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

Directory of Open Access Journals (Sweden)

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

Meltem KURUS

2014-05-01

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Radiation-induced stress effects following low dose exposure  

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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

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

International Nuclear Information System (INIS)

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

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Low dose radiation induced adaptive response in human T and B lymphocyte cell lines  

International Nuclear Information System (INIS)

Human peripheral blood lymphocytes can express a low dose radiation induced adaptive response to subsequent radiation or chemical challenge. We are screening human T and B cell lines for differential expression of this phenomenon. Such lines should facilitate the identification of the factors underlying this phenomenon, and the conditions required to observe it. Our initial studies have used the T cell lines Molt-3 and CEM-CM3 and the B cell lines WIL2-NS and TK6. Two exposure scenarios were used: (1) a single exposure to 0.05 GY of x-rays followed 6 hrs. later 1 Gy, or (2) three 0.05 Gy exposures with 24 hr. intervals followed by 1 Gy 4 hrs after the last low dose exposure. To date we have triplicate experiments for each line. Under these conditions, TK6 is the only line to show an effect near significance (1 Gy CE 0.190.04 vs 0.051 Gy CE 0.240.05, p=0.08, two tailed paired t-test) which was limited to scenario 1. Recently, Rigaud et al. reported on low dose radiation induced adaptive response to HGPRT mutation in the AHH-1 B cell line. We exposed cells of the WIL2-NS line to a single 0.05 Gy X-ray exposure followed by 6 hrs. later by 3 Gy. To date we have performed 3 experiments. As with the above studies, there was no adaptive response for survival, however, there was a significant decrease in HGPRT mutation (73.214.9 x 10-6for 3 Gy vs 45.86.6 x 10-6 for 0.05+3 Gy). These preliminary results suggest that the detection of low dose radst that the detection of low dose radiation induced adaptive responses will depend upon cell line, exposure conditions, and biological endpoint measured

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2013-05-15

9

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

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

OpenAIRE

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 inv...

?urovi? Branka 1; Selakovi? Vesna M.; Spasi?-Joki? Vesna M.

2004-01-01

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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 protonses. 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 proto

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Mechanisms of Low Dose Radiation-induced T helper Cell Function  

Energy Technology Data Exchange (ETDEWEB)

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

Gridley, Daila S.

2008-10-31

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

OpenAIRE

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...

Morgan, William F.

2006-01-01

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

International Nuclear Information System (INIS)

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

15

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

International Nuclear Information System (INIS)

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

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

Directory of Open Access Journals (Sweden)

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.

?urovi? Branka 1

2004-01-01

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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 growted 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)

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

Science.gov (United States)

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

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

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

International Nuclear Information System (INIS)

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

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Chronic low dose ?-radiation induced increased cytogenetic damage in human population  

International Nuclear Information System (INIS)

In order to evaluate the biomedical effects of chronic low-dose ?-radiation exposure in residents stayed in buildings with Co-60 contaminated steel rods in Taiwan, two assays of micronucleus formation have been employed in their T-lymphocytes. The cytokinesis-block micronucleus (CBMN) and a cytosine arabinofuranoside (ARA-c) enhanced CBMN (CBMNA) were employed in 73 residents and 77 community controls. The exposed were shown with significantly increased CBMN (0.017 0.011) and CBMNA frequencies (0.030 0.019) than the controls (0.011 0.008 and 0.019 0.011, respectively; both by the Wilcoxon rank sum test, p values as 0.0001). To further evaluate the specificity of these increased micronuclei in the exposed than the controls by the CBMN assay, the all human ?-satellite centromere-specific probe (Oncor) was employed in fluorescence-situ-hybridization (FISH) to differentiate acentric fragments or whole chromosome inclusion in the micronuclei. The results demonstrated that the micronuclei in 16 exposed contained apparently less centromere signals (ranged 32.61-51.35%; mean 1 S.D. = 41.4 5.8%) than those of the controls (51.2 2.7%; Wilcoxon rank sum test p < 0.018). This suggested that more than one half of the micronuclei in the exposed did not contain centromere signals in them, but instead acentric chromosomal fragments. This was on the opposite of those spontaneously derived micronuclei or those in the controls. It suggests that the increased microsuggests that the increased micronuclei in the exposed residents were derived mostly from chronic low dose ?-radiation. The centromere-containing FISH analysis seems to enhance the specificity of the micronucleus assay in our study (supported partly by the NSC85.2331.010.045Z, Taiwan). (author)

21

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

International Nuclear Information System (INIS)

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

22

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

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

Diatloff-Zito, C.; Turleau, C.; Cabanis, M.O.; de Grouchy, J.

1984-10-01

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

24

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

International Nuclear Information System (INIS)

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

25

Radiation-induced risks at low dose: moving beyond controversy towards a new vision.  

Science.gov (United States)

The paper recently published by Mothersill and Seymour (Radiat Environ Biophys 2013, doi: 10.1007/s00411-013-0472-y ) is commented upon by emphasizing on the recommendation not to confound the fields of radiation protection and radiobiological science as a source of controversy. Instead, these authors are proposing a new vision which suggests novel lines of scientific investigations to be addressed. At the moment, these include moving beyond the conceptual approach of DNA alteration through energy deposition in cells, and exploring the striking parallel currently existing between the ongoing individual/population debate in radioecology and that for cells/tissues in radiobiology. These interesting issues are briefly discussed and supported. PMID:23689951

Brchignac, Franois; Paquet, Franois

2013-08-01

26

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

27

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

28

Surrogates of protection in repeated low-dose challenge experiments.  

Science.gov (United States)

A critical step toward developing a successful vaccine to control the human immunodeficiency virus pandemic entails evaluation of vaccine candidates in non-human primates (NHPs). Historically, these studies have usually entailed challenges (i.e., exposures) with very high doses of a simian version of human immunodeficiency virus, resulting in infection of all NHPs in the experiment after a single challenge. More recently, researchers have begun to conduct repeated low-dose challenge (RLC) studies in NHPs that are believed to more closely mimic typical exposure in natural human transmission settings. One objective of RLC studies is to assess whether measured immune responses to vaccination can serve as surrogate endpoints for the primary endpoint of interest, namely infection. In this paper, different designs of RLC studies for assessing a binary surrogate of protection are considered. Copyright 2015 John Wiley & Sons, Ltd. PMID:25628249

Long, Dustin M; Hudgens, Michael G; Wu, Chih-Da

2015-05-10

29

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 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)

30

CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION  

Science.gov (United States)

Carcinogenic Effects of Low Doses of Ionizing Radiation R Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 The form of the dose-response curve for radiation-induced cancers, particu...

31

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

International Nuclear Information System (INIS)

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

32

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

Science.gov (United States)

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

Azzam, Edouard

33

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

Science.gov (United States)

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

Nuth, Manunya; Kennedy, Ann R

2013-07-01

34

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

International Nuclear Information System (INIS)

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

35

Radiation induced cancer risk, detriment and radiation protection  

International Nuclear Information System (INIS)

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

36

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)

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

Fornace, Jr, A J

2007-03-03

37

Protection against radiation-induced performance decrement in mice  

International Nuclear Information System (INIS)

Recognizing that there is lack of information on the effects of low-level ionizing radiations and the modifying role of radioprotectors, an attempt has been made in this study to explore the relationship between impairment of spatial learning and low level of radiation exposure. A radial arm maze was utilised to evaluate radiation-induced behavioural alterations and performance decrement in mice. Immediately after whole body exposure to gamma radiation (absorbed dose, 1 Gy) significant perturbations in the learned behaviour of the animals were observed. The regular control movement became irregular and the food consumption time was reduced appreciably (40%). Recovery took place in four days. If diltiazem (7 mg/kg b.w.), a Ca2+ channel blocker and a radioprotector, was administered i.p. 20-30 min prior to irradiation, radiation-induced behavioural abnormalities were reduced. Mechanisms underlying protection by diltiazem against radiation-induced performance decrement observed in the present study need to be investigated. (author). 23 refs., 2 figs

38

Total body exposure to low-dose ionizing radiation induces long-term alterations to the liver proteome of neonatally exposed mice.  

Science.gov (United States)

Tens of thousands of people are being exposed daily to environmental low-dose gamma radiation. Epidemiological data indicate that such low radiation doses may negatively affect liver function and result in the development of liver disease. However, the biological mechanisms behind these adverse effects are unknown. The aim of this study was to investigate radiation-induced damage in the liver after low radiation doses. Neonatal male NMRI mice were exposed to total body irradiation on postnatal day 10 using acute single doses ranging from 0.02 to 1.0 Gy. Early (1 day) and late (7 months) changes in the liver proteome were tracked using isotope-coded protein label technology and quantitative mass spectrometry. Our data indicate that low and moderate radiation doses induce an immediate inhibition of the glycolysis pathway and pyruvate dehydrogenase availability in the liver. Furthermore, they lead to significant long-term alterations in lipid metabolism and increased liver inflammation accompanying inactivation of the transcription factor peroxisome proliferator-activated receptor alpha. This study contributes to the understanding of the potential risk of liver damage in populations environmentally exposed to ionizing radiation. PMID:25299163

Bakshi, Mayur V; Azimzadeh, Omid; Barjaktarovic, Zarko; Kempf, Stefan J; Merl-Pham, Juliane; Hauck, Stefanie M; Buratovic, Sonja; Eriksson, Per; Atkinson, Michael J; Tapio, Soile

2015-01-01

39

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)

40

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

OpenAIRE

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...

Scott, B. R.

2008-01-01

41

Protection from ionizing radiation induced damages by phytoceuticals and nutraceuticals  

International Nuclear Information System (INIS)

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

42

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

OpenAIRE

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

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

1981-01-01

43

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

44

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

OpenAIRE

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...

Nuth, Manunya; Kennedy, Ann R.

2013-01-01

45

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

46

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)

47

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

Energy Technology Data Exchange (ETDEWEB)

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.)

NONE

2014-02-15

48

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

International Nuclear Information System (INIS)

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

49

Spinacia oleracea protects against radiation induced lipid peroxidation in Swiss albino mice brain  

International Nuclear Information System (INIS)

Aim of the present study is to investigate protective effects of alcoholic extract of Spinacia oleracea (SE) against radiation induced lipid peroxidation in brain of Swiss albino mice which is a rich source of carotene and other substance (vit. B, C, minerals, thiamine and flavonoids, iron etc.). Brain is highly susceptible to radiation induced oxidative damage due to its high utilization of oxygen and rather poorly developed anti-oxidative defense mechanism

50

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)

51

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, hncy 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

52

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

Science.gov (United States)

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

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

2014-12-01

53

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

International Nuclear Information System (INIS)

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

54

Anti-apoptotic peptides protect against radiation-induced cell death  

International Nuclear Information System (INIS)

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

55

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)

56

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)

57

Protection against radiation-induced damage - Experimental radioprotection  

International Nuclear Information System (INIS)

Chemical radiation protection in rodents was first discovered in 1949 and clinical application in cases of acute radiation sickness seemed to be promising. Numerous chemicals were screened in various laboratories, but clinically available chemical protectors were not discovered. It was concluded in 1962 that although a number of compounds may be capable of efficient protection of mice when given before exposure to X or ? rays, none could be considered a practical agent for protection of humans. On the basis of synthesis, stability, and effectiveness of oral administration, as well as dose-reduction properties, S-(2-aminoethyl)isothiouronium (AET) would seem to be the drug of choice. However, preliminary tests of AET in humans indicated that the toxicity may be far too great. New chemical protectors have been reported, following two different lines of research in Japan and in the United States. In Japan, an adrenochrome derivative, adrenochrome monoguanylhydrazone methanesulfonate (AMM) and a new sulfhydrl compound, 2-mercaptopropionylglycine (MPG), which are both effective in much lower doses than their toxic dose in mice, were reported. In the United States, after a large screening of various kinds of derivatives of cysteamine, WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid was reported to have a very high dose-reduction factor of 2.5 or more, thus effective even at a less toxic dose. To make use of these chemicals in cases of cancer radiotherapy, differs in cases of cancer radiotherapy, differential protection between tumor and normal tissues has to be established. Studies along this line have been also carried out with WR-2721 and MPG. The results obtained so far are promising for the improvement of radiotherapy. In this chapter, experimental studies on these chemicals are reviewed, emphasizing the authors own research

58

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

International Nuclear Information System (INIS)

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

59

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.

60

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

International Nuclear Information System (INIS)

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

61

The protective effect of low-dose methotrexate on ischemia-reperfusion injury of the rabbit spinal cord.  

Science.gov (United States)

Methotrexate was developed as a cytostatic agent, but at low doses, it has shown potent anti-inflammatory activity. Previous studies have demonstrated that the anti-inflammatory effects of methotrexate are primarily mediated by the release of adenosine. In this study, we hypothesized that low-dose methotrexate has protective effects in spinal cord ischemia-reperfusion injury. Rabbits were randomized into the following four groups of eight animals each: group 1 (control), group 2 (ischemia), group 3 (methylprednisolone) and group 4 (methotrexate). In the control group only a laparotomy was performed. In all the other groups, the spinal cord ischemia model was created by the occlusion of the aorta just caudal to the renal artery. Neurological evaluation was performed with the Tarlov scoring system. Levels of myeloperoxidase, malondialdehyde and catalase were analyzed, as were the activities of xanthine oxidase and caspase-3. Histopathological and ultrastructural evaluations were also performed. After ischemia-reperfusion injury, increases were found in the serum and tissue myeloperoxidase levels, tissue malondialdehyde levels, xanthine oxidase activity and caspase-3 activity. In contrast, both serum and tissue catalase levels were decreased. After the administration of a low-dose of methotrexate, decreases were observed in the serum and tissue myeloperoxidase levels, tissue malondialdehyde levels, xanthine oxidase activity and caspase-3 activity. In contrast, both the serum and tissue catalase levels were increased. Furthermore, low-dose methotrexate treatment showed improved results concerning the histopathological scores, the ultrastructural score and the Tarlov scores. Our results revealed that low-dose methotrexate exhibits meaningful neuroprotective activity following ischemia-reperfusion injury of the spinal cord. PMID:23806252

Kertmen, Hayri; Grer, Bora; Y?lmaz, Erdal Re?it; Sanl?, Ahmet Metin; Sorar, Mehmet; Ar?kk, Ata Trker; Sargon, Mustafa Fevzi; Kanat, Mehmet Ali; Ergder, Berrin Imge; Sekerci, Zeki

2013-08-15

62

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

Energy Technology Data Exchange (ETDEWEB)

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

Jian Li

2012-11-07

63

The flavonolignan-silymarin protects enzymatic, hematological, and immune system against ?-radiation-induced toxicity.  

Science.gov (United States)

The main focus of this study is evaluation of radioprotective efficacy of silymarin, a flavonolignan, against ?-radiation-induced damage to hematological, vital organs (liver and intestine), and immune system. Survival studies revealed that silymarin (administered orally for 3 days) provided maximum protection (67%) at 70 mg/kg body weight (b.wt.) against lethal 9 Gy ?-irradiation (dose reduction factor?=?1.27). The study revealed significant (p nuclear and radiological emergencies. 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014. PMID:25411116

Adhikari, Manish; Arora, Rajesh

2014-11-20

64

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

International Nuclear Information System (INIS)

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

65

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

Energy Technology Data Exchange (ETDEWEB)

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

Mothersil, C.; Seymour, C. [McMaster Univ., Medical Physics and Applied Radiation Sciences Unit, Hamilton, ON (Canada)

2005-07-01

66

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

OpenAIRE

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

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

2006-01-01

67

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.)

68

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

Science.gov (United States)

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

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

2012-03-01

69

The Ku-Dependent Non-Homologous End-Joining Pathway Contributes to Low-Dose Radiation-Stimulated Cell Survival  

OpenAIRE

Low-dose (?0.1 Gy) radiation-induced adaptive responses could protect cells from high-challenge dose radiation-induced killing. The protective role is believed to promote the repair of DNA double-strand breaks (DSBs) that are a severe threat to cell survival. However, it remains unclear which repair pathway, homologous recombination repair (HRR) or non-homologous end-joining (NHEJ), is promoted by low-dose radiation. To address this question, we examined the effects of low-dose (0.1 Gy) on ...

Yu, Xiaoyan; Wang, Hongyan; Wang, Ping; Chen, Benjamin P. C.; Wang, Ya

2011-01-01

70

Protection of cellular DNA and membrane from ?-radiation-induced damages and enhancement in DNA repair by sesamol.  

