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1

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

International Nuclear Information System (INIS)

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

2

Low-Dose Radiation-Induced Protective Process and Implications for Risk Assessment, Cancer Prevention, and Cancer Therapy  

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A low-dose protective apoptosis-mediated (PAM) process is discussed that appears to be turned on by low-dose gamma and X rays but not by low-dose alpha radiation. PAM is a bystander effect that involves cross-talk between genomically compromised [e.g., mutants, neoplastically transformed, micronucleated] cells and nongenomically compromised cells. A novel neoplastic cell transformation model, NEOTRANS3, is discussed that includes PAM. With NEOTRANS3, PAM is activated by low doses and inhibited by moderate or high doses and is, therefore, a hormetic process. A low-dose region of suppression of the transformation frequency below the spontaneous frequency relates to the hormetic zone over which PAM is presumed to operate. The magnitude of suppression relates to what is called the hormetic intensity. Both the hormetic intensity and width of the hormetic zone are expected to depend on dose rate, being more pronounced after low dose rates. It is expected that PAM likely had a significant role in the following observations after chronic irradiation: (1) what appears to be a tremendous reduction in the cancer incidence below the spontaneous level for Taiwanese citizens residing for years in cobalt-60 contaminated apartments; and (2) the published reductions in the lung cancer incidence below the spontaneous level in humans after protracted X irradiation and after chronic gamma plus alpha irradiation. Implications of PAM for cancer prevention and low-dose cancer therapy are briefly discussed. PMID:18648600

Scott, B.R.

2007-01-01

3

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

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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

4

Low-Dose Bevacizumab Is Effective in Radiation-Induced Necrosis  

Science.gov (United States)

Background Radiation-induced necrosis is a complication of brain irradiation. Treatment options are limited. Methods The response to treatment with low-dose bevacizumab in 2 patients with radiation-induced necrosis was reported. Results Both patients with metastatic melanoma, aged 48 and 51 years, had significant symptomatic and radiological improvement with low-dose bevacizumab treatment. Doses as low as 5 mg/kg every 6 weeks and 7.5 mg/kg i.v. every 4 weeks were used and were highly effective. Conclusions Low-dose bevacizumab is a solid option in the management of edema associated with radiation necrosis. PMID:24474923

Alessandretti, Matheus; Buzaid, Antonio C.; Brandao, Raphael; Brandao, Erika P.

2013-01-01

5

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

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

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

2011-01-01

6

Radiation-Induced Bystander Effects: Evidence for an Adaptive Response to Low Dose Exposures?  

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This paper reviews our current knowledge of the mechanisms underlying the induction of bystander effects by low dose, low-LET ionizing radiation and discusses how they may be related to observed adaptive responses or other protective effects of low dose exposures. Bystander effects appear to be the result of a generalized stress response in tissues or cells. The signals may be produced by all exposed cells, but the response appears to require a quorum in order to be expressed. The major respo...

Mothersill, Carmel; Seymour, Colin

2006-01-01

7

Radiation-induced attenuation in polarization maintaining fibers - Low dose rate response, stress, and materials effects  

Science.gov (United States)

The loss induced in polarization-maintaining (PM) fibers by a low dose rate of less than 0.01 Gy/h, where 1 Gy = 100 rads(Si) radiation exposure, has been found to vary from less than 0.4 to about 6 dB/km-10 Gy, depending on the wavelength of measurement and the fiber. Correlations have been established between low dose rate response and the 'permanent' induced loss determined by fitting the recovery of the induced loss following high dose rate exposure to nth-order kinetics. Using this technique, both 0.85- and 1.3-micron PM fibers have been found which show virtually no permanent incremental loss and would therefore appear to be resistant to low dose rate radiation environments. The asymmetric stress inherent in PM fibers has been shown to reduce the permanent induced loss, while the recovery of the radiation-induced attenuation was found to be enhanced in fibers with Ge-F-doped silica clads.

Friebele, E. Joseph; Gingerich, Michael E.; Brambani, Louise A.; Hickey, Steven J.; Onstott, James R.

1989-12-01

8

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

International Nuclear Information System (INIS)

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

9

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)

10

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

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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

11

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

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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

12

Mechanisms of Low Dose Radiation-induced T helper Cell Function  

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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

13

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

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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

14

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)

15

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

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

?urovi? Branka 1

2004-01-01

16

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

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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.

17

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)

18

Chronic low dose {gamma}-radiation induced increased cytogenetic damage in human population  

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In order to evaluate the biomedical effects of chronic low-dose {gamma}-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 {alpha}-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 micronuclei in the exposed residents were derived mostly from chronic low dose {gamma}-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)

Chang, W.P.; Chen, Dingping; Hwang, Bing-fan [National Yang Ming Univ., Taipei, TW (China). School of Medicine

1996-12-31

19

Will radiation-induced bystander effects or adaptive responses impact on the shape of the dose response relationships at low doses of ionizing radiation?  

Science.gov (United States)

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 potential impact of these two low dose effects on the shape of the dose response relationship will be discussed. PMID:18648589

Morgan, William F

2006-01-01

20

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

International Nuclear Information System (INIS)

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

 
 
 
 
21

High and low doses of ionizing radiation induce different secretome profiles in a human skin model.  

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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. PMID:24642900

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

2014-01-01

22

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)

23

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

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

24

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

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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

25

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

International Nuclear Information System (INIS)

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

26

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

Science.gov (United States)

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

Bréchignac, François; Paquet, François

2013-08-01

27

Low doses of ionizing radiation induce nuclear activity in human tumour cell lines which catalyses homologous double-strand recombination  

International Nuclear Information System (INIS)

Activity catalysing double-strand DNA recombination has been investigated in human tumour cell lines using an in vitro assay in which nuclear extracts from tumour cells are used to catalyse homologous recombination between deletion plasmids. The cell lines investigated showed comparable constitutive levels of recombination activity. In several cell lines a two- to fourfold increase in the frequency of double-strand recombinational events catalysed by nuclear extracts was observed if the cells were exposed to low doses of ionizing radiation. The response was greatest for cells harvested at 6 h after radiation exposure, and the dose to produce an optimal effect was 25 cGy. Cell lines showing this response included a relatively radioresistant human colon cancer line and two cis-DDP (cis-diamminedichloroplatinum II) resistant ovarian tumour cell lines which are cross-resistant to radiation. Sub-lethal doses of cis-DDP were also effective in inducing up-regulation of recombinational activity in the cis-DDP resistant cell lines. No change in recombinational activity was seen for a radiation/drug-sensitive ovarian cell line following exposure to low drug or radiation doses. These findings are of particular interest since they involve a radiation-induced process with potential for direct involvement in DNA repair. Further studies will be aimed at determining if the extent of resistance to cytotoxic agents is causally related to the degree of inducible recombination activity. (orig.). With 1 fig., 3 tabs

28

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

29

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

2014-01-01

30

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

International Nuclear Information System (INIS)

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

31

The Dose Window for Radiation-Induced Protective Adaptive Responses  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Mitchel, Ronald E. J.

2010-01-01

32

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

33

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

International Nuclear Information System (INIS)

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

34

Enhancement of Bio-Protective Functions by Low Dose/Dose-Rate Radiation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Effects of low-dose-rate gamma-irradiation on the process of tumorigenesis were investigated in mice treated with a carcinogenic agent or irradiated with high dose X-rays at a high dose rate. A prolonged gamma irradiation at approximately 1 mGy/hr suppressed the appearance of skin tumors induced by methylcholanthrene and delayed the appearance of radiation-induced thymic lymphomas in C57BL/6 mice. We also investigated the effects of low-dose-rate irradiation on disease model mice. In Type II ...

Sakai, Kazuo; Nomura, Takaharu; Ina, Yasuhiro

2006-01-01

35

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)

36

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

International Nuclear Information System (INIS)

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

37

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

Science.gov (United States)

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

Azzam, Edouard

38

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

International Nuclear Information System (INIS)

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

39

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)

40

Immunological Mechanism of the Low-Dose Radiation-Induced Suppression of Cancer Metastases in a Mouse Model  

Digital Repository Infrastructure Vision for European Research (DRIVER)

According to the doctrine underlying the current radiation protection regulations each, no matter how small, exposure to ionizing radiation may be carcinogenic. However, numerous epidemiological observations demonstrate that cancer incidence and/or mortality are not elevated among inhabitants of the high- versus low-natural-background radiation areas and homes. Results of our own and other authors’ studies described in this paper bear testimony to the possibility that stimulation of the ant...

Nowosielska, Ewa M.; Cheda, Aneta; Wrembel-wargocka, Jolanta; Janiak, Marek K.

2010-01-01

 
 
 
 
41

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

42

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

Science.gov (United States)

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

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

2014-03-01

43

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? 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

44

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

45

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

46

Liv. 52 protection against radiation induced lesions in mammalian liver  

Energy Technology Data Exchange (ETDEWEB)

Effect of Liv. 52 on mammalian liver was studied after whole-body exposure to 5.5 Gy of /sup 60/Co 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.

Saini, M.R.; Saini, N. (Rajasthan Univ., Jaipur (India); E.S.I. Hospital, Jaipur (India))

1985-01-01

47

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

48

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

Scott, B. R.

