesis and leukaemogenesis. In the UNSCEAR report of 1958-1962 this.problem was mentioned as being of considerable importance from the point of view of estimation of risk to the population from environmental radiation. In 1964 a special report was prepared by UNSCEAR on radiation- induced carcinogenesis. In the ICRP publication No. 8, a chapter dealing with assessment of somatic risks discussed the problem of leukaemia and other neoplasms and particularly stressed the problem of thyroid carcinoma-and bone sarcoma. WHO panels of experts discussed the problem in 1960-1966 and made some recommendations for international activity in this field. In spite of the amount of scientific attention that has been given in recent years to experimental radiobiology in animals and lower forms, it has become abundantly clear that information directly applicable to humans is woefully inadequate and that there is a desperate need for carefully collected data from man on which to base public health planning and day to day work in radiation protection. This has long been recognized in the technical program of WHO in the emphasis given to the practical importance of epidemiology in human radiobiology and the degree to which it depends upon international collaboration

  9. Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract.

    Science.gov (United States)

    Sinha, Mahuya; Das, Dipesh Kr; Datta, Sanjukta; Ghosh, Santinath; Dey, Sanjit

    2012-03-01

    Protective effect of Moringa oleifera leaf extract (MoLE) against radiation-induced lipid peroxidation has been investigated. Swiss albino mice, selected from an inbred colony, were administered with MoLE (300 mg/kg body wt) for 15 days before exposing to a single dose of 5 Gy 60Co-gamma radiation. After treatments, animals were necropsied at different post irradiation intervals (days 1, 7 and 15) and hepatic lipid peroxidation and reduced glutathione (GSH) contents were estimated to observe the relative changes due to irradiation and its possible amelioration by MoLE. It was observed that, MoLE treatment restored GSH in liver and prevented radiation induced augmentation in hepatic lipid peroxidation. Phytochemical analysis showed that MoLE possess various phytochemicals such as ascorbic acid, phenolics (catechin, epicatechin, ferulic acid, ellagic acid, myricetin) etc., which may play the key role in prevention of hepatic lipid peroxidation by scavenging radiation induced free radicals. PMID:22439436

  10. Amelioration of ionizing radiation induced lipid peroxidation in mouse liver by Moringa oleifera Lam. leaf extract

    International Nuclear Information System (INIS)

    Protective effect of Moringa oleifera leaf extract (MoLE) against radiation-induced lipid peroxidation has been investigated. Swiss albino mice, selected from an inbred colony, were administered with MoLE (300 mg/kg body wt) for 15 days before exposing to a single dose of 5 Gy 60Co-gamma radiation. After treatments, animals were necropsied at different post irradiation intervals (days 1, 7 and 15) and hepatic lipid peroxidation and reduced glutathione (GSH) contents were estimated to observe the relative changes due to irradiation and its possible amelioration by MoLE. It was observed that, MoLE treatment restored GSH in liver and prevented radiation induced augmentation in hepatic lipid peroxidation. Phytochemical analysis showed that MoLE possess various phytochemicals such as ascorbic acid, phenolics (catechin, epicatechin, ferulic acid, ellagic acid, myricetin) etc., which may play the key role in prevention of hepatic lipid peroxidation by scavenging radiation induced free radicals. (author)

  11. Chinese prescription Shenlingbaizhu extract prevents radiation-induced small intestinal injury in mice

    International Nuclear Information System (INIS)

    Objective: to investigate the therapeutic effect of traditional Chinese prescription Shenlingbaizhu Extract on radiation-induced intestinal injury in mice. Methods: Proliferation improvement of irradiated intestinal epithelial cells (IEC-6) was tested by MTT assay in vitro. The preventive effect of the prescription was also tested in vivo. Mice were treated with Shenlingbaizhu by intragastric administration immediately after receiving local irradiation to the abdomen at a dose of 10 Gy (60Co ?-ray). The body mass, diarrhea and survival were recorded. The pathological changes in the jejunum of mice were stained by HE and observed. Results: Shenlingbaizhu Extract could significantly promote the proliferation of irradiated intestinal epithelial cells in vitro. Shenlingbaizhu Extract treatment reduced the diarrhea of irradiated mice, improved the intestinal structural recovery and increased the mice survival. Conclusion: Traditional Chinese prescription Shenlingbaizhu Extract shows significant protective effect on radiation-induced intestinal injury in mice, providing data for clinical treatment of radiation-induced intestinal injury. (authors)

  12. Radiation induced dielectric effect in polymers

    International Nuclear Information System (INIS)