Science.gov (United States)

Sesamol (SM), a nutritional phenolic antioxidant compound present in sesame seeds, protected pBR 322 DNA from gamma radiation-induced damages. SM prevented gamma radiation-induced degradation of covalently closed circular form of plasmid DNA in a concentration-dependent manner. Also SM protected cellular DNA of mouse blood leukocytes exposed to 4?Gy gamma radiation, ex vivo, as revealed by the data from alkaline comet assay studies. SM (5 mM) showed a faster time-dependant decrease of the radiation-induced DNA damage in mouse blood leukocytes following postirradiation incubation ex vivo, which could be attributed to enhanced DNA repair. SM protected the biomembranes from radiation-induced lipid peroxidation. Thus, SM could act as a radioprotector for the biomembranes and cellular DNA against the deleterious effects of ionizing radiation. PMID:21204756

Nair, Gopakumar Gopinathan; Nair, Cherupally Krishnan Krishnan

2010-12-01

71

Protection against radiation induced oxidative stress by Syzygium cumini seed extract  

International Nuclear Information System (INIS)

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

72

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.

73

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)

74

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

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

Fatma Nesrin Turan

2012-12-01

75

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

International Nuclear Information System (INIS)

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

76

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)

77

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

Energy Technology Data Exchange (ETDEWEB)

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

Scott, Bobby, R., Ph.D.

2003-06-27

78

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

Science.gov (United States)

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

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

2014-06-12

79

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

International Nuclear Information System (INIS)

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

80

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

International Nuclear Information System (INIS)

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

81

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

Science.gov (United States)

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

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

2008-07-01

82

Lycopene protects the structure of the small intestine against gamma-radiation-induced oxidative stress.  

Science.gov (United States)

The small intestine displays numerous morphological and functional alterations after exposure to ionizing radiations. Oxidative stress and changes in monoamines levels may contribute toward some of these alterations. The objective of the current work is to evaluate the efficacy of lycopene on radiation-induced damage in the small intestine. Lycopene (5 mg/kg BW) was given to male albino rats, via gavages for 7 days before whole body exposure to gamma ray (6 Gy). Irradiated animals, sacrificed 7 days after irradiation, showed sloughing villi, ulcers, and ruptured goblet cells, shrinkage of submucosa layers, more fibers and fibroblasts. Histopathological changes were associated with a significant increase in thiobarbituric acid reactive substances (TBARS) and alteration in xanthine oxidoreductase system (XOR). In parallel, significant decreases in reduced glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT) activities were recorded. Gamma irradiation has also induced a significant decrease in the level of monoamines: serotonin (5-HT), dopamine (DA), norepinephrine (NE), and epinephrine (EPI) associated with an increase in monoamine-oxidase (MAO) activity. Lycopene pretreatment has significantly improved the oxidant/antioxidant status, which was associated with significant regeneration of the small intestine, and improved monoamines levels. Based on these results, it is concluded that lycopene may protect the small intestine against radiation-induced damage. PMID:20041432

Saada, Helen N; Rezk, Rene G; Eltahawy, Noaman A

2010-06-01

83

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

84

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

International Nuclear Information System (INIS)

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

85

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)

86

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

International Nuclear Information System (INIS)

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

87

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

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

Cem Uzal

2012-03-01

88

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

89

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

International Nuclear Information System (INIS)

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

90

Protective Effects of 5-Androstendiol (5-AED) on Radiation-induced Intestinal Injury  

International Nuclear Information System (INIS)

We examined the radioprotective effects of 5-androstendiol (5-AED), a natural hormone produced in the reticularis of the adrenal cortex, as a result of intestinal damage in gamma-irradiated C3H/HeN mice. Thirty mice (C3H/HeN) were divided into three groups; 1) non-irradiated control group, 2) irradiated group, and 3) 5-AED-treated group prior to irradiation. Next, 5-AED (50 mg/kg per body weight) was subcutaneously injected 24 hours before irradiation. The mice were whole-body irradiated with 10 Gy for the histological examination of jejunal crypt survival and the determination of the villus morphology including crypt depth, crypt size, number of villi, villus height, and length of basal lamina, as well as 5 Gy for the detection of apoptosis. The 5-AED pre-treated group significantly increased the survival of the jejunal crypt, compared to irradiation controls (p<0.05 vs. irradiation controls at 3.5 days after 10 Gy). The evaluation of morphological changes revealed that the administration of 5-AED reduced the radiation-induced intestinal damages such as villus shortening and increased length of the basal lamina of enterocytes (p<0.05 vs irradiation controls on 3.5 day after 10 Gy, respectively). The administration of 5-AED decreased the radiation-induced apoptosis in the intestinal crypt, with no significant difference between the vehicle and 5-AED at 12 hours after 5 Gy. The results of this study suggest that the administration of 5-AED has a protective effect on inion of 5-AED has a protective effect on intestinal damage induced by ?-irradiation. In turn, these results suggest that 5-AED could be a useful candidate for radioprotection against intestinal mucosal injury following irradiation.

91

An extract of Phyllanthus amarus protects mouse chromosomes and intestine from radiation induced damages.  

Science.gov (United States)

We reported earlier on our preliminary study of the radioprotective effect of Phyllanthus amarus (P.amarus) in mice. P.amarus was found to inhibit the myelosuppression and elevated the levels of antioxidant enzymes in the blood and liver. In the present study we have evaluated the protective effect of P.amarus against radiation-induced changes in the intestine and mouse chromosomal damage. P.amarus at concentrations of 250 & 750 mg/Kg. b. wt were found to elevate the antioxidant enzymes in the intestine and decrease the lipid peroxidation levels. Histopathological evaluations of the intestine revealed decreased damage to intestinal cells, demonstrating that P.amarus protected the intestine. The genotoxic effects of radiation on mouse chromosomes were evaluated by assaying the micronuclei formation and chromosomal aberrations. P.amarus was found to protect the clastogenic effects of radiation as seen from decreased number of micronuclei. The administration of P.amarus was also found to decrease the percentage of chromosomal aberrations. Based on our present and previous reports it could be concluded that P.amarus extract has significant radioprotective activity. PMID:17917369

Harikumar, Kuzhuvelil Bhaskaran Nair; Kuttan, Ramadasan

2007-11-01

92

An extract of Phyllanthus amarus protects mouse chromosomes and intestine from radiation induced damages  

International Nuclear Information System (INIS)

We reported earlier on our preliminary study of the radioprotective effect of Phyllanthus amarus (P.amarus) in mice. P.amarus was found to inhibit the myelosuppression and elevated the levels of anti-oxidant enzymes in the blood and liver. In the present study we have evaluated the protective effect of P.amarus against radiation-induced changes in the intestine and mouse chromosomal damage. P.amarus at concentrations of 250 and 750 mg/Kg. b. wt were found to elevate the antioxidant enzymes in the intestine and decrease the lipid peroxidation levels. Histopathological evaluations of the intestine revealed decreased damage to intestinal cells, demonstrating that P.amarus protected the intestine. The genotoxic effects of radiation on mouse chromosomes were evaluated by assaying the micronuclei formation and chromosomal aberrations. P.amarus was found to protect the clastogenic effects of radiation as seen from decreased number of micronuclei. The administration of P.amarus was also found to decrease the percentage of chromosomal aberrations. Based on our present and previous reports it could be concluded that P.amarus extract has significant radioprotective activity. (author)

93

Protective Effects of 5-Androstendiol (5-AED) on Radiation-induced Intestinal Injury  

Energy Technology Data Exchange (ETDEWEB)

We examined the radioprotective effects of 5-androstendiol (5-AED), a natural hormone produced in the reticularis of the adrenal cortex, as a result of intestinal damage in gamma-irradiated C3H/HeN mice. Thirty mice (C3H/HeN) were divided into three groups; 1) non-irradiated control group, 2) irradiated group, and 3) 5-AED-treated group prior to irradiation. Next, 5-AED (50 mg/kg per body weight) was subcutaneously injected 24 hours before irradiation. The mice were whole-body irradiated with 10 Gy for the histological examination of jejunal crypt survival and the determination of the villus morphology including crypt depth, crypt size, number of villi, villus height, and length of basal lamina, as well as 5 Gy for the detection of apoptosis. The 5-AED pre-treated group significantly increased the survival of the jejunal crypt, compared to irradiation controls (p<0.05 vs. irradiation controls at 3.5 days after 10 Gy). The evaluation of morphological changes revealed that the administration of 5-AED reduced the radiation-induced intestinal damages such as villus shortening and increased length of the basal lamina of enterocytes (p<0.05 vs irradiation controls on 3.5 day after 10 Gy, respectively). The administration of 5-AED decreased the radiation-induced apoptosis in the intestinal crypt, with no significant difference between the vehicle and 5-AED at 12 hours after 5 Gy. The results of this study suggest that the administration of 5-AED has a protective effect on intestinal damage induced by {gamma}-irradiation. In turn, these results suggest that 5-AED could be a useful candidate for radioprotection against intestinal mucosal injury following irradiation.

Kim, Joong Sun; Lee, Seung Sook; Jang, Won Suk; Lee, Sun Joo; Park, Sun Hoo; Kim, MinSook; Cho, Soo Youn [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Moon, Chang Jong; Kim, Sung Ho [Chonnam National University College of Veterinary Medicine, Gwangju (Korea, Republic of)

2010-11-15

94

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

International Nuclear Information System (INIS)

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

95

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

Science.gov (United States)

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 sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year. PMID:25706776

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

2015-03-01

96

Mucosal protective effects of vitamin E and misoprostol during acute radiation-induced enteritis in rats.  

Science.gov (United States)

Cytotoxic effects of ionizing radiation on gastrointestinal epithelium may be mediated by oxygen free radicals. Therapeutic intervention directed toward oxidant scavenging and increasing tissue oxygen tension may provide a novel approach to management. We investigated the effects of a nonenzymatic oxygen radical scavenger (vitamin E) and an exogenous PGE1 analog known to increase mucosal blood flow (misoprostol) on acute radiation enteritis. Rats were pretreated with: (1) vitamin E, (2) misoprostol, or (3) a combination of both agents prior to 10 Gy abdominal radiation. Three days following irradiation, net fluid absorption using in vivo isolated loops, mucosal histology, and mucosal morphometry using a computerized videoplan were determined in jejunum, ileum, and colon. Nonirradiated control intestine demonstrated net fluid absorption in all segments, which was not altered by vitamin E and/or misoprostol treatment. Irradiation significantly reduced net fluid absorption in jejunum, ileum, and colon. Vitamin E administered prior to irradiation maintained jejunal, ileal, and colonic fluid absorption near control levels. In contrast misoprostol or a combination of vitamin E and misoprostol did not provide protection against the injury caused by abdominal irradiation. Alterations in intestinal fluid absorption occurred without significant changes in histologic or morphometric appearance. In conclusion, ionizing radiation reduces in vivo intestinal fluid absorption without significant changes in histologic or morphometric appearance. Treatment with vitamin E, but not misoprostol, protects gastrointestinal mucosa against radiation-induced absorptive injury. PMID:1735337

Empey, L R; Papp, J D; Jewell, L D; Fedorak, R N

1992-02-01

97

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

International Nuclear Information System (INIS)

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

98

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)

99

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

International Nuclear Information System (INIS)

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

100

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

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...

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

2014-01-01

101

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

Science.gov (United States)

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

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

2014-11-15

102

Protective Effects and Its Relative Mechanisms of Low Dose Ionizing Radiation on pancreatic cells of Male Diabetic Rats  

OpenAIRE

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...

Hanaa F Waer, Seham A. Helmy

2012-01-01

103

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)

104

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

Science.gov (United States)

The radioprotective effect of an extract of the plant Phyllanthus amarus (P. amarus) was investigated in adult BALB/c mice. P. amarus extract (750 mg/kg b.wt and 250 mg/kg b.wt) was administered orally to mice for five days prior to whole body radiation (6 Gy) and for one month after radiation. The animals were sacrificed on days 3, 9, 12, and 30 after radiation. P. amarus significantly increased the total W.B.C count, bone marrow cellularity, and alpha-esterase activity as compared to untreated radiation-exposed animals. P. amarus treatment also increased the activity of various antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPX), and glutathione reductase (GR), both in blood and tissue, which were reduced by radiation treatment. There was also a significant increase in the glutathione (GSH) levels of blood and tissue. Lipid peroxidation levels, which were increased after radiation, were significantly reduced by P. amarus treatment, both in serum and liver. The results collectively indicate that P. amarus extract could increase the antioxidant defense mechanism in mice and there by protect the animals from radiation-induced cellular damage. PMID:15133301

Kumar, K B Hari; Kuttan, Ramadasan

2004-03-01

105

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

International Nuclear Information System (INIS)

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

106

Protection of murine spermatogenesis against ionizing radiation-induced testicular injury by a green tea polyphenol.  

Science.gov (United States)

Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol in green tea, exerts antiapoptotic activity and prevents tissue damage against different stimuli. Herein, we investigated the effects of EGCG treatment to simultaneously improve spermatogenesis following ionizing radiation (IR) (at a dose of 2 Gy). Mice were intraperitoneally injected with 50 mg/kg EGCG or vehicle control 3 days prior to the irradiation, and the treatment lasted intermittently for 24 days. Supplement with exogenous EGCG protected against short-term germ cell loss and attenuated IR-elicited testicular oxidative stress. Mechanistically, prosurvival effects of EGCG treatment upon IR stress were regulated, at least in part, via the mitogen-activated protein kinase/BCL2 family/caspase 3 pathway. Consistently, at post-IR Day 21, histological analyses revealed tubule damage, desquamation of germ cells, and impairment of caudal parameters in irradiated testis, which could be significantly improved by intermittent EGCG treatment. In addition, long-term EGCG application ameliorated the IR-induced blood-testicular barrier permeability and suppressed testicular steroidogenesis, thus exerting a stimulatory effect on the spermatogenic recovery. Collectively, EGCG appeared to efficiently prevent germ cells from radiation-induced cell death via multiple mechanisms. Employment of this bioactive polyphenol should be an attractive strategy to preserve fertility in males exposed to conventional radiation therapy and warrants further investigation. PMID:25395675

Ding, Jin; Wang, Hui; Wu, Zhen-Biao; Zhao, Jie; Zhang, Shun; Li, Wei

2015-01-01

107

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

International Nuclear Information System (INIS)

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

108

Protection of cellular DNA from gamma-radiation-induced damages and enhancement in DNA repair by troxerutin.  

Science.gov (United States)

The effect of troxerutin on gamma-radiation-induced DNA strand breaks in different tissues of mice in vivo and formations of the micronuclei were studied in human peripheral blood lymphocytes ex vivo and mice blood reticulocytes in vivo. Treatments with 1 mM troxerutin significantly inhibited the micronuclei induction in the human lymphocytes. Troxerutin protected the human peripheral blood leucocytes from radiation-induced DNA strand breaks in a concentration dependent manner under ex vivo condition of irradiation (2 Gy). Intraperitoneal administration of troxerutin (175 mg/kg body weight) to mice before and after whole body radiation exposure inhibited micronuclei formation in blood reticulocytes significantly. The administration of different doses (75, 125 and 175 mg/kg body weight) of troxerutin 1 h prior to 4 Gy gamma-radiation exposure showed dose-dependent decrease in the yield of DNA strand breaks in murine blood leucocytes and bone marrow cells. The dose-dependent protection was more pronounced in bone marrow cells than in blood leucocytes. Administration of 175 mg/kg body weight of the drug (i.p.) 1 h prior or immediately after whole body irradiation of mice showed that the decrease in strand breaks depended on the post-irradiation interval at which the analysis was done. The observed time-dependent decrease in the DNA strand breaks could be attributed to enhanced DNA repair in troxerutin administered animals. Thus in addition to anti-erythrocytic, anti-thrombic, fibrinolytic and oedema-protective rheological activity, troxerutin offers protection against gamma-radiation-induced micronuclei formation and DNA strand breaks and enhances repair of radiation-induced DNA strand breaks. PMID:16311905

Maurya, Dharmendra Kumar; Balakrishnan, Sreedevi; Salvi, Veena Prakash; Nair, Cherupally Krishnan Krishnan

2005-12-01

109

Low doses of radiation reduce risks in vivo  

Energy Technology Data Exchange (ETDEWEB)

The 'Linear No Threshold' hypothesis, used in all radiation protection practices, assumes that all doses, no matter how low, increase risk. The protective effects of adaptive responses to radiation, shown to exist in lower organisms and in human and other mammalian cells, are inconsistent with this hypothesis. An in vivo test of the hypothesis in mice showed that a 100-mGy dose of {gamma}-radiation protected the mice by increasing latency for acute myeloid leukemia initiated by a subsequent large dose. A similar result was observed in cancer prone mice, where a 10-mGy adapting exposure prior to a large acute dose increased latency for lymphomas without altering frequency. Increasing the adapting dose to 100-mGy eliminated the protective effect. In the cancer prone mice, a 10-mGy dose alone, without a subsequent high dose, increased latency for spontaneous osteosarcomas and lymphomas without altering frequency. Increasing the dose to 100-mGy decreased latency for spontaneous osteosarcomas but still increased latency for lymphomas, indicating that this higher dose was in a transition zone between reduced and increased risk, and that the transition dose from protective to detrimental effects is tumor type specific. In genetically normal fetal mice, prior low doses also protected against radiation induced teratogenic effects. In genetically normal adult male mice, high doses induce mutations in sperm stem cells, detectable as heritable mutations in the offspring of these mice. A prior 100 mGy dose protected the male mice from induction of these heritable mutations by the large dose. We conclude that adaptive responses are induced by low doses in normal or cancer prone mice, and that these responses can reduce the risk of cancer, teratogenesis and heritable mutations. At low doses in vivo, the relationship between dose and risk is not linear, and low doses can reduce risk. (author)