2008-01-01

49

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?G6PDH activity). Dietary lipotropes prevented these effects completely or partially and the effects were lipotrope dependent. Kinetics (maximum velocity value V max, catalytic efficiency and Michaelis constant K m) of G6PDH enzyme from crude extracts of liver and kidney indicated inhibition due to endosulfan but lipotropes could protect enzyme and showed a stabilizing effect. The supplements also helped maintain integrity of histoarchitecture of the hepatocytes in endosulfan-exposed fish to a great extent. Feeding lipotropes to fish reared in endosulfan-free water also improved hematological and serum protein and lipid profiles and were immunostimulatory. In conclusion, dietary lipotropes, especially betaine and lecithin at the levels used, improve erythropoiesis, serum protein and lipid profile, anti-oxidant status, immunocompetence, neurotransmission, and protect the livers of L. 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

50

Protection of liposomal lipids against radiation induced oxidative damage  

International Nuclear Information System (INIS)

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

51

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

International Nuclear Information System (INIS)

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

52

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)

53

Current study on the biological effects of low dose radiation and molecular epidemiology in radiation protection  

International Nuclear Information System (INIS)

Summarization was made of some important problems in the biological effects of low dose radiation studies, such as the Linear-No-Threshold Hypothesis, the evaluation of the risk of radiation carcinogensis, the mechanisms of radiation carcinogensis and the bystander effect of radiation. At the same time, the application of the molecular epidemiology in studies of radiation protection and its current status were introduced briefly. (authors)

54

Epidemiologic studies of nuclear workers suggest a protective effect of exposure at low doses and low dose rates  

International Nuclear Information System (INIS)

Scientific and epidemiological studies of nuclear facility workers and their interpretation can profoundly influence energy policies of our nations into the 21st century. There are 4 basic premises to be examined; 1. Precise estimation of small occupational hazards has required the development of new epidemiological techniques, including the combination of results of many different studies, these methods are now available; 2. data from a relatively small number of reliable study cohorts of nuclear facility workers, including nuclear energy workers, support the belief that occupational hazards have been small, but the data are still insufficient to provide precise estimates of their size; 3. the few studies that can be used, limited because of their disparate approaches to analysis of data, to relate risk quantitatively to low levels of dose received at low dose rates appear compatible with risks predicted from experience of persons exposed acutely to high doses; 4. Several unsolved biological problems relating to the mechanisms of cancer induction, such as confounding and exposure to other carcinogens in the workplace, complicate accurate predictions of risk. (author). 13 refs

55

Low-dose cancer risk modeling must recognize up-regulation of protection.  

Science.gov (United States)

IONIZING RADIATION PRIMARILY PERTURBS THE BASIC MOLECULAR LEVEL PROPORTIONAL TO DOSE, WITH POTENTIAL DAMAGE PROPAGATION TO HIGHER LEVELS: cells, tissues, organs, and whole body. There are three types of defenses against damage propagation. These operate deterministically and below a certain impact threshold there is no propagation. Physical-static defenses precede metabolic-dynamic defenses acting immediately: scavenging of toxins; - molecular repair, especially of DNA; - removal of damaged cells either by apoptosis, necrosis, phagocytosis, cell differentiation-senescence, or by immune responses, - followed by replacement of lost elements. Another metabolic-dynamic defense arises delayed by up-regulating immediately operating defense mechanisms. Some of these adaptive protections may last beyond a year and all create temporary protection against renewed potentially toxic impacts also from non-radiogenic endogenous sources. Adaptive protections have a maximum after single tissue absorbed doses around 100 to 200 mSv and disappear with higher doses. Low dose rates initiate maximum protection likely at lower cell doses delivered repetitively at certain time intervals. Adaptive protection preventing only about 2 - 3 % of endogenous life-time cancer risk would fully balance a calculated induced cancer risk at about 100 mSv, in agreement with epidemiological data and concordant with an hormetic effect. Low-dose-risk modeling must recognize up-regulation of protection. PMID:20585440

Feinendegen, Ludwig E; Pollycove, Myron; Neumann, Ronald D

2010-01-01

56

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

57

[Protective effect of natural dietary antioxidants on space radiation-induced damages].  

Science.gov (United States)

This paper described the radiation-induced damage on human body in space and summarized the studies of antioxidants such as Vit C, Vit E, Vit A, beta-carotene, flavonoids, polysaccharide, green-tea and Spirulina protection against radiation-induced damage. Application prospects of natural antioxidants in space food were also put forward in this article. PMID:14989308

Chen, Bin; Zhou, Xi-cheng

2003-01-01

58

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

International Nuclear Information System (INIS)

omic 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)

59

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 prejudice

60

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  

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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

 
 
 
 
61

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

International Nuclear Information System (INIS)

rocytes, increased PCE/NCE ratio, increase in the GSH, GST, SOD, CAT and decreased LPx levels were observed in ZO by pretreated group when compared to the irradiated animals. Our in vitro and in vivo studies demonstrate the potential of ZO in mitigating radiation-induced cytotoxic, genotoxicity, apoptosis in cell culture and animal mortality, cytogenetic damage, intestinal and bone marrow protection in vivo. Radioprotective potential of ZO may be attributed to the inhibition radiation-induced decline in the endogenous antioxidant levels, scavenging of radiation-induced free radicals and by the suppression of lipid peroxidation as well as oxidative stress. (author)

62

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

63

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

64

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

International Nuclear Information System (INIS)

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

65

Prevention of ?-radiation induced cellular genotoxicity by tempol: protection of hematopoietic system.  

Science.gov (United States)

Tempol (TPL) under in vitro conditions reduced the extent of gamma radiation induced membrane lipid peroxidation and disappearance of covalently closed circular form of plasmid pBR322. TPL protected cellular DNA from radiation-induced damage in various tissues under ex vivo and in vivo conditions as evidenced by comet assay. TPL also prevented radiation induced micronuclei formation (in peripheral blood leucocytes) and chromosomal aberrations (in bone marrow cells) in whole body irradiated mice. TPL enhanced the rate of repair of cellular DNA (blood leucocytes and bone marrow cells) damage when administered immediately after radiation exposure as revealed from the increased Cellular DNA Repair Index (CRI). The studies thus provided compelling evidence to reveal the effectiveness of TPL to protect hematopoietic system from radiation injury. PMID:22609778

Ramachandran, Lakshmy; Nair, Cherupally Krishnan Krishnan

2012-09-01

66

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)

67

Leflunomide protects mice from multiple low dose streptozotocin (MLD-SZ)-induced insulitis and diabetes  

Science.gov (United States)

In certain animal models of autoimmunity the isoxasol derivative leflunomide has been reported to exert a protective effect against autodestruction. In the present study, the immunomodulatory potential of the main metabolite of leflunomide, A77 1726, in experimentally induced autoimmune diabetes was investigated. The disease was induced in genetically susceptible CBA/H mice by multiple low doses of streptozotocin (MLD-SZ, 40 mg/kg per day, given intraperitoneally for 5 consecutive days). Effects of leflunomide were evaluated by two treatment protocols: mice treated with MLD-SZ were injected intraperitoneally with A77 1726 for 10 consecutive days, either during the first 10 days of the disease (early treatment), or starting from day 10 after disease induction (late treatment). Disease manifestations defined by hyperglycaemia, mononuclear infiltration into pancreas, expression of interferon-gamma (IFN-?) and inducible nitric oxide synthase (iNOS) and destruction of the islets of Langerhans were reduced in a dose-dependent fashion after early treatment with A77 1726 (dose range of 5–35 mg/kg per day). Moreover, late treatment with the high dose of the drug (25 mg/kg per day), started when the autoimmune disease was already apparent, arrested progression of ongoing inflammatory response. Analysis of the effects of A77 1726 on the adhesive interactions of spleen-derived or peripheral blood-derived mononuclear cells from MLD-SZ-treated and normal mice demonstrated that the drug inhibits both ex vivo and in vitro spontaneous mononuclear cell aggregation, thus suggesting that an important component of leflunomide's immunomodulatory action is suppression of adhesive interactions. These results demonstrate both preventive and therapeutic effects of leflunomide in a model of MLD-SZ-induced diabetes and suggest that the drug may be considered a potent therapeutic tool for autoimmune inflammatory disorders, including diabetes. PMID:10403914

STOSIC-GRUJICIC, S; DIMITRIJEVIC, M; BARTLETT, R

1999-01-01

68

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)

69

Liv.52 protection against radiation induced lesions in mammalian liver  

International Nuclear Information System (INIS)

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

70

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

International Nuclear Information System (INIS)

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

71

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

International Nuclear Information System (INIS)

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

72

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

International Nuclear Information System (INIS)

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

73

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

Energy Technology Data Exchange (ETDEWEB)

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

Jian Li

2012-11-07

74

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

Science.gov (United States)

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

DU, SHASHA; YAO, QIWEI; TAN, PEIXIN; XIE, GUOZHU; REN, CHEN; SUN, QUANQUAN; ZHANG, XIAO; ZHENG, RONG; YANG, KAIJUN; YUAN, YAWEI; YUAN, QUAN

2013-01-01

75

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

Science.gov (United States)

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

Kertmen, Hayri; Gürer, Bora; Y?lmaz, Erdal Re?it; Sanl?, Ahmet Metin; Sorar, Mehmet; Ar?kök, Ata Türker; Sargon, Mustafa Fevzi; Kanat, Mehmet Ali; Ergüder, Berrin Imge; Sekerci, Zeki

2013-08-15

76

Health effect of low dose/low dose rate radiation  

International Nuclear Information System (INIS)

lly conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose radiation effects may affect the concept of human carcinogenic process. (T.T.)

