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

OpenAIRE

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: ...

Kurus, Meltem; Taslidere, Elif; Elbe, Hulya; Ugras, Murat; Otlu, Ali

2014-01-01

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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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Low-dose radiation-induced endothelial cell retraction  

International Nuclear Information System (INIS)

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

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Radiation Induced Cancer from Low Doses of Ionizing Radiation : Risk Analysis Using the Cell Dose Concept  

Directory of Open Access Journals (Sweden)

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

L.E. Feinendegen

2013-04-01

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Low dose radiation induced bystander effect and its mechanism  

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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

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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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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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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 0.19±0.04 vs 0.05±1 Gy CE 0.24±0.05, 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 (73.2±14.9 x 10-6for 3 Gy vs 45.8±6.6 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 Â?Â?Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

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

2013-05-15

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

OpenAIRE

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

Scott, Bobby R.; Walker, Dale M.; Tesfaigzi, Yohannes; Scho?llnberger, Helmut; Walker, Vernon

2003-01-01

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

CERN Document Server

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

Lu Ping; Kulkarni, N S; Brown, K

1999-01-01

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Biophysical analysis of radiation-induced chromatid and chromosome aberrations at low doses and dose rates  

International Nuclear Information System (INIS)

In the present study, two sets of experimental data have been analyzed: (i) in vitro and in vivo exposures of human blood lymphocytes to alpha particles from short-lived radon decay products, and (ii) in vitro irradiation of rat hepatocytes with gamma radiation (with and without pre-irradiation). The biophysical multi-stage model for radiation-induced chromosomal damage used in these analyses is derived from earlier models for radiation-induced transformation and liver carcinogenesis. (author)

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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

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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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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 Mousespleen after a low-dose irration  

Science.gov (United States)

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

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

24

Investigation of the low-dose ? -irradiation effect on the spontaneous and high-dose radiation-induced level of cytogenetic damage in mouse bone marrow cells in vivo  

International Nuclear Information System (INIS)

Full text: Our investigation was aimed at studying the effect of low-dose gamma-irradiation of mice on the spontaneous and high-dose radiation-induced level of cytogenetic damage during aging of animals. SHK male mice were used in all the experiments. At the moment of low-dose adapting gamma-irradiation (0.1 or 0.2 Gy with a dose rate of 0.125 Gy/min) animals were 2 months old. In the experiments using standard adaptive response protocol the challenge dose was 1.5 Gy (1 Gy/min). Frequency of micronucleated polychromatic erythrocytes mouse bone marrow was assessed at various times of animal life span using the micronucleus test. The results of our study demonstrate that: 1) a single low-dose of gamma-radiation induces the cytogenetic adaptive response in mouse bone marrow cells which persists for up to 12 months after irradiation; 2) young and aged mice are equal in ability to manifest low-dose radiation-induced adaptive response, i.e. ability in inducing adaptive response does not depend on the age of animals at the moment of adapting irradiation; 3) single low-dose g-irradiation decreases the cytogenetic damage to a level below the spontaneous rate at the end of lifetime (20 months) of animals. The mechanisms underlying adaptive response not only protect from cytogenetic damage induced by high-dose irradiation but also may play a role in spontaneous mutagenesis during aging

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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.

26

Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells.  

Science.gov (United States)

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of gamma-rays (0.01 Gy) 4 or 20 hrs prior to high dose gamma-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose gamma-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose gamma-ray irradiation to high dose gamma-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis. PMID:18975154

Kim, J H; Hyun, S J; Yoon, M Y; Ji, Y H; Cho, C K; Yoo, S Y

1997-06-01

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Research of prediction method of radiation induced leakage current at low dose rate irradiation in space environment  

International Nuclear Information System (INIS)

A radiation response model of total dose effect for CMOS devices in a space environment is presented to predict the radiation-induced leakage current. Total effects for CC4007RH and C4007B devices at different dose rates irradiation of ? rays were calculated by using the established model. So long as total dose irradiation test and post-irradiation annealing test at room temperature were carried out by choosing one dose rate at random, total dose irradiation effects at other dose rates can be predicted by using the established models. Finally, the prediction results of 10-4-10-2 rad·s-1 low dose rate irradiation for CC4007RH and C4007B devices in space environment were presented. (authors)

28

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)

29

Low dose radiation induced hormesis and its mechanism of free radicals  

International Nuclear Information System (INIS)

Objective: To investigate whether the supernatant (the stimulating fluid) centrifuged from myeloid cells suspension after low dose radiation in vitro can produce hormesis on the normal or radiation damage cells. The mechanism of free radical was probed. Methods: Mouse myeloid cell suspension was irradiated respectively by 0, 2 and 5 Gy, and cultured in vitro. MTT method was used to measure the reproductive activity of cells. Meanwhile, Cytochrome C reduction method was used to determine the concentration of O2-. Lastly, the concentration of O2- was decreased or increased by adding DPI or PMA, and the effect of such changes on 'the stimulating fluid' was observed. Results: Co-cultured with 'the stimulating fluid', the reproductive activity of the myeloid cells after large dose radiation or the normal myeloid cells were enhanced. Decreasing the concentration of O2-; may degrade the proliferation of the cells after radiation damage; while increasing it may lead to the opposite result. Conclusions: The stimulating fluid can enhance the proliferation of the myeloid cells after radiation damage and also the normal ones. The mechanism of above-mentioned phenomena might be related with the changes of O2- concentration. (authors)

30

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

31

Low dose radiation induced products in mouse spleen and their biological activity  

International Nuclear Information System (INIS)

Low dose radiation (LDR) induced products were extracted from mouse spleen and its biological activity was preliminarily detected. The mouse spleen cells were sonicated and the induced products in the lysate were obtained with centrifugation. The method of radioactive isotope incorporation was used and the DPM as an index for evaluating the biological activity of the induced products. To investigate the possible influence of variant factors on the activity of the products, tests were carried out under different conditions: different time for extraction, different radiation doses, different volumes of extracted products for stimulation, and different radiation modes. Results showed that the transformation ability of mouse spleen cells was significantly enhanced after stimulation of these cells with LDR-induced products. And the above-mentioned changes in experimental conditions could influence the activity of the induced products to different extents. It was indicated from this study that the active LDR-induced products could be extracted 2-16 h after irradiation with a dose range from 5 to 15 cGy, and the effective composition of the induced products may be belonged to newly synthesized protein

32

Low?dose radiation?induced apoptosis in human leukemia K562 cells through mitochondrial pathways.  

Science.gov (United States)

High?dose total body irradiation (TBI) has an established role as preparative regimen for bone?marrow transplantation in the treatment of chronic myelogenous leukemia (CML), but this regimen still has a relatively high rate of acute and late toxicity. Low?dose radiation (LDR) induces apoptosis of tumor cells and has numerous beneficial effects on normal tissues, including radiation homeostasis and adaptive response. Based on the previous evidence, in the present study, K562 cells were exposed to LDR, high?dose radiation (HDR), and LDR in combination with HDR to investigate the possible mechanism of the apoptotic effect and hypersensitivity induced by LDR. The apoptotic rate increased in all radiation groups in a time?dependent manner. An upregulation of Bax protein expression and a downregulation of Bcl?xl in a dose?dependent manner in human leukemia K562 cells was observed. However, the expression of p53 protein did not change in all of the radiation cell groups. The mitochondrial membrane potential (??m) in K562 cells decreased in all of the radiation cell groups in a dose?dependent manner. Furthermore, the decrease of ??m was enhanced in the LDR/HDR group compared with that in the LDR or HDR groups. The activity of caspase?3 was enhanced in all of the radiation groups. In the LDR/HDR group, the activity of caspase?3 was higher than that in the HDR or LDR groups. The present study provided preliminary experimental evidence of LDR being beneficial in combination with TBI in the treatment of CML. PMID:25060925

Xin, Yong; Zhang, Hai-Bin; Tang, Tian-You; Liu, Gui-Hong; Wang, Jian-She; Jiang, Guan; Zhang, Long-Zhen

2014-09-01

33

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

Science.gov (United States)

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

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

2014-05-01

34

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

35

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

36

Low Doses of Radiation are Protective In Vitro and In Vivo: Evolutionary Origins  

OpenAIRE

Research reports using cells from bacteria, yeast, alga, nematodes, fish, plants, insects, amphibians, birds and mammals, including wild deer, rodents or humans show non-linear radio-adaptive processes in response to low doses of low LET radiation. Low doses increased cellular DNA double-strand break repair capacity, reduced the risk of cell death, reduced radiation or chemically-induced chromosomal aberrations and mutations, and reduced spontaneous or radiation-induced malignant transformati...

Mitchel, R. E. J.

2006-01-01

37

Low dose radiation adaptive protection to control neurodegenerative diseases.  

Science.gov (United States)

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

Doss, Mohan

2014-05-01

38

Halofuginone Mediated Protection against Radiation-Induced Leg Contracture  

OpenAIRE

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

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

2009-01-01

39

Radiation-induced reactions of the lungs: Hormesis, guideline on radiation protection in medicine  

International Nuclear Information System (INIS)

The proceedings contain almost all full papers presented at the 34th annual meeting of the Vereinigung Deutscher Strahlenschutzaerzte e.V., held in Dresden from May 3-5, 1993. There were three main topics selected for this meeting: radiation-induced reactions in the lungs, radiation hormesis, and the German regulatory guide for Radiation Protection in Medicine, as amended in mid-1993. The papers discuss the pathogenesis of radiation-induced lesions in the lungs, results of animal experiments applying partial and whole-lung irradiation, clinical experience and diagnostics, lung function impairment, and X-ray signs of the thorax after radiation exposure of the respiratory organ. The two papers discussing the effects of low doses of ionizing radiation, radiation hormesis and adaptive response in biological systems have been presented by experts in this matter which give a picture of the current scientific knowledge and of the items of controversy. (orig./MG)

40

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

Science.gov (United States)

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

Lin, Z W

2014-04-01

41

Imaging analysis of the mechanisms of low dose radiation-induced DNA double-strand break repair  

International Nuclear Information System (INIS)

Mechanism of DNA double-strand break (DSB) induced by low-dose radiation (X-rays or micro-beams of heavy-particles) and its repair processes (radiation adaptive responses) were studied using immunity-specific image analysis based on focus which is formed by the repaired enzyme at the site of DSB as a marker. Background due to DSB formation during DNA reproduction was eliminated using an antibody specific to phosphor-oxidized site of repaired DNA. The author could analyze quantitatively DSB formation and its repair processes induced by low-dose of X-rays down to 0.1 Gy. In the case of heavy-ion experiment, it was found that DSB repaired enzymes were localized along the path of heavy particles and some giant focus still existed even at 8 hours after the irradiation while the focus formed by X-rays disappeared. The paper concludes that imaging analysis with focus formation of repaired protein from DSB as a marker can be used as a biological dosimeter. (S. Ohno)

42

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...

43

Halofuginone mediated protection against radiation-induced leg contracture.  

Science.gov (United States)

Fibrosis of normal tissues often accompanies radiation treatment of cancer. Activation of the transforming growth factor-beta (TGF-beta) signaling pathway is thought to play a major role in radiation-induced fibrosis and has prompted the development and assessment of low molecular weight inhibitors of the pathway. Previous studies with halofuginone have shown it to inhibit TGF-beta signaling in vitro and protect mice from radiation-induced leg contraction (a model for soft tissue fibrosis). The current study confirms these findings for HaCaT cells stimulated with exogenous TGF-beta treatment. Reducing the halifuginone treatment from 7 days/week (used previously) to 5 days/week post-radiation exposure provided significant protection against radiation-induced leg contraction in mice 3 and 4 months post-radiation treatment. Halofuginone treatment was shown to attenuate TGF-beta signaling molecules taken from irradiated skin including TGF-betaRII, pSmad3, Smad7, and TSP1. The latter, TSP1, a co-activator of TGF-beta may serve as a suitable biomarker for monitoring the efficacy of halofuginone should it be evaluated in a clinical setting for protection against radiation-induced fibrosis. PMID:19578745

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

2009-08-01

44

Adaptive Response to ionizing Radiation Induced by Low Doses of Gamma Rays in Human Lymphoblastoid Cell Lines  

International Nuclear Information System (INIS)

When cells are exposed to low doses of a mutagenic or clastogenic agents, they often become less sensitive to the effects of a higher does administered subsequently. Such adaptive responses were first described in Escherichia coli and mammalian cells to low doses of an alkylating agent. Since most of the studies have been carried out with human lymphocytes, it is urgently necessary to study this effect in different cellular systems. Its relation with inherent cellular radiosensitivity and underlying mechanism also remain to be answered. In this study, adaptive response by 1 cGy of gamma rays was investigated in three human lymphoblastoid cell lines which were derived from ataxia telangiectasia homozygote, ataxia telangiectasia heterozygote, and normal individual. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher does (50 cGy). The expression of this adaptive response was similar among three cell lines despite of their different radiosensitivity. When 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the tested cell lines. Therefore it is suggested that the adaptive response can be observed in human lymphoblastoid cell lines. Which was first documented through this study. The efirst documented through this study. The expression of adaptive response was similar among the cell lines regardless of their radiosensitivity. The elimination of the adaptive response by 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromosomal repair mechanism

45

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

46

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)

47

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)

48

Low-Dose Radiation and Genotoxic Chemicals Can Protect Against Stochastic Biological Effects  

OpenAIRE

A protective apoptosis-mediated (PAM) process that is turned on in mammalian cells by low-dose photon (X and ?) radiation and appears to also be turned on by the genotoxic chemical ethylene oxide is discussed. Because of the PAM process, exposure to low-dose photon radiation (and possibly also some genotoxic chemicals) can lead to a reduction in the risk of stochastic effects such as problematic mutations, neoplastic transformation (an early step in cancer occurrence), and cancer. These find...

Scott, Bobby R.; Walker, Dale M.; Walker, Vernon E.