Mitchel, R.E.J. [Atomic Energy of Canada Ltd., Chalk River, Ontario (Canada)

2004-05-01

110

Low doses of radiation reduce risks in vivo  

International Nuclear Information System (INIS)

The 'Linear No Threshold' hypothesis, used in all radiation protection practices, assumes that all doses, no matter how low, increase risk. The protective effects of adaptive responses to radiation, shown to exist in lower organisms and in human and other mammalian cells, are inconsistent with this hypothesis. An in vivo test of the hypothesis in mice showed that a 100-mGy dose of ?-radiation protected the mice by increasing latency for acute myeloid leukemia initiated by a subsequent large dose. A similar result was observed in cancer prone mice, where a 10-mGy adapting exposure prior to a large acute dose increased latency for lymphomas without altering frequency. Increasing the adapting dose to 100-mGy eliminated the protective effect. In the cancer prone mice, a 10-mGy dose alone, without a subsequent high dose, increased latency for spontaneous osteosarcomas and lymphomas without altering frequency. Increasing the dose to 100-mGy decreased latency for spontaneous osteosarcomas but still increased latency for lymphomas, indicating that this higher dose was in a transition zone between reduced and increased risk, and that the transition dose from protective to detrimental effects is tumor type specific. In genetically normal fetal mice, prior low doses also protected against radiation induced teratogenic effects. In genetically normal adult male mice, high doses induce mutations in sperm stem cells, detectable as heritable mutations in the offspring of these mice.mutations in the offspring of these mice. A prior 100 mGy dose protected the male mice from induction of these heritable mutations by the large dose. We conclude that adaptive responses are induced by low doses in normal or cancer prone mice, and that these responses can reduce the risk of cancer, teratogenesis and heritable mutations. At low doses in vivo, the relationship between dose and risk is not linear, and low doses can reduce risk. (author)

111

Growth hormone and insulin-like growth factor I protect intestinal cells from radiation induced apoptosis.  

Science.gov (United States)

We studied whether programmed cell death (or apoptosis) is the predominant mechanism in radiation-induced cell damage to rat intestinal mucosa and investigated the mechanism of the protective effect of GH and IGF-I in the same model. Male albino Wistar rats were divided into four groups: controls, radiation, radiation plus GH and radiation plus IGF-I. Radiation was administered on the first day and on day 4. All animals were sacrificed and segments of the terminal ileum were stained with hematoxylin-eosin. Apoptosis of the epithelial cells was identified at the cellular level by the TUNEL stain and was distinguished from necrosis by the characteristic morphology of the cells (cytoplasmic shrinkage, marginal chromatin condensation and generation of nuclear apoptotic bodies). Apoptotic cells in the control animals were few and detected only at the tips of the villi while in the irradiated animals almost all the epithelial cells were apoptotic, distributed from the crypts to the tips of the villi and the mucosa showed severe epithelial atrophy and ulceration. The histologic picture of the mucosa in the GH and IGF-I treated animals was similar to normal controls and apoptotic cells were restricted only at the tips of the villi. DNA and RNA from the mucosa cells were isolated and analyzed by electrophoresis. DNA fragmentation and RNA 28s band ribonuclease cleavage was observed only in the irradiated animals. We have shown that abdominal radiation causes intestinal epithelial cell damage mainly through the induction of apoptosis and the treatment with GH and IGF-I inhibits apoptosis of the cells and preserves the mucosal integrity. PMID:10715545

Mylonas, P G; Matsouka, P T; Papandoniou, E V; Vagianos, C; Kalfarentzos, F; Alexandrides, T K

2000-02-25

112

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

Science.gov (United States)

The protective effects of Mentha piperita leaf extract against radiation-induced damage in testis of Swiss albino mice have been studied. Animals (Male Swiss albino mice) were given M. piperita leaf extract orally (1 g/kg body weight/day) for three consecutive days before radiation exposure (8 Gy gamma-radiation). Mice were autopsied at 1, 3, 7, 14, and 30 days after irradiation to evaluate the radiomodulatory effect in terms of histological alterations, lipid peroxidation, and acid and alkaline phosphatases levels in testis. Radiation treatment showed reduction in the testis weight during all days of observation, however, in the M. piperita leaf extract-pretreated irradiated group there was a significant increase in testis weight. Radiation treatment induced moderate to severe testicular atrophy with degeneration of germ cells in seminiferous tubules. The tubules were shrunken and greatly depleted of germ cells. Sertoli cells with few germ cells were observed in the lumen. However, animals pre-treated with M. piperita leaf extract and exposed to radiation showed normal testicular morphology with regular arrangement of germ cells and slight degeneration of seminiferous epithelium. Significant decreases in the lipid peroxidation and acid phosphatase level and increase in level of alkaline phosphatase were observed in testis. The M. piperita leaf extract showed high amount of phenolic content, flavonoids content and flavonols. The results of the present study suggest that M. piperita has a significant radioprotective effect and the amount of phenolic compounds, the content of flavonoids and flavonols of M. piperita leaf extract may be held responsible for radioprotective effect due to their antioxidant and radical scavenging activity. PMID:19320637

Samarth, Ravindra M; Samarth, Meenakshi

2009-04-01

113

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

Science.gov (United States)

Exposure of the brain to ionizing radiation can cause neurocognitive deficiencies. The pathophysiology of these neurological changes is complex and includes radiation-induced apoptosis in the subgranular zone of the hippocampus. We have recently found that inhibition of glycogen synthase kinase 3? (GSK-3?) resulted in significant protection from radiation-induced apoptosis in hippocampal neurons. The molecular mechanisms of this cytoprotection include abrogation of radiation-induced accumulation of p53. Here we show that pretreatment of irradiated HT-22 hippocampal-derived neurons with small molecule inhibitors of GSK-3? SB216763 or SB415286, or with GSK-3?-specific shRNA resulted in accumulation of the p53-specific E3 ubiquitin ligase MDM2. Knockdown of MDM2 using specific shRNA or chemical inhibition of MDM2-p53 interaction prevented the protective changes triggered by GSK-3? inhibition in irradiated HT-22 neurons and restored radiation cytotoxicity. We found that this could be due to regulation of apoptosis by subcellular localization and interaction of GSK-3?, p53 and MDM2. These data suggest that the mechanisms of radioprotection by GSK-3? inhibitors in hippocampal neurons involve regulation of MDM2-dependent p53 accumulation and interactions between GSK-3?, MDM2 and p53. PMID:21738215

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

2012-03-01

114

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

International Nuclear Information System (INIS)

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

115

Low dose gamma irradiation enhances defined signaling components of intercellular reactive oxygen-mediated apoptosis induction  

International Nuclear Information System (INIS)

Transformed cells are selectively removed by intercellular ROS-mediated induction of apoptosis. Signaling is based on the HOCl and the NO/peroxynitrite pathway (major pathways) and the nitryl chloride and the metal-catalyzed Haber-Weiss pathway (minor pathways). During tumor progression, resistance against intercellular induction of apoptosis is acquired through expression of membrane-associated catalase. Low dose radiation of nontransformed cells has been shown to enhance intercellular induction of apoptosis. The present study was performed to define the signaling components which are modulated by low dose gamma irradiation. Low dose radiation induced the release of peroxidase from nontransformed, transformed and tumor cells. Extracellular superoxide anion generation was strongly enhanced in the case of transformed cells and tumor cells, but not in nontransformed cells. Enhancement of peroxidase release and superoxide anion generation either increased intercellular induction of apoptosis of transformed cells, or caused a partial protection under specific signaling conditions. In tumor cells, low dose radiation enhanced the production of major signaling components, but this had no effect on apoptosis induction, due to the strong resistance mechanism of tumor cells. Our data specify the nature of low dose radiation-induced effects on specific signaling components of intercellular induction of apoptosis at defined stages of multistep carcinogenesis.istep carcinogenesis.

116

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

International Nuclear Information System (INIS)

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

117

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

International Nuclear Information System (INIS)

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

118

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

119

Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome  

OpenAIRE

High-dose ionizing radiation induces severe DNA damage in the epithelial stem cells in small intestinal crypts and causes gastrointestinal syndrome (GIS). Although the tumour suppressor p53 is a primary factor inducing death of crypt cells with DNA damage, its essential role in maintaining genome stability means inhibiting p53 to prevent GIS is not a viable strategy. Here we show that the innate immune receptor Toll-like receptor 3 (TLR3) is critical for the pathogenesis of GIS. Tlr3?/? m...

Takemura, Naoki; Kawasaki, Takumi; Kunisawa, Jun; Sato, Shintaro; Lamichhane, Aayam; Kobiyama, Kouji; Aoshi, Taiki; Ito, Junichi; Mizuguchi, Kenji; Karuppuchamy, Thangaraj; Matsunaga, Kouta; Miyatake, Shoichiro; Mori, Nobuko; Tsujimura, Tohru; Satoh, Takashi

2014-01-01

120

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

Science.gov (United States)

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

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

2007-06-01

121

Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome.  

Science.gov (United States)

High-dose ionizing radiation induces severe DNA damage in the epithelial stem cells in small intestinal crypts and causes gastrointestinal syndrome (GIS). Although the tumour suppressor p53 is a primary factor inducing death of crypt cells with DNA damage, its essential role in maintaining genome stability means inhibiting p53 to prevent GIS is not a viable strategy. Here we show that the innate immune receptor Toll-like receptor 3 (TLR3) is critical for the pathogenesis of GIS. Tlr3(-/-) mice show substantial resistance to GIS owing to significantly reduced radiation-induced crypt cell death. Despite showing reduced crypt cell death, p53-dependent crypt cell death is not impaired in Tlr3(-/-) mice. p53-dependent crypt cell death causes leakage of cellular RNA, which induces extensive cell death via TLR3. An inhibitor of TLR3-RNA binding ameliorates GIS by reducing crypt cell death. Thus, we propose blocking TLR3 activation as a novel approach to treat GIS. PMID:24637670

Takemura, Naoki; Kawasaki, Takumi; Kunisawa, Jun; Sato, Shintaro; Lamichhane, Aayam; Kobiyama, Kouji; Aoshi, Taiki; Ito, Junichi; Mizuguchi, Kenji; Karuppuchamy, Thangaraj; Matsunaga, Kouta; Miyatake, Shoichiro; Mori, Nobuko; Tsujimura, Tohru; Satoh, Takashi; Kumagai, Yutaro; Kawai, Taro; Standley, Daron M; Ishii, Ken J; Kiyono, Hiroshi; Akira, Shizuo; Uematsu, Satoshi

2014-01-01

122

Protective effect of superoxide dismutase in radiation-induced intestinal inflammation  

International Nuclear Information System (INIS)

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

123

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

International Nuclear Information System (INIS)

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

124

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

International Nuclear Information System (INIS)

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

125

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

International Nuclear Information System (INIS)

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

126

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

International Nuclear Information System (INIS)

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

127

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 (r 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)

128

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)

129

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 ofibrate 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.

130

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

Science.gov (United States)

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

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

2015-03-01

131

Protective mechanism of p53 against radiation-induced teratological lesions  

Energy Technology Data Exchange (ETDEWEB)

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

Kato, Fumio; Ootsuyama, Akira; Nomoto, Satoshi; Norimura, Toshiyuki [Univ. of Occupational and Environmental Health, Kitakyushu (Japan)

2000-09-01

132

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2002-07-01

133

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

International Nuclear Information System (INIS)

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

134

Radiation Leukemogenesis at Low Dose Rates  

Energy Technology Data Exchange (ETDEWEB)

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.

Weil, Michael; Ullrich, Robert

2013-09-25

135

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

136

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

Science.gov (United States)

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.

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

2005-01-01

137

Process for producing radiation-induced self-terminating protective coatings on a substrate  

Science.gov (United States)

A gas and radiation are used to produce a protective coating that is substantially void-free on the molecular scale, self-terminating, and degradation resistant. The process can be used to deposit very thin (.apprxeq.5-20 .ANG.) coatings on critical surfaces needing protection from degradative processes including, corrosion and contamination.

Klebanoff, Leonard E. (Dublin, CA)

2001-01-01

138

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

OpenAIRE

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 proliferati...

Chang, Jae Won; Park, Keun Hyung; Hwang, Hye Sook; Shin, Yoo Seob; Oh, Young-taek; Kim, Chul-ho

2013-01-01

139

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% ofhile 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

140

Protective action of OK-432 (Picibanil) on the radiation-induced myelosuppression  

International Nuclear Information System (INIS)

This report aims to examine the alleviating action of OK-432 against the radiation-induced myelosuppression in the whole body irradiated mice. The mice treated with OK-432 were given OK-432 with the dose of 5.0 KE by intraperitoneal injection 24 hours before irradiation, while the control group was given 1.0 ml of saline according to the same procedure as the OK-432 group. The fifty percent lethal dose on the 30th day after the whole body irradiation is 700R in the OK-432 group, while it is 580R in the control group. The dose reduction factor (DRF) is 1.21 in this series. The white blood cell counts decreased after irradiation with 300R in both groups. The recovery of WBC counts in the OK-432 group began at the 6th or 7th day after irradiation, while the decreased level continued until the 20th day in the control group. The WBC counts and the spleen weights were examined on the 10th day after irradiation. The WBC counts of the OK-432 group were higher than those of the control group, the difference of which was statistically significant at the 5 % level at 300R. The spleens of the OK-432 group were heavier and larger than those of the control group, the difference of which was statistically significant at the 0.1 % level for the dose range from 300 to 500R. The HE-stained spleen of the OK-432 group on the 10th day after irradiation showed the increase of hematopoietic cells in the enlarged sinus in comparison with that of the control group. The timing of OK-432 adminicontrol group. The timing of OK-432 administration and the percentage of the survival of the OK-432 group on 30th day, irradiated with 600R to the whole body, were examined. The 5.0 KE of OK-432 was injected from 4 days before and upto 4 days after irradiation to each group. When OK-432 was inected from 2 days before and upto 12 hours after irradiation, the OK-432 group showed the good survival rate in comparison with the control group. (J.P.N.)

141

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

International Nuclear Information System (INIS)

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

142

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

International Nuclear Information System (INIS)

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

143

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1996-11-01

144

Study of changes in cellular membrane permeability with lanthanum tracer in radiation-induced myocardial injury and protective effect of radix salivae miltiorrhizae  

International Nuclear Information System (INIS)

The permeability of cardiac membrane system with the model of radiation-induced myocardial injury and the effect of Radix salviae miltiorrhizae (RSM) protection were tested by using lanthanum tracer technique and stereological methods. The results indicated that when 20 Gy was given, lanthanum granules entered the sarcoplasmic tubules and deposited on the outer surface of mitochondria, which was the same as the result of RSM protected groups of 40 Gy. With increasing radiation doses, Vv and Nv of mitochondria increased and diminished respectively. Ultrastructural cardiac changes became gradually serious. The difference between the RSM protected and the control groups was significant. This suggested that RSM had protective effect against radiation-induced myocardial injury

145

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

146

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

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

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

2015-01-01

147

Low dose irradiation and biological defense mechanisms  

International Nuclear Information System (INIS)

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

148

A Tocotrienol-Enriched Formulation Protects against Radiation-Induced Changes in Cardiac Mitochondria without Modifying Late Cardiac Function or Structure.  

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Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling. PMID:25710576

Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K; Moros, Eduardo G; Melnyk, Stepan B; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan

2015-03-01

149

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

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

150

Baicalin protects human skin fibroblasts from ultraviolet A radiation-induced oxidative damage and apoptosis.  