77

Delta-tocotrienol protects mice from radiation-induced gastrointestinal injury.  

Science.gov (United States)

We recently demonstrated that natural delta-tocotrienol (DT3) significantly enhanced survival in total-body irradiated (TBI) mice, and protected mouse bone marrow cells from radiation-induced damage through Erk activation-associated mTOR survival pathways. Here, we further evaluated the effects and mechanisms of DT3 on survival of radiation-induced mouse acute gastrointestinal syndrome. DT3 (75-100 mg/kg) or vehicle was administered as a single subcutaneous injection to CD2F1 mice 24 h before 10-12 Gy (60)Co total-body irradiation at a dose rate of 0.6 Gy/min and survival was monitored. In a separate group of mice, jejunum sections were stained with hematoxylin and eosin and the surviving crypts in irradiated mice were counted. Apoptosis in intestinal epithelial cells was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining and bacterial translocation from gut to heart, spleen and liver in irradiated mice were evaluated. DT3 (75 mg/kg) significantly enhanced survival in mice that received 10, 10.5, 11 or 12 Gy TBI. Administration of DT3 protected intestinal tissue, decreased apoptotic cells in jejunum and inhibited gut bacterial translocation in irradiated mice. Furthermore, DT3 significantly inhibited radiation-induced production of pro-inflammatory factors interleukin-1? and -6 and suppressed expression of protein tyrosine kinase 6 (PTK6), a stress-induced kinase that promotes apoptosis in mouse intestinal cells. Our data demonstrate that administration of DT3 protected mice from radiation-induced gastrointestinal system damage. PMID:24294967

Li, Xiang Hong; Ghosh, Sanchita P; Ha, Cam T; Fu, Dadin; Elliott, Thomas B; Bolduc, David L; Villa, Vilmar; Whitnall, Mark H; Landauer, Michael R; Xiao, Mang

2013-12-01

78

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

International Nuclear Information System (INIS)

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

79

Protection against radiation induced oxidative stress by Syzygium cumini seed extract  

International Nuclear Information System (INIS)

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

80

Melatonin protects human blood lymphocytes from radiation-induced chromosome damage  

Energy Technology Data Exchange (ETDEWEB)

Cells in human peripheral blood were treated in vitro with increasing concentrations of melatonin (0.5 or 1.0 or 2.0 mM) for 20 min at 37[+-]1C and then exposed to 150 cGy [gamma]-radiation from a [sup 137]Cs source. The lymphocytes which were pre-treated with melatonin exhibited a significant and concentration-dependent decrease in the frequency of radiation-induced chromosome damage as compared with the irradiated cells which did not receive the pre-treatment. The extent of the reduction in radiation-induced chromosome damage observed with 2.0 mM melatonin was similar to that found in lymphocytes pre-treated with 1.0 M dimethyl sulfoxide, a known free radical scavenger. Melatonin at 2.0 mM (a 500x lower concentration) was as effective in decreasing the radiation-induced chromosome damage as dimethyl sulfoxide at 1.0 M. These observations may have implications for human protection against damage due to endogenously produced free radicals and also due to exposure to free radical producing physical and chemical mutagens and carcinogens

Vijayalaxmi; Meltz, Martin L. (Department of Radiology, The University of Texas Health Science Center, San Antonio, TX (United States)); Reiter, Russel J. (Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, TX (United States))

1995-01-01

 
 
 
 
81

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.

82

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

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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)

83

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

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icant 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

84

Protection against radiation-induced damage of 6-propyl-2-thiouracil (PTU) in thyroid cells.  

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Many epidemiologic studies have shown that the exposure to high external radiation doses increases thyroid neoplastic frequency, especially when given during childhood or adolescence. The use of radioprotective drugs may decrease the damage caused by radiation therapy and therefore could be useful to prevent the development of thyroid tumors. The aim of this study was to investigate the possible application of 6-propyl-2-thiouracil (PTU) as a radioprotector in the thyroid gland. Rat thyroid epithelial cells (FRTL-5) were exposed to different doses of ? irradiation with or without the addition of PTU, methimazole (MMI), reduced glutathione (GSH) and perchlorate (KClO4). Radiation response was analyzed by clonogenic survival assay. Cyclic AMP (cAMP) levels were measured by radioimmunoassay (RIA). Apoptosis was quantified by nuclear cell morphology and caspase 3 activity assays. Intracellular reactive oxygen species (ROS) levels were measured using the fluorescent dye 2',7'-dichlorofluorescein-diacetate. Catalase, superoxide dismutase and glutathione peroxidase activities were also determined. Pretreatment with PTU, MMI and GSH prior to irradiation significantly increased the surviving cell fraction (SF) at 2 Gy (P < 0.05), while no effect was observed with KClO4. An increase in extracellular levels of cAMP was found only in PTU treated cells in a dose and time-dependent manner. Cells incubated with agents that stimulate cAMP (forskolin and dibutyril cAMP) mimicked the effect of PTU on SF. Moreover, pretreatment with the inhibitor of protein kinase A, H-89, abolished the radioprotective effect of PTU. PTU treatment diminished radiation-induced apoptosis and protected cells against radiation-induced ROS elevation and suppression of the antioxidant enzyme's activity. PTU was found to radioprotect normal thyroid cells through cAMP elevation and reduction in both apoptosis and radiation-induced oxidative stress damage. PMID:23398355

Perona, Marina; Dagrosa, María A; Pagotto, Romina; Casal, Mariana; Pignataro, Omar P; Pisarev, Mario A; Juvenal, Guillermo J

2013-03-01

85

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

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

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

2010-01-01

86

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

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Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiation-induced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways. PMID:24078877

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

2014-03-01

87

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

88

Cancer and Low Dose Responses In Vivo: Implications for Radiation Protection  

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The Linear No Threshold (LNT) hypothesis states that ionizing radiation risk is directly proportional to dose, without a threshold. This hypothesis, along with a number of additional derived or auxiliary concepts such as radiation and tissue type weighting factors, and dose rate reduction factors, are used to calculate radiation risk estimates for humans, and are therefore fundamental for radiation protection practices. This system is based mainly on epidemiological data of cancer risk in hum...

Mitchel, R. E. J.

2007-01-01

89

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

International Nuclear Information System (INIS)

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

90

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

91

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

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

92

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

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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)

93

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

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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)

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 naïve 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  

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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

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

International Nuclear Information System (INIS)

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

97

Protective effect of an aminothiazole compound against ?-radiation induced oxidative damage.  

Science.gov (United States)

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. During radiotherapy of cancer, one of the undesirable side-effects is toxicity to normal cells. Compounds with antioxidant activities are being tried as 'prophylactic radioprotectants' to overcome this problem. We evaluated the protective effect of an aminothiazole compound, in the form of dendrodoine analogue (DA) originally derived from a marine tunicate, against ?-radiation-induced damage to lipid, protein, and DNA besides its cytotoxicity. Oxidative damage was examined by different biochemcial assays. Our studies reveal that DA gave significant protection, in fairly low concentrations, against damage induced by ?-radiation to rat liver mitochondria, plasmid pBR322 DNA, and mouse splenic lymphocytes in vitro. It also protected against oxidative damage in whole-body irradiated mice exposed to therapeutic dose of radiation (2 Gy) in vivo. Spleen, a major target organ for radiation damage, of the irradiated mice showed significant protection when treated with DA, as examined by histopathology. In conclusion, due to the possible protective effects against normal cells/tissues both in vitro and in vivo, DA shows potential to be a radioprotector for possible use during radiotherapy. PMID:21923621

De, Strayo; Devasagayam, Thomas P A

2011-11-01

98

Partial neural protection with prophylactic low-dose melatonin after asphyxia in preterm fetal sheep.  

Science.gov (United States)

Melatonin is a naturally occurring indolamine with mild antioxidant properties that is neuroprotective in perinatal animals. There is limited information on its effects on preterm brain injury. In this study, 23 chronically instrumented fetal sheep received 25?minutes of complete umbilical cord occlusion at 101 to 104 days gestation (term is 147 days). Melatonin was administered to the ewe 15?minutes before occlusion (0.1?mg/kg bolus followed by 0.1?mg/kg per hour for 6?hours, n=8), or the equivalent volume of vehicle (2% ethanol, n=7), or saline (n=8), or maternal saline plus sham occlusion (n=8). Sheep were killed after 7 days recovery in utero. Fetal blood pressure, heart rate, nuchal activity, and temperature were similar between groups. Vehicle infusion was associated with improved neuronal survival in the caudate nucleus, but greater neuronal loss in the regions of the hippocampus, with reduced proliferation and increased ameboid microglia in the white matter (P<0.05). Maternal melatonin infusion was associated with faster recovery of fetal EEG, prolonged reduction in carotid blood flow, similar neuronal survival to vehicle, improved numbers of mature oligodendrocytes, and reduced microglial activation in the white matter (P<0.05). Prophylactic maternal melatonin treatment is partially protective but its effects may be partly confounded by ethanol used to dissolve melatonin. PMID:24103904

Drury, Paul P; Davidson, Joanne O; Bennet, Laura; Booth, Lindsea C; Tan, Sidhartha; Fraser, Mhoyra; van den Heuij, Lotte G; Gunn, Alistair J

2014-01-01

99

Lipotropes protect against pathogen-aggravated stress and mortality in low dose pesticide-exposed fish.  