2004-01-01

49

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

International Nuclear Information System (INIS)

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

50

Protection against Radiation Induced Performance Decrement in Mice  

Directory of Open Access Journals (Sweden)

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

S. K. Mukherjee

2013-04-01

51

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

Fornace, Jr, A J

2007-03-03

52

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

2014-10-17

53

Inducible HSP70 Protects Radiation-Induced Salivary Gland Damage  

International Nuclear Information System (INIS)

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

54

Inducible HSP70 Protects Radiation-Induced Salivary Gland Damage  

Energy Technology Data Exchange (ETDEWEB)

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

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

2006-07-01

55

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)

56

Radiation protection and environment day the low doses in everyday life  

International Nuclear Information System (INIS)

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

57

Protective effects of Paeonia japonica against radiation-induced damage  

Energy Technology Data Exchange (ETDEWEB)

We investigated the effect of Paeonia Japonica (PJ) on radiation-induced oxidative damage to macromolecules in vitro and in vivo. The PJ reduced the Tail Moment (TM), which was a marker of DNA strand break in Single-Cell Gel Electrophoresis (SCGE; comet assay) in the human peripheral blood lymphocytes. Lipid peroxidation in the liver of the ICR mouse, measured as MalonDiAldehyde (MDA), was also reduced by PJ administration. Ethanol fraction of PJ was more effective than polysaccharide fraction of that on reduction of TM in SCGE and lipid peroxidation. Also, their activities to scavenge DPPH radicals and hydroxyl radicals were observed in vitro, and the activities were due to its ethanol fraction. It is plausible that scavenging of free radicals by PJ extract may have played an important role in providing the protection against the radiation-induced damage. These results indicated that Paeonia Japonica might be a useful radioprotector, especially since it is a relatively nontoxic natural product.

Oh, Heon; Park, Hae Ran; Jeong, Ill Yun; Jo, Sung Kee [KAERI, Daejeon (Korea, Republic of); Kim, Sung Ho [Chonnam National Univ., Gwangju (Korea, Republic of)

2002-09-15

58

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

International Nuclear Information System (INIS)

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

59

Radiation induced diffusion as a method to protect surface  

International Nuclear Information System (INIS)

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

60

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

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 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.

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

61

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

62

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

International Nuclear Information System (INIS)

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 fomic 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)

63

Low doses of ionizing radiation incurred at low dose rates  

International Nuclear Information System (INIS)

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

64

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

Directory of Open Access Journals (Sweden)

Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

Olga Loseva

2014-07-01

65

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

66

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

International Nuclear Information System (INIS)

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

67

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

68

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

69

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

International Nuclear Information System (INIS)

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

70

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)

71

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

72

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

73

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

Science.gov (United States)

An experiment was conducted to evaluate the role of different lipotropes in modulating immunity and biochemical plasticity under conditions of sublethal low-dose pesticide-induced stress in fish. Labeo rohita fish fingerlings were divided in two sets with one set of fish continuously exposed to low-dose endosulfan (1/10th of 96-h LC50) for 21 days, the other was unexposed, and both sets of fish were fed with practical diets supplemented with either 2 % lecithin, 0.5 % betaine, or 0.1 % choline and compared against unsupplemented diet. Low-dose endosulfan exposure had adverse effects (P?rohita fingerlings even when continuously exposed to low-dose endosulfan. PMID:23666764

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

2014-01-01

74

Low-dose radiation induces adaptive response in normal cells, but not in tumor cells. In vitro and in vivo studies  

International Nuclear Information System (INIS)

Biological effects of low-dose radiation (LDR) are distinguishable from those of high-dose radiation. Hormetic and adaptive responses are such two examples. However, whether adaptive response could be induced in tumor cells by LDR, especially under in vivo condition, remains elusive, and was systemically investigated in the present study. Four tumor cell lines: two human leukemia cell lines (erythroleukemia cell line K562, and acute promyelocytic leukemia cell line HL60), and two human solid tumor cell lines (lung carcinoma cell line NCI-H446 and glioma cell line U251), along with one normal cell line (human fibroblast cells, MRC-5), were irradiated with LDR at 75 mGy of X-rays as D1 and then 4 Gy of X-rays as D2 (i.e.: D1+D2) or only 4 Gy of X-rays (D2 alone). Three tumor-bearing animal models were also used to further define whether LDR induces adaptive response in tumor cells in vivo. Adaptive response was observed only in normal cell line, but not in four tumor cell lines, in response to LDR, showing a resistance to subsequent D2-induced cell growth inhibition. Three tumor-bearing mouse models with U251, NCI-H446 or S180 tumor cells were used to confirm that pre-exposure of tumor-bearing mice to D1 did not induce the resistance of tumor cells in vivo to D2-induced tumor growth inhibition. Furthermore, a higher apoptotic effect, along with higher expression of apoptosis-related genes P53 and Bax and lower expression of anti-apoptosis gene Bcl-2, was found in tumor -apoptosis gene Bcl-2, was found in tumor cells of the tumor-bearing mice exposed to D1+D2 than those in the tumor cells of the tumor-bearing mice exposed to D2 alone. These results suggest that LDR does not induce adaptive response in the tumor cells under both in vitro and in vivo conditions, which is a very important, clinic-relevant phenomenon. (author)

75

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

Directory of Open Access Journals (Sweden)

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

Meckling Kelly A

2005-03-01

76

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)

77

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

OpenAIRE

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

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

2013-01-01

78

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

79

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

OpenAIRE

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 accumul...

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

2011-01-01

80

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

81

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-ÎşB-Mediated HER2 Overexpression in Radiation-Adaptive Resistance. Another is on NF-ÎşB-mediated adaptive resistance to ionizing radiation.

Jian Li

2012-11-07

82

WR1065 protection against radiation-induced mutations at the HGPRT locus in V79 cells  

International Nuclear Information System (INIS)

WR1065 protects against radiation-induced cell killing and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster lung fibroblast cells. At a concentration of 4 mM, WR1065 effectively protected against cell death only if present during irradiation, e.g., a dose modification factor (DMF) of 1.9. No protective effect was observed if WR1065 was added within 5 min after irradiation or 3 h later, e.g., DMFs of 1.0 and 1.1, respectively. In contrast, WR1065 effectively reduced radiation-induced mutations regardless of when it was administered. Following a dose of 1000 rad of /sup 60/Co ? rays, the mutation frequencies observed per 10/sup 6/ survivors were 77+-8, 27+-6, 42+-7, and 42+-7 for radiation only, and WR1065 present during, immediately after, or 3 h after irradiation. These data suggest that although a segment of radiation induced damage leading to reproductive death cannot be modulated through the postirradiation action of WR1065, processes leading to the fixation of gross genetic damage and mutation induction in surviving cells can be effectively altered and interfered with leading to a marked reduction in mutation frequency

83

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

84

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

OpenAIRE

Background: The impact of cadmium (Cd) on male infertility may be related to the interaction with metal-binding proteins known as metallothioneins (Mts). Trace elements like zinc (Zn) have protective effects on testicular damage induced by Cd. Objective: We determined the effect of Zn and low-dose Cd pre-treatment on the expression of Mt1 and Mt2 genes on testicular Sertoli cells. Materials and Methods: The cultured TM4 mouse sertoli cells were treated with 50 ?M ZnSO4 (Zn pre-treated group;...

Fatemeh Kheradmand; Issa Nourmohammadi; Mohamad Amin Ahmadi-Faghih; Mohsen Firoozrai; Mohammad Hossein Modarressi

2013-01-01

85

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.

86

Protection by pantothenol and ?-carotene against liver damage produced by low-dose ? radiation  

International Nuclear Information System (INIS)

Rats were exposed to a total dose of 0.75 Gy of ? radiation from a 60Co source, receiving three doses of 0.25 Gy at weekly intervals. During two days before each irradiation, the animals received daily intragastric doses of 26 mg pantothenol or 15 mg ?-carotene per kg body mass. The animals were killed after the third irradiation session, and their blood and livers were analyzed. As found previously, in livers of animals not supplied with either pantothenol or ?-carotene and killed one hour after the irradiation, a large accumulation of lipid peroxidation products, as conjugated dienes, ketotrienes and thiobarbituric acid-reactive substances, could be observed. The contents of CoA, pantothenic acid, total phospholipids, total glutathione and GSH/GSSG ratio were considerably decreased, whereas the NAD/NADH ratio was increased. All these effects were alleviated in animals supplied with beta-carotene and were completely abolished in animals supplied with pantothenol. In the present paper, we extended our observations of irradiation effects over a period of up to 7 days after the last irradiation session. We found that most of these changes, with the exception of GSH/GSSG ratio, disappeared spontaneously, whereas supplementation with beta-carotene shortened the time required for the normalization of biochemical parameters. In addition, we found that the activities of glutathione reductase, glutathione peroxidase, catalase and NADP-dependent malate (decarboxyse and NADP-dependent malate (decarboxylating) dehydrogenase ('malic enzyme') in liver were also significantly decreased one hour after irradiation but returned to the normal level within 7 days. Little or no decrease in these activities, already 1 h after the irradiation, could be seen in animals supplemented with either beta-carotene or pantothenol. It is concluded that pantothenol is an excellent radioprotective agent against low-dose ? radiation. (author)

87

Low Doses of Carbon Monoxide Protect Against Experimental Focal Brain Ischemia  

OpenAIRE

Carbon monoxide (CO) is associated with central nervous system toxicity. However, evidence also indicates that CO can be protective, depending on its concentration. To determine if CO can be neuroprotective after ischemic brain injury, we subjected mice to transient middle cerebral artery occlusion and exposed them to different concentrations of CO. We found that in mice, low CO levels protected the brain from injury following 90-min transient focal ischemia and 48 h of reperfusion. When inha...

Zeynalov, Emil; Dore?, Sylvain

2009-01-01

88

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

International Nuclear Information System (INIS)

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

89

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

International Nuclear Information System (INIS)

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

90

Protection by dinitrophenol against radiation-induced hemolysis in hen erythrocytes  

International Nuclear Information System (INIS)

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

91

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

International Nuclear Information System (INIS)

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

92

Prunus armeniaca L (apricot) protects rat testes from detrimental effects of low-dose x-rays.  

Science.gov (United States)

Exposure to low x-ray doses damages the spermatozoa, mainly by late-onset (ie, after 3 months) oxidative stress. Antioxidants ameliorate oxidation and prevent tissue damage. Prunus armeniaca L (apricot), rich in carotenoids and vitamins, is a potent natural antioxidant. We hypothesized that an apricot-rich diet might ameliorate the detrimental effects of low-dose x-rays on testis tissue. A 20% apricot diet was composed isoenergetically to the regular rodent diet. The total phenolic content, reducing power, and antioxidant capacity of both diets were determined. Sprague-Dawley rats received apricot-rich diets before and after x-ray exposure. Regular diets were given to controls. Rats were exposed to 0.2 Gy x-rays at the eighth week and were euthanized at the 20th postexposure week. Testicular oxidative status was determined by tissue thiobarbituric acid-reactive substances, reduced glutathione, superoxide dismutase, and catalase activities. For histologic evaluation, qualitative and quantitative microscopic determinations were performed, and Leydig and Sertoli cell counts and Johnsen scores were measured. The control diet group had significant testicular oxidative stress and mild tissue deterioration. Leydig and Sertoli cell counts, tubule diameters, and Johnsen scores were significantly decreased in the exposure groups. Apricot-rich diet significantly ameliorated the oxidative status and prevented the damage in tubular histology. The protective effects were prominent when the diet was maintained throughout the time course and were partially protected when the diet was initiated after exposure. The natural antioxidant activity of apricot ameliorates the delayed detrimental effects of low-dose irradiation on testis tissue. The high total antioxidant capacity of the apricot deserves further investigation. PMID:20417881

Ugras, Murat Y; Kurus, Meltem; Ates, Burhan; Soylemez, Haluk; Otlu, Ali; Yilmaz, Ismet

2010-03-01

93

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

Directory of Open Access Journals (Sweden)

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

Fatemeh Kheradmand

2013-06-01

94

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?5×11-88) or eight (Fla?8×11-88) genital HPV types. Immunogenicity and bioactivity of Fla-L2 constructs were assessed using an in vitro neutralization and cell-based TLR-5 binding assay, respectively. Efficacy was evaluated following active immunization of rabbits or mice administered 3 intramuscular doses of Fla-L2 recombinants without exogenous adjuvant, followed by challenge. In addition, passive immunization studies of naďve rabbits with serial dilutions of pooled immune sera were used to determine End-Point Protection Titers (EPPT) for each formulation against a broader spectrum of HPV quasivirions. Efficacy was assessed for up to 10 weeks on the basis of wart volume induced following challenge and results compared to licensed L1-VLP vaccines (Gardasil and Cervarix). Following active immunization at doses as low as 1 ?g, Fla-L2 fusions afforded complete protection against infection (mice) and disease (rabbits) following either homologous or heterologous HPV challenge. Passive immunization with anti-L2 immune sera discriminated between the different vaccine candidates under evaluation, demonstrated the protective role of antibody and suggested the superiority of this oligomeric L2-TLR5 agonist fusion approach compared to L1-based vaccines in its ability to cross-protect against non-vaccine HPV types. PMID:24780250

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

95

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

Directory of Open Access Journals (Sweden)

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

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

2008-05-01

96

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

Scott, Bobby, R., Ph.D.

2003-06-27

97

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)

98

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

Science.gov (United States)

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-alpha, IL-1beta and IL-6) and lactate dehydrogenase were elevated in irradiated groups as compared to control. PPE treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Furthermore, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in irradiated animals, while PPE reversed these effects. PPE supplementation reduced oxidative damage in the ileal tissues, probably by a mechanism that is associated with the decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms. Adjuvant therapy of PPE may have a potential to support a successful radiotherapy by protecting against radiation-induced enteritis. PMID:19478462

Toklu, Hale Z; Sehirli, Ozer; Ozyurt, Hazan; Mayada?li, A Alpaslan; Ek?io?lu-Demiralp, Emel; Cetinel, Sule; Sahin, Hülya; Ye?en, Berrak C; Ulusoylu Dumlu, Melek; Gökmen, Vural; Sener, Göksel

2009-07-01

99

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)

100

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

101

Low dose fenoterol aerosol protects against histamine-induced bronchoconstriction in mild asthmatics: a dose response study.  