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Reactive oxygen species (ROS) are an important factor in the development of skin photodamage after ultraviolet A (UVA) radiation. A flavonoid antioxidant, baicalin, can selectively neutralize super-oxide anion (O(2)(-)) while having no significant effect on ()OH. Fibroblasts are a key component of skin dermis. In the present study, we investigated the protective effects of baicalin on human skin fibroblasts (HSFs) under UVA induced oxidative stress. Fluorescence microscopy and flow cytometry were used to assay the intracellular O(2)(-), NO, ROS concentrations and the mitochondrial membrane potential. Cell viability was determined using the Cell Counting Kit-8 (CCK-8). The concentrations of cellular MDA, SOD, GSH, T-AOC, and 8-oxo-dG were also measured. Cellular apoptosis was measured by flow cytometry and caspase-3 detection. The results revealed that UVA radiation could cause oxidative stress and apoptosis in HSFs. Interestingly, the use of baicalin after UVA radiation significantly reduced the level of intracellular O(2)(-), NO, and ROS, stabilized the mitochondrial membrane potential, and attenuated production of MDA and 8-oxo-dG. These efficiently enhanced the antioxidative defense system and protected the HSFs from subsequent oxidative stress damage and apoptosis. In other words, baicalin decreased the excessive generation of intracellular ROS and NO, and elevated the cellular antioxidative defense, which eventually mitigate the UVA-induced apoptosis. Based on our results, baicalin may have applications in the treatment of skin photodamage caused by UVA irradiation. PMID:22946442

Zhou, Bing-rong; Yin, Hui-bin; Xu, Yang; Wu, Di; Zhang, Zhao-hui; Yin, Zhi-qiang; Permatasari, Felicia; Luo, Dan

2012-12-01

151

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

Science.gov (United States)

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

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

2004-12-01

152

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)

153

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

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

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

2013-02-01

154

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

International Nuclear Information System (INIS)

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

155

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.)

156

Protection by rosemary leaves extract against radiation-induced hepatic injuries  

International Nuclear Information System (INIS)

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

157

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

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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/(kgd SNPS group (SNPS 70 group, 140mg/(kgd SNPS group (SNPS 140 group and 280mg/(kgd 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.

Ying HE

2012-10-01

158

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 demonprotective 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)

159

Tualang Honey protects keratinocytes from ultraviolet radiation induced inflammation and DNA damage  

Science.gov (United States)

Malaysian tualang honey possesses strong antioxidant and anti-inflammatory properties. Here, we evaluated the effect of tualang honey on early biomarkers of photocarcinogenesis employing PAM212 mouse keratinocyte cell line. Keratinocytes were treated with tualang honey (1.0%, v/v) before a single UVB (150 mJ/cm2) irradiation. We found that treatment of tualang honey inhibited UVB-induced DNA damage, and enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7, 8-dihydro-2?-deoxyguanosine (8-oxodG). Treatment of tualang honey inhibited UVB-induced nuclear translocation of NF-?B, and degradation of I?B? in murine keratinocyte cell line. Treatment of tualang honey also inhibited UVB-induced inflammatory cytokines and inducible nitric oxide synthase protein expression. Furthermore, treatment of tualang honey inhibited UVB-induced COX-2 expression and PGE2 production. Taken together, we provide evidence that treatment of tualang honey to keratinocytes affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential. PMID:22276569

Ahmad, Israr; Jimenez, Hugo; Yaacob, Nik Soriani; Yusuf, Nabiha

2012-01-01

160

Tualang honey protects keratinocytes from ultraviolet radiation-induced inflammation and DNA damage.  

Science.gov (United States)

Malaysian tualang honey possesses strong antioxidant and anti-inflammatory properties. Here, we evaluated the effect of tualang honey on early biomarkers of photocarcinogenesis employing PAM212 mouse keratinocyte cell line. Keratinocytes were treated with tualang honey (1.0%, v/v) before a single UVB (150 mJ cm(-2) ) irradiation. We found that the treatment of tualang honey inhibited UVB-induced DNA damage, and enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers and 8-oxo-7,8-dihydro-2'-deoxyguanosine. Treatment of tualang honey inhibited UVB-induced nuclear translocation of NF-?B and degradation of I?B? in murine keratinocyte cell line. The treatment of tualang honey also inhibited UVB-induced inflammatory cytokines and inducible nitric oxide synthase protein expression. Furthermore, the treatment of tualang honey inhibited UVB-induced COX-2 expression and PGE2 production. Taken together, we provide evidence that the treatment of tualang honey to keratinocytes affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential. PMID:22276569

Ahmad, Israr; Jimenez, Hugo; Yaacob, Nik Soriani; Yusuf, Nabiha

2012-01-01

161

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

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

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

2008-09-15

162

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 nucleislight regenerative signs in the nuclei

163

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

International Nuclear Information System (INIS)

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

164

Radiation biology of low doses  

International Nuclear Information System (INIS)

Present risk assessments and standards in radiation protection are based on the so-called linear no-threshold (LNT) dose - effect hypothesis, i.e., on a linear, proportional relationship between radiation doses and their effects on biological systems. This concept presupposes that any dose, irrespective of its level and time of occurrence, carries the same risk coefficient and, moreover, that no individual biological effects are taken into account. This contribution presents studies of low energy transfer (LET) radiation which deal with the risk of cancer to individual cells. According to the LNT hypothesis, the relationship for the occurrence of these potential effects should be constant over the dose range: successful repair, cell death, mutation with potential carcinogenesis. The results of the studies presented here indicate more differentiated effects as a function of dose application as far as damage to cellular DNA by ionizing radiation is concerned. At the same overall dose level, multiple exposures to low doses sometimes give rise to much smaller effects than those arising from one single exposure to the total dose. These adaptive effects of cells are known from other studies. The results of the study allow the conclusion to be drawn that non-linear relationships must be assumed to exist for the LET radiation considered. Correspondingly, the linear no-threshold hypothesis model should at least be reconsidered with respect to the low dose range in the light ofpect to the low dose range in the light of recent biological findings. The inclusion of other topical research findings also could give rise to a new, revised, risk-oriented approach in radiological protection. (orig.)

165

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 assortss 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.

166

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2012-09-01

167

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

168

Low doses controversy  

International Nuclear Information System (INIS)

In this article is studied the question of low dose irradiation. From this question, the risk assessment and how it is perceived in public opinion is studied. Then, it is more generally, the question of public opinion and the information made by the media which is discussed. Different events and how they were related in press are reviewed: leukemia around La Hague, human guinea-pigs for plutonium, Chernobyl consequences, survivors from Hiroshima, nuclear nomads ( for temporary workers and their bad medical surveillance ), radioactive effluents releases from La Hague, Valduc or Cattenom. (N.C.)

169

Dietary lecithin potentiates thermal tolerance and cellular stress protection of milk fish (Chanos Chanos) reared under low dose endosulfan-induced stress.  

Science.gov (United States)

Endosulfan is an organochlorine pesticide commonly found in aquatic environments that has been found to reduce thermal tolerance of fish. Lipotropes such as the food additive, Lecithin has been shown to improve thermal tolerance in fish species. This study was conducted to evaluate the role of lipotropes (lecithin) for enhancing the thermal tolerance of Chanos chanos reared under sublethal low dose endosulfan-induced stress. Two hundred and twenty-five fish were distributed randomly into five treatments, each with three replicates. Four isocaloric and isonitrogenous diets were prepared with graded levels of lecithin: normal water and fed with control diet (En0/L0), endosulfan-treated water and fed with control diet (En/L0), endosulfan-treated water and fed with 1% (En/L1%), 1.5% (En/L 1.5%) and 2% (En/L 2%) lecithin supplemented feed. The endosulfan in treated water was maintained at the level of 1/40th of LC50 (0.52ppb). At the end of the five weeks, critical temperature maxima (CTmax), lethal temperature maxima (LTmax), critical temperature minima (CTmin) and lethal temperature minima (LTmin) were Determined. There was a significant (Plecithin on temperature tolerance (CTmax, LTmax, CTmin and LTmin) of the groups fed with 1, 1.5 and 2% lecithin-supplemented diet compared to control and endosulfan-exposed groups. Positive correlations were observed between CT max and LTmax (R(2)=0.934) as well as between CTmin and LTmin (R(2)=0.9313). At the end of the thermal tolerance study, endosulfan-induced changes in cellular stress enzymes (Catalase, SOD and GST in liver and gill and neurotansmitter enzyme, brain AChE) were significantly (plecithin. We herein report the role of lecithin in enhancing the thermal tolerance and protection against cellular stress in fish exposed to an organochlorine pesticide. PMID:25455939

Kumar, Neeraj; Minhas, P S; Ambasankar, K; Krishnani, K K; Rana, R S

2014-12-01

170

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

International Nuclear Information System (INIS)

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

171

Delta-Tocotrienol Suppresses Radiation-Induced MicroRNA-30 and Protects Mice and Human CD34+ Cells from Radiation Injury  

Science.gov (United States)

We reported that microRNA-30c (miR-30c) plays a key role in radiation-induced human cell damage through an apoptotic pathway. Herein we further evaluated radiation-induced miR-30 expression and mechanisms of delta-tocotrienol (DT3), a radiation countermeasure candidate, for regulating miR-30 in a mouse model and human hematopoietic CD34+ cells. CD2F1 mice were exposed to 0 (control) or 712.5 Gy total-body gamma-radiation, and CD34+ cells were irradiated with 0, 2 or 4 Gy of radiation. Single doses of DT3 (75 mg/kg, subcutaneous injection for mice or 2 ?M for CD34+ cell culture) were administrated 24 h before irradiation and animal survival was monitored for 30 days. Mouse bone marrow (BM), jejunum, kidney, liver and serum as well as CD34+ cells were collected at 1, 4, 8, 24, 48 or 72 h after irradiation to determine apoptotic markers, pro-inflammatory cytokines interleukin (IL)-1? and IL-6, miR-30, and stress response protein expression. Our results showed that radiation-induced IL-1? release and cell damage are pathological states that lead to an early expression and secretion of miR-30b and miR-30c in mouse tissues and serum and in human CD34+ cells. DT3 suppressed IL-1? and miR-30 expression, protected against radiation-induced apoptosis in mouse and human cells, and increased survival of irradiated mice. Furthermore, an anti-IL-1? antibody downregulated radiation-induced NF?Bp65 phosphorylation, inhibited miR-30 expression and protected CD34+ cells from radiation exposure. Knockdown of NF?Bp65 by small interfering RNA (siRNA) significantly suppressed radiation-induced miR-30 expression in CD34+ cells. Our data suggest that DT3 protects human and mouse cells from radiation damage may through suppression of IL-1?-induced NF?B/miR-30 signaling. PMID:25815474

Li, Xiang Hong; Ha, Cam T.; Fu, Dadin; Landauer, Michael R.; Ghosh, Sanchita P.; Xiao, Mang

2015-01-01

172

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

International Nuclear Information System (INIS)

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

173

The effect of low dose of radiation at the whole body level  

Energy Technology Data Exchange (ETDEWEB)

The interaction between body and radiation is reviewed partly based on author's research experiences. Radiation induces generation of free radicals in the body, and which produces chemical protectants like cytokines against the radicals. Those protectants interestingly have radio-protective effects. The author classifies the radiation adaptive responses into cellular and whole body levels in discussing the effect of radiation on cells. Activation of immune system by certain stimuli is described on experiments in 75-500 mGy X-irradiated mice in relation to T-cell maturation. Epidemiological investigations for the low dose radiation effects and risk assessment of carcinogenicity are summarized in such cases as Hiroshima and Nagasaki, Chernobyl accident, radiation workers and people living in high-level natural radiation dose area. Studies focusing on the radiation effect on the whole body as well as on the molecular level from the wide viewpoint are expected. (K.H.)

Matsubara, Junko [Nuclear Safety Commission, Tokyo (Japan)

2001-08-01

174

The effect of low dose of radiation at the whole body level  

International Nuclear Information System (INIS)

The interaction between body and radiation is reviewed partly based on author's research experiences. Radiation induces generation of free radicals in the body, and which produces chemical protectants like cytokines against the radicals. Those protectants interestingly have radio-protective effects. The author classifies the radiation adaptive responses into cellular and whole body levels in discussing the effect of radiation on cells. Activation of immune system by certain stimuli is described on experiments in 75-500 mGy X-irradiated mice in relation to T-cell maturation. Epidemiological investigations for the low dose radiation effects and risk assessment of carcinogenicity are summarized in such cases as Hiroshima and Nagasaki, Chernobyl accident, radiation workers and people living in high-level natural radiation dose area. Studies focusing on the radiation effect on the whole body as well as on the molecular level from the wide viewpoint are expected. (K.H.)

175

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

Energy Technology Data Exchange (ETDEWEB)

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

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

176

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

177

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

Directory of Open Access Journals (Sweden)

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

Xin Yang

2011-11-01

178

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

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english 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.

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

2013-09-27

179

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

Science.gov (United States)

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

Kojima, Shuji

2014-01-01

180

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 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)

181

Are low doses really so hazardous?  

International Nuclear Information System (INIS)

The ICRP as the competent organisation for matters of radiation protection recommends to assume a linear dose-response relationship down to a dose of zero, in order to be on the safe side when planning radiation protection measures. However, it is difficult to assess the true dose-response relationship down to no-dose, as the effects of very low doses are more difficult to detect the more they decrease to zero. Results available so far nonetheless indicate that assuming a linearly quadratic response better reflects the true conditions frequently observed than the linear model approach, and the first approach also indicates low doses to be less harmful than hitherto expected. (orig./SHA)

182

Isofraxidin, a potent reactive oxygen species (ROS) scavenger, protects human leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in p53-independent manner.  

Science.gov (United States)

Ionizing radiation (IR) leads to oxidizing events such as excessive reactive oxygen species (ROS) in the exposed cells, resulting in further oxidative damage to lipids, proteins and DNA. To screen the potential radio-protective drug, the intracellular ROS was measured in irradiated U937 cells pretreated with 80 candidate traditional herbal medicine, respectively. Isofraxidin (IF) was one possible radio-protector in these 80 drugs. This study investigated the radio-protective role of IF, a Coumarin compound, in human leukemia cell lines, for the first time. Results indicate that IF protects against IR-induced apoptosis in U937 cells in the time- and concentration- dependent manner. IF decreases IR-induced intracellular ROS generation, especially hydroxyl radicals formation, inhibits IR-induced mitochondrial membrane potential loss and reduces IR-induced high intracellular Ca(2+) levels regardless of ER stress. IF down-regulates the expression of caspase-3, phospho-JNK, phospho-p38 and activates Bax in mitochondria. IF inhibits cytochrome c release from mitochondria to cytosol. IF also moderates IR-induced Fas externalization and caspase-8 activation. IF also exhibits significant protection against IR-induced cell death in other leukemia cell lines such as Molt-4 cells and HL60 cells regardless of p53. Taken together, the data demonstrate that IF protects leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in a p53-independent manner. PMID:24692054

Li, Peng; Zhao, Qing-Li; Wu, Li-Hua; Jawaid, Paras; Jiao, Yu-Fei; Kadowaki, Makoto; Kondo, Takashi

2014-06-01

183

Radiation induced oral mucositis  

Directory of Open Access Journals (Sweden)

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

Satheesh Kumar P

2009-01-01

184

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

International Nuclear Information System (INIS)

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

185

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)

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

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

2014-10-01

186

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

International Nuclear Information System (INIS)

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

187

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

International Nuclear Information System (INIS)

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

188

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

International Nuclear Information System (INIS)

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

189

Low dose gamma knife surgery for small cerebral arteriovenous malformations  

International Nuclear Information System (INIS)

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

190

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

191

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

International Nuclear Information System (INIS)

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

192

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

193

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 enablend holistic research strategy which enables to enhance Japanese advantages such as low dose rate facilities and animal facilities, as soon as possible. (author)

194

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)ERK signaling pathways. (author)

195

Low Dose IR Creates an Oncogenic Microenvironment by Inducing Premature  

Energy Technology Data Exchange (ETDEWEB)

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.

Yuan, Zhi-Min [Harvard School of Public Health

2013-04-28

196

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

Science.gov (United States)

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. PMID:24024148

Tseng, Bertrand P.; Lan, Mary L.; Tran, Katherine K.; Acharya, Munjal M.; Giedzinski, Erich; Limoli, Charles L.

2013-01-01

197

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)

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.

Bertrand P. Tseng

2013-01-01

198

Mice drinking goji berry juice (Lycium barbarum) are protected from UV radiation-induced skin damage via antioxidant pathways.  