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The decline of freshwater fish biodiversity corroborates the trends of unsustainable pesticide usage and increase of disease incidence in the last few decades. Little is known about the role of nonlethal exposure to pesticide, which is not uncommon, and concurrent infection of opportunistic pathogens in species decline. Moreover, preventative measures based on current knowledge of stress biology and an emerging role for epigenetic (especially methylation) dysregulation in toxicity in fish are lacking. We herein report the protective role of lipotropes/methyl donors (like choline, betaine and lecithin) in eliciting primary (endocrine), secondary (cellular and hemato-immunological and histoarchitectural changes) and tertiary (whole animal) stress responses including mortality (50%) in pesticide-exposed (nonlethal dose) and pathogen-challenged fish. The relative survival with betaine and lecithin was 10 and 20 percent higher. This proof of cause-and-effect relation and physiological basis under simulated controlled conditions indicate that sustained stress even due to nonlethal exposure to single pollutant enhances pathogenic infectivity in already nutritionally-stressed fish, which may be a driver for freshwater aquatic species decline in nature. Dietary lipotropes can be used as one of the tools in resurrecting the aquatic species decline. PMID:24690771

Kumar, Neeraj; Gupta, Subodh; Chandan, Nitish Kumar; Aklakur, Md; Pal, Asim Kumar; Jadhao, Sanjay Balkrishna

2014-01-01

100

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

 
 
 
 
101

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

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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

102

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

103

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

International Nuclear Information System (INIS)

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

104

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

International Nuclear Information System (INIS)

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

105

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

International Nuclear Information System (INIS)

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

106

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

International Nuclear Information System (INIS)

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

107

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)

108

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

International Nuclear Information System (INIS)

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

109

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

International Nuclear Information System (INIS)

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

110

Protective effects of Korean red ginseng on radiation-induced oral mucositis in a preclinical rat model.  

Science.gov (United States)

Numerous studies' attempts to improve radiation-induced oral mucositis have not produced a qualified treatment yet. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in an in vivo rat model. After 20 Gy of irradiation, rats were divided randomly into the following 4 groups: control, KRG only, radiotherapy (RT) only, and RT + KRG group. The rats were monitored in terms of survival rate, activity, mucositis grade, oral intake, and body weight. The tongue, buccal mucosa, and submandibular gland (SMG) were harvested, and the weight of the SMG was analyzed. The samples then underwent hematoxylin and eosin, TUNEL, and immunohistochemical staining. Radiation-induced severe oral mucositis and SMG injury led to poor oral intake and delayed healing, resulting in the death of some rats. We found that survival rate, oral intake, and body weight increased. Moreover, rats treated with KRG showed less severe mucositis and decreased histologic changes of the oral mucosa and SMG. Furthermore, we showed that the protective effects of KRG were caused by inhibition of the apoptotic signal transduction pathway linked to caspase-3. In conclusion, KRG protects the oral mucosa and SMG from radiation-induced damage by inhibiting caspase-mediated apoptosis in rats. PMID:24617451

Chang, Jae Won; Choi, Jae Won; Lee, Bum Hei; Park, Ju Kyeong; Shin, Yoo Seob; Oh, Young-Taek; Noh, O Kyu; Kim, Chul-Ho

2014-01-01

111

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

International Nuclear Information System (INIS)

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

112

Experimental study of the protective effect of ambroxol on radiation-induced pulmonary injury  

International Nuclear Information System (INIS)

Objective: To evaluate the protective effect of ambroxol on radiation induced pulmonary injury. Methods: 240 BALB/c male mice were divided randomly into control group (C), irradiation alone (SI) and irradiation plus ambroxol (SI + A) groups. The right chests (size:2 cm x 2.5 cm) of mice were irradiated by 4 MV linear accelerator for a total doses of 25 Gy, 5 Gy/time, one time /day, 5 time/week; ambroxol was orally administered (50 mg · kg-1 ·d-1) from one week before irradiation until the mice were killed. Hydroxyproline content of lung-irradiated tissue and plasma TGF-?1 level were detected from 1 to 8 months. Results: Hydroxyproline content increased starting from 3 month, reaching peak at 5 and 6 month, and it was higher in SI group than that in A + SI group; contents in A + SI group was also higher than that of C group in 5-6 months respectively. Cell ultramicro-structure of lung tissue was damaged at different level in 1 and 3 months, a large fribric tissue was even accumulated at 6 months in SI group, while above cases were obviously slight in SI + A group. Conclusions: Irradiation could induce the hydroxyproline increase in lung-irradiated tissue, change plasma TGF-?1 level lung tissue, ambroxol may reduce the radiation lung injury. (authors)

113

Protective effect of cerium ion against ultraviolet B radiation-induced water stress in soybean seedlings.  

Science.gov (United States)

Effects of cerium ion (Ce(III)) on water relations of soybean seedlings (Glycine max L.) under ultraviolet B radiation (UV-B, 280-320 nm) stress were investigated under laboratory conditions. UV-B radiation not only affected the contents of two osmolytes (proline, soluble sugar) in soybean seedlings, but also inhibited the transpiration in soybean seedlings by decreasing the stomatal density and conductance. The two effects caused the inhibition in the osmotic and metabolic absorption of water, which decreased the water content and the free water/bound water ratio. Obviously, UV-B radiation led to water stress, causing the decrease in the photosynthesis in soybean seedlings. The pretreatment with 20 mg L(-1) Ce(III) could alleviate UV-B-induced water stress by regulating the osmotic and metabolic absorption of water in soybean seedlings. The alleviated effect caused the increase in the photosynthesis and the growth of soybean seedlings. It is one of the protective effect mechanisms of Ce(III) against the UV-B radiation-induced damage to plants. PMID:22095292

Mao, Chun Xia; Chen, Min Min; Wang, Lei; Zou, Hua; Liang, Chan Juan; Wang, Li Hong; Zhou, Qing

2012-06-01

114

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)

115

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

International Nuclear Information System (INIS)

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

116

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

117

Protection of T cells from radiation-induced apoptosis by Cepharanthin.  

Science.gov (United States)

Cepharanthin (CE) is a medicine that contains several biscoclaurine alkaloids. We examined the effects of CE on radiation-induced T cell apoptosis. Radiation induced apoptosis on T cells in a dose-dependent manner, while CE inhibited radiation-induced apoptosis. CE also attenuated the cytotoxic effects of radiation on the proliferative response of T cells. CE inhibited not only the loss of mitochondrial transmembrane potential but also the activation of caspase 3 in irradiated T cells. Radiation plus CE induced the up-regulation of Bax and the down-regulation of Bcl-2 in T cells in comparison with radiation alone. These results suggest that CE inhibits the signal transduction pathway of apoptosis induced by radiation, regardless of the expression of Bcl-2 or Bax. PMID:11710538

Oyaizu, H; Adachi, Y; Yasumizu, R; Ono, M; Ikebukuro, K; Fukuhara, S; Ikehara, S

2001-11-01

118

Protection of DNA and membrane from ?-radiation induced damage by the extract of Acorus calamus Linn.: An in vitro study.  

Science.gov (United States)

Acorus calamus, an ethnomedicinally important plant, was investigated for its protecting activity against radiation induced DNA and membrane damage. The in vitro free radical scavenging activity of the extract (water:ethanol, 1:1) of A. calamus was studied by parameters viz DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical scavenging activity, hydroxyl radical scavenging activity, and superoxide radical scavenging activity. Membrane damage due to radiation exposure was measured as the peroxidation of lipids in terms of thiobarbituric acid reacting substance (TBARS). The in vitro DNA damage was monitored by assessing the radiation induced relaxation of supercoiled plasmid DNA (pBR322). Damage to cellular DNA induced by ?-radiation (6Gy) was monitored by alkaline single cell gel electrophoresis or comet assay in murine cells and human peripheral blood leukocytes. Enhancement of DNA repair mechanism was also monitored. The extract effectively scavenged free radicals in a concentration dependent manner. Presence of A. calamus extract during irradiation prevented peroxidation of membrane lipids in mouse liver homogenate. It helped to reduce the disappearance of the covalently closed circular (ccc) form of plasmid DNA following exposure to ?-radiation. Also the A. calamus extract effectively protected DNA from radiation induced strand breaks and enhanced the DNA repair process. Hence A. calamus extract can be used as a good source of natural radioprotecting agent. PMID:21787617

Sandeep, Divyasree; Nair, Cherupally Krishnan Krishnan

2010-05-01

119

Requirements for Identification of Low Dose and Non-Linear Mutagenic Responses to Ionising Radiation  

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Cancer results from multiple changes in gene expression that can occur both genetically and epigenetically. High doses of radiation can lead to mutations and cancer. At high doses the number of mutations caused by radiation is essentially linear with dose. Low dose radiation induced protective responses observed for cancer in vivo and cellular transformation in vitro would predict that hormetic responses would also be observed in mutation assays. Although there are a large number of different...