Science.gov (United States)

Sixteen subjects with mild stable asthma participated in a randomized double blind study on the effects of low dose fenoterol against histamine induced bronchoconstriction. Fenoterol aerosol at concentrations of 10, 50 and 200 micrograms and placebo were delivered at random through a metered dose inhaler as a single dose 30 min before histamine challenges on four separate occasions. Compared to placebo a fenoterol dose of 10 micrograms provided significant bronchodilatation (sRaw [s.d.] 8.3 [2.73] vs 6.3 [1.74] cm H2O* s [P less than 0.05]) and protection (PC100 sRaw [s.e.m.] 0.72 (1.31) vs 1.45 (1.39) mg/ml). The bronchodilatory and protective actions of fenoterol were more pronounced after the inhalation of 200 micrograms (P less than 0.05) with no difference between 10 and 50 micrograms fenoterol aerosol. The magnitude of bronchodilatation and protection was not correlated (r = 0.15). The results from this acute study may suggest that fenoterol at doses up to 20 times lower than routinely recommended may be an effective treatment in mild asthmatics. PMID:1504891

Magnussen, H; Rabe, K F

1992-07-01

102

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

International Nuclear Information System (INIS)

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

103

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 < 0.05) changes in levels of catalase (12.57?±?2.58 to 30.24?±?4.89 units), glutathione peroxidase (6.23?±?2.95 to 13.26?±?1.36 µg of reduced glutathione consumed/min/mg protein), glutathione reductase (0.25?±?5.6 to 11.65?±?2.83 pM NADPH consumed/min/mg protein), and superoxide dismutase (11.74?±?0.2 to 16.09?±?3.47 SOD U/mg of protein) activity at 30th day. Silymarin pretreated irradiated group exhibited increased proliferation in erythrocyte count (1.76?±?0.41 × 10(6) to 9.25?±?0.24 × 10(6) ), hemoglobin (2.15?±?0.48g/dL to 14.77?±?0.25g/dL), hematocrit (4.55?±?0.24% to 37.22?±?0.21%), and total leucocyte count (1.4?±?0.15 × 10(6) to 8.31?±?0.47 × 10(6) ) as compared with radiation control group on 15th day. An increase in CD4:CD8 ratio was witnessed (0.2-1%) at 30th day time interval using flow cytometry. Silymarin also countered radiation-induced decrease (p < 0.05) in regulatory T-cells (Tregs ) (11.23% in radiation group at 7th day versus 0.1% in pretreated silymarin irradiated group at 15th day). The results of this study indicate that flavonolignan-silymarin protects enzymatic, hematological, and immune system against ?-radiation-induced toxicity and might prove useful in management of nuclear and radiological emergencies. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014. PMID:25411116

Adhikari, Manish; Arora, Rajesh

2014-11-20

104

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.

105

Lack of Protection following Passive Transfer of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies  

Science.gov (United States)

Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred highly functional non-neutralizing polyclonal antibodies, purified from an EC, to assess the potential impact of polyclonal non-neutralizing antibodies on a stringent SHIV-SF162P3 challenge in rhesus monkeys. Passive transfer of a low-dose of ADCC inducing antibodies did not protect from infection following SHIV-SF162P3 challenge. Passively administered antibody titers and gp120-specific, but not gp41-specific, ADCC and antibody induced phagocytosis (ADCP) were detected in the majority of the monkeys, but did not correlate with post infection viral control. Thus these data raise the possibility that gp120-specific ADCC activity alone may not be sufficient to control viremia post infection but that other specificities or Fc-effector profiles, alone or in combination, may have an impact on viral control and should be tested in future passive transfer experiments. PMID:24820481

Dugast, Anne-Sophie; Chan, Ying; Hoffner, Michelle; Licht, Anna; Nkolola, Joseph; Li, Hualin; Streeck, Hendrik; Suscovich, Todd J.; Ghebremichael, Musie; Ackerman, Margaret E.; Barouch, Dan H.; Alter, Galit

2014-01-01

106

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

Science.gov (United States)

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

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

2011-04-25

107

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

International Nuclear Information System (INIS)

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

108

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

Directory of Open Access Journals (Sweden)

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

Omaima Soliman Eissa* and Nehal Aly Moustafa

2007-06-01

109

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

110

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

International Nuclear Information System (INIS)

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

111

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)

112

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)

113

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

114

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; Cerne, Darko; Marc, Janja; Drevenšek, Gorazd; Sabovi?, Mišo

2014-11-15

115

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

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

116

Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans.  

Science.gov (United States)

Cutaneous immunity, which is a key defence against the development of skin cancers, is suppressed by even small doses of ultraviolet (UV) radiation. Preventing this UV-induced immunosuppression may therefore reduce the incidence of skin cancer. Nicotinamide (vitamin B3) has immune-protective and cancer-preventive effects against UV radiation in mice, and we have shown previously that topical nicotinamide is immune protective in humans. Using the Mantoux model of skin immunity in healthy volunteers, we compared oral nicotinamide to placebo (both administered for 1 week) in a randomized, double-blinded, crossover design against the effects of solar-simulated ultraviolet (ssUV) radiation on delayed-type hypersensitivity to tuberculin purified protein derivative. Discrete areas of the back were irradiated with low doses of ssUV daily for three consecutive days. Immunosuppression, calculated as the difference in Mantoux-induced erythema of irradiated sites compared with unirradiated control sites, was determined in volunteers taking oral nicotinamide and placebo. Significant immunosuppression occurred in an UV dose-dependent manner in the presence of placebo. Oral nicotinamide, at doses of either 1500 or 500 mg daily, was well tolerated and significantly reduced UV immunosuppression with no immune effects in unirradiated skin. Oral nicotinamide is safe and inexpensive and looks promising as a chemopreventive supplement for reducing the immunosuppressive effects of sunlight. PMID:19028705

Yiasemides, Eleni; Sivapirabu, Geetha; Halliday, Gary M; Park, Joohong; Damian, Diona L

2009-01-01

117

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

Energy Technology Data Exchange (ETDEWEB)

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

NONE

2007-07-01

118

Grape seed extract Vitis vinifera protects against radiation-induced oxidative damage and metabolic disorders in rats.  

Science.gov (United States)

Whole body exposure to ionizing radiation induces the formation of reactive oxygen species (ROS) in different tissues provoking oxidative damage, organ dysfunction and metabolic disturbances. The present study was designed to determine the possible protective effect of grape seed extract (GSE), rich in proanthocyanidins against gamma-radiation-induced oxidative stress in heart and pancreas tissues associated with serum metabolic disturbances. Irradiated rats were whole body exposed to 5 Gy gamma-radiation. GSE-treated irradiated rats received 100 mg GSE/kg/day, by gavage, for 14 days before irradiation. The animals were killed on days 1, 14 and 28 after irradiation. Significant decreases of SOD, CAT and GSH-Px activities associated with significant increases of TBARS levels were recorded in both tissues after irradiation. GSE administration pre-irradiation significantly attenuated the radiation-induced oxidative stress in heart tissues which was substantiated by a significant amelioration of serum LDH, CPK and AST activities. GSE treatment also attenuated the oxidative stress in pancreas tissues which was associated with a significant improvement in radiation-induced hyperglycemia and hyperinsulinemia. In conclusion, the present data demonstrate that GSE would protect the heart and pancreas tissues from oxidative damage induced by ionizing irradiation. PMID:19003940

Saada, Helen N; Said, Ussama Z; Meky, Nefissa H; Abd El Azime, Afrag S

2009-03-01

119

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

120

Protective effect of saccharides on radiation-induced hemolysis of rabbit erythrocytes  

International Nuclear Information System (INIS)

The influence of radiation on the hemolysis of the extracted rabbit blood induced by cooling and the effects of glucose, sucrose, and galactose on the influence were examined. The degree of the hemolysis of the blood, which was stored in the cold room kept at a temperature of 70C, increased in proportion to the increase of the days during which the blood was stored, and the hemolysis was evident after 14 days. When the extracted blood had been irradiated by the cobalt radiation at intensities more than 2,000 R, the hemolysis of the blood stored in the cold room was considerably accelerated. The cooling- and radiation-induced hemolysis was reduced by the addition of an isotonic glucose, sucrose, or galactose solution at concentrations higher than 12.5 volume percent of the irradiated blood. From the results, it was assumed that the membrane of rabbit erythrocyte might be influenced by the radiation at such low intensity as 2,000 R, and that the addition of isotonic glucose solution could protect the blood from the hemolysis induced by cooling and radiation. (author)

121

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

International Nuclear Information System (INIS)

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

122

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

123

Low-Dose Amphotericin B and Murine Dialyzable Spleen Extracts Protect against Systemic Candida Infection in Mice  

Science.gov (United States)

Candida albicans causes opportunistic systemic infections with high mortality (30%–50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used for the treatment of this serious fungal infection. Therefore, alternative treatments are urgently needed. Dialyzable leukocyte extracts have been used successfully to treat patients with mucocutaneous candidiasis, but their effectiveness in systemic candidiasis has not been evaluated. In this study, low-dose AmB (0.1?mg/kg) plus 10?pg of murine dialyzable spleen extracts (mDSE) were tested in a systemic candidiasis mouse model. Survival, tissue fungal burden, kidney damage, kidney cytokines, and serum levels of IL-6 and hepcidin were evaluated. Our results showed that the combined treatment of low-dose AmB plus mDSE improved survival and reduced kidney fungal burden and histopathology; these effects correlated with increased kidney concentration of IFN-? and TGF-?1, decreased levels of TNF-?, IL-6, and IL-10, as well as high levels of systemic IL-6 and hepcidin. Low-dose AmB and mDSE synergized to clear the infectious agent and reduced tissue damage, confirming the efficacy of a low dose of AmB, which might decrease the risk of drug toxicity. Further studies are necessary to explore these findings and its implications in future therapeutic approaches. PMID:24106515

Robledo-Ávila, F.; Pérez-Tapia, M.; Limón-Flores, A.; Pavon, L.; Hernández-Pando, R.; Wong-Baeza, I.; González-González, G.; Tovar, C.; Estrada-Parra, S.; Estrada-García, I.

2013-01-01

124

Esomeprazole for prevention and resolution of upper gastrointestinal symptoms in patients treated with low-dose acetylsalicylic acid for cardiovascular protection: the OBERON trial.  

Science.gov (United States)

Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ?1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P 70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk. PMID:23188121

Scheiman, James M; Herlitz, Johan; Veldhuyzen van Zanten, Sander J; Lanas, Angel; Agewall, Stefan; Nauclér, Emma C; Svedberg, Lars-Erik; Nagy, Péter

2013-03-01

125

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

126

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

127

Protection against Noise-Induced Hearing Loss in Young CBA/J Mice by Low-Dose Kanamycin  

OpenAIRE

Animal studies indicate that a combination of kanamycin (KM) and noise produces a synergistic effect, whereby the threshold shift from the combination is greater than the sum of the shifts caused by either agent alone. Most such studies have focused on adult animals, and it has remained unclear whether younger, presumably more susceptible, animals show an even greater synergistic effect. The present study tested the hypothesis that young CBA/J mice receiving a low dose of KM (300 mg/kg, 2×/...

Fernandez, Elizabeth A.; Ohlemiller, Kevin K.; Gagnon, Patricia M.; Clark, William W.

2010-01-01

128

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.

129

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

Energy Technology Data Exchange (ETDEWEB)

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.

Bauer, G, E-mail: georg.bauer@uniklinik-freiburg.de [Abteilung Virologie, Institut fuer Medizinische Mikrobiologie und Hygiene, Universitaet Freiburg, Freiburg (Germany)

2011-01-01

130

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

International Nuclear Information System (INIS)

Although the protective effect of the polyhydroxylated fullerene derivative C60(OH)n against ionizing radiation is an area of much interest, the mechanisms relating to how polyhydroxylated fullerene derivatives improve mitochondrial dysfunction remain unknown. In order to find new and effective radioprotective agents, we synthesized a new polyhydroxylated fullerene molecule with 24 hydroxyl groups of known positions on C60 and studied its protective effects in mice subjected to irradiation. Mice were pretreated with C60(OH)24 for 2 weeks (daily, 40 mg/kg i. p.), then subjected to a lethal dose of whole body ?-irradiation (from a 60Co source). Survival was observed for 30 days after irradiation. Immune and mitochondrial dysfunction and oxidative damage were analyzed in mice with the same C60(OH)24 pretreatment and irradiation except that the animals were euthanized at day 5 after the irradiation. It was found that 2-week C60(OH)24 pretreatment effectively reduced whole body irradiation-induced mortality without apparent toxicity. C60(OH)24 pretreatment also showed significant protective effects against ionizing-radiation-induced decreases in immune and mitochondrial function and antioxidant defense in the liver and spleen. These results suggest that the polyhydroxylated fullerene derivative C60(OH)24 protects against0(OH)24 protects against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.

131

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

International Nuclear Information System (INIS)

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

132

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

International Nuclear Information System (INIS)

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

133

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

OpenAIRE

Objective?To investigate the protective effects of Sipunculus nudus polysaccharides (SNPS) on rats injured by low-dose irradiation combined with carbon monoxide, benzene and noise. Methods?Fifty SD rats were randomly divided into normal control group, model control group, 70mg/(kg·d) SNPS group (SNPS 70 group), 140mg/(kg·d) SNPS group (SNPS 140 group) and 280mg/(kg·d) SNPS group (SNPS 280 group). SNPS was administrated intragastrically once a day before ? irradiation for 7 days. Model...

He, Ying; Shen, Xian-rong; Jiang, Ding-wen; Liu, Yu-ming; Hou, Deng-yong; Chen, Wei; Li, Ke-xian; Wang, Qing-rong; Mo, Lin-fang; Qian, Tian-tian; Wang, Yan

2012-01-01

134

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

135

Radiation protection of fiber optic materials: Effect of cerium doping on the radiation-induced absorption  

International Nuclear Information System (INIS)

High-numerical-aperature lead silicate and barium crown glass uncald fibers have been doped with cerium to decrease their radiation sensitivity. The radiation-induced optical loss in both the visible and near-infrared in these core materials has been studied as a function of time (10-3--104 sec) after pulsed irradiation and cerium concentration (0--1 wt%). It has been determined that cerium is effective in decreasing the loss at a given time and increasing the decay rate of absorption

136

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

137

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

International Nuclear Information System (INIS)

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

138

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

139

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

140

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

International Nuclear Information System (INIS)

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

141

Polyphenolic fraction of Pilea microphylla (L.) protects Chinese hamster lung fibroblasts against ?-radiation-induced cytotoxicity and genotoxicity.  