Science.gov (United States)

The goji berry, Lycium barbarum, has long been recognised in traditional Chinese medicine for various therapeutic properties based on its antioxidant and immune-modulating effects. This study describes the potential for orally consumed goji berry juice to alter the photodamage induced in the skin of mice by acute solar simulated UV (SSUV) irradiation. In Skh:hr-1 hairless mice, 5% goji berry juice significantly reduced the inflammatory oedema of the sunburn reaction. Dilutions of goji berry juice between 1% and 10% dose-dependently protected against SSUV-induced immunosuppression, and against suppression induced by the mediator, cis-urocanic acid, measured by the contact hypersensitivity reaction. The immune protection could not be ascribed to either the minor excipients in the goji juice, pear and apple juice, nor the vitamin C content, nor the preservative, and appeared to be a property of the goji berry itself. Antioxidant activity in the skin was demonstrated by the significant protection by 5% goji juice against lipid peroxidation induced by UVA radiation. Furthermore, two known inducible endogenous skin antioxidants, haem oxygenase-1 and metallothionein, were found to be involved in the photoimmune protection. The results suggest that consumption of this juice could provide additional photoprotection for susceptible humans. PMID:20354657

Reeve, Vivienne E; Allanson, Munif; Arun, Sondur Jayappa; Domanski, Diane; Painter, Nicole

2010-04-01

199

Again about low doses of ionizing radiation  

International Nuclear Information System (INIS)

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

200

Roles of DNA repair genes in sustaining cell proliferation under low dose-rate irradiation  

International Nuclear Information System (INIS)

Radiation-induced DNA double-strand break (DSB) initiates various kinds of biological effects. There is accumulating evidence indicating that the biological effects of low dose and low dose-rate radiation are different from those of high dose and high dose-rate radiation. To elucidate the molecular mechanisms, it is essential to clarify the role of DSB repair-related genes in the repair of low dose and low dose-rate radiation-induced DSBs. Here, we show that the cell growth rate of non-homologous end-joining-related Ku70 and DNA-PKcs knockout chicken DT40 cells irradiated with ?-rays at 1.0 mGy/hr were significantly lower than that of homologous recombination-related Rad54 and NBS1 knockout cells and Rad54/Ku70 double-knockout cells, as well as wild-type cells. On the other hand, the growth of Rad54-/- cells irradiated with 2 Gy of X-rays at 0.9 Gy/min was arrested as well as Ku70-/- and DNA-PKcs-/-/- cells. In addition, Rad54-/- Ku70-/- cells showed the strongest growth delay in all of knockout cells. However, NBS1-/-/- cells did not show the significant growth delay. These findings provide that the role of DSB repair-related genes in the repair of low dose-rate radiation-induced DSBs is noticeably different from that of high dose-rate. The growth delay observed in the mutants Ku70-/- and DNA-PKcs-/-/- cells irradiated with low dose-rate radiation, suggesting that these non-homoladiation, suggesting that these non-homologous end-joining-related genes may be utilized for the molecular marker to predict the sensitivity to low dose and low dose-rate radiation. (author)

201

Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats.  

OpenAIRE

Possible protective effects of the agonist [D-Trp6]LH-RH (analog of luteinizing hormone-releasing hormone in which Gly-6 is replaced by D-tryptophan) and antagonist N-Ac-[D-Phe(pCI)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating horm...

Schally, A. V.; Paz-bouza, J. I.; Schlosser, J. V.; Karashima, T.; Debeljuk, L.; Gandle, B.; Sampson, M.

1987-01-01

202

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

Science.gov (United States)

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

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

203

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

International Nuclear Information System (INIS)

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

204

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

International Nuclear Information System (INIS)

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

205

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

International Nuclear Information System (INIS)

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

206

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)

207

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.)

208

Suppression subtractive hybridization in construction of radiation-induced EST library  

International Nuclear Information System (INIS)

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

209

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

210

protective effect of certain vitamins against radiation-induced biochemical and histological changes in kidney of male albino rats  

International Nuclear Information System (INIS)

Ionizing radiation is a potent mutagenic and carcinogenic agent due to the liberation of free radicals. It is, therefore, essential to search for radioprotective measures. Some antioxidant cocktails are considered as free radical scavengers, which ameliorate the effects of ionizing radiation. The antioxidant action of some vitamins including vitamins E, A and C beside selenium (selenium vit) can designate them as radio-protective agents. Fifty five male Swiss albino rats were divided into 4 groups, the first one served as control. Rats of the second group were exposed to 7 Gy of whole body gamma irradiation. Rats of the third group were subjected to daily oral administration of selenium vit (0.45 g/kg body weight) for 15 days. The fourth group of animals received the same dose of selenium vit followed by radiation exposure.The protective effect of selenium vit was monitored by studying the serum levels of sodium (Na), potassium (K), urea and creatinine.The results showed that whole body gamma irradiation of rats at 7 Gy (single dose) induced significant elevations in the levels of K, urea and creatinine after 3 and 10 days post-irradiation exposure. Conversely, the level of serum Na showed significant depletion. The histopathological results showed different distortion in the renal corpuscles and renal convoluted tubular epithelial cells. These distortions varied from swelling, vacillation to necrosis and complete degeneration of the epithelial cells of the proximal a of the epithelial cells of the proximal and distal tubules. The kidney glomeruli were shrunken and obvious lesions in the fine structure of the renal tissue were detected such as swelling and cristalysis of the mitochondria. The rough endoplasmic reticulum (RER) exhibited various degrees of damage dilatation, fragmentation, degranulation and destruction. Lysosomes were abundant and destruction of the brush border was evident. The nuclei showed irregular nuclear membrane besides clumped marginal chromatin

211

Radiation carcinogenesis following low dose or low dose rate exposures  

International Nuclear Information System (INIS)

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

212

Interaction of low dose irradiation with subsequent mutagenic treatment  

International Nuclear Information System (INIS)

Study of interaction of low dose irradiation with subsequent mutagenic treatment could be a way of evaluating effects of low dose irradiation. This type of research is linked to a biological phenomenon in which cells actually sense environmental adversity mostly through exposure to low doses and then respond to various types of stress by means of a change in gene expression. In this respect there is now a considerable body of evidence showing that exposure of cells to very low doses of ionizing radiation can 'adapt' them such that they show reduced response to a subsequent higher dose. The initial dose may protect by inducing or priming a repair mechanism. This 'adaptive response' is demonstrated by numerous authors using different material and different end points. This paper presents results of experiments carried out using cultures of blood from donors which in previous experiments displayed no adaptive response or synergistic response. (author). 13 refs., 2 tabs

213

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)

214

Molecular Tools and the Biology of Low-dose Effects  

Science.gov (United States)

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

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

2009-09-01

215

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

216

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)

217

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

International Nuclear Information System (INIS)

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

218

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

International Nuclear Information System (INIS)

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

219

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

2006-06-15

220

Synthesis and structural characterization of dioxomolybdenum and dioxotungsten hydroxamato complexes and their function in the protection of radiation induced DNA damage.  

Science.gov (United States)

The synthesis and structural characterization of two novel dioxomolybdenum(VI) (1) and dioxotungsten(VI) (2) complexes with 2-phenylacetylhydroxamic acid (PAHH) [M(O)2(PAH)2] [M = Mo, W] have been accomplished. The dioxomolybdenum(VI) and dioxotungsten(VI) moiety is coordinated by the hydroxamate group (-CONHO(-)) of the 2-phenylacetylhydroxamate (PAH) ligand in a bi-dentate fashion. In both the complexes the PAHH ligand is coordinated through oxygen atoms forming a five membered chelate. The hydrogen atom of N-H of the hydroxamate group is engaged in intermolecular H-bonding with the carbonyl oxygen of another coordinated hydroxamate ligand, thereby forming an extended 1D chain. The ligand as well as both the complexes exhibit the ability to protect from radiation induced damage both in CTDNA as well as in pUC19 plasmid DNA. As the damage to DNA is caused by the radicals generated during radiolysis, its scavenging imparts protection from the damage to DNA. To understand the mechanism of protection, binding affinities of the ligand and the complex with DNA were determined using absorption and emission spectral studies and viscosity measurements, whereby the results indicate that both the complexes and the hydroxamate ligand interact with calf thymus DNA in the minor groove. The intrinsic binding constants, obtained from UV-vis studies, are 7.2 10(3) M(-1), 5.2 10(4) M(-1) and 1.2 10(4) M(-1) for the ligand and complexes 1 and 2 respectively. The Stern-Volmer quenching constants obtained from a luminescence study for both the complexes are 5.6 10(4) M(-1) and 1.6 10(4) M(-1) respectively. The dioxomolybdenum(VI) complex is found to be a more potent radioprotector compared to the dioxotungsten(VI) complex and the ligand. Radical scavenging chemical studies suggest that the complexes have a greater ability to scavenge both the hydroxyl as well as the superoxide radicals compared to the ligand. The free radical scavenging ability of the ligand and the complexes was further established by EPR spectroscopy using a stable free radical, the DPPH, as a probe. The experimental results of DNA binding are further supported by molecular docking studies. PMID:24336831

Paul, Shiv Shankar; Selim, Md; Saha, Abhijit; Mukherjea, Kalyan K

2014-02-21

221

Radiation- induced aneuploidy in mammalian germ cells  

International Nuclear Information System (INIS)

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

222

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2004-07-01

223

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)

224

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

225

Biological effects of low-dose exposure  

International Nuclear Information System (INIS)

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

226

Global DNA methylation responses to low dose radiation exposure  

International Nuclear Information System (INIS)

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

227

Estimation of radiation risk at low dose levels: Is it science or trans-science  

International Nuclear Information System (INIS)

Estimation of carcinogenic risk of radiation, particularly at low doses and low dose rates, is very difficult due to concurrent natural incidence of cancers which are clinically indistinguishable from radiation-induced ones. To estimate carcinogenic risk of radiation exposure of 1 rad annually, the size of population which must be surveyed has been calculated to be a quarter million for thyroid cancer and 32 million for lung cancer. These populations must be surveyed over a period of 20 to 30 years and further they have to be properly sampled taking into consideration biological and environmental factors which initiate and promote malignancies. (M.G.B.)

228

Some remarks on the significance of low doses  

International Nuclear Information System (INIS)

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

229

Low dose response analysis through a cytogenetic end-point  

International Nuclear Information System (INIS)

The effects of low doses were studied on human lymphocytes of various individuals. The frequency of micronuclei in cytokinesis-blocked cultured lymphocytes was taken as end-point. The probability distribution of radiation-induced increment was statistically proved and identified as to be asymmetric when the blood samples had been irradiated with doses of 0.01-0.05 Gy of X-rays, similarly to that in unirradiated control population. On the contrary, at or above 1 Gy the corresponding normal curve could be accepted only reflecting an approximately symmetrical scatter of the increments about their mean value. It was found that the slope as well as the closeness of correlation of the variables considerably changed when lower and lower dose ranges had been selected. Below approximately 0.2 Gy even an unrelatedness was found betwen the absorbed dose and the increment

230

The effects of chronic low dose irradiation on drosophila melanogaster  

International Nuclear Information System (INIS)

It was investigated the influence of the chronic gamma-irradiation in the dose rate of 0.17 cGy/h on the rate of genetic variability and on the life-span in the laboratory strains of Drosophila melanogaster with genotypic distinguishes in mobile genetic elements and defects in the DNA repair processes. It is shown that the radiation-induced alteration of the traits under study depends from genotype of investigated strains. In the different strains we have observed an increase as well as a decrease of the mutation rate and life-span. Also it was established that irradiation leads to the frequencies of the GD-sterility and mutability of the snw and h(w+) in the P-M and H-E dysgenic crosses. The obtained results suggest that mobile genetic elements play an important role in the forming of genetic effects in response to low dose irradiation. (author)

231

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

Science.gov (United States)

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.

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

232

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

International Nuclear Information System (INIS)

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

233

Radiation induced polymerization  

International Nuclear Information System (INIS)

Fundamental aspects of radiation induced polymerization are reviewed. In addition, some recent progress on the study of the mechanism of radiation induced cationic polymerization is introduced, and the possible mechanism for the initiation, propagation steps is proposed. The significant progress in this field is due to pulse radiolysis technique. Applying this technique, one can observe directly several transient species which play important roles in the early stage of polymerization. Finally, applied research in this field is mentioned. There are several products which were synthesized firstly by radiation polymerization. Some of those products have been found to have excellent properties for their practical uses, and are now being produced as commercial products. Two examples of fluoropolymers are introduced. (author)

234

Esophageal cancer treated by low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta  

International Nuclear Information System (INIS)

Eight patients with esophageal cancer were treated by a new treatment schedule consisting of low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta. As monitored endoscopically, therapeutic responses were satisfactory : seven out of 8 patients have survived for a range of 3 to 20 months and still active at work or cancer-free. However, one patient suffered from a second malignancy of adenocarcinoma of the upper esophagus different from the initial squamous cell carcinoma at the lower esophagus which had successfully been treated 3 months before. The present therapeutic design aims at treatment of lymphatic spreads in the adjacent structures as well as the original tumor in the esophagus and submucosal invasions. It is basically a consecutive, multimodal integration of selective concentration of therapeutic effects (extensive radiotherapy, topical application of bleomycin polyacrylate pasta, lymphatic chasing with colloidal bleomycin, and spatial concentration of cisplatin as the result of radiation-induced inflammation), perpetuation of the repairable DNA damage, and biological amplifications (protection against esophageal perforation with polyacrylate coating, and specific cancer cell recruitment). Application of the present theraeputic design is being expanded to the treatment of cancer of other specific sites such as the head and neck tumors and rectal cancer with undeniable prospects. (author)

235

Differentially Expressed Genes Associated with Low-Dose Gamma Radiation  

Science.gov (United States)

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.

Hegyesi, Hargita; Sndor, Nikolett; Schilling, Boglrka; Kis, Enik?; Lumniczky, Katalin; Sfrny, Gza

236

Low Dose Risk, Decisions, and Risk Communication  

International Nuclear Information System (INIS)

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

237

Molecular targets for radioprotection by low dose radiation exposure  

International Nuclear Information System (INIS)

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

238

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

239

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

Energy Technology Data Exchange (ETDEWEB)

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.

Cheryl G. Burrell, Ph.D.

2012-05-14

240

The risk to health from low doses of ionising radiation  

Energy Technology Data Exchange (ETDEWEB)

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)

Wakeford, R.; Tawn, E.J

2005-05-15

241

Cyclooxygenase and radiation-induced gastrointestinal injury  

International Nuclear Information System (INIS)

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

242

Radiation induced pesticidal microbes  

Energy Technology Data Exchange (ETDEWEB)

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.

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

2001-01-01

243

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

244

Importance and present state of the research in radiation-induced bystander responses  

International Nuclear Information System (INIS)

Radiation-induced bystander responses (RIBR) 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 it is shown that the importance and current issues of RIBR in the low dose radiation risk assessment. (author)

245

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

International Nuclear Information System (INIS)

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

246

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

International Nuclear Information System (INIS)

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

247

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

International Nuclear Information System (INIS)

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

248

Organ Specific Gene Expression by Low Dose Radiation  

Energy Technology Data Exchange (ETDEWEB)

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.

Lee, Woo Jung; Kang, Chang Mo; Lee, Dea Hoon; Bae, Snag Woo; Lee, Yun Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2005-07-01

249

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

International Nuclear Information System (INIS)

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

250

Accidental chronic exposure to low dose radiation in Taiwan  

International Nuclear Information System (INIS)

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

251

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!

252

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)

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)

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

2012-03-15

253

Cytogenetic effects of extremely low doses of plutonium-238 alpha-particle irradiation in CHO K-1 cells.  

Science.gov (United States)

CHO K-1 cells were irradiated during the G1 phase with 0.5-6 rad of alpha particles. There was no appreciable cell killing in this low dose range. Significantly increased frequencies of sister-chromatid exchanges were induced by doses as low as 0.5 rad of alpha-particle irradiation, whereas increased numbers of chromosomal aberrations were observed following exposure to 2 rad. These results suggest that very low doses of alpha radiation may lead to radiation-induced genetic alterations. PMID:2366817

Nagasawa, H; Little, J B; Inkret, W C; Carpenter, S; Thompson, K; Raju, M R; Chen, D J; Strniste, G F

1990-07-01

254

Factors that modify risks of radiation-induced cancer.  

Science.gov (United States)

The collective influence of biologic, physical, and other factors that modify risks of radiation-induced cancer introduces uncertainties and assumptions that limit precision of estimates of human cancer risk that can be calculated for populations exposed to low-dose radiation. The important biologic characteristics include the tissue sites and cell types, baseline cancer incidence, latent periods, time-to-tumor recognition, and individual host (e.g., age and sex) and competing etiologic influences. Physical factors include radiation dose, dose rate, and radiation quality. Statistical factors include time-response projection models, risk coefficients, and dose-response relationships. Sources that modify risk also include other carcinogens and biologic factors (e.g., hormonal conditions, immune status, hereditary factors). Discussion includes examples of known influences that modify radiation-associated cancer risks and how they have been dealt with in the risk-estimation process, including extrapolation to low doses, use of relative risk models, and other uncertainties. PMID:2358362

Fabrikant, J I

1990-07-01

255

Low dose prednisolone in nephrotic syndrome.  

OpenAIRE

Sixteen patients with steroid responsive nephrotic syndrome were treated on 29 separate occasions with a low dose of prednisolone (30 mg/m2/day). All went into remission within 14 days. The duration of remission in the six patients who had had previous relapses treated with a higher dose of prednisolone was similar.

Choonara, I. A.; Heney, D.; Meadow, S. R.