Sykes, Pamela J.; Day, Tanya K.

2007-01-01

120

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

 
 
 
 
121

Low doses of radiation reduce risks in vivo  

International Nuclear Information System (INIS)

The 'Linear No Threshold' hypothesis, used in all radiation protection practices, assumes that all doses, no matter how low, increase risk. The protective effects of adaptive responses to radiation, shown to exist in lower organisms and in human and other mammalian cells, are inconsistent with this hypothesis. An in vivo test of the hypothesis in mice showed that a 100-mGy dose of ?-radiation protected the mice by increasing latency for acute myeloid leukemia initiated by a subsequent large dose. A similar result was observed in cancer prone mice, where a 10-mGy adapting exposure prior to a large acute dose increased latency for lymphomas without altering frequency. Increasing the adapting dose to 100-mGy eliminated the protective effect. In the cancer prone mice, a 10-mGy dose alone, without a subsequent high dose, increased latency for spontaneous osteosarcomas and lymphomas without altering frequency. Increasing the dose to 100-mGy decreased latency for spontaneous osteosarcomas but still increased latency for lymphomas, indicating that this higher dose was in a transition zone between reduced and increased risk, and that the transition dose from protective to detrimental effects is tumor type specific. In genetically normal fetal mice, prior low doses also protected against radiation induced teratogenic effects. In genetically normal adult male mice, high doses induce mutations in sperm stem cells, detectable as heritable mutations in the offspring of these mice. 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)

122

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 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

123

Protective Effects of Lycopene on the ?-radiation Induced Chromosomal Damage and Cell Killing in Cultured Human Fibroblast Cells  

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Full Text Available Background and Objectives: Lycopene is one of the most potent antioxidants. It is a red, fat soluble pigment found in certain plants and microorganisms. Several studies have demonstrated the ability of lycopene to protect the cells from ionizing radiation induced damage, however, the mechanisms involved are remained to be clear. In the present study, we investigated the radioprotective effect of lycopene on ?-radiation induced cytotoxicity and genotoxicity in human cultured fibroblasts. Subjects and Methods: In irradiated groups fibroblast cells were irradiated with 1, 2 and 4Gy. In lycopene groups fibroblast cells were pretreated with different concentrations of lycopene (2, 10 and 20uM then exposed to different doses of gamma radiation. The extent of cytotoxicity was determined by colony formation assay. The level of genotoxicity was detected by analysis of chromosmome breaks. Results: Using colony formation assay, we observed the increase in cell killing with the increase in ?-radiation dose (1, 2 and 4Gy. Pre-treatment with lycopene (2, 10 and 20?M restored the cell survival, suggesting that lycopene can protect the cells from killing by ionizing radiation. Similarly, lycopene significantly diminished the level of chromosome and chromatid breaks induced by gamma radiations. The maximum protection of fibroblast cells was observed at 10?M of lycopene pretreatment. Conclusion: Data showed that pretreatment with lycopene reduced the level of cell killing and chromosomal breaks and this protecive activity was dependent on the concentration of lycopene. Our finding indicate that lycopene protects human cells from radiation-induced genomic instability, and can reduce the cancerogenic effect of ionizing radiation.Sci Med J 2011;10(5:573-81

AH Saberi

2011-11-01

124

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

International Nuclear Information System (INIS)

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

125

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 against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.

126

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

127

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

International Nuclear Information System (INIS)

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

128

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

129

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.

130

Zinc- or cadmium-pre-induced metallothionein protects human central nervous system cells and astrocytes from radiation-induced apoptosis.  

Science.gov (United States)

We have shown the protection of human central nervous system (CNS) cultures by zinc (Zn) or cadmium (Cd)-pre-induced metallothionein (MT) synthesis from radiation-induced cytotoxicity (lactate dehydrogenase (LDH) release and neuronal dendritic injury). The present study is to further define the types of cell death induced by different dose levels of radiation and investigate the effect of MT induction (by Zn or Cd) on radiation-induced apoptosis in primary human CNS and astrocyte cultures. Apoptosis was detected by fragmented DNA electrophoresis, TUNEL technique, and propidium iodide staining. Expression of MT protein was examined by immunofluorescent staining. Results showed that exposure of primary human CNS cultures to 15 and 30 Gy gamma-radiation predominantly induced apoptotic cell death, while exposure to 60 Gy gamma-radiation predominantly induced necrotic cell death. Normal primary human CNS cultures showed weak MT staining, while primary human CNS cultures exposed to Zn or Cd showed intense MT staining. The induced apoptotic cell death by exposure to 30 Gy gamma-radiation increased to a maximum level at 12 and 24 h, and was reduced significantly by Zn or Cd pre-induced MT. Using primary human astrocytes, the induction of MT protein by Zn or Cd was further confirmed. The enhanced MT expression also afforded a significant protection from 30 Gy gamma-ray-induced apoptosis in the primary human astrocytes. These results suggest that MT protected human CNS cells from apoptosis following ionizing radiation, probably through its antioxidant property. PMID:14687759

Cai, Lu; Iskander, Sammy; Cherian, M George; Hammond, Robert R

2004-02-01

131

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

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

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

2014-12-01

132

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

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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

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

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

Hanaa F. Waer, **Seham A. Helmy

2012-10-01

134

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

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

135

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

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

Qian Liren

2010-01-01

136

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

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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  

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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

Protection by Low-Dose Kanamycin against Noise-Induced Hearing Loss in Mice: Dependence on Dosing Regimen and Genetic Background  

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We recently demonstrated that sub-chronic low-dose kanamycin (KM, 300 mg/kg sc, 2x/day, 10 days) dramatically reduces permanent noise-induced hearing loss (NIHL) and hair cell loss in 1 month old CBA/J mice (Fernandez et al., 2010, J. Assoc. Res. Otolaryngol. 11, 235–244). Protection by KM remained for at least 48 hours after the last dose, and appeared to involve a cumulative effect of multiple doses as part of a preconditioning process. The first month of life lies within the early ‘sen...

Ohlemiller, Kevin K.; Rice, Mary E. Rybak; Rosen, Allyson D.; Montgomery, Scott C.; Gagnon, Patricia M.

2011-01-01

139

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

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

140

Protective effect of superoxide dismutase in radiation-induced intestinal inflammation  

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

 
 
 
 
141

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

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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

142

Low-dose immunization of northern bobwhites (Colinus virginianus) with Eimeria lettyae provides protection against a high-dose challenge.  

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To determine whether northern bobwhite quail (Colinus virginianus) could be immunized against Eimeria lettyae by a low-dose inoculation of oocysts, we inoculated 30 birds each with either 100 or 1000 oocysts at 2 days of age (given orally by pipette). Four weeks after immunization, the immunized birds and unimmunized controls were challenged with 1 x 10(6) E. lettyae oocysts. Eight days after challenge, birds were killed and weighed, and their intestines examined for gross lesions. Effectiveness of the immunization was measured by analyzing weight gain, intestinal lesions, severity of diarrhea, feed conversion ratio, and oocyst production. After challenge, birds immunized with 100 or 1000 oocysts gained an average of 33.3 g and 28.9 g, respectively, whereas unimmunized challenged birds gained an average of 11.5 g. Immunized quail produced approximately 99.7% fewer oocysts, had minimal gross intestinal and cecal lesions, had minimal diarrhea, and had a 50% lower feed conversion ratio compared to unimmunized challenged controls. These findings indicate that vaccination is a viable option for controlling coccidiosis in quail and that further research into vaccination is warranted. PMID:21313842

Gerhold, R W; Fuller, A L; Beckstead, R B; McDougald, L R

2010-12-01

143

Radiation-induced genomic instability and bystander effects: implications for radiation protection  

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Evidence has emerged over the past decade for the existence of two cellular phenomenons which challenge the standard paradigms for the induction of biological effects by ionizing radiation. In both cases, important genetic changes arise in cells that in themselves receive no radiation exposure. In the first, radiation induces a type of transmissible genomic instability in cells that leads to a persistent enhancement in the rate at which genetic alterations including mutations and chromosomal aberrations arise in the descendants of the original irradiated cell after many generations of replication. In the bystander effect, damage signals are transmitted from irradiated to non-irradiated cells in the population, leading to the occurrence of biologic effects in these 'bystander' cells. In this review, our current knowledge concerning these two phenomena is described and their potential impact on the estimation of risks of low level radiation exposure discussed. (author)

144

Protection by S-2-(3-aminopropylamino)ethylphosphorothioic acid against radiation-induced leg contractures in mice  

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S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR-2721) was shown to provide marked protection against development of radiation-induced leg contractures in C3Hf/Kam mice whose legs were exposed to single doses of gamma-radiation. The radiation doses ranged from 3300 to 6200 rads delivered to the right hind thighs from two parallelly opposed 137Cs sources. WR-2721 was given i.p. 30 min before irradiation. The severity of radiation-induced leg contractures in untreated and WR-2721-treated mice was followed for 342 days after irradiation. The degree of leg contractures in both control and WR-2721-treated mice increased up to 100 days after radiation, when the change stabilized, remaining more or less at the same level to the end of the observation period. During this entire period, the severity of contractures was less in WR-2721-treated mice. The dose-modifying factor for the level of 5 mm reduction in leg extension was 1.5 at 182 days after irradiation. Since WR-2721 did not prevent the radiocurability of 8-mm fibrosarcomas growing in the same legs, these data imply that WR-2721 has a high potential for increasing therapeutic gain when combined with irradiation in the treatment of tumors of an appreciable size

145

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

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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

146

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

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

147

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

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BrdU 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

148

Semiquinone fraction isolated from Bacillus sp. INM-1 protects hepatic tissues against ?-radiation induced toxicity.  