    Radiation induced dielectric effect in pure (PE, PET, PS, PVAc, POD, PTFE, PDT) as well as composite (PVAc + Al2O3) polymers is investigated under pulse irradiation conditions (pulse length 0.1 to 3 ms, electron energy 65 keV, dose per pulse 102 to 104 Gy, ac bias field frequence 103 to 105 Hz). Tests are conducted in vacuum of 3 x 10 -3 Pa at room temperature in such a way as to allow direct comparison with the conventional radiation induced conductivity. Experiments carried out with loaded polymers proved the applicability of the proposed technique exhibiting good agreement with the straightforward theory in the absence of any adjustable parameters. The radiation induced dielectric effect in pure polymers (with the only exception of PDT) increases the in-phase component of the ac conductivity only. In PDT on the other hand a reversible change of the dielectric constant is observed. A theory of the effect accounting for the formation of the neutral radiation products, geminate ion pairs and free charges by pulse radiolysis is put forward. (author)

  13. Radiation induced glioblastoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Naoki; Kayama, Takamasa; Sakurada, Kaori; Saino, Makoto; Kuroki, Akira [Yamagata Univ. (Japan). School of Medicine

    2000-05-01

    We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma. At the age of 34, the patient was diagnosed to have a non-functioning pituitary adenoma. It was partially removed followed by 50 Gy focal irradiation with a 5 x 5 cm lateral opposed field. Twenty years later, she suffered from rapidly increasing symptoms such as aphasia and right hemiparesis. MRI showed a large mass lesion in the left temporal lobe as well as small mass lesions in the brain stem and the right medial temporal lobe. These lesions situated within the irradiated field. Magnetic resonance spectroscopy revealed relatively high lactate signal and decreased N-acetyl aspartate, choline, creatine and phosphocreatine signals. Increased lactate signal meant anaerobic metabolism that suggested the existence of a rapidly growing malignant tumor. Thus, we planned surgical removal of the left temporal lesion with the diagnosis of a radiation induced malignant glioma. The histological examination revealed a glioblastoma with radiation necrosis. MIB-1 staining index was 65%. Postoperatively, her symptoms improved, but she died from pneumonia 1 month after the surgery. A autopsy was obtained. The lesion of the left temporal lobe was found to have continuity to the lesion in the midbrain, the pons and the right temporal lobe as well. High MIB-1 staining index suggested that a radiation induced glioblastoma had high proliferative potential comparing with a de novo and secondary glioblastoma. (author)

  14. The nature and principles of the radiation-induced cancerogenesis

    International Nuclear Information System (INIS)

    The paper represents the analysis of the authors and literary data concerning the nature and principles of the radiation-induced neoplasms. The mechanisms of the radiation-induced cancerogenesis development are not clear understood. The experimental data altogether do not allow developing the mathematical model of the radiation-induced cancerogenesis at the molecular level. This model has to take into account all necessary indices including radiation factor and the state of the organism. The general principles of the radiation-induced cancerogenesis have been formulated in the present review. It is possible to use these principles in order to predict and calculate the risks of the radiation-induced neoplasms

  15. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information that will be useful in estimating human health risks due to radiation that may occur during exposures in the work environment, nuclear/radiological catastrophes, as well as radiotherapy. Several papers have been published, accepted for publication or are in preparation. A number of poster and oral presentations have been made at scientific conferences and workshops. Archived tissues of various types will continue to be evaluated via funding from other sources (the DoE Low Dose Radiation Research Program, Office of Science and this specific grant will be appropriately included in the Acknowledgements of all subsequent publications/presentations). A post-doc and several students have participated in this study. More detailed description of the accomplishments is described in attached file.

  16. Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Freiin von Neubeck, Claere H.; Shankaran, Harish; Karin, Norman J.; Kauer, Paula M.; Chrisler, William B.; Wang, Xihai; Robinson, Robert J.; Waters, Katrina M.; Tilton, Susan C.; Sowa, Marianne B.

    2012-04-17

    The concern over possible health risks from exposures to low doses of ionizing radiation has been driven largely by the increase in medical exposures, the routine implementation of X-ray backscatter devices for airport security screening, and, most recently, the nuclear incident in Japan. Due to a paucity of direct epidemiological data at very low doses, cancer risk must be estimated from high dose exposure scenarios. However, there is increasing evidence that low and high dose exposures result in different signaling events and may have different mechanisms of cancer induction. We have examined the radiation induced temporal response of an in vitro three dimensional (3D) human skin tissue model using microarray-based transcriptional profiling. Our data shows that exposure to 100 mGy of X-rays is sufficient to affect gene transcription. Cell type specific analysis showed significant changes in gene expression with the levels of > 1400 genes altered in the dermis and > 400 genes regulated in the epidermis. The two cell types rarely exhibited overlapping responses at the mRNA level. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) measurements validated the microarray data in both regulation direction and value. Key pathways identified relate to cell cycle regulation, immune responses, hypoxia, reactive oxygen signaling, and DNA damage repair. We discuss in particular the role of proliferation and emphasizing how the disregulation of cellular signaling in normal tissue may impact progression towards radiation induced secondary diseases.