1989-01-01

256

Radiation induced nano structures  

International Nuclear Information System (INIS)

Full text: Nanometer-size silicon clusters have been attracting much attention due to their technological importance, in particular, as promising building blocks for nano electronic and nano photonic systems. Particularly, silicon wires are of great of interest since they have potential for use in one-dimensional quantum wire high-speed field effect transistors and light-emitting devices with extremely low power consumption. Carbon and metal nano structures are studied very intensely due to wide possible applications. Radiation material sciences have been dealing with sub-micron objects for a long time. Under interaction of high energy particles and ionizing radiation with solids by elastic and inelastic mechanisms, at first point defects are created, then they form clusters, column defects, disordered regions (amorphous colloids) and finally precipitates of another crystal phase in the matrix. Such irradiation induced evolution of structure defects and phase transformations was observed by X-diffraction techniques in dielectric crystals of quartz and corundum, which exist in and crystal modifications. If there is no polymorphism, like in alkali halide crystals, then due to radiolysis halogen atoms are evaporated from the surface that results in non-stoichiometry or accumulated in the pores formed by metal vacancies in the sub-surface layer. Nano-pores are created by intensive high energy particles irradiation at first chaotically and then they are ordered and in partally and then they are ordered and in part filled by inert gas. It is well-known mechanism of radiation induced swelling and embrittlement of metals and alloys, which is undesirable for construction materials for nuclear reactors. Possible solution of this problem may come from nano-structured materials, where there is neither swelling nor embrittlement at gas absorption due to very low density of the structure, while strength keeps high. This review considers experimental observations of radiation induced nano-inclusions in insulating, semiconducting and conducting materials and a few examples of computer modeling of Si and C nano-clusters, which have been carried out at the Institute of Nuclear Physics recently. After a long term gamma-irradiation of graphite at elevated temperature and pressure, nano-precipitates of diamond are formed with the critical size and definite orientation. The structure of graphite matrix changes so as to ensure the minimal lattice strains at the boundary with diamond nano-crystallites. Recently we suggested a regular, quasi-one dimensional growth pattern of Si clusters, that is energetically competitive with a growth pattern predicted by ab initio methods for clusters of up to 20 Si atoms. We used computer simulations to find the maximum size to which clusters from this regular pattern can grow, and to identify a mechanism that restricts such a growth. These simulations were performed using a combination of the non-conventional tight-binding method with a molecular-dynamics approach. Spherical clusters with a diamond-like core were also studied. We found that clusters with a diamond-like core were less stable than the clusters from this one-dimensional growth pattern, over the range of cluster sizes considered. The diamond-like structures of the former tend to become amorphous because of a large number of surface states; the mixing of fully and partially occupied states initiates a great variety of distortions from the ideal quasi-spherical diamond-like structure

257

Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-? administered to the buccal mucosa.  

Science.gov (United States)

Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses. PMID:25111905

Strayer, David R; Carter, William A; Stouch, Bruce C; Stittelaar, Koert J; Thoolen, Robert J M M; Osterhaus, Albert D M E; Mitchell, William M

2014-10-01

258

Enhanced DNA stability as a result of low doses of ?- and ?-irradiation  

International Nuclear Information System (INIS)

The differential effect of ?- vs ?-irradiation on the stability of the mammalian macromolecular DNA was studied by thermal transition spectrophotometry (TTS) and Pulsed Field Gel Electrophoresis (PFGE). In this work ?-rays from 60Co and ?-particles from an 241Am surface source emitting in vacuum were utilized. The results indicate that the DNA molecules exposed to ?-rays and to ?-particles show an increased over that of the control helix stability at the radio-biologically important region of low doses. At the same region a relative increase at the molecular weight (MW) occurs as it was measured by PFGE. At higher doses, ?- and ?-irradiation induces the expected decrease in the stability of the double helical structure combined with a decrease MW. These results will be discussed in relation to possible formation of crosslinks between the DNA strands and radiation induced conformational changes of the DNA double helix at low doses. (authors)

259

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)

260

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., 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)

261

Low dose irradiation reduces cancer mortality rates  

Energy Technology Data Exchange (ETDEWEB)

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 hlumg 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 {sup 60}Co 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)

Luckey, T.D.

2000-05-01

262

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

Energy Technology Data Exchange (ETDEWEB)

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.

Acheva, A; Georgieva, R; Rupova, I; Boteva, R [Laboratory Molecular Radiobiology and Epidemiology, National Centre of Radiobiology and Radiation Protection, 132 Kliment Ohridski blvd, Sofia 1756 (Bulgaria); Lyng, F [Radiation and Environmental Science Center, Dublin Institute of Technology, Kevin st, Dublin 8 (Ireland)], E-mail: anjin_a@mail.bg

2008-02-01

263

Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review.  

OpenAIRE

At the request of the U.S. Environmental Protection Agency (U.S. EPA), the National Toxicology Program organized an independent and open peer review to evaluate the scientific evidence on low-dose effects and nonmonotonic dose-response relationships for endocrine-disrupting chemicals in mammalian species. For this peer review, "low-dose effects" referred to biologic changes that occur in the range of human exposures or at doses lower than those typically used in the standard testing paradigm ...

Melnick, Ronald; Lucier, George; Wolfe, Mary; Hall, Roxanne; Stancel, George; Prins, Gail; Gallo, Michael; Reuhl, Kenneth; Ho, Shuk-mei; Brown, Terry; Moore, John; Leakey, Julian; Haseman, Joseph; Kohn, Michael

2002-01-01

264

Converting low dose radiation to redox signaling.  

Science.gov (United States)

In contrast to the damaging effects of high doses, low dose radiation (UV, gamma) has been reported to provoke constructive changes in plants. However, the mechanisms by which plants recognize and respond to low dose radiation are not understood. We have shown recently that polygalacturonic acid, cell wall polysaccharide, converts the highly reactive product of radiation - hydroxyl radical into superoxide which may be further dismutated to hydrogen peroxide. Superoxide has been proposed to act as a signaling molecule, while hydrogen peroxide is known to be the key species in redox signaling cascades which are involved in the regulation of various physiological processes. Hence we propose that polygalacturonic acid may operate as radiation-signaling convertor. The outlined principles of radiation-sensing could also be valid for mammalian cells, with some other molecules mediating the conversion. PMID:23299433

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

2013-02-01

265

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

266

Tardive dyskinesia with low dose amisulpride  

OpenAIRE

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...

Tharoor, Hema; Padmavati, R.

2013-01-01

267

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

268

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

269

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

Science.gov (United States)

Ionizing radiation (IR) induces DNA strand breaks leading to cell death or deleterious genome rearrangements. In the present study, we examined the role of N-acetyl-L-cysteine (NAC), a clinically proven safe agent, for it's ability to protect against gamma-ray-induced DNA strand breaks and/or DNA deletions in yeast and mammals. In the yeast Saccharomyces cerevisiae, DNA deletions were scored by reversion to histidine prototrophy. Human lymphoblastoid cells were examined for the frequency of gamma-H2AX foci formation, indicative of DNA double strand break formation. DNA strand breaks were also measured in mouse peripheral blood by the alkaline comet assay. In yeast, NAC reduced the frequency of IR-induced DNA deletions. However, NAC did not protect against cell death. NAC also reduced gamma-H2AX foci formation in human lymphoblastoid cells but had no protective effect in the colony survival assay. NAC administration via drinking water fully protected against DNA strand breaks in mice whole-body irradiated with 1Gy but not with 4Gy. NAC treatment in the absence of irradiation was not genotoxic. These data suggest that, given the safety and efficacy of NAC in humans, NAC may be useful in radiation therapy to prevent radiation-mediated genotoxicity, but does not interfere with efficient cancer cell killing. PMID:19427509

Reliene, Ramune; Pollard, Julianne M; Sobol, Zhanna; Trouiller, Benedicte; Gatti, Richard A; Schiestl, Robert H

2009-06-01

270

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

International Nuclear Information System (INIS)

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

271

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2009-06-01

272

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  

Energy Technology Data Exchange (ETDEWEB)

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

NONE

2009-07-01

273

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

International Nuclear Information System (INIS)

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

274

Radiation-induced tumors of the nervous system  

International Nuclear Information System (INIS)

Therapeutic and nontherapeutic ionizing radiation has long been recognized as a putative carcinogenic agent, but the evidence that radiation causes tumors is circumstantial at worst and statistically significant at best. There are no distinct histological, biochemical, cytogenetic, or clinical criteria that can be used to determine if an individual tumor was caused directly by previous irradiation of the anatomic area. Additional supportive evidence for radiation-induced tumors includes a position correlation between radiation dose and tumor incidence (usually in the low dose range) and experimental induction of the same neoplasm in appropriate animal models. even if these criteria are fulfilled, coincidental development of a second tumor can never be discounted in an individual patient, particularly if there is an underlying diathesis to develop multiple tumors of different histology, such as in Recklinghausen's disease, or if there is an strong family history for the development of neoplastic disease. In this paper, the authors critically evaluate the available evidence to support the hypothesis that radiation induces tumors in the nervous system. The current concepts of radiation carcinogenesis are discussed and are followed by a discussion of animal data and clinical experience in humans. Finally, a brief discussion on treatment of radiation-induced nervous system tumors is presented

275

Low-dose aspirin for migraine prophylaxis.  

OpenAIRE

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial that studied low-dose aspirin (325 mg every other day) therapy among 22,071 US male physicians aged 40 to 84 years. Annual follow-up questionnaires requested information on the occurrence of numerous medical conditions including migraine. At the end of 60 months, morbidity follow-up was 99.7% complete, and the reported consumption of aspirin or other platelet-active drugs was 86% in the aspirin group and 14% ...

Buring, Je; Peto, R; Hennekens, Ch

1990-01-01

276

Low-dose radiography of children.  

Science.gov (United States)

During the past five years, over 50,000 routine examinations in pediatric radiology have been performed utilizing a high-speed, rare-earth system. A detailed study of the physical characteristics as well as subjective qualities of all of the commercially available rare-earth systems was performed. Our extensive clinical experience with a gadolinium oxysulfide system is described in detail. Practical points on how to avoid certain pitfalls when instituting a system of low-dose radiography are discussed. The present system allows a significant reduction in radiation dosage with maintenance of fine to excellent radiographic resolution. PMID:7384433

Wesenberg, R L; Blumhagen, J D; Rossi, R P; Hilton, S V; Gilbert, J M; Nedeau, D J

1980-01-01

277

Food preservation by irradiation at low doses  

Energy Technology Data Exchange (ETDEWEB)

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)

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

278

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)

279

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

2014-07-29

280

Risk of low-doses in radiodiagnosis  

International Nuclear Information System (INIS)

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

281

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.)

282

Homeostatic balance as an indicator of prolonged technogenic exposure in low dose range  

International Nuclear Information System (INIS)

Full text: Indication of changes induced by ionizing radiation starting up a wide range of pathologic reactions in the disease developments still poses a significant problem in radiation medicine. It mainly concerns exposure to low dose-rate ionizing radiation, since its effects are still open to question, and today any researcher acknowledges that radiation induced pathological changes can accumulate at both subclinical and prenosological stages and develop not only in exposed persons, but also in their offspring. The subject of this study was workers of reactor and radiochemical productions of Siberian Group of Chemical Enterprises (SGCE) exposed to external and combined (external and internal) radiation respectively. Two comparative groups were formed: reactor and radiochemical production workers. In the reactor production group of workers the cumulative dose of external ?-radiation was up to 300 mSv, in the radiochemical production group - up to 150 mSv. Age ranged from 40 to 50 years. The two groups were compared between each other. Above all, there were formed 'insider control' groups (workers of the same productions with zero doses) to assess the impact of radiation factor on central homeostatic mechanisms. These groups were created using pair technique in order to level somatic disorders influence on the parameters under study. Numbers of full and biochemical blood examinations, energy metabolism between cells, hormones of homeostasis by the adaptive hormone level - insulin and cortisol, lipid peroxidation and antioxidant protection systems, immune and vegetative systems were all analyzed. Analyses of the systems performed, it was found out that in persons having been exposed to long term occupational radiation there were significant changes indicating lipid peroxidation system activation, antioxidant protection system depression, as well as lowered energy metabolism. The higher external ?-doses the bigger these changes are. Results from the two groups of radiation and radiochemical production workers compared, it was shown that the recorded changes were of identical character which possibly indicates the absence of specific effects of any particular radiation on central homeostatic mechanisms. Detection of the 'target' systems for radiation effects is the ground for developing approaches to pathogenesis based correction and prevention of homeostatic disorders among people exposed to prolonged occupational radiation at a preclinical stage of main diseases development. (author)

283

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

284

Melatonin ameliorates radiation induced mutilation of learning in mice  

International Nuclear Information System (INIS)

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

285

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

International Nuclear Information System (INIS)

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

286

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)

287

Low-dose effects hypothesis and results  

International Nuclear Information System (INIS)

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

288

Culmination of low-dose pesticide effects.  

Science.gov (United States)

Pesticides applied in agriculture can affect the structure and function of nontarget populations at lower doses and for longer timespans than predicted by the current risk assessment frameworks. We identified a mechanism for this observation. The populations of an aquatic invertebrate (Culex pipiens) exposed over several generations to repeated pulses of low concentrations of the neonicotinoid insecticide (thiacloprid) continuously declined and did not recover in the presence of a less sensitive competing species (Daphnia magna). By contrast, in the absence of a competitor, insecticide effects on the more sensitive species were only observed at concentrations 1 order of magnitude higher, and the species recovered more rapidly after a contamination event. The underlying processes are experimentally identified and reconstructed using a simulation model. We conclude that repeated toxicant pulse of populations that are challenged with interspecific competition may result in a multigenerational culmination of low-dose effects. PMID:23859631

Liess, Matthias; Foit, Kaarina; Becker, Anne; Hassold, Enken; Dolciotti, Ida; Kattwinkel, Mira; Duquesne, Sabine

2013-08-01

289

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.)

290

Low-Dose Radiotherapy in Indolent Lymphoma  

International Nuclear Information System (INIS)

Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 months (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and n, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.

291

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

292

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

Energy Technology Data Exchange (ETDEWEB)

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.

Simon Bouffler

2010-07-28

293

Quantification of the radiation-induced genetic risk  

International Nuclear Information System (INIS)

The estimation of the radiation-induced genetic risk of human populations is based on the extrapolation of results from animal experiments. Radiation-induced mutations are stochastic events. The probability of the event depends on the dose; the degree of the damage does not. The different methods to estimate the radiation-induced genetic risk will be discussed. The accuracy of the predicted results will be evaluated by comparison with the observed incidence of dominant mutations in offspring born to radiation exposed survivors of the Hiroshima and Nagasaki atomic bombings. These methods will be used to predict the genetic damage from the fallout of the reactor accident at Chernobyl. For the exposure dose we used the upper limits of the mean effective life time equivalent does from the fallout values in the Munich region. According to the direct method for the risk estimation we will expect for each 100 to 500 spontaneous dominant mutations one radiation-induced mutation in the first generation. With the indirect method we estimate a ratio of 100 dominant spontaneous mutations to one radiation-induced dominant mutation. The possibilities and the limitations of the different methods to estimate the genetic risk will be discussed. The discrepancy between the high safety standards for radiation protection and the low level of knowledge for the toxicological evaluation of chemical mutagens will be emphasized. (orig./MG)

294

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

International Nuclear Information System (INIS)

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

295

Radiation-induced defects method  

International Nuclear Information System (INIS)

A radiation-induced defect method recommended for application to prospecting for and forecasting of uranium deposits for estimation of radiogeochemical anomalies, tracing migration ways of ore-bearing solution and clarification of uranium mineralization age is described. The method is based on determination of ionizing radiation dose absorbed by rocks. Ionizing radiation of natural radioelements gives rise to electron-hole centres in the crystal structure; these centres are associated with point radiation defects, the concentration of which depends on radiation intensity and duration and it is determined using the electron spin resonance method. Quartz is the most effective mineral-dosimeter. Results of horizontal paleodosimetric mapping for studying conditions for formation of stratiform uranium mineralization are considered as an example of using the radiation-induced defect method

296

Radiological risk and low doses: between false debate and experience  

International Nuclear Information System (INIS)

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

297

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

Energy Technology Data Exchange (ETDEWEB)

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.

Spitz, Douglas R.