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Present study was focused on evaluation of a semiquinone glucoside derivative (SQGD) isolated from radioresistant bacterium Bacillus sp. INM-1 for its ability against ? radiation induced oxidative stress in irradiated mice. Animals were divided into four group, i.e., (i) untreated control mice; (ii) SQGD treated (50 mg/kg b. wt. i.p.) mice; (iii) irradiated (10 Gy) mice; and (iv) irradiated mice which were pre-treated (-2 h) with SQGD (50 mg/kg b. wt. i.p.). Following treatment, liver homogenates of the treated mice were subjected to endogenous antioxidant enzymes estimation. Result indicated that SQGD pre-treatment, significantly (P induced superoxide dismutase (SOD) (19.84 ± 2.18% at 72 h), catalase (CAT) (26.47 ± 3.11% at 12 h), glutathione (33.81 ± 1.99% at 24 h), and glutathione-S-transferase (24.40 ± 2.65% at 6 h) activities in the liver of mice as compared with untreated control. Significant (P liver homogenate of H2 O2 treated mice which were found to be significantly inhibited in H2 O2 treated mice pre-treated with SQGD. Thus, it can be concluded that SQGD treatment neutralizes oxidative stress caused by irradiation not only by enhancing endogenous antioxidant enzymes but also by improving total antioxidant status of cellular system and thus cumulative effect of the phenomenon may contributes to radioprotection. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1471-1478, 2014. PMID:23766268

Mishra, Saurabh; Bansal, Deen Dayal; Malhotra, Poonam; K Reddy, D Sudheer; Jamwal, Vishawdeep S; Patel, Dev Dutt; Gupta, Ashutosh Kumar; Singh, Praveen Kumar; Javed, Saleem; Kumar, Raj

2014-12-01

149

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

150

Radiation-induced adaptive response for protection against micronucleus formation and neoplastic transformation in C3H 10T1/2 mouse embryo cells  

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We have monitored the end points of cellular survival, micronucleus formation and neoplastic transformation frequency to assess adaptation to ionizing radiation in the C3H 10T1/2 mouse embryo cell system. Plateau-phase cells were pre-exposed to an adapting dose of 0.1 to 1.5 Gy low-dose-rate ? radiation 3.5 h prior to an acute challenge dose of 4 Gy. No adapting dose improved clonogenic survival detectably, whether the cells were plated immediately after the acute exposure or held in plateau phase for 3.5 h before plating. However, all chronic adapting doses resulted in both a reduction of micronucleus frequency in binucleate cells and about a twofold reduction in neoplastic transformation frequency per viable cell when cells were subsequently exposed to the 4-Gy challenge dose. Our data suggest that a low-dose-rate pre-exposure to ionizing radiation induces an adaptive response in C3H 10T1/2 cells, and that this response enhances DNA double-strand break repair when cells are subsequently exposed to a second radiation dose. This enhanced repair appears to be error-free since these adapted cells are also less susceptible to radiation-induced neoplastic transformation. 10 refs., 2 tabs

151

Radiation induced bystander effects  

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

152

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

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

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

2002-07-01

153

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

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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

154

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.

155

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.)

156

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.

157

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

International Nuclear Information System (INIS)

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

158

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

International Nuclear Information System (INIS)

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

159

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

International Nuclear Information System (INIS)

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

160

SOD2-mediated Adaptive Responses Induced by Low Dose Ionizing Radiation via TNF Signaling and Amifostine  

Science.gov (United States)

Manganese superoxide dismutase (SOD2)-mediated adaptive processes that protect against radiation-induced micronuclei formation can be induced in cells following a 2 Gy exposure by previously exposing them to either low dose ionizing radiation (10 cGy) or WR1065 (40 µM), the active thiol form of amifostine. While both adaptive processes culminate with elevated levels of SOD2 enzymatic activities, the underlying pathways differ in complexity, with the tumor necrosis factor ? (TNF?) signaling pathway implicated in the low dose radiation-induced response, but not in the thiol-induced pathway. The goal of this study was the characterization of the effects of TNF? receptors1 and 2 (TNFR1, 2) on the adaptive responses induced by low dose irradiation or thiol exposures using micronuclei formation as an endpoint. BFS-1 wild type (WT) cells with functional TNFR1 and 2 were exposed 24 h prior to a 2 Gy dose of ionizing radiation to either 10 cGy or a 40 µM dose of WR1065. BFS2C-SH02 cells defective in TNFR1 and BFS2C-SH22 cells defective in both TNFR1 and 2, generated from BFS2C-SH02 cells by transfection with a murine TNFR2 targeting vector and confirmed to be TNFR2 defective by quantitative PCR, were also exposed under similar conditions for comparison. A 10 cGy dose of radiation induced a significant elevation of SOD2 activity in BFS-1 (P WR1065 significantly induced elevations in SOD2 activity in all three cell lines (P = 0.001; P = 0.007; P = 0.020; respectively). A significant reduction in the frequency of radiation-induced micronuclei was observed in each cell line when exposure to a 2 Gy challenge dose of radiation occurred during the period of maximal elevation in SOD2 activity. However, this adaptive effect was completely inhibited if the cells were transfected 24 h prior to low dose radiation or thiol exposure with SOD2 siRNA. Under the conditions tested, TNFR1,2 inhibition negatively impacted the low dose radiation-induced but not the thiol-induced adaptive responses observed to be mediated by elevations in SOD2 activity. PMID:21945096

Murley, J.S.; Baker, K.L.; Miller, R.C.; Darga, T.E.; Weichselbaum, R.R.; Grdina, D.J.

2011-01-01

 
 
 
 
161

Protection by low-dose kanamycin against noise-induced hearing loss in mice: dependence on dosing regimen and genetic background.  

Science.gov (United States)

We recently demonstrated that sub-chronic low-dose kanamycin (KM, 300 mg/kg sc, 2×/day, 10 days) dramatically reduces permanent noise-induced hearing loss (NIHL) and hair cell loss in 1 month old CBA/J mice (Fernandez et al., 2010, J. Assoc. Res. Otolaryngol. 11, 235-244). Protection by KM remained for at least 48 h after the last dose, and appeared to involve a cumulative effect of multiple doses as part of a preconditioning process. The first month of life lies within the early 'sensitive period' for both cochlear noise and ototoxic injury in mice, and CBA/J mice appear exquisitely vulnerable to noise during this period (Ohlemiller et al., 2011; Hearing Res. 272, 13-20). From our initial data, we could not rule out 1) that less rigorous treatment protocols than the intensive one we applied may be equally-or more-protective; 2) that protection by KM is tightly linked to processes unique to the sensitive period for noise or ototoxins; or 3) that protection by KM is exclusive to CBA/J mice. The present experiments address these questions by varying the number and timing of fixed doses (300 mg/kg sc) of KM, as well as the age at treatment in CBA/J mice. We also tested for protection in young C57BL/6J (B6) mice. We find that nearly complete protection against at least 2 h of intense (110 dB SPL) broadband noise can be observed in CBA/J mice at least for ages up to 1 year. Reducing dosing frequency to as little as once every other day (a four-fold decrease in dosing frequency) appeared as protective as twice per day. However, reducing the number of doses to just 1 or 2, followed by noise 24 or 48 h later greatly reduced protection. Notably, hearing thresholds and hair cells in young B6 mice appeared completely unprotected by the same regimen that dramatically protects CBA/J mice. We conclude that protective effects of KM against NIHL in CBA/J mice can be engaged by a wide range of dosing regimens, and are not exclusive to the sensitive period for noise or ototoxins. While we cannot presently judge the generality of protection across genetic backgrounds, it appears not to be universal, since B6 showed no benefit. Classical genetic approaches based on CBA/J × B6 crosses may reveal loci critical to protective cascades engaged by kanamycin and perhaps other preconditioners. Their human analogs may partly determine who is at elevated risk of acquired hearing loss. PMID:21645602

Ohlemiller, Kevin K; Rybak Rice, Mary E; Rosen, Allyson D; Montgomery, Scott C; Gagnon, Patricia M

2011-10-01

162

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

International Nuclear Information System (INIS)

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

163

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-¿ (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-¿ 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; RØnn, S G

2011-01-01

164

Single intravenous low-dose injections of connexin 43 mimetic peptides protect ischemic heart in vivo against myocardial infarction.  