  17. Uncommon toxicity of low-dose methotrexate: case report

    Directory of Open Access Journals (Sweden)

    Zohreh Yousefi

    2015-10-01

    Full Text Available Background: Standard treatment of Gestational Trophoblastic Disease (GTD is chemotherapy. Single-agent chemotherapy regime including Methotrexate (MTX or Actinomycin. Single-agent is widely used in treatment of persistent trophoblastic disease. We reported an uncommon toxicity of low-dose single-agent methotrexate in a patient. Case Presentation: A 20-year-old woman, primary gravid after two months missed period and spotting with diagnosis of incomplete abortion with uterine size equivalent of ten weeks pregnancy (8-10 cm underwent evacuation curettage. In serial follow-up, based on rise of beta-hCG titer and absence of metastatic disease, it was categorized as low-risk persistent trophoblastic disease. She was referred to gynecology oncology center of Ghaem Hospital, Mashhad University of Medical Sciences in May 2014. Because of rise of beta-hCG titer, after complete metastatic work-up and lack of disease in other sites, persistent disease was diagnosed and candidate for chemotherapy (single agent low-dose. The patient received first course of therapy with MTX (50 mg/m˛, intra muscular. Unfortunately, after two days of treatment she developed uncommon severe toxicity, fever, severe nausea and vomiting, tachycardia, and generalized weakness. Also, we found hematologic abnormality (WBC: -14000-15000 µI, platelet- 540 µI and sever neutropenia, and abnormal rising in liver function test (SGOT, SGPT (three to four times and renal function test (BUN and Creatinine (two times. In addition, she had disseminated erosive lesion in all of body especially in face. Due to the fatal side effects of chemotherapy, she was admitted to intensive care unit (ICU. Fortunately, after two to three weeks, she was improved by conservative management. After few weeks beta-hCG titer was in normal limit. However she had normal serial beta-hCG in one year of follow-up. Conclusion: It is important to emphasis unpredictable side effects of chemotherapy with low-dose methotrexate.

  18. An insight in to effect of dose, dose rate and confounding factors on radiation induced DNA damage and repair using comet assay

    International Nuclear Information System (INIS)

    Ionizing radiation is known to induce a variety of DNA lesions such as single strand breaks (SSBs), double strand breaks (DSBs), and oxidative damage to bases, interstrand cross-links and locally multiplies damaged sites (LMDs). However, the most dangerous DNA lesions which are responsible for the origin of lethal effects, mutagenesis, genomic instability and carcinogenesis are the DSBs and LMDs. Humans are at high risk of exposure to low doses of ionizing radiation either through environmental or occupational exposures. It is known that following exposure to doses below 10 cGy mammalian cells adapt to subsequent higher doses of ionizing radiation exposures a phenomenon known as adaptive response. Neither the changes induced by low dose ionizing radiation nor the biochemical pathways that signal this low dose radiation effect are well studied. The genetic effect of ionizing radiation depends on the radiation dose as well as on the dose rate at which it is delivered. The radiation induced cellular effects such as chromosome aberrations, sister chromatid exchange, micronucleus formation, transformation, mutations and changes in gene expression can cause cancer, cell death or damage can transmitted to subsequent generations. Contradictory reports exist in literature about variation in genetic response as function of dose and dose rates. There are different methods available to detect the DNA damage such as Neutral and Alkaline elution assay, DNA unwinding assay, Comet assay, Halo assay, FISH-comet assay, gamma-H2AX. Comet assay is a valuable technique which allows detection of DNA damage and repair at single cell level and provides a unique opportunity to investigate intercellular differences in any eukaryotic cell population. Thus, there is need to evaluate the utility and accuracy of different techniques used for estimation of radiation induced DNA damage. Here, we report our observations on the effect of low-dose, low dose rates, low dose limit, type of radiation, cell type responsiveness and effects of confounding factors such as age and gender using comet assay in different models. (author)

  19. The effects of low dose irradiation on immunological paramters

    International Nuclear Information System (INIS)

    Investigations into the lymphocytes of individuals exposed to radiation have revealed phenomena that are suggestive of the occurence of hormesis. Increased repair capacities were proven for emmployees receiving extremely low doses (between 0,14 mSr and 0.9 mSr per month) at their working places. This improvement of the investigated repair mechanisms cannot be explained by shifts in the lymphocyte distribution pattern to the favour of radiation-resistent subpopulations. At present, attempts are being made to gain more insights into the functional activity of lymphocytes. (DG)

  20. Problems of the effect of low-dose irradiation

    International Nuclear Information System (INIS)

    The main aim and purpose of this meeting was to increase the knowlodge of radiation risk and to remove once and for all widespread false estimates. In 12 papers presented at this Congress the current applications of irradiation are critically discussed. Consideration was given as to how and in which instances this method of investigation can usefully be applied. The essential recognition strived for at this Congress was the maximum application of irradiation at minimum risk. Research into repair mechanisms revealed new findings concerning the biopositive effect of low doses of ionising radiation and this was also treated during the course of the meeting. (orig.)