Science.gov (United States)

Present study was designed to compare cytoprotective and antigenotoxic activity of the polyphenolic fraction of Pilea microphylla (PM1) with that of its active polyphenolic constituents against ?-radiation in V79 cells. PM1 was standardized with respect to the polyphenols present by RP-HPLC. It was evaluated for its free radical scavenging potential using Fenton reaction-induced DNA damage and lipid peroxidation. Further, PM1 was subjected against ?-radiation-induced cytotoxicity and genotoxicity in V79 cells. PM1 significantly reduced free radical-mediated calf thymus DNA damage and lipid peroxidation. Among the concentrations tested (12.5, 25 and 50 ?g/ml) for radioprotection, PM1 at 25 ?g/ml exhibited maximum protection. Further, when compared with constituent polyphenols viz., rutin, quercetin and chlorogenic acid (concentrations equivalent to that present in PM1-25 ?g/ml), a combination of polyphenols was found most effective in preventing ?-radiation-induced cytotoxicity and genotoxicity. To conclude, radioprotection is possibly a synergistic effect of the phytochemicals present in the herbal extract, rather than any single component. PMID:22196050

Paul, Piya; Bansal, Punit; Nayak, Pawan G; Pannakal, Steve Thomas; Priyadarsini, K I; Unnikrishnan, M K

2012-01-01

142

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

International Nuclear Information System (INIS)

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

143

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)

144

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.

145

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)

146

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

147

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

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

Can DEM?REL

2008-01-01

148

Infrared radiation-induced matrix metalloproteinase in human skin: implications for protection.  

Science.gov (United States)

Human skin is exposed to infrared radiation (IR) from natural and artificial sources. In previous studies, near IR radiation (IRA; 760-1,440 nm) was shown to elicit a retrograde mitochondrial signaling response leading to induction of matrix metalloproteinase-1 (MMP-1) expression. These studies, however, have exclusively employed cultured human skin fibroblasts ex vivo. Here, we have assessed the in vivo relevance of these observations by exposing healthy human skin in vivo to physiologically relevant doses of IRA. Eighty percent of the tested individuals responded to IRA radiation by upregulating of MMP-1 expression. Specifically, IRA irradiation caused increased expression of MMP-1 in the dermis, but not in the epidermis. Raman spectroscopy revealed that IRA radiation also caused a significant decrease in the antioxidant content of human skin. In vitro studies had previously shown that IRA-induced MMP-1 expression was mediated through an oxidative stress response, which originates from the mitochondrial electron transport chain. We now report that incubation of cultured human dermal fibroblasts or treatment of human skin with specific antioxidants prevented IRA radiation-induced MMP-1 expression in vitro and in vivo. Thus, IRA irradiation most likely promotes premature skin aging and topical application of appropriate antioxidants represents an effective photoprotective strategy. PMID:18449210

Schroeder, Peter; Lademann, Juergen; Darvin, Maxim E; Stege, Helger; Marks, Corinna; Bruhnke, Susanne; Krutmann, Jean

2008-10-01

149

The protective effect of low-dose inhaled fenoterol against methacholine and exercise-induced bronchoconstriction in asthma: a dose-response study.  

Science.gov (United States)

We compared in a randomized, double-blind study the protective effect of low doses of fenoterol on the airway response to exercise during cold air breathing and an inhalation challenge with methacholine. In six asymptomatic asthmatic persons (mean age, 20.3 years) exercise and methacholine challenges were performed under control conditions and 15 minutes after the inhalation from a metered-dose inhaler of either placebo or 30, 50, 100, and 200 micrograms fenoterol, resulting in 12 separate study sessions within a 3-week period. Airway response was determined by measuring specific airway resistance (sRaw). Exercise tests were standardized by maintaining a constant respiratory heat exchange, with an average (range) of 1.28 (1.15 to 1.45) kcal/min. Methacholine was inhaled at increasing doses until sRaw had doubled (PD100sRaw). Mean postexertional increase of sRaw (SD) after control conditions, placebo, and 30, 50, 100, and 200 micrograms fenoterol aerosol was 27.8 (6.9), 28.9 (10.0), 7.20 (2.7), 9.33 (3.8), 5.57 (2.3), and 5.28 (1.6) cm H2O.s. Fenoterol aerosol was equally effective at all doses administered, whereas methacholine-induced bronchoconstriction was attenuated in a dose-dependent manner. From these observations we suggest that low-dose fenoterol protects against bronchoconstriction induced by exercise, a naturally occurring stimulus reflecting airway hyperresponsiveness. PMID:1430709

Magnussen, H; Rabe, K F

1992-11-01

150

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

151

The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats  

International Nuclear Information System (INIS)

Purpose: Radiation-induced lung toxicity is a significant dose-limiting side effect of radiotherapy for thoracic tumors. Recombinant human keratinocyte growth factor (rHuKGF) has been shown to be a mitogen for type II pneumocytes. The purpose of this study was to determine whether rHuKGF prevents or ameliorates the severity of late lung damage from fractionated irradiation in a rat model. Methods and materials: Female Fisher 344 rats were irradiated to the right hemithorax with a dose of 40 Gy/5 fractions/5 days. rHuKGF at dose of 5 mg/kg or 15 mg/kg was given via a single intravenous injection 10 min after the last fraction of irradiation. Animals were followed for 6 months after irradiation. Results: The breathing rate increased beginning at 6 weeks and reached a peak at 14 weeks after irradiation. The average breathing frequencies in the irradiated groups with rHuKGF (5 mg/kg and 15 mg/kg) treatment were significantly lower than that in the group receiving radiation without rHuKGF (116.5 ± 1.0 and 115.2 ± 0.8 vs 123.5 ± 1.2 breaths/min, p < 0.01). The severity of lung fibrosis and the level of immunoreactivity of integrin ?v?6, TGF?1, type II TGF? receptor, Smad3, and phosphorylated Smad2/3 were significantly decreased only in the group receiving irradiation plus high-dose rHuKGF treatment compared with irradiation plus vehicle group, suggesting a dose response for the effect of rHuKGF. Conclusions: This study is the first to demonstrate that rHuKGF treatmento demonstrate that rHuKGF treatment immediately after irradiation protects against late radiation-induced pulmonary toxicity. These results suggest that restoration of the integrity of the pulmonary epithelium via rHuKGF stimulation may downregulate the TGF-?-mediated fibrosis pathway. These data also support the use of rHuKGF in a clinical trial designed to prevent radiation-induced lung injury

152

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

DEFF Research Database (Denmark)

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

Börjesson, A; RŘnn, S G

2011-01-01

153

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

154

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

155

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

International Nuclear Information System (INIS)

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

156

Evidence of existence of low dose radiation induced tumor immunity  

International Nuclear Information System (INIS)

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

157

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

158

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)

159

Protection from radiation-induced damage to spermatogenesis by hormone treatment  

International Nuclear Information System (INIS)

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

160

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

International Nuclear Information System (INIS)

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

161

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

162

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

OpenAIRE

Backgrounds: This study deals with evaluation of the histological and some histochemical alterations in rat testes induced by whole body gamma irradiation as well as evaluation of the protective effect of septilin (a herbal preparation) against these effects. Results : The obtained results indicated that doses of (3 Gy and 6 Gy) gamma radiation have testicular toxic effects in rats. The histological lesions observed in the testes varied between vacuolation, swelling, pyknosis and even necrosi...

Omaima Soliman Eissa* and Nehal Aly Moustafa

2007-01-01

163

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

International Nuclear Information System (INIS)

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

164

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

International Nuclear Information System (INIS)

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

165

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

International Nuclear Information System (INIS)

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

166

Protective effect of atorvastatin on radiation-induced endothelial cell injury  

International Nuclear Information System (INIS)

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

167

Low Dose Effects: Testing the Assumptions  

International Nuclear Information System (INIS)

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

168

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

169

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

International Nuclear Information System (INIS)

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

170

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.

171

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

International Nuclear Information System (INIS)

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

172

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

Energy Technology Data Exchange (ETDEWEB)

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

173

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

174

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

175

Protective Effect of Anthocyanins from Lingonberry on Radiation-induced Damages  

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

Shuang-Qi Tian

2012-12-01

176

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

177

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

Directory of Open Access Journals (Sweden)

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

Ying HE

2012-10-01

178

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.

179

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

180

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

Science.gov (United States)

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

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

2015-01-01

181

Ginkgo biloba extract protects against ionizing radiation-induced oxidative organ damage in rats.  

Science.gov (United States)

The present study was designed to determine the possible protective effects of Ginkgo biloba extract (EGb) against oxidative organ damage induced by irradiation (IR). Sprague-Dawley rats were exposed to whole-body IR (800 cGy) after a 15-day pretreatment with either saline or EGb (50 mg/kg/day), intraperitoneally, and treatments were repeated immediately after the IR. Then the rats were decapitated at either 6 h or 72 h after IR, where EGb or saline injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde, glutathione levels, myeloperoxidase activity and collagen contents, while oxidant-induced DNA fragmentation was evaluated in the ileal tissues. All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH)-an indicator of tissue damage and TNF-alpha were assayed in serum samples. In the saline-treated irradiation groups, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity and collagen content were increased in the tissues (p < 0.01-0.001), which were in parallel with the increases in luminol and lucigenin CL values. In the EGb treated-IR groups, all of these oxidant responses were prevented significantly (p < 0.05-0.01). LDH and TNF-alpha levels, which were increased significantly (p < 0.01-0.001) following IR, were decreased (p < 0.05-0.001) with EGb treatment. In conclusion, the present data demonstrate that EGb, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that EGb may have a potential benefit in enhancing the success of radiotherapy. PMID:16412663

Sener, Göksel; Kabasakal, Levent; Atasoy, Beste Melek; Erzik, Can; Velio?lu-O?ünç, Ayliz; Cetinel, Sule; Gedik, Nursal; Ye?en, Berrak C

2006-03-01

182

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

International Nuclear Information System (INIS)

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

183

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

184

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)

185

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 (Ptemperature 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 (ptolerance 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

186

SENSITIVITY TO RADIATION-INDUCED CANCER IN HEMOCHROMATOSIS  

Science.gov (United States)

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

187

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

International Nuclear Information System (INIS)

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

188

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

189

Silymarin Protects Epidermal Keratinocytes from Ultraviolet Radiation-Induced Apoptosis and DNA Damage by Nucleotide Excision Repair Mechanism  

OpenAIRE

Solar ultraviolet (UV) radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. Earlier, we have shown that topical treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum marianum), inhibits photocarcinogenesis in mice; however it is less understood whether chemopreventi...

Katiyar, Santosh K.; Mantena, Sudheer K.; Meeran, Syed M.

2011-01-01

190

Low doses effects and gamma radiations low dose rates  

International Nuclear Information System (INIS)

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

191

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

International Nuclear Information System (INIS)

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

192

The carcinogenic of low dose radiations  

International Nuclear Information System (INIS)

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

193

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

OpenAIRE

The aim of this study was to investigate radioprotective effect of the polysaccharides from soybean meal (SMP) against X-ray radiation-induced damage in mouse spleen lymphocytes. MTT and comet assay were performed to evaluate SMP’s ability to prevent cell death and DNA damage induced by radiation. The results show that, X-ray radiation (30 KV, 10 mA, 8 min (4 Gy)) can significantly increase cell death and DNA fragmentation of mouse spleen lymphocytes. Pretreatment with SMP for 2 h before ra...

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

2011-01-01

194

Renal protection by low dose irbesartan in diabetic nephropathy is paralleled by a reduction of inflammation, not of endoplasmic reticulum stress.  

Science.gov (United States)

Diabetes can disrupt endoplasmic reticulum (ER) homeostasis which leads to ER stress. ER stress-induced renal apoptosis seems to be involved in the development of diabetic nephropathy. The present study was designed to investigate the contribution of reduced ER stress to the beneficial effects of an angiotensin receptor blocker. Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats. After 2weeks animals were treated with 0.7mg/kg/day irbesartan. Blood glucose, blood pressure and protein excretion were assessed. Expression of ER stress markers was measured by real-time PCR. Immunohistochemistry was performed to detect markers of ER stress, renal damage and infiltrating cells. Glomerulosclerosis and apoptosis were evaluated. Diabetic mRen2-transgenic rats developed renal injury with proteinuria, tubulointerstitial cell proliferation as well as glomerulosclerosis and podocyte injury. Moreover, an increase in inflammation, podocyte ER stress and apoptosis was detected. Irbesartan somewhat lowered blood pressure and reduced proteinuria, tubulointerstitial cell proliferation and glomerulosclerosis. Podocyte damage was ameliorated but markers of ER stress (calnexin, grp78) and apoptosis were not reduced by irbesartan. On the other hand, inflammatory cell infiltration in the tubulointerstitium and the glomerulus was significantly attenuated. We conclude that irbesartan reduced renal damage even in a very low dose. The beneficial effects of low dose irbesartan were paralleled by a reduction of blood pressure and inflammation but not by a reduction of ER stress and apoptosis. Thus, sustained endoplasmic reticulum stress in the kidney does not necessarily lead to increased inflammation and tubulointerstitial or glomerular injury. PMID:24418215

Hartner, Andrea; Cordasic, Nada; Klanke, Bernd; Menendez-Castro, Carlos; Veelken, Roland; Schmieder, Roland E; Hilgers, Karl F

2014-04-01

195

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

International Nuclear Information System (INIS)

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

196

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2009-07-01

197

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

198

Radiation biology of low doses  

Energy Technology Data Exchange (ETDEWEB)

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 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.) [German] Derzeit angewandte Risikoabschaetzungen und Standards im Strahlenschutz basieren auf der so genannten 'Linearen-Dosis-Wirkungs-Beziehung ohne Schwellwert' (Linear No-Threshold Hypothesis (LNT)), d.h. einem linearen, proportionalen Zusammenhang zwischen Strahlendosis und Wirkung auf biologische Systeme. Dies setzt voraus, dass jede Dosis, unabhaengig von Hoehe und zeitlichem Auftreten, mit einem gleichen Risikokoeffizienten behaftet ist und dass zudem keine individuellen biologischen Effekte Beruecksichtigung finden. Im vorliegenden Beitrag werden Untersuchungen mit LET-Strahlung (low energy transfer) vorgestellt, die sich mit dem Krebsrisiko fuer einzelne Zellen beschaeftigen. Entsprechend der LNT-Hypothese muesste das Verhaeltnis fuer das Auftreten der moeglichen Effekte: erfolgreiche Reparatur, Zelltod, Mutation mit moeglicher Krebsentstehung, konstant ueber dem Dosenbereich sein. Die vorgestellten Ergebnisse der Untersuchungen weisen fuer die Schaedigung von Zell-DNA durch LET-Strahlung hingegen differenzierte Effekte in Abhaengigkeit von der Dosenapplikation nach. Bei gleicher Gesamt-Dosenhoehe sind bei mehrfacher Bestrahlung mit kleineren Dosen zum Teil erheblich geringere Effekte festzustellen, als bei einfacher Bestrahlung mit der Gesamtdosis. Diese adaptiven Effekte der Zelle sind aus weiteren Untersuchungen bekannt. Die Untersuchungsergebnisse lassen den Schluss zu, dass fuer die betrachtete LET-Strahlung nicht lineare Zusammenhaenge angenommen werden muessen. Entsprechend sollte das Modell der Linearen-Dosis-Wirkungs-Beziehung ohne Schwellwert zumindest in Bezug auf den Bereich kleiner Dosen mit den neueren biologischen Erkenntnissen ueberdacht werden. Unter Einbeziehung weiterer aktueller Forschungsergebnisse waere zudem ein neuer, revidierter, risikoorientierter Ansatz fuer den Strahlenschutz ingesamt denkbar. (orig.)