2009-11-09

298

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

International Nuclear Information System (INIS)

Exposure to ionizing radiation results in the immediate formation of free radicals and other reactive oxygen species (ROS). It has been assumed that the subsequent injury processes leading to genomic instability and carcinogenesis following radiation, derive from the initial oxidative damage caused by these free radicals and ROS. It is now becoming increasingly obvious that metabolic oxidation/reduction (redox) reactions can be altered by irradiation leading to persistent increases in steady-state levels of intracellular free radicals and ROS that contribute to the long term biological effects of radiation exposure by causing chronic oxidative stress. The objective during the last period of support (DE-FG02-05ER64050; 5/15/05-12/31/09) was to determine the involvement of mitochondrial genetic defects in metabolic oxidative stress and the biological effects of low dose/low LET radiation. Aim 1 was to determine if cells with mutations in succinate dehydrogenase (SDH) subunits C and D (SDHC and SDHD in mitochondrial complex II) demonstrated increases in steady-state levels of reactive oxygen species (ROS; O2- and H2O2) as well as demonstrating increased sensitivity to low dose/low LET radiation (10 cGy) in cultured mammalian cells. Aim No.2 was to determine if mitochondrially-derived ROS contributed to increased sensitivity to low dose/low LET radiation in mammalian cells containing mutations in SDH subunits. Aim No.3 was to determine if a causal relationship existed between increases in mitochondrial ROS production, alterations in electron transport chain proteins, and genomic instability in the progeny of irradiated cells. Evidence gathered in the 2005-2009 period of support demonstrated that mutations in genes coding for mitochondrial electron transport chain proteins (ETC); either Succinate Dehydrogenase (SDH) subunit C (SDHC) or subunit D (SDHD); caused increased ROS production, increased genomic instability, and increased sensitivity to low dose/low LET radiation that could be mitigated by over expression of the H2O2 metabolizing enzyme, catalase, and/or the mitochondrial form of superoxide dismutase (MnSOD). Furthermore, using radiation-induced genomically unstable cells, it was shown that steady-state levels of H2O2 were significantly elevated for many cell generations following exposure, catalase suppressed the radiation-induced mutator phenotype when added long after radiation exposure, unstable clones showed evidence of mitochondrial dysfunction some of which was characterized by improper assembly of SDH subunits (particularly subunit B), and chemical inhibitors of SDH activity could decrease steady-state levels of H2O2 as well as mutation frequency. These results support the hypotheses that (1) SDH mutations could contribute to transformation by inducing genomic instability and a mutator phenotype via increasing steady-state levels of ROS; (2) metabolic sources of O2- and H2O2 play a significant role in low dose radiation induced injury and genomic instability; and (3) increased mutation rates in irradiated mammal cells can be suppressed by scavengers of H2O2 (particularly catalase) long after radiation exposure. Overall the results obtained during this period of support provide clear evidence in support of the hypothesis that abnormal oxidative metabolism in mitochondria that result in increases in steady-sate levels of H2O2 and other ROS are capable of significantly contributing to radiation-induced mutator phenotypes in mammalian cells.

299

Radiation-induced chromosomal instability  

Energy Technology Data Exchange (ETDEWEB)

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/{mu}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.)

Ritter, S. [GSI, Biophysics, Darmstadt (Germany)

1999-03-01

300

Radiation-induced genomic instability  

Science.gov (United States)

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

Kronenberg, A.

1994-01-01

301

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)

302

Radiation-induced genomic instability  

International Nuclear Information System (INIS)

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

303

Role of DNA double-strand break repair genes in cell proliferation under low dose-rate irradiation conditions.  

Science.gov (United States)

Radiation-induced DNA double-stand breaks (DSBs) lead to numerous biological effects. To elucidate the molecular mechanisms involved in cellular responses to low dose and low dose-rate radiation, it is informative to clarify the roles of DSB repair related genes. In higher vertebrate cells, there are at least two major DSB repair pathways, namely non-homologous end-joining (NHEJ) and homologous recombination (HR). Here, it is shown that in chicken DT40 cells irradiated with gamma-rays at a low dose-rate (2.4 cGy/day), the growth delay in NHEJ-related KU70- and PRKDC (encoding DNA-PKcs)-defective cells were remarkably higher than in cells defective for the HR-related RAD51B and RAD54 genes. DNA-PKcs- defective human M059J cells also showed an obvious growth delay when compared to control M059K cells. RAD54(-/-)KU70(-/-) cells demonstrated their highest degree of growth delay after an X-irradiation with a high dose-rate of 0.9 Gy/min. However they showed a lower degree of growth delay than that seen in KU70(-/-) and PRKDC(-/-/-) cells exposed to low dose-rate irradiation. These findings indicate that cellular responses to low dose-rate radiation are remarkably different from those to high dose-rate radiation. The fact that both DT40 and mammalian NHEJ-defective cells were highly sensitive to low dose-rate radiation, provide a foundation for the concept that NHEJ-related factors may be useful as molecular markers to predict the sensitivity of humans to low dose-rate radiation. PMID:18797158

Tomita, Masanori; Morohoshi, Fumiko; Matsumoto, Yoshihisa; Otsuka, Kensuke; Sakai, Kazuo

2008-09-01

304

Role of DNA double-strand break repair genes in cell proliferation under low dose-rate irradiation conditions  

International Nuclear Information System (INIS)

Radiation-induced DNA double-stand breaks (DSBs) lead to numerous biological effects. To elucidate the molecular mechanisms involved in cellular responses to low dose and low dose-rate radiation, it is informative to clarify the roles of DSB repair related genes. In higher vertebrate cells, there are at least two major DSB repair pathways, namely non-homologous end-joining (NHEJ) and homologous recombination (HR). Here, it is shown that in chicken DT40 cells irradiated with ?-rays at a low dose-rate (2.4 cGy/day), the growth delay in NHEJ-related KU70- and PRKDC (encoding DNA-PKcs)-defective cells were remarkably higher than in cells defective for the HR-related RAD51B and RAD54 genes. DNA-PKcs-defective human M059J cells also showed an obvious growth delay when compared to control M059K cells. RAD54-/-KU70-/- cells demonstrated their highest degree of growth delay after an X-irradiation with a high dose-rate of 0.9 Gy/min. However they showed a lower degree of growth delay than that seen in KU70-/- and PRKDC-/-/- cells exposed to low dose-rate irradiation. These findings indicate that cellular responses to low dose-rate radiation are remarkably different from those to high dose-rate radiation. The fact that both DT40 and mammalian NHEJ-defective cells were highly sensitive to low dose-rate radiation, provide a foundation for the concept that NHEJ-related factors may be useful as molecular markers to predict the sensitivityecular markers to predict the sensitivity of humans to low dose-rate radiation. (author)

305

P2Y6 receptors and ADAM17 mediate low-dose gamma-ray-induced focus formation (activation) of EGF receptor.  

Science.gov (United States)

The EGF receptor (EGFR) is frequently expressed in tumors of epithelial origin. Although it is well known that ionizing radiation induces activation of EGFR, the mechanism remains unknown. Recently, we reported that activation of P2Y receptors is involved in ?-radiation-induced activation of extracellular signal-regulated kinase1/2 (ERK1/2), which is dependent on activation of EGFR. Here we focused on the mechanism of activation of EGFR in response to low-dose ? radiation, mainly in terms of the activation-associated formation of EGFR foci in A549 cells. Irradiation of cells with 0.1 Gy ? rays induced biphasic phosphorylation of EGFR and ERK1/2 as well as biphasic formation of EGFR foci. The radiation-induced focus formation of EGFR was abolished by ecto-nucleotidase, P2Y receptor antagonists and knockdown of P2Y6 receptor, suggesting the involvement of extracellular nucleotides and activation of P2Y6 receptors in this process. Further, a disintegrin and metalloprotease 17 (ADAM17) is expressed in A549 cells and an ADAM17 inhibitor significantly blocked the radiation-induced focus formation of EGFR. We conclude that activation of both P2Y6 receptors and ADAM17 mediates the low-dose ?-radiation-induced activation of EGFR, as evaluated in terms of focus formation, in A549 cells. PMID:21268712

Tamaishi, Nana; Tsukimoto, Mitsutoshi; Kitami, Akihiro; Kojima, Shuji

2011-02-01

306

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 agmed 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.)

307

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)

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.)

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

308

The new in molecular mechanisms of the action of the irradiation in low doses  

International Nuclear Information System (INIS)

The data about nontarged effect after ionizing irradiation in low doses are considered. It is noted that activate or inhibit the synthesis of protein factor leading to cell cycle arrest in the checkpoints, to apoptosis in intact cells. Potential prospective research directions in radiobiology in connection with the data of bystander effect, adaptive protection are reviewed.

309

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)

310

Radiation-induced cisplatin resistance in two human cell lines  

International Nuclear Information System (INIS)

Cisplatin resistance has been induced in human HT-29 and HeLa cells after low-dose fractionated ?-irradiation. The drug resistance is modest and does not confer cross-resistance to irradiation. Alterations that were recently shown to correlate with radiation-induced cisplatin resistance in murine cells are not involved in the resistant HeLa-C3 cells. Scavengers, such as GSH or metallothioneins are unchanged and there is no alteration of the cGMP transduction pathway. Preliminary results in HeLa-C3 cells indicate that resistance is associated with differences of the apoptotic pathway, with enhancement of the p53 suppressor protein after cisplatin treatment but unchanged bcl-2 protein expression. (authors)

311

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.)

312

Contraception. Low-dose pill launched.  

Science.gov (United States)

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

1993-01-01

313

Prevention of radiation induced taste aversion in rats  

International Nuclear Information System (INIS)

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

314

Dose rate effect in radiation-induced malformation  

International Nuclear Information System (INIS)

Full text: Dose rate effect is observed widely in radiation biological effect such as cell death, chromosomal anomalies, gene mutation and carcinogenesis. In general, the dose rate effect of radiation is closely related to the repairing ability of DNA damage. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In previous experiments, we found that mouse embryonic or fetal tissues have a p53-dependent 'guardian' that aborts cells with radiation-induced teratogenic damage. In order to elucidate the ability to p53-dependent apoptotic tissue repair of teratogenic damage, we compared the incidence of radiation-induced malformations in wild-type p53(+/+) mice and null p53(-/-) mice exposed at high dose rate or low dose rate. X-irradiation with 2 Gy at high dose rate (450 mGy/min) on day 9.5 of gestation induced 50% for p53(+/+) mice and 76% for p53(-/-) mice which are unable to carry out apoptosis. When an equal dose of 2 Gy was given at a low dose rate (1.2 mGy/min), this dose did not become teratogenic for p53(+/+) mice, whereas malformation incidences increased 17% above control level for p53(-/-) mice. After irradiation with 2 Gy, frequency of apoptotic cells vigorously increased for p53(+/+) mice and did not increased at all for p53(-/-) mice. Furthermore, after fractionated irradiation of 2 Gy (two equal fraction at high dose rate), malformation incidences decreased with increase in radiation-free interval for p53(+/+) mice, buiation-free interval for p53(+/+) mice, but were 24% higher than the control level for p53(-/-) mice, even at 24 h intervals. These results suggest that there is a dose rate effect due to the p53-dependent apoptotic tissue repair in addition to the DNA repair

315

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.)

316

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)

317

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)

318

6. LOWRAD International Conference on Low dose radiation effects on human health and environment  

International Nuclear Information System (INIS)

On the behalf of the Organising Committee, the International Journal of Low Radiation, the Hungarian Biophysical Society and the 'Frederic Joliot-Curie' National Research Institute for Radiobiology and Radiohygiene has been held the 6th International Conference on Low Dose Radiation Effects on Human Health and Environment (LOWRAD2007). LOWRAD2007 in Budapest, Hungary through October 18-20, 2007. The main topics was low radiation effect in the area of the radiology and nuclear medicine, radiation protection, dosimetry, environmental issues and waste management etc. One of the major goals of LOWRAD2007 is to encourage international cooperation and communication in all fields of low dose radiation science. This meeting provided a forum for the exchange of scientific ideas for all scientists of various countries. All aspects of low dose radiation research has been included in the scientific program. The program contained educational lectures to facilitate contacts between young and established scientists. (S.I.)

319

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

Science.gov (United States)

Purpose/Objectives(s) 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 (SPEs), 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 2 Gray (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, known as the LD50, of ferrets was established at ~ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 post-irradiation, 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 times post-irradiation when coagulopathies were present and progressively becoming more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions The 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 solely due 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. PMID:24495588

Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R.

2014-01-01

320

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

321

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

Energy Technology Data Exchange (ETDEWEB)

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).

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

1990-10-01

322

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

323

Dose and Time Dependence of Targeted and Untargeted Effects after Very Low Doses of ?-Particle Irradiation of Human Lung Cancer Cells  

OpenAIRE

Understanding the effects to human health resulting from exposure to low doses of ionizing radiation is a persisting challenge. No one questions the deleterious consequences for humans following exposure to high radiation doses; however, in the low dose range, the complex and to some extent unknown cellular responses raise important misgivings about the resulting protective or potentially detrimental effects. Bystander effects are involved in low dose exposures, being characterized by the app...

Belchior, A.; Gil, O. Monteiro; Almeida, P.; Vaz, P.

2012-01-01

324

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)

325

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 p53 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 a aspect of the defense system for radiation induced cancer. (author)

326

International Conference on Low Doses of Ionising Radiation  

International Nuclear Information System (INIS)

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

327

Computed tomographic findings of radiation-induced acute adrenal injury with associated radiation nephropathy: a case report  

OpenAIRE

Radiation nephropathy was first recognized in 1906. The kidney is a radiosensitive organ with a tolerance dose (5% complications in 5 years) of 20 Gray. The imaging findings of acute and chronic radiation induced renal injury are previously described. Radiation-induced adrenal injury, to our knowledge, has not been described in the literature. Unlike the kidneys and other upper abdominal organs, the adrenal glands are traditionally thought to be radio-resistant, protected from radiation-induc...

Schieda, Nicola; Ramchandani, Parvati; Siegelman, Evan S.

2013-01-01

328

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

Science.gov (United States)

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

Tomita, Masanori; Maeda, Munetoshi

2015-03-01

329

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

Directory of Open Access Journals (Sweden)

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.

Shawna M. Hengel

2014-07-01

330

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

International Nuclear Information System (INIS)

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

331

Radiation Induced Degradation of Galactomannan Polysaccharides  

International Nuclear Information System (INIS)

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

332

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

Energy Technology Data Exchange (ETDEWEB)

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.

Munira A Kadhim

2010-03-05

333

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

334

Cytogenetic effects of low-dose radiation with different LET in human peripheral blood lymphocytes.  

Science.gov (United States)

Chromosome damage and the spectrum of aberrations induced by low doses of gamma-irradiation, X-rays and accelerated carbon ions (195 MeV/u, LET 16.6 keV/microm) in peripheral blood lymphocytes of four donors were studied. G0-lymphocytes were exposed to 1-100 cGy, stimulated by PHA, and analyzed for chromosome aberrations at 48 h post-irradiation by the metaphase method. A complex nonlinear dose-effect dependence was observed over the range of 1 to 50 cGy. At 1-7 cGy, the cells showed the highest radiosensitivity per unit dose (hypersensitivity, HRS), which was mainly due to chromatid-type aberration. According to the classical theory of aberration formation, chromatid-type aberrations should not be induced by irradiation of unstimulated lymphocytes. With increasing dose, the frequency of aberrations decreased significantly, and in some cases it even reached the control level. At above 50 cGy the dose-effect curves became linear. In this dose range, the frequency of chromatid aberrations remained at a low constant level, while the chromosome-type aberrations increased linearly with dose. The high yield of chromatid-type aberrations observed in our experiments at low doses confirms the idea that the molecular mechanisms which underlie the HRS phenotype may differ from the classical mechanisms of radiation-induced aberration formation. The data presented, as well as recent literature data on bystander effects and genetic instability expressed as chromatid-type aberrations on a chromosomal level, are discussed with respect to possible common mechanisms underlying all low-dose phenomena. PMID:17031661

Nasonova, E A; Shmakova, N L; Komova, O V; Mel'nikova, L A; Fadeeva, T A; Krasavin, E A; Ritter, S

2006-11-01

335

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

Energy Technology Data Exchange (ETDEWEB)

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.

Eric Y. Chuang

2006-08-31

336

Ionizing radiation affects 26s proteasome function and associated molecular responses, even at low doses  

International Nuclear Information System (INIS)

Background and purpose: Ionizing radiation is known to activate certain signal transduction pathways, the regulation of which could involve post-transcriptional as well as transcriptional mechanisms. One of the most important post-transcriptional pathways in eukaryotic cells is the ATP- and ubiquitin-dependent degradation of proteins by the 26s proteasome. This process controls initiation of many cellular stress responses, as well as inflammatory responses under control of the transcription factor NF-?B. The literature on the relationship between radiation and inflammation seems somewhat paradoxical. At high doses, radiation is generally pro-inflammatory. On the other hand, low dose radiation has a long history of use in the treatment of inflammatory disease. This suggests the involvement of multiple mechanisms that may operate differentially at different dose levels. Materials and methods: In this paper, the ability of different doses of ionizing radiation to directly affect 26s proteasome activity was tested in ECV 304 cells. Proteasome activity, I?B? protein levels, and NF-?B activation were monitored. Results: Inhibition of chymotrypsin-like 20s and 26s proteasome activity was observed immediately after low- and high-dose irradiation either of cells or purified proteasomes. The inhibitory effect was independent of the availability of the known endogenous proteasome inhibitor heat shock protein 90 (hsp90). Levels of I?B?, a physiological 26s proteasome substr physiological 26s proteasome substrate, were increased only at low doses (0.25 Gy) and unaltered at higher doses whereas only the highest doses (8 and 20 Gy) activated NF-?B. Conclusions: We conclude that the proteasome is a direct target of ionizing radiation and suggest that inhibition of proteasome function provides a molecular framework within which low dose anti-inflammatory effects of radiation, and radiation-induced molecular responses in general, should be considered

337

Biological impact of low dose-rate simulated solar particle event radiation in vivo.  