  1. Low-dose exposure and the induction of adaptation

    International Nuclear Information System (INIS)

    When cells are irradiated with low doses of ionizing radiation, one of the most readily noticed and extensively studied effects is the induction of chromosome and chromatid aberrations. Because genetic integrity is not maintained when aberrant cells undergo mitosis, the induction of aberrations is responsible for most of the cell killing observed after irradiation. Even many of the viable somatic effects, such as the induction of cancer, can be related to chromosomal effects like deletions or translocations that either remove suppressors of oncogenes or promote their activity. (author). 44 refs

  2. Exposure to low dose ionising radiation: Molecular and clinical consequences.

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2014-07-10

    This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications\\/relevance of the effect.

  3. Application of low dose radiation for preservation of sea foods

    International Nuclear Information System (INIS)

    Treatment of food with low doses of gamma radiation has been recognized to have two main advantages. These consist of: (1) improvement of food safety by elimination of pathogens and (2) reduction of microbial spoilage and extension of shelf life of perishable items by reducing the number of viable spoilage organisms. Studies during the last few decades have conclusively proved the beneficial effects of radiation with respect to fishery products. The three potential areas of application to fish products include: (i) radurization for shelf life extension (ii) radicidation to eliminate food borne pathogens in the products and (iii) radiation treatment to dried products to control insects

  4. Problems in estimating the risk of low dose environmental radiation

    International Nuclear Information System (INIS)

    Three aspects of the problem of estimating health effects due to small increments in radiation dose are discussed: statistical power, control populations, and low-dose extrapolation. It is still impossible to verify the existence or absence of additional risk of the order of one part per million per person-year or less from excess exposure of 1 rem or less. In high dose studies, substantial errors of one or more orders of magnitude can be made if the control population is skewed or if an incorrect form of the dose-response function is used

  5. Pelvimetry by digital radiography: a low-dose examination

    International Nuclear Information System (INIS)

    Digital radiographs obtained with a CT scanner were evaluated as an alternative to conventional pelvimetry. Dosimetry studies demonstrated an absorbed radiation dose of 22 mrad for each digital radiograph, approximately 3% of the dose for comparable standard radiographs. Distance measurements were accurately made on digital radiographs and axial CT sections by cursor placement and a computer program with no need to correct for magnification. Clinical studies of 10 patients confirmed that pelvimetry using digital radiographs is an accurate, simple, and extremely low-dose precedure which could replace the conventional method

  6. Pelvimetry by digital radiography: a low-dose examination

    International Nuclear Information System (INIS)

    Digital radiographs obtained with a CT scanner were evaluated as an alternative to conventional pelvimetry. Dosimetry studies demonstrated an absorbed radiation dose of 22 mrad for each digital radiograph, approximately 3% of the dose for comparable standard radiographs. Distance measurements were accurately made on digital radiographs and axial CT sections by cursor placement and a computer program with no needs to correct for magnification. Clinical studies of 10 patients confirmed that pelvimetry using digital radiographs is an accurate, simple, and extremely low-dose procedure which could replace the conventional method

  7. Role of radiation-induced grain boundary segregation in irradiation assisted stress corrosion cracking

    International Nuclear Information System (INIS)

    Isolation of microstructural and microchemical effects on irradiation assisted stress corrosion cracking (IASCC) was attempted by means of low-dose high-temperature neutron irradiation in a material test reactor to get better under-standing on IASCC. Microstructure, grain boundary segregation, hardness and SCC susceptibility were examined on stainless steels irradiated to 0.8 dpa at around 673 K. The irradiation caused well-developed grain boundary segregation without notable hardening or microstructural changes. No IASCC was found in 593 K hydrogenated water where-as the steels were highly susceptible to IASCC in 561 K oxygenated water. The results suggest that grain boundary segregation, probably Cr depletion, is sufficient to cause IASCC in oxygenated water and that other radiation-induced changes such as microstructure and hardening are required for IASCC in hydrogenated water. (author)

  8. Physical characteristics of a low-dose gas microstrip detector for orthopedic x-ray imaging.

    Science.gov (United States)

    Després, Philippe; Beaudoin, Gilles; Gravel, Pierre; de Guise, Jacques A

    2005-04-01

    A new scanning slit gas detector dedicated to orthopedic x-ray imaging is presented and evaluated in terms of its fundamental imaging characteristics. The system is based on the micromesh gaseous structure detector and achieves primary signal amplification through electronic avalanche in the gas. This feature, together with high quantum detection efficiency and fan-beam geometry, allows for imaging at low radiation levels. The system is composed of 1764 channels spanning a width of 44.8 cm and is capable of imaging an entire patient at speeds of up to 15 cm/s. The resolution was found to be anisotropic and significantly affected by the beam quality in the horizontal direction, but otherwise sufficient for orthopedic studies. As a consequence of line-by-line acquisition, the images contain some ripple components due to mechanical vibrations combined with variations in the x-ray tube output power. The reported detective quantum efficiency (DQE) values are relatively low (0.14 to 0.20 at 0.5 mm(-1)) as a consequence of a suboptimal collimation geometry. The DQE values were found to be unaffected by the exposure down to 7 microGy, suggesting that the system is quantum limited even for low radiation levels. A system composed of two orthogonal detectors is already in use and can produce dual-view full body scans at low doses. This device could contribute to reduce the risk of radiation induced cancer in sensitive clientele undergoing intensive x-ray procedures, like young scoliotic women. PMID:15895603