Mitchel, R.E.J. [AECL, Chalk River Labs., ON (Canada). Radiation Biology and Health Physics Branch

2002-01-01

199

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

200

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

International Nuclear Information System (INIS)

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

201

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)

202

Doe Program—Developing a Scientific Basis for Responses to Low-Dose Exposures: Impact on Dose-Response Relationships  

OpenAIRE

The DOE Low Dose Radiation Research Program focuses on biological mechanisms involved in response to low doses of both low and high-LET radiation (<0.1Gy). This research program represents a merging of new technologies with cutting edge biological techniques associated with genomics. This merger enables observation of radiation-induced cellular and molecular changes previously undetectable. These low-dose responses define mechanisms of interaction of radiation with living systems, and charact...

Brooks, Antone L.; Couch, Lezlie

2006-01-01

203

Suppression of Neoplastic Transformation In Vitro by Low Doses of Low Let Radiation  

OpenAIRE

A major concern of exposure to low doses of radiation is the risk of cancer induction. Epidemiologic data are rarely powerful enough to accurately discriminate this risk at doses <10 cGy. In order to gain insight into events at these low doses, laboratory-based studies of relevant endpoints are required. One such endpoint is radiation-induced neoplastic transformation in vitro. Such studies can provide quantitative dose-response data, as well as insights into underlying cellular and molecular...

Redpath, J. Leslie

2006-01-01

204

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

OpenAIRE

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

Liu, Shu-zheng

2007-01-01

205

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

International Nuclear Information System (INIS)

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

206

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

International Nuclear Information System (INIS)

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

207

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

International Nuclear Information System (INIS)

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

208

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2012-09-15

209

Low doses effects of ionizing radiation on Saccharomyces cerevisiae  

International Nuclear Information System (INIS)

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

210

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)

211

Neomercazole protection against radiation-induced changes in bioamines and testicular metabolism of rats during starvation stress  

International Nuclear Information System (INIS)

Effect of X rays was studied on normally fed and starved rats vis-a-vis neomercazole, a sulfur containing carbimazone as a chemical radioprotector. Levels of 5-hydroxyindoleacetic acid and vinylmandelic acid which were found rising following exposure to X-rays, were significantly curtailed by the treatment with radioprotector in the protected-cum-irradiated rats. Administration of neomercazole offered protection to the testes against radiation injury by increasing alkaline phophatase and cholesterol contents in the testes of drug-treated-cum-irradiated animals. Pretreatment of neomercazole reduced the rate of mortality in the starvation-cum-irradiated animals as compared to the nontreated starvation-cum-irradiated animals. (author)

212

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

International Nuclear Information System (INIS)

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

213

Low Dose Vaccination with Attenuated Francisella tularensis Strain SchuS4 Mutants Protects against Tularemia Independent of the Route of Vaccination  

OpenAIRE

Tularemia, caused by the Gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protec...

Rockx-brouwer, Dedeke; Chong, Audrey; Wehrly, Tara D.; Child, Robert; Crane, Deborah D.; Celli, Jean; Bosio, Catharine M.

2012-01-01

214

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

215

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

International Nuclear Information System (INIS)

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

216

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

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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

217

Low dose radiation and diabetes mellitus  

International Nuclear Information System (INIS)

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

218

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

International Nuclear Information System (INIS)

Possible protective effects of the agonist [D-Trp6]LH-RH and antagonist N-Ac[D-Phe(pCl)/sup 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 hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group give 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist [D-Trp6]LH-RH. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist [D-Trp6]LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions

219

Radiation Induces Acute Alterations in Neuronal Function  

OpenAIRE

Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain ...

Wu, Peter H.; Coultrap, Steven; Pinnix, Chelsea; Davies, Kurtis D.; Tailor, Ramesh; Ang, Kian K.; Browning, Michael D.; Grosshans, David R.

2012-01-01

220

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

International Nuclear Information System (INIS)

Purpose: The ability of heat shock protein 27 (Hsp27) to protect cells from stressful stimuli and its increased levels in tumors resistant to anticancer therapeutics suggest that it may represent a target for sensitization to radiotherapy. In this study, we investigate the protective role of Hsp27 against radiation-induced apoptosis and the effect of its attenuation in highly expressing radioresistant cancer cell lines. Methods and Materials: We examined clonogenic death and the kinetics of apoptotic events in different tumor cell lines overexpressing or underexpressing Hsp27 protein irradiated with photons. The radiosensitive Jurkat cell line, which does not express Hsp27 constitutively or in response to ?-rays, was stably transfected with Hsp27 complementary DNA. Attenuation of Hsp27 expression was accomplished by antisense or RNAi (interfering RNA) strategies in SQ20B head-and-neck squamous carcinoma, PC3 prostate cancer, and U87 glioblastoma radioresistant cells. Results: We measured concentration-dependent protection against the cytotoxic effects of radiation in Jurkat-Hsp27 cells, which led to a 50% decrease in apoptotic cells at 48 hours in the highest expressing cells. Underlying mechanisms leading to radiation resistance involved a significant increase in glutathione levels associated with detoxification of reactive oxygen species, a delay in mitochondrial collapse, and caspase activation. Conversely, attenuation of Hsp27 in SQ20B cells, characterized by thesp27 in SQ20B cells, characterized by their resistance to apoptosis, sensitizes cells to irradiation. This was emphasized by increased apoptosis, decreased glutathione basal level, and clonogenic cell death. Sensitization to irradiation was confirmed in PC3 and U87 radioresistant cells. Conclusion: Hsp27 gene therapy offers a potential adjuvant to radiation-based therapy of resistant tumors

221

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

222

Low doses of the selective adenosine A2A receptor agonist CGS21680 are protective in a rat model of transient cerebral ischemia.  

Science.gov (United States)

Evidence indicate that adenosine A2A receptor subtype is of critical importance in stroke. An overexpression of A2A adenosine receptors occurs at central level on neurons and microglia of ischemic striatum and cortex after focal ischemia. Adenosine A2A receptor subtype is localized not only at central level but also peripherally on blood cells, where it is known to exert antiinflammatory effect. Purpose of the present work was to investigate the putative neuroprotective effect of the adenosine A2A receptor agonist CGS21680 in a rat model of transient medial cerebral artery occlusion (MCAo). Transient cerebral ischemia was induced by 1h occlusion of MCA. CGS21680 (0.01 and 0.1mg/kg, i.p.) was administered starting 4h after ischemia according to a chronic protocol (twice/day for 7 days). CGS21680, at the dose of 0.1mg/kg transiently increased heart frequency but did not modify blood pressure. At the dose of 0.01mg/kg the drug did not modify either heart frequency or blood pressure. Following transient MCAo, CGS21680 at both doses protected from neurological deficit from the first day up to 7 days thereafter. At this time, it has reduced microgliosis, astrogliosis and improved myelin organization in the striatum and cytoarchitecture of the ischemic cortex and striatum. Two days after transient MCAo, CGS21680 has reduced the number of infiltrated granulocytes into the ischemic tissue. Data indicate that CGS21680 systemically administered is protective by immunosuppressive effects. PMID:24457041

Melani, Alessia; Corti, Francesca; Cellai, Lucrezia; Giuliana Vannucchi, Maria; Pedata, Felicita

2014-03-10

223

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)

224

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

225

Application of Bayesian inference to characterize risks associated with low doses of low-LET radiation.  

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Improved risk characterization for stochastic biological effects of low doses of low-LET radiation is important for protecting nuclear workers and the public from harm from radiation exposure. Here we present a Bayesian approach to characterize risks of stochastic effects from low doses of low-LET radiation. The stochastic effect considered is neoplastic transformation of cells because it relates closely to cancer induction. We have used a published model of neoplastic transformation called NEOTRANS1. It is based on two different classes of cellular sensitivity for asynchronous, exponentially growing populations (in vitro). One sensitivity class is the hypersensitive cell; the other is the resistant cell. NEOTRANS1 includes the effects of genomic damage accumulation, DNA repair during cell cycle arrest, and DNA misrepair (non-lethal repair errors). The model-associated differential equations are solved for conditions of in vitro irradiation at a fixed rate. Previously published solutions apply only to high dose rates and were incorrectly assumed to apply to only high-LET radiation. Solutions provided here apply to any fixed dose rate and to both high- and low-LET radiations. Markov chain Monte Carlo methods are used to carry out the Bayesian inference of the low-dose risk for neoplastic transformation of aneuploid C3H 10T1/2 cells for X-ray doses from 0 to 1000 mGy. We have assumed that for this low-dose range only the hypersensitive fraction of the cells are affected. Our results indicate that the initial slope of the risk vs dose relationship for neoplastic transformation is as follows: (1) directly proportional to the fraction, f1, of hypersensitive cells; (2) directly proportional to the radiosensitivity of the genomic target; and (3) inversely proportional to the rate at which hypersensitive cells with radiation-induced damage are committed to undergo correct repair of genomic damage. Further, our results indicate that very fast molecular events are associated with the commitment of cells to the correct repair pathway. Results also indicate a relatively large probability for misrepair that leads to genomic instability. Our results are consistent with the view that for very low doses, dose rate is not an important variable for characterizing low-LET radiation risks so long as age-related changes in sensitivity do not occur during irradiation. PMID:11565407

Schöllnberger, H; Scott, B R; Hanson, T E

2001-09-01

226

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

227

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

Science.gov (United States)

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-beta-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 (60)Co gamma-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 anti-apoptotic 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. PMID:20606300

Bing, So Jin; Kim, Min Ju; Park, Eunjin; Ahn, Ginnae; Kim, Dae Seung; Ko, Ryeo Kyeong; Lee, Nam Ho; Shin, Taekyun; Park, Jae Woo; Jee, Youngheun

2010-01-01

228

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)

229

Radiation-induced efflux of potassium ions and haemoglobin in bovine erythrocytes at low doses and low dose-rates  

International Nuclear Information System (INIS)

This short communication presents the first results of x radiation dose-rate effect studies on bovine erythrocyte permeability. There appeared to be an enhanced leakage of haemoglobin and potassium ions through the plasma membrane with lower dose rates. With a dose rate of about 0.001 Gy per minute haemoglobin loss after a dose as low as 0.1 Gy could be demonstrated. Inverse dose-rate effects were also observed for rabbit erythrocytes. (U.K.)

230

A comparative study on the protection effect in the radiation-induced oxidation of liquid paraffins and polypropylene  

International Nuclear Information System (INIS)

Comparison of protection effect of additives in liquid paraffins and polypropylene (PP) irradiation under pure oxygen atmosphere has been carried out. Gas product analysis and mechanical properties measurement of PP films indicate that the presence of additives reduces O2 uptake, gas evolution and molecular degradation. These facts are attributed to energy and charge transfer, and radical scavenging action of the additive molecules regardless the physical state difference of the substrates. Oxidation pathway in liquid paraffin is shorter than that in solid PP, and the main part of the consumed O2 are converted into carboxylic acids. The excess of H2 evolution observed in PP oxidation is produced during the oxidation step, and transformation of the additives in their function as protector. (author)

231

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

232

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

International Nuclear Information System (INIS)

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

233

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

International Nuclear Information System (INIS)

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

234

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2006-11-22

235

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.)

236

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

237

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

Science.gov (United States)

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

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

2003-12-01

238

Protection from Radiation-Induced Oral Mucositis by Misoprostol, a Prostaglandin E(1) Analog: A Placebo-Controlled, Double-Blind Clinical Trial.  

Science.gov (United States)

Misoprostol, a prostaglandin E(1) analog, is an effective radioprotector in animal studies. Based on this evidence, a prospective, randomized, placebo-controlled, double-blind study was conducted to determine if misoprostol protected the oral and pharyngeal mucosa of irradiated head and neck cancer patients from radiation mucositis. Postsurgical patients who had no detectable cancer and who were referred for postoperative irradiation were candidates for this study. Thirty-four Hines VA and 35 Loyola University patients were accrued (69 total) over a 2-year period. A misoprostol tablet (200 &mgr;g) or an identical placebo tablet was dissolved in water and administered as an oral rinse daily about 20 min before irradiation. Conventional fractionated radiotherapy, consisting of five weekly doses of 2 Gy day(minus sign1), was delivered. The degree of mucositis was scored on a scale from 0 (no mucositis) to 4. In the 17 patients randomly assigned to the misoprostol arm at the Hines VA, no advantage was seen compared to the 17 placebo-treated patients. However, there was significantly less mucositis (p < 0.01, analysis of variance) from weeks 3--6 in the 17 patients treated with misoprostol at Loyola compared to the 18 placebo-treated patients. Several problems in the study were identified at the VA, including adherence to the protocol design. Other problems such as adequate mucositis scoring, radiation scatter from fillings, and, in particular, adequate timing between misoprostol and irradiation were identified at both locations. Absorption studies in healthy volunteers showed significant plasma levels at 10 min after an oral rinse, suggesting that initial clinical trials should be confined to topical misoprostol until more is known regarding the effect of misoprostol on tumors. The results of this pilot study suggest that misoprotol may protect the oral and pharyngeal mucosa from radiation-induced mocositis if adequate time between topical administration and radiation is allowed. PMID:11854798

Hanson, W. R.; Marks, J. E.; Reddy, S. P.; Simon, S.; Mihalo, W. E.; Tova, Y.