Science.gov (United States)

The opening of unapposed connexin 43 hemichannels (Cx43Hc) under ischemic stress leads to cell death and irreversible tissue injury. Here, we investigate for the first time in vivo the cardioprotective potentials of two unique Cx43 structural-mimetic peptides (Cx43MPs) presumed specific blockers of Cx43Hc, Gap26 and Gap27, when injected intravenously using a rat model of myocardial infarction.Sprague Dawley rats were utilized. Myocardial infarction was induced by occluding the left anterior descending coronary for 40 min followed by 2 days of reperfusion. Interestingly, single bolus injections of Gap26 or Gap27 (1 ?g/kg) into the jugular vein caused infarct size reductions by up to 61% with reference to control rats injected with saline at similar timings. Infarct reductions did not vary significantly whether peptides were administered before or after the onset of ischemia. Although the two peptides allegedly interact with distinct structures of Cx43, co-administration of Gap26/Gap27 in equal doses did not confer additive protection to hearts (maximum infarct reduction by 64%). Using patch clamp technique, we provide unique and direct evidence for the inhibitory effect of Cx43MPs on genuine human Cx43Hc transiently expressed in the ion channel-deficient tsA201 cells. In concordance with the cardioprotective effect observed in vivo, co-application of both peptides did not cause cumulative current inhibition. A safety profile of Cx43MPs was also addressed.Our results reveal great therapeutic potential of Cx43MPs in treatment of myocardial infarction. Their practical way and timing of administration and their apparent safe profile make them promising tools to fight ischemic heart disease. PMID:22841862

Hawat, Ghayda; Hélie, Pierre; Baroudi, Ghayath

2012-10-01

165

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

166

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

International Nuclear Information System (INIS)

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

167

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

168

Low dose rate proton irradiation of quartz crystal resonators  

International Nuclear Information System (INIS)

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

169

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

170

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

Energy Technology Data Exchange (ETDEWEB)

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.

Oldfield, E.H.; Friedman, R.; Kinsella, T.; Moquin, R.; Olson, J.J.; Orr, K.; DeLuca, A.M. (National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (USA))

1990-05-01

171

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 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)

172

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

173

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

International Nuclear Information System (INIS)

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

174

Protection of DNA and membrane from gamma radiation induced damage by gallic acid.  

Science.gov (United States)

Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a naturally occurring plant phenol. In vitro and in vivo studies have shown that this phytochemical protected DNA and membranes against ionizing radiation. Rat liver microsomes and plasmid pBR322 DNA were exposed to various doses of gamma radiation in presence and absence of GA. Exposure of the microsomes to gamma radiation resulted in the formation of peroxides of membrane lipids measured as thiobarbituric acid reactive substances and presence of GA during irradiation prevented the formation of lipid peroxidation. Gamma irradiation of plasmid DNA resulted in induction of strand breaks in DNA resulting in disappearance of the supercoiled (ccc) form. Presence of GA during irradiation protected the DNA from undergoing the strand breaks. In in vivo studies it was found that whole body exposure of mice to gamma radiation (4 Gy) increased the formation of lipid peroxides in various tissues and damage to cellular DNA (as measured by alkaline comet assay) in peripheral blood leucocytes. Administration of GA to mice prior to whole body radiation exposure reduced the peroxidation of lipids and the damage to the cellular DNA indicating in vivo radiation protection of membranes and DNA by GA. PMID:16180096

Gandhi, Nitin Motilal; Nair, Cherupally Krishnan Krishnan

2005-10-01

175

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

International Nuclear Information System (INIS)

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

176

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

International Nuclear Information System (INIS)

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

177

Semiquinone derivative isolated from Bacillus sp. INM-1 protects cellular antioxidant enzymes from ?-radiation-induced renal toxicity.  

Science.gov (United States)

This study was focused to evaluate protection of indigenous antioxidant system of mice against gamma radiation-induced oxidative stress using a semiquinone (SQGD)-rich fraction isolated from Bacillus sp. INM-1. Male C57bl/6 mice were administered SQGD (50 mg/kgb.w.i.p.) 2 h before irradiation (10 Gy) and modulation in antioxidant enzymes activities was estimated at different time intervals and compared with irradiated mice which were not pretreated by SQGD. Compared to untreated controls, SQGD pretreatment significantly (p < 0.05) accelerates superoxide dismutase, catalase, GSH, and glutathione-S-transferase activities. Similarly, significant (p < 0.05) increase in the expression of superoxide dismutase, catalase, GSH, and glutathione-S-transferase was observed in irradiated mice pretreated by SQGD, compared to only irradiated groups. Total antioxidant status equivalent to trolox was estimated in renal tissue of the mice after SQGD administration. Significant ABTS(+) radical formation was observed in H2O2-treated kidney homogenate, due to oxidative stress in the tissue. However, significant decrease in the levels of ABTS(+) radical was observed in kidney homogenate of the mice pretreated with SQGD. Therefore, it can be concluded that SQGD neutralizes oxidative stress by induction of antioxidant enzymes activities and thus improved total antioxidant status in cellular system and hence contributes to radioprotection. PMID:23543190

Mishra, S; Reddy, D S K; Jamwal, V S; Bansal, D D; Patel, D D; Malhotra, P; Gupta, A K; Singh, P K; Jawed, S; Kumar, Raj

2013-07-01

178

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

International Nuclear Information System (INIS)

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

179

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1997-06-01

180

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

International Nuclear Information System (INIS)

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

 
 
 
 
181

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

Science.gov (United States)

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 VITC, VA and HS significantly (p < 0.05) decreased the levels of unconjugated bilirubin, while VIT C and VA alone decreased the levels of conjugated bilirubin. Furthermore, treatment with VA (400 and 800 mg/kg) decreased the serum ALT activities by 25% and 34%, respectively, at 5 weeks after irradiation. Similarly, alkaline phosphatase and 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. PMID:18250564

Adaramoye, Oluwatosin; Ogungbenro, Bayo; Anyaegbu, Oluchi; Fafunso, Michael

2008-03-01

182

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

183

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)

184

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 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.

185

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

186

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

International Nuclear Information System (INIS)

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

187

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2008-09-15

188

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

189

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

190

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

International Nuclear Information System (INIS)

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

191

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

192

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

193

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.

194

Effects of low doses  

International Nuclear Information System (INIS)

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

195

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

196

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

197

Low-Dose Pretreatment for Radiation Therapy  

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In radiotherapy, a large radiation dose must be applied to both cancer and neighboring healthy cells. Recent experiments have shown that a low dose of ionizing radiation turns on certain protective mechanisms that allow a cell to better survive a subsequent high dose of radiation. This adaptive response can have important and positive consequences for radiotherapy. This paper describes a simple change in treatment procedures to make use of these beneficial effects. A low dose applied only to ...

Blankenbecler, Richard

2010-01-01

198

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

International Nuclear Information System (INIS)

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

199

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

International Nuclear Information System (INIS)

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

200

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

Science.gov (United States)

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

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

2014-04-29

 
 
 
 
201

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...

202

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

International Nuclear Information System (INIS)

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

203

SOD2-mediated adaptive responses induced by low-dose ionizing radiation via TNF signaling and amifostine.  

Science.gov (United States)

Manganese superoxide dismutase (SOD2)-mediated adaptive processes that protect against radiation-induced micronucleus formation can be induced in cells after a 2-Gy exposure by previously exposing them to either low-dose ionizing radiation (10cGy) or WR1065 (40?M), the active thiol form of amifostine. Although both adaptive processes culminate in elevated levels of SOD2 enzymatic activity, the underlying pathways differ in complexity, with the tumor necrosis factor ? (TNF?) signaling pathway implicated in the low-dose radiation-induced response, but not in the thiol-induced pathway. The goal of this study was the characterization of the effects of TNF? receptors 1 and 2 (TNFR1, TNFR2) on the adaptive responses induced by low-dose irradiation or thiol exposure using micronucleus formation as an endpoint. BFS-1 wild-type cells with functional TNFR1 and 2 were exposed 24h before a 2-Gy dose of ionizing radiation to either 10cGy or a 40?M dose of WR1065. BFS2C-SH02 cells, defective in TNFR1, and BFS2C-SH22 cells, defective in both TNFR1 and TNFR2 and generated from BFS2C-SH02 cells by transfection with a murine TNFR2-targeting vector and confirmed to be TNFR2 defective by quantitative PCR, were also exposed under similar conditions for comparison. A 10-cGy dose of radiation induced a significant elevation in SOD2 activity in BFS-1 (PWR1065 significantly induced elevations in SOD2 activity in all three cell lines (P=0.001, P=0.007, P=0.020, respectively). A significant reduction in the frequency of radiation-induced micronuclei was observed in each cell line when exposure to a 2-Gy challenge dose of radiation occurred during the period of maximal elevation in SOD2 activity. However, this adaptive effect was completely inhibited if the cells were transfected 24h before low-dose radiation or thiol exposure with SOD2 siRNA. Under the conditions tested, TNFR1 and 2 inhibition negatively affected the low-dose radiation-induced but not the thiol-induced adaptive responses observed to be mediated by elevations in SOD2 activity. PMID:21945096