  9. Health effects of low doses at low dose rates: dose-response relationship modeling in a cohort of workers of the nuclear industry

    International Nuclear Information System (INIS)

    The aim of this thesis is to contribute to a better understanding of the health effects of chronic external low doses of ionising radiation. This work is based on the French cohort of CEA-AREVA NC nuclear workers. The mains stages of this thesis were (1) conducting a review of epidemiological studies on nuclear workers, (2) completing the database and performing a descriptive analysis of the cohort, (3) quantifying risk by different statistical methods and (4) modelling the exposure-time-risk relationship. The cohort includes monitored workers employed more than one year between 1950 and 1994 at CEA or AREVA NC companies. Individual annual external exposure, history of work, vital status and causes of death were reconstructed for each worker. Standardized mortality ratios using French national mortality rates as external reference were computed. Exposure-risk analysis was conducted in the cohort using the linear excess relative risk model, based on both Poisson regression and Cox model. Time dependent modifying factors were investigated by adding an interaction term in the model or by using exposure time windows. The cohort includes 36, 769 workers, followed-up until age 60 in average. During the 1968- 2004 period, 5, 443 deaths, 2, 213 cancers, 62 leukemia and 1, 314 cardiovascular diseases were recorded. Among the 57% exposed workers, the mean cumulative dose was 21.5 milli-sieverts (mSv). A strong Healthy Worker Effect is observed in the cohort. Significant elevated risks of pleura cancer and melanoma deaths were observed in the cohort but not associated with dose. No significant association was observed with solid cancers, lung cancer and cardiovascular diseases. A significant dose-response relationship was observed for leukemia excluding chronic lymphatic leukemia, mainly for doses received less than 15 years before and for yearly dose rates higher than 10 mSv. This PhD work contributes to the evaluation of risks associated to chronic external radiation exposure. Our study finds a risk of leukemia associated with chronic external exposure and allows taking into account modifying factors of this relation. Additional follow-up allows to improve the precision of the estimated dose-response relationship. A combined analysis including the present cohort and other nuclear cohorts could quantify more precisely the risks associated with low doses at low dose rates, in order to validate current underlying hypotheses of the radiation protection system. (author)

  10. Epidemiology assessment of cancer risk at low doses and dose rates

    International Nuclear Information System (INIS)

    There are difficulties in predicting the effects of protracted exposure to low doses of ionizing radiation delivered at low dose rates from the well documented effects of exposure to high doses. There are substantial numbers of radiation workers employed in the nuclear industry, most of whose past occupational exposure comes from external sources and is well recorded. From these populations, it is possible to examine the effects of increasing cumulative radiation dose. A number of such studies have now been carried out and reported. Current radiological protection practices have reduced occupational doses to the point where it is unlikely that new entrants to the industry will add significantly to the power of the studies. It is, therefore, very important that studies of historically exposed populations are continued until the majority of subjects have died. The statistical power of a worldwide study would permit a reasonably accurate estimate of overall mortality risk, and perhaps distinguish between absolute and relative risk models. The problems of combining studies on worker populations of differing nationalities and lifestyles, and therefore of differing natural cancer incidence, are formidable. The potential and requirements for such a study are to be considered under the auspices of the International Agency for Research on Cancer at Lyon. A meeting is being arranged which will bring together epidemiologists and representatives of organizations employing large numbers of radiation workers to study the compatibility of existing datasets and requirements for future data gathering exercises. The compilation of international databases by some reputable scientific body which can ensure confidentiality of personal dose statistics and cancer/mortality incidence data is to be encouraged. From the point of view of operators of nuclear plants, of occupationally exposed persons, and of those responsible for health regulations, it is important to determine directly the risk from radiation at the low dose rates of practical concern; the present opportunity will not recur. 12 refs, 2 figs

  11. Hesperidin and low dose gamma irradiation alleviate rosiglitazone -induced cardiotoxicity in type 2 diabetic rats

    International Nuclear Information System (INIS)

    Aim: The present study was designed to investigate the cardio protective effect of hesperidin and low dose ?- irradiation (LDR) against rosiglitazone cardiotoxicity. Experiment: Type 2 diabetes mellitus (T2DM) was induced in rats by single intraperitoneal injection of streptozotocin (STZ) followed by nicotinamide (NIC) (65 and 110 mg/kg b.wt, respectively). The diabetic rats were divided into 5 groups: untreated, LDR, LDR+ rosiglitazone, LDR + Hesperidin, LDR+ rosiglitazone + Hesperidin for one month, and blood and tissue samples were collected. Results: The diabetic rats showed elevated serum creatine kinase (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP), hyaluronidase activity, and reduced serum nitric oxide (NO) level, hematocrit % as well as final body weight, and pathological alterations in myocardial tissue. Treatment with LDR + rosiglitazone + Hesperidin ameliorated all these abnormalities approaching control levels. Conclusion: Results indicate the possible cardio protective role of hesperidin and LDR against rosiglitazone cardiotoxicity.