1995-11-01

239

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2009-07-01

240

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)

241

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

242

Two pediatric cases of high dose radiation-induced meningiomas  

International Nuclear Information System (INIS)

There have been many reports of low dose radiation-induced meningiomas, and the number of reports of high dose radiation-induced meningiomas has been increasing recently. In this report, we present two cases of pediatric radiation-induced meningiomas, one 14 years after 36 Gy of radiation therapy for medulloblastoma and the other 8 years after 20 Gy of local radiation therapy for germinoma. Both patients underwent surgical removal of the meningiomas. The case of medulloblastoma was later revealed to be basal cell phacomatosis syndrome. Basal cell phacomatosis syndrome is a disease that occurs as a result of abnormality of chromosome 9. We speculate that the occurrence of radiation-induced meningioma may have been related to the basic genetic vulnerability of the patients. (author)

243

Characteristics of repair following very low doses  

International Nuclear Information System (INIS)

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

244

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

International Nuclear Information System (INIS)

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

245

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

246

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

International Nuclear Information System (INIS)

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

247

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)

248

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)

249

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

250

Radiation-induced tumors  

International Nuclear Information System (INIS)

The present report deals with 32 patients with biopsy and surgery proven radiation-induced tumors. Radiation-induced tumors were classified as malignant tumors (MT) induced by radiation therapy (RT) for MT (Group I, n = 19), MT by RT for benign tumors (BT) (Group II, n = 5), BT by RT for MT (Group III, n = 5), and BT by RT for BT (Group IV, n = 3). The most common first disease was cervical cancer in Group I, breast cancer in Group III, and skin disease such as foot trichophytia in Groups II and IV. Radiation-induced MT was histologically squamous cell carcinoma in all patients of Group II, as opposed to Group I having a histologically varied type of cancer. Latent period was 15.0 yr in Group I, 31.6 yr in Group II, 12.0 yr in Group III, and 27.0 yr in Group IV. (Namekawa, K.)

251

Cell cycle alterations, apoptosis, and response to low-dose-rate radioimmunotherapy in lymphoma cells  

Energy Technology Data Exchange (ETDEWEB)

In an attempt to elucidate some aspects of the radiobiological basis of radioimmunotherapy, we have evaluated the in vitro cellular response patterns for malignant lymphoma cell lines exposed to high- and low-dose-rate radiation administered within the physiological context of antibody cell-surface binding. We used two different malignant lymphoma cell lines, a Thy1.2{sup +} murine T-lymphoma line called EL-4 and a CD20{sup +} human B-lymphoma line called Raji. Irradiated cells were evaluated for viability, cell-cycle changes, patterns of post-radiation morphologic changes, and biochemical hallmarks of radiation-associated necrosis and programmed cell death. The EL-4 line was sensitive to both high-dose-rate and low-dose-rate irradiation, while the Raji showed efficient cell kill only after high-dose-rate irradiation. Studies of radiation-induced cell cycle changes demonstrated that both cell lines were efficiently blocked at the G2/M interface by high-dose-rate irradiation, with the Raji cells appearing somewhat more susceptible than the EL-4 cells to low-dose-rate radiation-induced G2/M block. Electron microscopy and DNA gel electrophoresis studies showed that a significant proportion of the EL-4 cells appeared to be dying by radiation-induced programmed cell death (apoptosis) while the Raji cells appeared to be dying primarily by classical radiation-induced cellular necrosis. We propose that the unusual clinical responsiveness of some high and low grade lymphomas to modest doses of low-dose-rate radioimmunotherapy may be explained in part by the induction of apoptosis. The unusual dose-response characteristics observed in some experimental models of radiation-induced apoptosis may require a reappraisal of standard linear quadratic and alpha/beta algorithms used to predict target tissue cytoreduction after radioimmunotheraphy. 34 refs., 4 figs.

Macklis, R.M.; Beresford, B.A.; Palayoor, S.; Sweeney, S.; Humm, J.L. [Dana Farber Cancer Institute and Harvard Medical School, Boston, MA (United States)

1993-10-20

252

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

253

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.

254

Radiation-Induced Bioradicals  

Science.gov (United States)

This chapter is part one of a review in which the production and application of radiation-induced bioradicals is discussed. Bioradicals play a pivotal role in the complex chain of processes starting with the absorption of radiation in biological materials and ending with the radiation-induced biological after-effects. The general aspects of the four consecutive stages (physical, physicochemical, chemical and biological) are discussed from an interdisciplinary point of view. The close relationship between radiation dose and track structure, induced DNA damage and cell survival or killing is treated in detail. The repair mechanisms that cells employ, to insure DNA stability following irradiation, are described. Because of their great biomedical importance tumour suppressor genes involved in radiation-induced DNA repair and in checkpoint activation will be treated briefly, together with the molecular genetics of radiosensitivity. Part two of this review will deal with modern theoretical methods and experimental instrumentation for quantitative studies in this research field. Also an extensive overview of the applications of radiation-induced bioradicals will be given. A comprehensive list of references allows further exploration of this research field, characterised in the last decade by a substantial advance, both in fundamental knowledge and in range of applications.

Mondelaers, Win; Lahorte, Philippe

255

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.)

256

Immunological aspects of low doses gamma-irradiation effects  

International Nuclear Information System (INIS)

Low dose gamma-radiation effect on the nonspecific protection factors and immune reactions of agricultural birds (diurnal broiler chicks Broiler-6) was studied. Quantitative and qualitative composition of crest skin autoflora and oral cavity mucosa, level of essential antibodies in blood serum, activity of lysozyme, ?-lysines, general bactericidal properties of blood serum were determined. It is shown that low dose irradiation promotes the enhancement of antimicrobial properties of skin and oral cavity mucosa, blood serum bactericidal properties due to the increase in lysozyme content as well as beta-lysines and normal antibodies. Radiation affect the formation of immune intensity and favourable result of infectious process

257

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)

258

Risks to health from radiation at low dose rates  

International Nuclear Information System (INIS)

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

259

Modelling radiation-induced bystander effect and cellular communication  

International Nuclear Information System (INIS)

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

260

The researches on the effects of low doses irradiation  

International Nuclear Information System (INIS)

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

261

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

International Nuclear Information System (INIS)

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

262

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1994-08-01

263

Radiation-induced gliomas  

OpenAIRE

Radiation-induced gliomas represent a relatively rare but well-characterized entity in the neuro-oncologic literature. Extensive retrospective cohort data in pediatric populations after therapeutic intracranial radiation show a clearly increased risk in glioma incidence that is both patient age- and radiation dose/volume-dependent. Data in adults are more limited but show heightened risk in certain groups exposed to radiation. In both populations, there is no evidence linking increased risk a...

Prasad, Gautam; Haas-kogan, Daphne A.

2009-01-01

264

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

OpenAIRE

There are now several independent studies that indicate that the dose-response for the endpoint of radiation-induced neoplastic transformation in vitro is non-linear for low linear energy transfer (LET) radiation. At low doses (<10 cGy) the transformation frequency drops below that seen spontaneously. Importantly, this observation has been made using fluoroscopic energy x-rays, a commonly used modality in diagnostic radiology, the practice of which is responsible for the majority of radiation...

Redpath, J. Leslie

2005-01-01

265

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

266

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

267

Low dose, low dose rate and DREF values  

International Nuclear Information System (INIS)

Biophysical modelling is used to derive an analysis of the influence of dose rate on the shape of dose-effect relationships. Experimental results are used to support the tenet that DNA double strand breaks are crucial lesions leading to cell killing, chromosomal aberrations and mutations. The model is extended to describe cell transformation and malignancy and, by combining this extension with dose rate effect, an equation is derived to describe the Dose Rate Effectiveness Factor (DREF) as a function of dose. It is shown that for cell transformation per irradiated cell and for malignancy, DREF increases with dose to a maximum value and then decreases at higher doses and can become less than one. Consideration of radiobiological data indicates that maximum DREF value will rarely exceed 6.5 and a range from 1.5 to 5 is more probable for sparsely ionising radiation. An example is given where a constant DREF could be used in radiological protection. (author)

268

Adaptive response to ionizing radiation induced by low doses of gamma rays in human cell lines  

International Nuclear Information System (INIS)

Purpose: The aim of this study was to investigate whether the adaptive response could be induced in human lymphoblastoid cell lines and human tumor cell lines. The time necessary for the expression of the adaptive response was also investigated. Materials and Methods: Three lymphoblastoid cell lines from ataxia telangiectasia (AT) homozygote (GM 1526), AT heterozygote (GM 3382), and normal individual (3402p) and two hepatoma cell lines, Hep G2 and Hep 3B, were used in this study. Experiments were carried out by delivering 0.01 Gy followed by 0.5 Gy of gamma radiation to the exponentially growing cells. The time necessary for the expression of the adaptive response was determined by varying the time interval between the two doses from 1 to 72 h. In some experiments, 3-aminobenzamide, a potent inhibitor of poly (ADP-ribose) polymerase, was added immediately after the 0.5 Gy exposure. The cultures were fixed 30 min (for the G2 chromatid) and 6 h (for the S chromatid) after the 0.5 Gy exposure. Metaphase chromosome assay was carried out to score chromatid breaks as an end point. Results: A prior exposure to 0.01 Gy of gamma rays significantly reduced the number of chromatid breaks induced by subsequent higher doses (0.5 Gy) in all the tested cell lines. The magnitude of the adaptive response was similar among the cell lines despite their different radiosensitivities. In the G2 chromatids, the adaptive response was observed both at short-time intervale was observed both at short-time intervals, as early as 1 h, and at long-time intervals. In the S chromatids, however, the adaptive response was shown only at long-time intervals. When 3-aminobenzamide was added after the 0.5 Gy, the adaptive responses were abolished in all the experimental groups. Conclusion: The adaptive response was observed in human lymphoblastoid cell lines and hepatoma cell lines. The magnitude of the adaptive response did not seem to be related to the radiosensitivity of the cells. The elimination of the adaptive response with 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromasomal repair mechanisms

269

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

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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

270

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

International Nuclear Information System (INIS)

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

271

Radiation-induced lung injury  

International Nuclear Information System (INIS)

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

272

Radiation-induced segregation and phase stability in ferritic-martensitic alloy T 91  

International Nuclear Information System (INIS)

Radiation-induced segregation in ferritic-martensitic alloy T 91 was studied to understand the behavior of solutes as a function of dose and temperature. Irradiations were conducted using 2 MeV protons to doses of 1, 3, 7 and 10 dpa at 400 deg. C. Radiation-induced segregation at prior austenite grain boundaries was measured, and various features of the irradiated microstructure were characterized, including grain boundary carbide coverage, the dislocation microstructure, radiation-induced precipitation and irradiation hardening. Results showed that Cr, Ni and Si segregate to prior austenite grain boundaries at low dose, but segregation ceases and redistribution occurs above 3 dpa. Grain boundary carbide coverage mirrors radiation-induced segregation. Irradiation induces formation of Ni-Si-Mn and Cu-rich precipitates that account for the majority of irradiation hardening. Radiation-induced segregation behavior is likely linked to the evolution of the precipitate and dislocation microstructures.

273

Radiation-induced segregation and phase stability in ferritic-martensitic alloy T 91  

Energy Technology Data Exchange (ETDEWEB)

Radiation-induced segregation in ferritic-martensitic alloy T 91 was studied to understand the behavior of solutes as a function of dose and temperature. Irradiations were conducted using 2 MeV protons to doses of 1, 3, 7 and 10 dpa at 400 deg. C. Radiation-induced segregation at prior austenite grain boundaries was measured, and various features of the irradiated microstructure were characterized, including grain boundary carbide coverage, the dislocation microstructure, radiation-induced precipitation and irradiation hardening. Results showed that Cr, Ni and Si segregate to prior austenite grain boundaries at low dose, but segregation ceases and redistribution occurs above 3 dpa. Grain boundary carbide coverage mirrors radiation-induced segregation. Irradiation induces formation of Ni-Si-Mn and Cu-rich precipitates that account for the majority of irradiation hardening. Radiation-induced segregation behavior is likely linked to the evolution of the precipitate and dislocation microstructures.

Wharry, Janelle P.; Jiao Zhijie; Shankar, Vani [University of Michigan, 2355 Bonisteel Blvd, Ann Arbor, MI 48109-2104 (United States); Busby, Jeremy T. [Oak Ridge National Laboratory, 1 Bethel Valley Rd, Oak Ridge, TN 37831 (United States); Was, Gary S., E-mail: gsw@umich.edu [University of Michigan, 2355 Bonisteel Blvd, Ann Arbor, MI 48109-2104 (United States)

2011-10-01

274

Radiation-induced segregation and phase stability in ferritic-martensitic alloy T 91  

Science.gov (United States)

Radiation-induced segregation in ferritic-martensitic alloy T 91 was studied to understand the behavior of solutes as a function of dose and temperature. Irradiations were conducted using 2 MeV protons to doses of 1, 3, 7 and 10 dpa at 400 °C. Radiation-induced segregation at prior austenite grain boundaries was measured, and various features of the irradiated microstructure were characterized, including grain boundary carbide coverage, the dislocation microstructure, radiation-induced precipitation and irradiation hardening. Results showed that Cr, Ni and Si segregate to prior austenite grain boundaries at low dose, but segregation ceases and redistribution occurs above 3 dpa. Grain boundary carbide coverage mirrors radiation-induced segregation. Irradiation induces formation of Ni-Si-Mn and Cu-rich precipitates that account for the majority of irradiation hardening. Radiation-induced segregation behavior is likely linked to the evolution of the precipitate and dislocation microstructures.

Wharry, Janelle P.; Jiao, Zhijie; Shankar, Vani; Busby, Jeremy T.; Was, Gary S.

2011-10-01

275

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)

276

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

277

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

278

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2006-01-06

279

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

280

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

281

LOW DOSE MAGNESIUM SULPHATE REGIME FOR ECLAMPSIA  

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

Bangal V

2009-09-01

282

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.)

283

Radiation Induced Genomic Instability  

Energy Technology Data Exchange (ETDEWEB)

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

Morgan, William F.

2011-03-01

284

Organ Specific Gene Expression by Low Dose Radiation  

International Nuclear Information System (INIS)

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

285

Mutagenic effect of low dose ionizing radiation on mammalian cells  

International Nuclear Information System (INIS)

It was the aim of this study to investigate into the mutagenic effet of low dose ionizing radiation on mammalian cells, particularly as regards its relation to the dose rate. For this purpose, a procedure was developed for the continuous cultivation of mamalian cells that permitted expontential growth phases to be maintained over several weeks. The tests were carried out on V79 cells from Chinese hamsters as well as TK6 cells and SP3 cells from humans. The cells were challenged using a 60Co-gamma source, with dose rates varying between 2 and 200 mGy per hour. Acute dose-effect curves for 300 kV X-radiation were plotted as a reference standard. The key finding of the study was that frequencies of mutation determined in any of the cell systems following exposure to extremely small doses were no lower than those seen after acute irradation. The mutation rates were not significantly different in human cells and, surprisingly, even showed substantial increases for V79 cells. The generally expected decrease of mutation yields in proportion to the dose rate was confirmed by this study solely for the intermediate range (50-500 mGy/hour). This statement must be qualified by the fact that the systems investigated here were cell populations characterized by exponential growth. Circumstances may be different in tissues, where the growth fractions are only small. Nevertheless, the results still are of great relevance to the evaluation of risks from radiation-induced mutuation of risks from radiation-induced mutation, both at the genetic and somatic levels. (orig.)