Science.gov (United States)

C57Bl6-lacZ animals were exposed to a range of low dose-rate simulated solar particle event (sSPE) radiation at the NASA-sponsored Research Laboratory (NSRL) at Brookhaven National Laboratory (BNL). Peripheral blood was harvested from animals from 1 to 12 days after total body irradiation (TBI) to quantify the level of circulating reticulocytes (RET) and micronucleated reticulocytes (MN-RET) as an early indicator of radiation-induced genotoxicity. Bone marrow lymphocytes and hippocampal tissues from each animal were collected at 12 days and up to two months, to evaluate dose-dependent late effects after sSPE exposure. Early hematopoietic changes show that the % RET was reduced up to 3 days in response to radiation exposure but recovered at 12 days postirradiation. The % MN-RET in peripheral blood was temporally regulated and dependant on the total accumulated dose. Total chromosome aberrations in lymphocytes increased linearly with dose within a week after radiation and remained significantly higher than the control values at 4 weeks after exposure. The level of aberrations in the irradiated animals returned to control levels by 8 weeks postirradiation. Measurements of chromosome 2 and 8 specific aberrations indicate that, consistent with conventional giemsa-staining methods, the level of aberrations is also not significantly higher than in control animals at 8 weeks postirradiation. The hippocampus was surveyed for differential transcriptional regulation of genes known to be associated with neurogenesis. Our results showed differential expression of neurotrophin and their associated receptor genes within 1 week after sSPE exposure. Progressive changes in the profile of expressed genes known to be involved in neurogenic signaling pathways were dependent on the sSPE dose. Our results to date suggest that radiation-induced changes in the hematopoietic system, i.e., chromosome aberrations in lymphocytes, are transient and do not persist past 4 weeks after radiation. On the other hand, alteration in the profile of genes known to be involved in neurotrophic functions in the hippocampal tissue appears to persist for up to 8 weeks after radiation exposure. Such temporal changes confirm that, although cytogenetic changes after a single dose of low-dose and low-dose-rate protons appear to be transient, the impact of this exposure is sufficient to lead to persistent dynamic changes in neuronal tissues long after the initial radiation exposure. PMID:20473680

Chang, P Y; Doppalapudi, R; Bakke, J; Wang, A; Menda, S; Davis, Z

2010-08-01

338

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

Energy Technology Data Exchange (ETDEWEB)

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.

Kathy Held; Kevin Prise; Barry Michael; Melvyn Folkard

2002-12-14

339

Hormesis: are low doses of ionizing radiation harmful or beneficial?  

International Nuclear Information System (INIS)

A review is provided of the literature on radiation hormesis, hormesis being any physiological effect that occurs at low doses and which cannot be anticipated by extrapolating from toxic effects noted at high doses. Epidemiological studies suggesting beneficial effects are considered, and experimental evidence for the existence of hormesis is then appraised. In the latter context, there are possible low-dose effects at the molecular level, at the cellular level and on the organism as a whole. It is concluded that while it is difficult to analyse the effects of low-dose radiation with statistical significance, the concept does permit the reconsideration of the validity of currently accepted notions. (orig.)

340

Health risks from low doses of ionising radiation  

International Nuclear Information System (INIS)

During 1990-1997, we carried out a combined program of investigations on the effects of low dose irradiation on biochemical, biophysical and functional parameters of cells of various organs of animals exposed to low-doserate ?-irradiation (137Cs). For all parameters, a bimodal dose-effect dependency was found, i.e. the effect increases with dose at low doses, reaches a low dose maximum, then decreases - in some cases even to values below the control level - and increases again with increasing dose. (orig.)

341

Health risks from low doses of ionising radiation  

Energy Technology Data Exchange (ETDEWEB)

During 1990-1997, we carried out a combined program of investigations on the effects of low dose irradiation on biochemical, biophysical and functional parameters of cells of various organs of animals exposed to low-doserate {gamma}-irradiation ({sup 137}Cs). For all parameters, a bimodal dose-effect dependency was found, i.e. the effect increases with dose at low doses, reaches a low dose maximum, then decreases - in some cases even to values below the control level - and increases again with increasing dose. (orig.)

Burlakova, E.B. [Emanuel Inst. of Biochemical Physics, Russian Academy of Sciences, Moscow (Russian Federation)

2001-07-01

342

Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation  

International Nuclear Information System (INIS)

Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk evaluation model. (author)

343

Radiation induced methods of labeling  

International Nuclear Information System (INIS)

In biomedical research labeled molecules are required as tracers for radioimmunoassay, distribution, metabolism and functional studies at the cellular levels. These labeled molecules may encompass a wide range of compounds from drugs, natural plant products, antibiotics, glucosides, etc. to peptides and proteins. Tagging these molecules with carbon-14 involves elaborate chemical syntheses that are often laborious and costly, and in many cases chemical syntheses are not even feasible. The long life of carbon-14 also limits the maximum specific activity that can be achieved with carbon-14 labeled compounds to 62 mCi per millimole. For radiobinding assays and receptor studies labeled substances of this relatively low specific activity lack the sensitivity required and compounds labeled at higher specific activities with tritium are more desirable. Tritiu, the radioactive isotope of hydrogen, has a specific activity of 29 Ci per milliatom or 58 Ci per millimole in the carrier-free state. Since hydrogen binds by 1s orbital to carbon, nitrogen and oxygen atoms in the organic molecule, it is highly likely that the hydrogen atoms in organic compounds can be exchanged with tritium atoms without the disruption of the carbon skeleton. In this paper the authors compare the merits and limitations of the various radiation-induced methods of labeling with tritium gas and point out the trends for future development

344

Radiation induced sulfur dioxide removal  

International Nuclear Information System (INIS)

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

345

Radiation-induced heat diseases  

Energy Technology Data Exchange (ETDEWEB)

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.

Grollier, G.; Commeau, P.; Potier, J.C.

1986-04-26

346

Risk of cancer subsequent to low-dose radiation  

Energy Technology Data Exchange (ETDEWEB)

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. (PCS)

Warren, S.

1980-01-01

347

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)

348

Low dose rate Ir-192 interstitial brachytherapy for prostate cancer  

Energy Technology Data Exchange (ETDEWEB)

From December 1997 through January 1999, fifteen prostatic cancer patients were treated with low dose rate Ir-192 interstitial brachytherapy using TRUS and perineal template guidance without external radiotherapy. Up to now, as no apparent side effects were found, the safety of this treatment is suggested. In the future, in order to treat prostatic cancer patients with interstitial brachytherapy using I-125 or Pd-103, more investigation for this low dose rate Ir-192 interstitial brachytherapy is needed. (author)

Oki, Yosuke; Dokiya, Takushi; Yorozu, Atsunori; Suzuki, Takayuki; Saito, Shiro; Monma, Tetsuo; Ohki, Takahiro [National Tokyo Medical Center (Japan); Murai, Masaru; Kubo, Atsushi

2000-04-01

349

Low dose rate Ir-192 interstitial brachytherapy for prostate cancer  

International Nuclear Information System (INIS)

From December 1997 through January 1999, fifteen prostatic cancer patients were treated with low dose rate Ir-192 interstitial brachytherapy using TRUS and perineal template guidance without external radiotherapy. Up to now, as no apparent side effects were found, the safety of this treatment is suggested. In the future, in order to treat prostatic cancer patients with interstitial brachytherapy using I-125 or Pd-103, more investigation for this low dose rate Ir-192 interstitial brachytherapy is needed. (author)

350

Radiation induced estane polymer crosslinking  

International Nuclear Information System (INIS)

The exposure of polymeric materials to radiation has been known to induce the effects of crosslinking and degradation. The crosslinking phenomena comes about when two long chain polymers become linked together by a primary bond that extends the chain and increases the viscosity, molecular weight and the elastic modules of the polymer. This process has been observed in relatively short periods of time with fairly high doses of radiation, on the order of several megarads/hour. This paper address low dose exposure over long periods of time to determine what the radiation effects are on the polymeric binder material in PBX 9501. An experimental sample of binder material without explosives will be placed into a thermal and radiation field produced from a W-48 put mod 0. Another sample will be placed in a thermal environment without the radiation. The following is the test plan that was submitted to the Pantex process. The data presented here will be from the first few weeks of exposure and this test will be continued over the next few years. Subsequent data will hopefully be presented in the next compatibility and aging conference

351

Radiation induced estane polymer crosslinking  

Energy Technology Data Exchange (ETDEWEB)

The exposure of polymeric materials to radiation has been known to induce the effects of crosslinking and degradation. The crosslinking phenomena comes about when two long chain polymers become linked together by a primary bond that extends the chain and increases the viscosity, molecular weight and the elastic modules of the polymer. This process has been observed in relatively short periods of time with fairly high doses of radiation, on the order of several megarads/hour. This paper address low dose exposure over long periods of time to determine what the radiation effects are on the polymeric binder material in PBX 9501. An experimental sample of binder material without explosives will be placed into a thermal and radiation field produced from a W-48 put mod 0. Another sample will be placed in a thermal environment without the radiation. The following is the test plan that was submitted to the Pantex process. The data presented here will be from the first few weeks of exposure and this test will be continued over the next few years. Subsequent data will hopefully be presented in the next compatibility and aging conference.

Fletcher, M. [Los Alamos National Lab., NM (United States); Foster, P. [Masson Hanger Pantex Plant, Amarillo, TX (United States)

1997-12-01

352

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

Energy Technology Data Exchange (ETDEWEB)

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.

Barry D. Michael; Kathryn Held; Kevin Prise

2002-12-19

353

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

International Nuclear Information System (INIS)

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

354

Radiation-induced graft polymerization of acrylic monomers on polyglycolide fiber surface  

International Nuclear Information System (INIS)

The graft polymerization reaction of acrylic acid and its esters for a polyglycolide fiber modification is studied. The reaction proceeds under direct irradiation in a monomer solution and vapors, as well as according to the post-effect technique. Irradiation was carried out by up to 5 Mrad doses at isotope installations of different 60Co ? radiation dose rates (20-1100 rad/s) and electron accelerator EhU-04. It is shown that the most acceptable way of radiation-induced surface modification of polylactone fibers is direct irradiation in monomer vapors at low dose rates

355

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

Energy Technology Data Exchange (ETDEWEB)

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 responseand 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.

Skov, K.A. [Advanced Therapeutics, BC Cancer Research Centre, 601 W. 10th Ave., Vancouver, BC (Canada)

1999-12-06

356

Effects of low doses of cyclophosphamide and low doses of irradiation on the regulation of induced erythrocyte autoantibodies in mice  

Energy Technology Data Exchange (ETDEWEB)

Some of the characteristics of a suppressor cell which is capable of regulating a rat RBC-induced autoantibody response against mouse RBCs are described. This cell, which appears to function as an inducer of suppression on transfer to naive recipients, is sensitive to low doses of cyclophosphamide, and its generation is affected by low doses of irradiation. However, the recipients of these cells are insensitive to cyclophosphamide treatment, suppression still being induced in such animals.

Hutchings, P.; Cooke, A. (Middlesex Hospital, London (UK). Medical School); Naor, D. (Hebrew Univ., Jerusalem (Israel). Hadassah Medical School)

1985-01-01

357

Effects of low doses of cyclophosphamide and low doses of irradiation on the regulation of induced erythrocyte autoantibodies in mice  

International Nuclear Information System (INIS)

Some of the characteristics of a suppressor cell which is capable of regulating a rat RBC-induced autoantibody response against mouse RBCs are described. This cell, which appears to function as an inducer of suppression on transfer to naive recipients, is sensitive to low doses of cyclophosphamide, and its generation is affected by low doses of irradiation. However, the recipients of these cells are insensitive to cyclophosphamide treatment, suppression still being induced in such animals. (author)

358

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)

359

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

Directory of Open Access Journals (Sweden)

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

MarieArchambault

2014-04-01

360

Radiation-induced adaptive response and intracellular signal transduction pathways  

International Nuclear Information System (INIS)

As an essential biological function, cells can sense the radiation even at low dose and respond to it, and which is one of bases of the radiation-induced adaptive response (AR) where effects caused by high dose radiation are reduced by prior exposure to low dose radiation (LDR). Here described are studies of AR in well established m5S cells on the intracellular signal transduction that involves sensing of LDR and transmitting of its signal within the cell network. The first signal for AR yielded by LDR on the cell membrane is exactly unknown though hydrogen peroxide and phorbol ester (PMA) can reportedly cause AR. As PMA activates protein kinase C (PKC) and its inhibitors suppress AR, participation of PKC in AR has been suggested and supported by studies showing PKC? activation by LDR. In addition, p38 mitogen-activated protein kinase (MAPK) is shown to participate in AR by those facts that the enzyme is activated by LDR, a p38 MAPK inhibitor suppresses AR, and PKC inhibitors suppress the enzyme activation, which also suggesting that the signaling from PKC to p38 MAPK can become operative by LDR. However, the possible reverse signaling is also suggested, and thus the activation of positive feedback mechanism is postulated in PKC/p38 MAPK/phospholipase ?1/ PKC pathway. Cells introduced with siRNA against Prkca gene (coding PKCs) produce reduced amount of the enzyme, particularly, of PKC?. In those cells, AR by 5 Gy X-ray is not observed and thereby PKC? is involved observed and thereby PKC? is involved in AR. The signaling in AR is only partly elucidated at present as above, and more detailed studies including identification of more PKC subtypes and signaling to DNA repair system are considered necessary. (K.T.)

361

Ultra-low dose cannabinoid antagonist AM251 enhances cannabinoid anticonvulsant effects in the pentylenetetrazole-induced seizure in mice.  

Science.gov (United States)

Several lines of evidence suggest that cannabinoid compounds are anticonvulsant since they have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o proteins. Surprisingly, both the analgesic and anticonvulsant effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist naltrexone and as opioid and cannabinoid systems interact, it has been shown that ultra-low dose naltrexone also enhances cannabinoid-induced antinociception. However, regarding the seizure modulating properties of both classes of receptors this study investigated whether ultra-low dose cannabinoid antagonist AM251 influences cannabinoid anticonvulsant effects. The clonic seizure threshold (CST) was tested in separate groups of male NMRI mice following injection of vehicle, the cannabinoid selective agonist arachidonyl-2-chloroethylamide (ACEA) and ultra-low doses of the cannabinoid CB1 antagonist AM251 and a combination of ACEA and AM251 doses in a model of clonic seizure induced by pentylenetetrazole (PTZ). Systemic administration of ultra-low doses of AM251 (10 fg/kg-100 ng/kg) significantly potentiated the anticonvulsant effect of ACEA at 0.5 and 1 mg/kg. Moreover, inhibition of cannabinoid induced excitatory signaling by AM251 (100 pg/kg) unmasked a strong anticonvulsant effect for very low doses of ACEA (100 ng/kg-100 microg/kg), suggesting that a presumed inhibitory component of cannabinoid receptor signaling can exert strong seizure-protective effects even at very low levels of cannabinoid receptor activation. A similar potentiation by AM251 (100 pg/kg and 1 ng/kg) of anticonvulsant effects of non-effective dose of ACEA (0.5 and 1 mg/kg) was also observed in the generalized tonic-clonic model of seizure. The present data suggest that ultra-low doses of cannabinoid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of cannabinoids. PMID:17870135

Gholizadeh, Shervin; Shafaroodi, Hamed; Ghasemi, Mehdi; Bahremand, Arash; Sharifzadeh, Mohammad; Dehpour, Ahmad Reza

2007-11-01

362

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

International Nuclear Information System (INIS)

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

363

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

364

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

LENUS (Irish Health Repository)

Exposure to infectious microbes is a likely confounder after a nuclear terrorism event. In combination with radiation, morbidity and mortality from an infection may increase significantly. Pulmonary damage after low-dose low-LET irradiation is characterized by an initial diffuse alveolar inflammation. By contrast, inhaled fungal spores produce localized damage around pulmonary bronchioles. In the present study, we assessed lung injury in C57BL\\/6 mice after combined exposures to whole-body X radiation and inhaled fungal spores. Either animals were exposed to Aspergillus