  12. Neuroprotective effect of EGb761® and low-dose whole-body ?-irradiation in a rat model of Parkinson's disease.

    Science.gov (United States)

    El-Ghazaly, Mona A; Sadik, Nermin Ah; Rashed, Engy R; Abd-El-Fattah, Amal A

    2015-12-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The present study was undertaken to investigate the pretreatment effects of standardized Ginkgo biloba extract (EGb761(®)) and low-dose whole-body ?-irradiation on the neurological dysfunction in the reserpine model of PD. Male Wistar rats were pretreated orally with EGb761 or fractionated low-dose whole-body ?-irradiation or their combination, then subjected to intraperitoneal injection of reserpine (5 mg/kg body weight) 24 h after the final dose of EGb761 or radiation. Reserpine injection resulted in the depletion of striatal dopamine (DA) level, increased catalepsy score, increased oxidative stress indicated via depletion of glutathione (GSH), increased malondialdehyde (MDA) and iron levels, decreased DA metabolites metabolizing enzymes; indicated by inhibition by glutathione-S-transferase, and nicotinamide adenine dinucleotide phosphate (NADPH)-quinone oxidoreductase (NQO) activities, mitochondrial dysfunction; indicated by declined complex I activity, and adenosine triphosphate (ATP) level and increased apoptosis; indicated by decreased mitochondrial B cell lymphoma-2 (Bcl-2) protein level and by transmission electron microscope. EGb761 and low-dose ?-radiation ameliorated the reserpine-induced state of oxidative stress, mitochondrial dysfunction, and apoptosis in brain. It can be concluded that EGb761, a widely used herbal medicine and low dose of ?-irradiation have protective effects for combating Parkinsonism possibly via replenishment of GSH levels. PMID:23696346

  13. People in Their 50s Benefit Most from Low-Dose Aspirin, Report Says

    Science.gov (United States)

    ... in Their 50s Benefit Most From Low-Dose Aspirin, Report Says Heart-disease preventive may simultaneously reduce ... Sept. 14, 2015 (HealthDay News) -- Daily low-dose aspirin is best used as a preventive measure against ...

  14. Pomalidomide Plus Low-Dose Dexamethasone Improves Survival for Patients with Multiple Myeloma

    Science.gov (United States)

    ... Low-Dose Dexamethasone Improves Survival for Patients with Multiple Myeloma Summary Results from a randomized phase III trial ... low-dose dexamethasone may benefit some patients with multiple myeloma that has worsened (progressed) despite other treatments. Patients ...

  15. Low doses of neutrons induce changes in gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E.; Chang-Liu, C.M. (Argonne National Lab., IL (United States)); Panozzo, J.; Libertin, C.R. (Loyola Univ., Maywood, IL (United States))

    1993-01-01

    Studies were designed to identify genes induced following low-dose neutron but not following [gamma]-ray exposure in fibroblasts. Our past work had shown differences in the expression of [beta]-protein kinase C and c-fos genes, both being induced following [gamma]-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not [gamma]-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to [gamma] rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  16. Low doses of neutrons induce changes in gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E.; Chang-Liu, C.M. [Argonne National Lab., IL (United States); Panozzo, J.; Libertin, C.R. [Loyola Univ., Maywood, IL (United States)

    1993-06-01

    Studies were designed to identify genes induced following low-dose neutron but not following {gamma}-ray exposure in fibroblasts. Our past work had shown differences in the expression of {beta}-protein kinase C and c-fos genes, both being induced following {gamma}-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not {gamma}-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to {gamma} rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  17. Low doses of neutrons induce changes in gene expression

    International Nuclear Information System (INIS)

    Studies were designed to identify genes induced following low-dose neutron but not following ?-ray exposure in fibroblasts. Our past work had shown differences in the expression of ?-protein kinase C and c-fos genes, both being induced following ?-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not ?-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to ? rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure

  18. Low dose scatter correction for digital chest tomosynthesis

    Science.gov (United States)

    Inscoe, Christina R.; Wu, Gongting; Shan, Jing; Lee, Yueh Z.; Zhou, Otto; Lu, Jianping

    2015-03-01

    Digital chest tomosynthesis (DCT) provides superior image quality and depth information for thoracic imaging at relatively low dose, though the presence of strong photon scatter degrades the image quality. In most chest radiography, anti-scatter grids are used. However, the grid also blocks a large fraction of the primary beam photons requiring a significantly higher imaging dose for patients. Previously, we have proposed an efficient low dose scatter correction technique using a primary beam sampling apparatus. We implemented the technique in stationary digital breast tomosynthesis, and found the method to be efficient in correcting patient-specific scatter with only 3% increase in dose. In this paper we reported the feasibility study of applying the same technique to chest tomosynthesis. This investigation was performed utilizing phantom and cadaver subjects. The method involves an initial tomosynthesis scan of the object. A lead plate with an array of holes, or primary sampling apparatus (PSA), was placed above the object. A second tomosynthesis scan was performed to measure the primary (scatter-free) transmission. This PSA data was used with the full-field projections to compute the scatter, which was then interpolated to full-field scatter maps unique to each projection angle. Full-field projection images were scatter corrected prior to reconstruction. Projections and reconstruction slices were evaluated and the correction method was found to be effective at improving image quality and practical for clinical implementation.