286

The assessment of the carcinogenic effects of low dose radiation  

International Nuclear Information System (INIS)

It is concluded that the exclusion of patients for the purposes of risk estimation, the choice of a particular relative risk projection model and of a dose reduction factor equal to 2 are all decisions which result in an overestimation of the actual risk. These choices can be understood when the aim is radiation protection and when it is safer to overestimate the risk; however, they are open to criticism if the aim is a realistic assessment of the risk. For low doses, below 50 mSv/year, and when all causes of uncertainty are added, the actual risk might be markedly lower than the risk estimated with the ICRP (1991) carcinogenic risk coefficient and the DRF estimated by ICRP. Future studies should aim at providing direct and more precise assessments of risk coefficients in the low dose region. (Author)

287

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

Energy Technology Data Exchange (ETDEWEB)

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

Karsli, Tijen [Children' s Healthcare of Atlanta, Atlanta, GA (United States); University of Tennessee, Pediatric Intensive Care, Memphis, TN (United States); Kalra, Mannudeep K. [Children' s Healthcare of Atlanta, Department of Radiology, Atlanta, GA (United States); Massachusetts General Hospital, Department of Radiology, Boston, MA (United States); Self, Julie L.; Rosenfeld, Jason Anders; Butler, Susan [Emory University, Department of Behavioral Sciences and Health Education, Atlanta, GA (United States); Simoneaux, Stephen [Children' s Healthcare of Atlanta, Department of Radiology, Atlanta, GA (United States)

2009-09-15

288

Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity  

Energy Technology Data Exchange (ETDEWEB)

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

Kleiman, Norman Jay [Columbia University

2013-11-30

289

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

International Nuclear Information System (INIS)

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

290

LOW DOSE RISK, DECISIONS, and RISK COMMUNICATION  

International Nuclear Information System (INIS)

The objective of this project is to conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low-dose exposures. Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low-dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals

291

Reduced oxygen enhancement ratio at low doses  

International Nuclear Information System (INIS)

The oxygen depletion rate in cell suspensions was measured using a Clark electrode. It was found that under experimental conditions used in this laboratory for hypoxic irradiations, the oxygen levels before the start of irradiation are always below 0.1?m, the levels which could give any significant enhancement to radiation inactivation by x-rays. The measured O/sub 2/ depletion rates were comparable to those reported in the literature. Chinese hamster cells (CHO) were made hypoxic by gas exchange, combined with metabolic consumption of oxygen by cells at 370C. Full survival curves were determined in the dose range 0 to 3Gy using the low dose survival assay. The results confirmed the authors' earlier finding that the OER decreases at low doses. The authors therefore believe that the dose-dependent OER is a true radiobiological phenomenon and not an artifact of the experimental method used in the low dose survival assay

292

Health benefits from low-dose irradiation  

International Nuclear Information System (INIS)

Whole-body exposures of mice and humans show no harm from low doses of ionizing radiation. Forty reports show statistically significant, p < 0.01, beneficial effects when cancer and total mortality rates were examined in mice. In vitro experiments indicate that radiogenic metabolism, adaptive repair mechanisms, such as DNA repair enzymes, and the essential nature of ionizing radiation are responsible for part of this activity. However, overwhelming evidence shows that low-dose irradiation increases immune competence. Such data negate the linear concept, which has no reliable whole-animal data to support it in the low-dose range. Cell culture data are not pertinent; such cells do not have a complete immune system

293

Radiation-induced cerebrovasculopathy  

International Nuclear Information System (INIS)

We reported a patient who suffered from cerebrovasculopathy after irradiation therapy for astrocytoma located at the left temporal lobe. An eleven year-old boy who presented with headache and vomiting received partial removal of a tumor. Histological diagnosis of the tumor was astrocytoma (grade II). His preoperative cerebral angiograms showed mass sign solely, without stenosis or occlusion of the cerebral vessel. Postoperatively, he was treated with irradiation therapy involving the whole brain with a total of 30 Gy, and gamma knife therapy. Six months after irradiation, he started suffering from frequent cerebral ischemic attacks, but there was no regrowth of the tumor visible on CT scans. Cerebral angiograms were made again, and revealed multifocal stenoses in the bilateral internal carotid arteries, middle cerebral arteries, and the anterior cerebral artery. His symptoms did not improve after conservative treatment with steroids, calcium antagonist, or low molecular weight dextran. Although he received a superficial temporal artery-middle cerebral artery (STA-MCA) anastomoses bilaterally, multiple cerebral infarctions appeared. Although irradiation therapy is acceptable in patients with brain tumor, cerebrovasculopathy after irradiation should be considered as one of the most important complications, and the risk incurred by irradiation therapy should lead to more careful consideration and caution when treating intracranial brain tumors, especially in children. Frl brain tumors, especially in children. From our experience, the usefulness of bypass surgery for radiation-induced cerebrovasculopathy is still controversial. (author)

294

[Radiation-induced neuropathy].  

Science.gov (United States)

Radiation-induced neuropathy is commonly observed among oncological patients. Radiation can affect the nervous tissue directly or indirectly by inducing vasculopathy or dysfunction of internal organs. Symptoms may be mild and reversible (e.g., pain, nausea, vomiting, fever, drowsiness, fatigue, paresthesia) or life-threatening (cerebral oedema, increased intracranial pressure, seizures). Such complications are clinically divided into peripheral (plexopathies, neuropathies of spinal and cranial nerves) and central neuropathy (myelopathy, encephalopathy, cognitive impairment). The degree of neuronal damages primarily depends on the total and fractional radiation dose and applied therapeutic methods. The conformal and megavoltage radiotherapy seems to be the safeties ones. Diagnostic protocol includes physical examination, imaging (in particular magnetic resonance), electromyography, nerve conduction study and sometimes histological examination. Prevention and early detection of neurological complications are necessary in order to prevent a permanent dysfunction of the nervous system. Presently their treatment is mostly symptomatic, but in same cases a surgical intervention is required. An experimental and clinical data indicates some effectiveness of different neuroprotective agents (e.g. anticoagulants, vitamin E, hyperbaric oxygen, pentoxifylline, bevacizumab, methylphenidate, donepezil), which should be administered before and/or during radiotherapy. PMID:24490474

Kolak, Agnieszka; Staros?awska, Elzbieta; Kieszko, Dariusz; Cisek, Pawe?; Patyra, Krzysztof Ireneusz; Surdyka, Dariusz; Dobrzy?ska-Rutkowska, Aneta; ?opacka-Szatan, Karolina; Burdan, Franciszek

2013-12-01

295

Radiation induced emulsion polymerization  

International Nuclear Information System (INIS)

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

296

Dose rate effectiveness in radiation-induced teratogenesis in mice  

International Nuclear Information System (INIS)

To investigate the role of p53 gene in tissue repair of teratogenic injury, we compared incidence of radiation-induced malformations in homozygous p53(-/-) mice, heterozygous p53(+/-) mice and wild-type p53(+/+) mice. After X-irradiation with 2 Gy at high dose rate on 9.5 days of gestation, p53(-/-) mice showed higher incidences of anomalies and higher resistance to prenatal deaths than p53(+/+) mice. This reciprocal relationship of radiosensitivity to anomalies and deaths supports the notion that embryos or fetuses have a p53-dependent 'guardian' that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of apoptotic cells was greatly increased in p53(+/+) fetuses but not in p53(-/-) fetuses. The same dose of ?-ray exposure at low dose rate on 9.5-10.5 day of gestation produced significant reduction of radiation-induced malformation in p53(+/+) and p53(+/-) mice, remained teratogenic for p53(-/-) mice. These results suggest that complete elimination of teratogenic damage from irradiated tissues requires the concerted cooperation of two mechanisms; proficient DNA repair and the p53-dependent apoptotic tissue repair. When concerted DNA repair and apoptosis functions efficiently, there is a threshold dose-rate for radiation-induced malformations. (author)

297

Factors that modify risks of radiation-induced cancer  

International Nuclear Information System (INIS)

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

298

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

299

Stimulation of seeds by low dose irradiation  

International Nuclear Information System (INIS)

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

300

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

International Nuclear Information System (INIS)

The polyamine spermine and the disulfide NN double-prime-(dithiodi-2,1-ethanediyl)bis-1,3-propanediamine (WR-33278) are structurally similar agents capable of binding to DNA. WR-33278 is the disulfide moiety of the clinically studied radioprotective agent (WR-2721). Because of their structural similarities, it was of interest to characterize and compare their radioprotective properties using the endpoints of cell survival and mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in Chinese hamster AA8 cells. In order to facilitate both the uptake of VM-33278 into cells and the direct comparison between the protective properties of WR-33278 and spermine, these agents were electroporated into cells. Electroporation alone reduced cell survival to 75% but had no effect on hprt mutation frequency. The electroporation of either spermine or WR-33278 at concentrations greater than 0.01 mM was extremely toxic. The exposure of cells to both electroporation and irradiation gave rise to enhanced cell killing and mutation induction. Cell survival values at a radiation dose of 750 cGy were enhanced by factors of 1.3 and 1.8 following electroporation of 0.01 mM of spermine and WR-33278, respectively, 30 min prior to irradiation. Neither agent was protective at a concentration of 0.001 mM. Protection against radiation-induced hprt mutations was observed for both spermine and WR-33278 under all experimental conditions tested

301

Protection against radiation-induced mutations at the hprt locus by spermine and N,N{double_prime}-(dithiodi-2,1-ethanediyl)bis-1,3-propanediamine (WR-33278)  

Energy Technology Data Exchange (ETDEWEB)

The polyamine spermine and the disulfide NN{double_prime}-(dithiodi-2,1-ethanediyl)bis-1,3-propanediamine (WR-33278) are structurally similar agents capable of binding to DNA. WR-33278 is the disulfide moiety of the clinically studied radioprotective agent (WR-2721). Because of their structural similarities, it was of interest to characterize and compare their radioprotective properties using the endpoints of cell survival and mutation induction at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in Chinese hamster AA8 cells. In order to facilitate both the uptake of VM-33278 into cells and the direct comparison between the protective properties of WR-33278 and spermine, these agents were electroporated into cells. Electroporation alone reduced cell survival to 75% but had no effect on hprt mutation frequency. The electroporation of either spermine or WR-33278 at concentrations greater than 0.01 mM was extremely toxic. The exposure of cells to both electroporation and irradiation gave rise to enhanced cell killing and mutation induction. Cell survival values at a radiation dose of 750 cGy were enhanced by factors of 1.3 and 1.8 following electroporation of 0.01 mM of spermine and WR-33278, respectively, 30 min prior to irradiation. Neither agent was protective at a concentration of 0.001 mM. Protection against radiation-induced hprt mutations was observed for both spermine and WR-33278 under all experimental conditions tested.

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

1993-06-01

302

Health risks associated with low doses of radiation. Final report  

International Nuclear Information System (INIS)

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

303

Low dose effects detected by micronucleus assay in lymphocytes  

International Nuclear Information System (INIS)

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

304

Cobalt radiation-induced comedones  

International Nuclear Information System (INIS)

Radiation-induced acneform lesions have been described after both radiation and cobalt therapy. This is a report of multiple comedo formation on the forehead and scalp of a patient who received cobalt therapy for a brain tumor

305

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

International Nuclear Information System (INIS)

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

306

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)

307

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

308

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)

309

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

Science.gov (United States)

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.; Lyng, F.

2008-02-01

310

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

311

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

312

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

313

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

314

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.

315

Repair processes in radiation-induced transformation  

International Nuclear Information System (INIS)

The authors used the cell system developed in the laboratory of Charles Heidelberger designated 10T1/2. These cells were derived from C3H mouse embryo tissue. Under normal circumstances, 10T1/2 cells form a confluent sheet of contact-inhibited cells. Focus formation, due to the sustained division of a transformant on top of a contact inhibited confluent layer of cells, is used as a quantitative measure of induced transformation. Some chemical carcinogens and near ultraviolet radiation induce transformation with little if any attendant cytotoxicity. In contrast, ionizing radiation is an inefficient inducer, which shows the dose dependencies of cell survival and transformation with 60Co ?-rays. To determine whether repair plays a role in transformation, both fractionation and low dose rate irradiation experiments were performed. In all instances, the effect of spreading the radiation treatment over time - while cells were maintained under conditions that support active growth and cultures were not confluent or crowded - was determined in terms of net survival as well as net transformation frequency. Comparisons were made with cells treated with single exposures delivered at a high dose rate

316

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

International Nuclear Information System (INIS)

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

317

Overexpression of glutamate–cysteine ligase protects human COV434 granulosa tumour cells against oxidative and ?-radiation-induced cell death  

OpenAIRE

Ionizing radiation is toxic to ovarian follicles and can cause infertility. Generation of reactive oxygen species (ROS) has been implicated in the toxicity of ionizing radiation in several cell types. We have shown that depletion of the antioxidant glutathione (GSH) sensitizes follicles and granulosa cells to toxicant-induced apoptosis and that supplementation of GSH is protective. The rate-limiting reaction in GSH biosynthesis is catalysed by glutamate–cysteine ligase (GCL), which consists...

Cortes-wanstreet, Mabel M.; Giedzinski, Erich; Limoli, Charles L.; Luderer, Ulrike

2009-01-01

318

Journal of Nuclear Materials - Radiation-induced segregation and phase stability in ferritic-martensitic alloy T 91  

International Nuclear Information System (INIS)

Radiation-induced segregation in ferritic martensitic alloy T 91 was studied to understand the behavior of solutes as a function of dose and temperature. Irradiations were conducted using 2 MeV protons to doses of 1, 3, 7 and 10 dpa at 400 C. Radiation-induced segregation at prior austenite grain boundaries was measured, and various features of the irradiated microstructure were characterized, including grain boundary carbide coverage, the dislocation microstructure, radiation-induced precipitation and irradiation hardening. Results showed that Cr, Ni and Si segregate to prior austenite grain boundaries at low dose, but segregation ceases and redistribution occurs above 3 dpa. Grain boundary carbide coverage mirrors radiation-induced segregation. Irradiation induces formation of Ni Si Mn and Cu-rich precipitates that account for the majority of irradiation hardening. Radiation-induced segregation behavior is likely linked to the evolution of the precipitate and dislocation microstructures.