  19. Low-dose ofatumumab for rituximab-resistant nephrotic syndrome.

    Science.gov (United States)

    Bonanni, Alice; Rossi, Roberta; Murtas, Corrado; Ghiggeri, Gian Marco

    2015-01-01

    Drug resistant idiopathic nephrotic syndrome (DRNS) remains a therapeutic dilemma. In this pilot study, the efficacy of the new fully humanised, anti-CD20 monoclonal antibody ofatumumab was tested in 4 children with persistence of proteinuria for at least 12?months in spite of a full drug approach (including rituximab). We used a low-dose 2-infusion ofatumumab model (300+700?mg/1.73?m(2) 2?weeks apart) using specified premedication. Transient normalisation of proteinuria (persisting for 2?months) was achieved in 1 child while another presented stable remission after 12?months; both had normal renal function. The outcome was not modified in the remaining 2 children presenting an impaired renal function. These results demonstrate that low-dose ofatumumab may induce remittance of proteinuria in children with a long story of DRNS and normal renal function. Further studies are needed to test whether higher doses of ofatumumab can also modify proteinuria in patients with impaired renal function. PMID:26376698

  20. A New Era of Low-Dose Radiation Epidemiology.

    Science.gov (United States)

    Kitahara, Cari M; Linet, Martha S; Rajaraman, Preetha; Ntowe, Estelle; Berrington de González, Amy

    2015-09-01

    The last decade has introduced a new era of epidemiologic studies of low-dose radiation facilitated by electronic record linkage and pooling of cohorts that allow for more direct and powerful assessments of cancer and other stochastic effects at doses below 100 mGy. Such studies have provided additional evidence regarding the risks of cancer, particularly leukemia, associated with lower-dose radiation exposures from medical, environmental, and occupational radiation sources, and have questioned the previous findings with regard to possible thresholds for cardiovascular disease and cataracts. Integrated analysis of next generation genomic and epigenetic sequencing of germline and somatic tissues could soon propel our understanding further regarding disease risk thresholds, radiosensitivity of population subgroups and individuals, and the mechanisms of radiation carcinogenesis. These advances in low-dose radiation epidemiology are critical to our understanding of chronic disease risks from the burgeoning use of newer and emerging medical imaging technologies, and the continued potential threat of nuclear power plant accidents or other radiological emergencies. PMID:26231501

  1. Low-dose chemotherapy for extra-abdominal desmoid tumor

    International Nuclear Information System (INIS)

    Objective was to assess the outcome of patients with extra-abdominaldesmoids tumor treated with low dose chemotherapy (methotrexate andvinblastine) both for tumor response and treatment related toxicity. Weretrospectively reviewed the outcome of 12 patients who underwent low dosechemotherapy for extra abdominal desmoid of different locations. The studytook place in the McGill University Health Center, Montreal, Canada between1996 and 2003. We evaluated the patients for their compliance, tumorresponse, complications of treatment and impact of treatment on symptoms.There were 7 females and 5 males with a mean age of 46 years. Disease relatedmorbidity included pain in 7 patients, functional limitation in 7 andcosmetic defects in 3. The mean tumor size was 11 cm (3-20 cm). The meanfollow-up was 43 months (15-71 months). Chemotherapy was administered weekly.Complications were significant. Only 2 patients did not experience thetoxicity. According to Response Evaluation Criteria in Solid Tumors, 6 tumorsshowed a partial response and 6 remained stable. None showed progression. Ofthe 7 patients who had painful tumors, 6 achieved significant symptom relief.Function was improved in 3 and restored to normal in 4. Cosmesis was improvedin 2 of the 3. At latest follow-up, tumors remained stable in 8, one hasmarkedly regressed and 3 exhibited progression at an average of 54 months.Only one patient required surgery. The only long term side effect was asensory peripheral neuropathy. Low dose chemotherapy was found to be avaluable adjunct to prevent local progression and improve symptoms. (author)

  2. Low-dose cancer risk from diagnostic radiation

    International Nuclear Information System (INIS)

    This paper describes authors' comments for low dose cancer risk of diagnostic radiation in relation to the article in a medical journal in 2004 mentioning that the risk is the highest in Japan. For this, they consider and discuss the exposure doses in diagnosis; current biological knowledge in radiation-related cancer involving DNA damage, genome instability, dose-response relationships and recent findings in leukemia; epidemiological findings on low dose exposure in workers in atomic energy industries, in A-bomb survivors and in others; and risk assessment of the exposure from fundamentals to dose-dose rate effect factor. They comment that there is no scientific conclusion for the problem at present. Since the exposure doses of diagnostic radiation are as low as 0.1-10 mSv, its risk is hardly detected even if a large scale, long period epidemiological investigation is conducted. This means that, though the threshold cannot be estimated, its possible risk relative to other carcinogenic factors is very small. They conclude that, despite above, because people's radiation exposure is mostly derived from medical sources, the communication for the risk between medical staff and patients will be more and more important as well as validation of diagnostic practice and optimization of dose for the minimum. (S.I.)

  3. Screening for lung cancer with low-dose computed tomography

    International Nuclear Information System (INIS)

    Lung cancer is the most common cause of death from malignancy. It is characterized by a favourable prognosis when treated in early stages and a poor prognosis in advanced stages. Populations at risk are relatively well defined, i.e. heavy smokers and workers exposed to asbestos and radon. Therefore, early detection using diagnostic techniques promises reduction of mortality from this tumor. Previous studies using chest radiography and sputum cytology were, however, disappointing due to poor sensitivity of these tests for early tumor stages. The new technique of low-dose computed tomography provides both high sensitivity for small tumors and a comfortable examination. As small benign pulmonary nodules are common reliable non-invasive diagnostic algorithms are required for classification of nodules. Preliminary studies using low-dose CT screening in smokers have provided promising results. Prior to a wide application of the technique in clinical routine more data are required as to inclusion criteria, examination intervals and the effect of screening on mortality reduction. (orig.)

  4. The low dose radiation exposure and its influence on human by the accident of the Fukushima nuclear power plant

    International Nuclear Information System (INIS)

    A large amount of radioactive materials was scattered in the atmosphere by the accident of the Fukushima Nuclear Power Plant and brings many nations radiation exposure and gives uneasiness. In this paper, the actual situation of a natural radiation and the artificial radiation and low dose radiation of radioactive materials are reviewed and biological effects on human, especially stochastic effects including induction of cancer are discussed. Moreover, recommendations and guidance on all aspects of protection against ionizing radiation are provided. (author)

  5. Sucralfate for the treatment of radiation induced mucositis

    International Nuclear Information System (INIS)

    Purpose: Radiotherapy, a cornerstone in the management of head and neck cancer, pelvic cancer, and esophageal cancer is associated with a marked mucosal toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical symptoms of radiation induced mucosal damage. Because there is no known way to obviate radiation mucositis all efforts to prevent aggravation and accelerate healing of mucosal changes are of great importance. Numerous agents including antimicrobials, local and systemic analgesics, antiinflammatory drugs, antidiarrheal drugs, in combination with intensive dietetic care are used to relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex sucralfate were suggested for the prevention and treatment of mucosal reactions. Since sucralfate protects ulcerated epithelium by coating, liberates protective prostaglandins and increases the local availability of protective factors this drug might directly interact with the pathogenesis of mucositis. Patients and Method: The results of available studies are analysed and discussed. Results: The results of several studies indicate that sucralfate treatment especially during radiotherapy for pelvic cancer leads to a significant amelioration of clinical symptoms and morphological changes. An application of sucralfate during radiotherapy of head and neck cancer reveals only limited benefits in most studies performed. Conclusion: Nevertheless sucralfate is a save, cheap and active drug for the is a save, cheap and active drug for the prevention and treatment of radiation mucositis especially in patients with pelvic irradiation. (orig.)Purpose: Radiotherapy, a cornerstone in the management of head and neck cancer, pelvic cancer, and esophageal cancer is associated with a marked mucosal toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical symptoms of radiation induced mucosal damage. Because there is no known way to obviate radiation mucositis all efforts to prevent aggravation and accelerate healing of mucosal changes are of great importance. Numerous agents including antimicrobials, local and systemic analgesics, antiinflammatory drugs, antidiarrheal drugs, in combination with intensive dietetic care are used to relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex sucralfate were suggested for the prevention and treatment of mucosal reactions. Since sucralfate protects ulcerated epithelium by coating, liberates protective prostaglandins and increases the local availability of protective factors this drug might directly interact with the pathogenesis of mucositis. Patients and Method: The results of available studies are analysed and discussed. Results: The results of several studies indicate that sucralfate treatment especially during radiotherapy for pelvic cancer leads to a significant amelioration of clinical symptoms and morphological changes. An application of sucralfate during radiotherapy of head and neck cancer reveals only limited benefits in most studies performed. Conclusion: Nevertheless sucralfate is a save, cheap and active drug for the

  6. Effects of low-dose fractionated external irradiation on metabolic and structural characteristics of rat thyroid

    Energy Technology Data Exchange (ETDEWEB)

    Nadolnik, L.; Niatsetskaya, Z. [Institute of Biochemistry, National Academy of