319

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2012-12-01

320

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

International Nuclear Information System (INIS)

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

321

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

International Nuclear Information System (INIS)

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

322

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

323

Protective effect of medroxyprogesterone acetate plus testosterone against radiation-induced damage to the reproductive function of male rats and their offspring.  

OpenAIRE

This study attempted to protect spermatogenesis and the reproductive performance of rats against the effects of acute scrotal exposure to x-rays. Daily subcutaneous injections of medroxyprogesterone acetate (8 mg/kg) plus testosterone (1 mg/kg) (MT group) were administered for 55 days (experiment A) or 15 days (experiment B). The rats were irradiated (3 grays) on the last day of MT pretreatment (MTX group). In both experiments, on days 1 and 130 posttreatment, rats from each of the four group...

Je?gou, B.; Velez La Calle, J. F.; Bauche?, F.

1991-01-01

324

Global DNA methylation responses to low dose radiation exposure  

International Nuclear Information System (INIS)

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

325

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

International Nuclear Information System (INIS)

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

326

Low doses: myth or true danger  

International Nuclear Information System (INIS)

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

327

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2011-03-01

328

Radiation-induced peritoneal mesothelioma  

International Nuclear Information System (INIS)

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

329

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)

330

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

331

Radiation-induced strand-breaks in poly(riboadenylic acid). A pulse radiolysis study on the protective action of cysteamine under anoxic conditions  

International Nuclear Information System (INIS)

Poly(riboadenylic acid) was irradiated in N2O-saturated dilute aqueous solution at pH 7.8 with single pulses (50-200 ns) of 16 MeV electrons, and the extent and rate of main-chain scission measured in the absence and presence of cysteamine (RSH). In both cases two modes of light scattering intensity (LSI) decrease were detected. It was concluded that two chemically different radical sites, giving rise to main-chain breakage, were produced by OH attack on the macromolecules. Cysteamine reduced the extent of LSI decrease and accelerated the rate of the slow mode of LSI decrease significantly. The fast mode of the LSI decrease is due to fragment diffusion and the influence of cysteamine on the rate of decay of the short-lived radical could not be studied. Assessment of the relative importance of OH scavenging and repair with respect to protection showed that in the case of the long-lived radical, repair contributes significantly at low RSG concentration (-4M); in the case of the short-lived radical, OH scavenging dominates and repair becomes noticeable only at [RSH] > 10-4M. The following were evaluated: 100 eV-yield of main-chain scission, G(sb) = 1.1; lifetimes of radicals: 50?s(short-lived), 0.6 s(long-lived), ksub(PA radical + rsh) = 3.4 x 106M-1s-1(long-lived radicals). (U.K.)

332

Exposition of human to low doses and low dose rate irradiation: and urgent need for new markers and new models  

International Nuclear Information System (INIS)

In human radiation protection, the shape of the dose effects curve for low dose irradiation (LDI) is assumed to be linear, extrapolated from the clinical consequences of Hiroshima and Nagasaki nuclear explosions. This extrapolation probably overestimates the risk below 200 mSv. In many circumstances, the living species and cells can develop some mechanisms of adaptation. Classical epidemiological studies will not be able to answer the question and there is a need to assess more sensitive biological markers of the effects of LDI. Researches should be focused on DNA effects (strand breaks), radioinduced expression of new genes and proteins involved in the response to oxidative stress and DNA repair mechanisms. New experimental bio-molecular techniques should be developed in parallel with more conventional ones. Such studies would permit to assess the new biological markers of radiosensitivity, which could be of great interest in radiation protection and radiooncology

333

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

International Nuclear Information System (INIS)

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

334

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

335

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

International Nuclear Information System (INIS)

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

336

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2011-08-19

337

Low dose neutron late effects: Cataractogenesis  

Energy Technology Data Exchange (ETDEWEB)

The work is formulated to resolve the uncertainty regarding the relative biological effectiveness (RBE) of low dose neutron radiation. The study exploits the fact that cataractogenesis is sensitive to the inverse dose-rate effect as has been observed with heavy ions and was an endpoint considered in the follow-up of the A-bomb survivors. The neutron radiations were initiated at the Radiological Research Accelerator facility (RARAF) of the Nevis Laboratory of Columbia University. Four week old ({plus minus} 1 day) rats were divided into eight dose groups each receiving single or fractionated total doses of 0.2, 1.0, 5.0 and 25.0 cGy of monoenergetic 435 KeV neutrons. Special restraining jigs insured that the eye, at the midpoint of the lens, received the appropriate energy and dose with a relative error of {plus minus}5%. The fractionation regimen consisted of four exposures, each administered at three hour ({plus minus}) intervals. The neutron irradiated groups are being compared to rats irradiated with 250kVp X-rays in doses ranging from 0.5 to 7 Gy. The animals are being examined on a biweekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit Lamp Imaging System (Zeiss). The follows-ups, entering their second year, will continue throughout the life-span of the animals. This is essential inasmuch as given the extremely low doses which are being utilized clinically detectable opacities were not anticipated until a significant fraction of the life span has lapsed. Current data support this contention. At this juncture cataracts in the irradiated groups are beginning to exceed control levels.

Worgul, B.V.

1991-12-01

338

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

339

Synergistic protective effects of escin and low?dose glucocorticoids against vascular endothelial growth factor?induced blood?retinal barrier breakdown in retinal pigment epithelial and umbilical vein endothelial cells.  

Science.gov (United States)

Previous studies have shown that escin possesses glucocorticoid (GC)?like anti?edematous and anti?in?ammatory effects. The present study was designed to investigate whether escin exhibits synergistic protective effects against blood?retinal barrier (BRB) breakdown when combined with GC in an in vitro monolayer BRB model, based on retinal pigment epithelial (RPE) cells and human umbilical vein endothelial cells (HUVECs). The results showed that low concentrations of escin and triamcinolone acetonide (TA) administered separately did not affect BRB trans?endothelial (epithelium) resistance (TEER). However, when administered together, escin and TA significantly inhibited reduced BRB TEER following treatment with vascular endothelial growth factor (VEGF). Furthermore, low?concentrations of escin and TA administered together significantly increased the expression levels of occludin and ZO?1. This demonstrates that escin and GC have synergistic protective effects against BRB breakdown, and the molecular mechanisms may be related to the upregulation of occludin and ZO?1 expression. The combination of escin with GC indicates a potential beneficial strategy for the treatment of breakdown of the BRB. PMID:25370688

Zhang, Fenglan; Man, Xuejing; Yu, Huajun; Liu, Limei; Li, Yuanbin

2015-02-01

340

Radiation-induced cancer risks  

International Nuclear Information System (INIS)

The author comments on the controversy over radiation induced cancer risk rates and the arguments of Russell-Jones, Tucker and Mole concerning the risks derived from the new dosimetry when applied to A-bomb survivors in Japan and the reactions of the I.C.R.P. Particular reference is made to the mathematical models used to fit dose-response data and to extrapolate to lifetime risk. (U.K.)

341

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

342

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

343

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

344

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)

345

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

346

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.

347

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

348

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.)

349

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

350

Oxidative stress, radiation-induced damage and  

Directory of Open Access Journals (Sweden)

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

Sevil KILÇIKSIZ

2008-01-01

351

APPLICATION OF BAYESIAN INFERENCE TO CHARACTERIZE RISKS ASSOCIATED WITH LOW DOSES OF LOW-LET RADIATION  

Science.gov (United States)

Improved risk characterization for stochastic biological effects of low doses of low-LET radiation is important for protecting nuclear workers and the public from harm from radiation exposure. Here we present a Bayesian approach to characterize risks of stochastic effects from l...

352

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)

353

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.)

354

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

355

Radiation-induced bladder carcinoma  

International Nuclear Information System (INIS)

A 69-year-old woman was referred to our hospital for the treatment of bladder carcinoma. The pathology of the tumor was mixed cancer of squamous cell carcinoma and transitional cell carcinoma. She had been operated on and irradiated for uterine cervical carcinoma 16 years before. Cystoscopy revealed non-papillary tumors about the bladder neck. Transurethral ultrasonography showed a tumor which pierced the bladder muscle plate, but total cystectomy was refused. 14 cases of radiation-induced bladder tumors, including our case, are collected from the publications and discussed. (author)

356

Low dose responses of different glyphosate formulations on plants  

OpenAIRE

Although glyphosate clearly has real and potential commercial uses as a growth regulator at low doses, its main commercial significance has been as an herbicide. An important prerequisite for low dose applications gaining significance is a high efficiency and reliability of effects. This, however, seems to be a major constraint, especially regarding the approach of increasing yield by glyphosate hormesis. Glyphosate is marketed in various formulations, but potential disparities in low dose re...

Belz, Regina G.; Leberle, Claudia

2012-01-01

357

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)

358

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.)

359

Radiation-induced cardiovascular effects  

Science.gov (United States)

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

Tapio, Soile

360

Statistical modeling of ultrastructural features of murine dermal collagen under chronic low-dose whole body X-irradiation.  

Science.gov (United States)

The present study investigated the changes in ultrastructural features of dermal collagen fibrils of mice following exposure to different cumulative chronic low-dose X-irradiation through digital image analysis-based statistical modeling. Pubertal mice were X-irradiated and dorsal skin biopsies were collected and processed for transmission electron microscopic (TEM) analysis. TEM features of collagen fibrils showed alteration in the cross-sectional area, population density and in the axial periodic pattern of light and dark bands. The mathematical analysis of histogram data from TEM images revealed some adaptive behavior in collagen structures of the X-irradiated group. This finding indicated that exposure to chronic low-dose X-radiation induced an altered steady state with adaptive variation in dermal collagen fibrils in irradiated mice. PMID:17931629

Chatterjee, Jyotirmoy; Mukherjee, Anirban; Mukherjee, Kanchan; Dutta, Pranab K; Chaudhuri, Keya

2007-10-30

361

Radiation-induced leiomyosarcoma of the oropharynx  

Directory of Open Access Journals (Sweden)

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

Maier Wolfgang

2006-08-01

362

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

363

Activation of Biodefense System by Low-Dose Irradiation or Radon Inhalation and Its Applicable Possibility for Treatment of Diabetes and Hepatopathy  

OpenAIRE

Adequate oxygen stress induced by low-dose irradiation activates biodefense system, such as induction of the synthesis of superoxide dismutase (SOD) and glutathione peroxidase. We studied the possibility for alleviation of oxidative damage, such as diabetes and nonalcoholic liver disease. Results show that low-dose ?-irradiation increases SOD activity and protects against alloxan diabetes. Prior or post-low-dose X- or ?-irradiation increases antioxidative functions in livers and inhibits fe...

Kataoka, Takahiro; Yamaoka, Kiyonori

2012-01-01

364

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)

365

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

366

Low-dose ursodeoxycholic acid prolongs cholesterol nucleation time in gallbladder bile of patients with cholesterol gallstones  

OpenAIRE

The high rate of stone recurrence represents a drawback of non-surgical therapy of cholesterol gallstone disease. Although most studies report that long-term bile acid treatment does not have protective effects, preliminary results suggest that low-dose ursodeoxycholic acid decreases the rate of gallstone recurrence in a subgroup of younger patients. To clarify the underlying mechanism we investigated whether low-dose ursodeoxycholic acid treatment influences biliary cholesterol saturation an...

Ju?ngst, Dieter; Brenner, Gerhard; Pratschke, Ekkehard; Paumgartner, Gustav

1989-01-01

367

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

Directory of Open Access Journals (Sweden)

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

Kova?evi? Milan S.

2013-01-01

368

The "low dose" hypothesis: validity and implications for human risk.  

Science.gov (United States)

In the late 1990s, a "low dose" hypothesis was proposed based on studies that purported to show that hormonally active environmental agents were causing a variety of effects, mainly reproductive and developmental, at "low doses." The supporters of this hypothesis claim that traditional "high-dose" toxicity studies are not adequate to assess adverse effects from these hormonally active agents in that they do not detect effects that are occurring at "low doses." In addition, it is claimed that these "low dose" effects are occurring at levels comparable to those to which humans are being exposed. These claims have been controversial and expert panels evaluated the evidence behind them in the early 2000s. Although these panels generally concluded that such "low dose" effects were not conclusively established, proponents of the "low dose" hypothesis assert that a large number of more recent studies now provide clear support for their hypothesis. This review carefully examines both recent and older studies that have been cited to support the "low dose" hypothesis, including their relevance for the human population. These include in vivo and in vitro laboratory studies as well as a very limited number of epidemiological investigations. Based on the evidence, it is concluded that these "low dose" effects have yet to be established, that the studies purported to support these cannot be validly extrapolated to humans, and the doses at which the studies have been performed are significantly higher than the levels to which humans are exposed. PMID:17365142

Kamrin, Michael A

2007-01-01

369

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

370

Simvastatin attenuates radiation-induced tissue damage in mice  

OpenAIRE

The aim of this study was to investigate the protective effect of simvastatin against radiation-induced tissue injury in mice. Mice were radiated with 4 Gy or 8 Gy after 20 mg/kg/d simvastatin treatment over 2 weeks. Morphological changes were observed in the jejunum and bone marrow, and apoptotic cells were determined in both tissues. Peripheral blood cells were counted, and the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) level in tissues of both thymus and spleen were ...

Zhao, Xinbin; Yang, Hong; Jiang, Guojun; Ni, Min; Deng, Yaping; Cai, Jian; Li, Zhangpeng; Shen, Fuming; Tao, Xia

2013-01-01

371

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

International Nuclear Information System (INIS)

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

372

Radiation-induced bladder carcinoma  

International Nuclear Information System (INIS)

Two cases are presented of radiation-induced bladder carcinoma which followed prior irradiation for cervical carcinoma of the uterus. One was a sixty-eight-year-old woman with bladder carcinoma fourteen years after irradiation (total dose of 4,500 rad) for cervical carcinoma of the uterus. The other was a sixty-four-year-old woman with bladder carcinoma twenty-five years after irradiation with 150-K volt apparatus for cervical carcinoma of the uterus. From the late radiation change of the skin, it was estimated that the total dose of prior radiation might be 4,000 rad or more. Both had high-grade, high-stage transitional cell bladder carcinoma, and the former was with marked mucus-forming adenomatous metaplasia

373

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