Murley, J S; Baker, K L; Miller, R C; Darga, T E; Weichselbaum, R R; Grdina, D J

2011-11-15

204

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

Science.gov (United States)

The effect of inhalation of hydrogen-containing gas (1.3% hydrogen + 20.8% oxygen + 77.9% nitrogen) (HCG) on radiation-induced dermatitis and on the healing of healing-impaired skin wounds in rats was examined using a rat model of radiation-induced skin injury. An X-ray dose of 20 Gy was irradiated onto the lower part of the back through two holes in a lead shield. Irradiation was performed before or after inhalation of HCG for 2 h. Inhalation of HCG significantly reduced the severity of radiodermatitis and accelerated healing-impaired wound repair. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and 8-hydroxy-2(')-deoxyguanosine (8-OHdG) showed that the proportion of apoptotic keratinocytes and the level of staining in the X-irradiated skin of rats that pre-inhaled HCG were significantly lower than that of rats which did not pre-inhale HCG. Cutaneous full-thickness wounds were then created in the X-irradiated area to examine the time-course of wound healing. X-irradiation significantly increased the time required for wound healing, but the inhalation of HCG prior to the irradiation significantly decreased the delay in wound healing compared with the control and post-inhalation of HCG groups. Therefore, radiation-induced skin injury can potentially be alleviated by the pre-inhalation of HCG. PMID:25034733

Watanabe, Sadahiro; Fujita, Masanori; Ishihara, Masayuki; Tachibana, Shoichi; Yamamoto, Yoritsuna; Kaji, Tatsumi; Kawauchi, Toshio; Kanatani, Yasuhiro

2014-11-01

205

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2011-07-01

206

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

207

Mammography-oncogenecity at low doses  

Energy Technology Data Exchange (ETDEWEB)

Controversy exists regarding the biological effectiveness of low energy x-rays used for mammography breast screening. Recent radiobiology studies have provided compelling evidence that these low energy x-rays may be 4.42 {+-} 2.02 times more effective in causing mutational damage than higher energy x-rays. These data include a study involving in vitro irradiation of a human cell line using a mammography x-ray source and a high energy source which matches the spectrum of radiation observed in survivors from the Hiroshima atomic bomb. Current radiation risk estimates rely heavily on data from the atomic bomb survivors, and a direct comparison between the diagnostic energies used in the UK breast screening programme and those used for risk estimates can now be made. Evidence highlighting the increase in relative biological effectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that the risks of radiation-induced breast cancers for mammography x-rays are potentially underestimated by a factor of four. A pooled analysis of three measurements gives a maximal RBE (for malignant transformation of human cells in vitro) of 4.02 {+-} 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higher energy x-rays. For the majority of women in the UK NHS breast screening programme, it is shown that the benefit safely exceeds the risk of possible cancer induction even when this higher biological effectiveness factor is applied. The risk/benefit analysis, however, implies the need for caution for women screened under the age of 50, and particularly for those with a family history (and therefore a likely genetic susceptibility) of breast cancer. In vitro radiobiological data are generally acquired at high doses, and there are different extrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro data have indicated a potential suppressive effect at very low dose rates and doses. Whilst mammography is a low dose exposure, it is not a low dose rate examination, and protraction of dose should not be confused with fractionation. Although there is potential for a suppressive effect at low doses, recent epidemiological data, and several international radiation risk assessments, continue to promote the linear no-threshold (LNT) model. Finally, recent studies have shown that magnetic resonance imaging (MRI) is more sensitive than mammography in detecting invasive breast cancer in women with a genetic sensitivity. Since an increase in the risk associated with mammographic screening would blur the justification of exposure for this high risk subgroup, the use of other (non-ionising) screening modalities is preferable.

Heyes, G J [Department of Medical Physics, University Hospital Birmingham NHS Foundation Trust, Birmingham B15 2TH (United Kingdom); Mill, A J; Charles, M W [Radiation Biophysics Group, School of Physics and Astronomy, University of Birmingham, Birmingham B15 2TT (United Kingdom)

2009-06-01

208

Mammography-oncogenecity at low doses  

International Nuclear Information System (INIS)

Controversy exists regarding the biological effectiveness of low energy x-rays used for mammography breast screening. Recent radiobiology studies have provided compelling evidence that these low energy x-rays may be 4.42 ± 2.02 times more effective in causing mutational damage than higher energy x-rays. These data include a study involving in vitro irradiation of a human cell line using a mammography x-ray source and a high energy source which matches the spectrum of radiation observed in survivors from the Hiroshima atomic bomb. Current radiation risk estimates rely heavily on data from the atomic bomb survivors, and a direct comparison between the diagnostic energies used in the UK breast screening programme and those used for risk estimates can now be made. Evidence highlighting the increase in relative biological effectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that the risks of radiation-induced breast cancers for mammography x-rays are potentially underestimated by a factor of four. A pooled analysis of three measurements gives a maximal RBE (for malignant transformation of human cells in vitro) of 4.02 ± 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higher energy x-rays. For the majority of women in the UK NHS breast screening programme, it is shown that the benefit safely exceeds the risk of possible cancer induction even when this higher biological effectiveness factor is applied. The al effectiveness factor is applied. The risk/benefit analysis, however, implies the need for caution for women screened under the age of 50, and particularly for those with a family history (and therefore a likely genetic susceptibility) of breast cancer. In vitro radiobiological data are generally acquired at high doses, and there are different extrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro data have indicated a potential suppressive effect at very low dose rates and doses. Whilst mammography is a low dose exposure, it is not a low dose rate examination, and protraction of dose should not be confused with fractionation. Although there is potential for a suppressive effect at low doses, recent epidemiological data, and several international radiation risk assessments, continue to promote the linear no-threshold (LNT) model. Finally, recent studies have shown that magnetic resonance imaging (MRI) is more sensitive than mammography in detecting invasive breast cancer in women with a genetic sensitivity. Since an increase in the risk associated with mammographic screening would blur the justification of exposure for this high risk subgroup, the use of other (non-ionising) screening modalities is preferable.

209

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.)

210

Influence of substances offering protection against radiation-induced delayed damage to the liver of the mouse. Der Einfluss von Strahlenschutzsubstanzen auf strahleninduzierte Spaetschaeden der Maeuseleber  

Energy Technology Data Exchange (ETDEWEB)

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)

Oehlert, W. (Institut fuer Pathologie, Histologie und Zytologie, Freiburg im Breisgau (Germany)); Moenig, H.

1993-01-01

211

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

Scientific Electronic Library Online (English)

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

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

2013-09-27

212

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)

213

Bystander effects of low dose ionising irradiation  

International Nuclear Information System (INIS)

Complete text of publication follows. Introduction: Many recent findings question the validity of the linear non-threshold model of stochastic radiation effects. In the low dose range the non DNA targeted effects might have high influence on radiation damages. We have investigated the consequences of low dose irradiation in directly exposed and bystander immortalized human fibroblast cells. Methods: Immortalized human fibroblast cells were irradiated with various doses (0.01, 0.04, 0.1, 0.5 and 2 Gy) of 60Co ?-radiation. To study bystander effects both the medium change and the co-culture technique was applied. Radiation induced damages were investigated by a modified micronucleus assay. Fibroblasts were seeded on cover glasses and irradiated 10-12 h later. After additional 6 hours 2 Tg/ml cythochalasin B were added and 48 hours later cells were stained either with Giemsa or ethidium-bromide. The ratio of binucleated cells and the frequency of micronuclei in 1000 binucleated cells were evaluated. Results: In directly irradiated cells the ratio of binucleated cells decreased with dose beyond 0.1 Gy. We detected a moderate hypersensitivity at 10 mGy. The frequency of micronuclei increased with dose beyond 0.1 Gy. Again, slight hypersensitivity was detected at 10 mGy. Bystander treatment had no effect on the frequency of binucleated cells. The ratio of micronuclei increased at doses higher than 0.1 Gy. Conclusions: Our preliminary data suggest that human fibroblast cells might respond to low doses in a hypersensitive manner.

214

Low dose proteasome inhibition affects alternative splicing.  

Science.gov (United States)

Protein degradation by the ubiquitin proteasome system ensures controlled degradation of structural proteins, signaling mediators, and transcription factors. Inhibition of proteasome function by specific proteasome inhibitors results in dose-dependent cellular effects ranging from induction of apoptosis to protective stress responses. The present study seeks to identify nuclear regulators mediating the protective stress response to low dose proteasome inhibition. Primary human endothelial cells were treated with low doses of the proteasome inhibitor MG132 for 2 h, and proteomic analysis of nuclear extracts was performed. Using a 2-D differential in gel electrophoresis (DIGE) approach, we identified more than 24 splice factors to be differentially regulated by low dose proteasome inhibition. In particular, several isoforms of hnRNPA1 were shown to be increased, pointing toward altered posttranslational modification of hnRNPA1 upon proteasome inhibition. Elevated levels of splice factors were associated with a different alternative splicing pattern in response to proteasome inhibition as determined by Affymetrix exon array profiling. Of note, we observed alternative RNA processing for stress associated genes such as caspases and heat shock proteins. Our study provides first evidence that low dose proteasome inhibition affects posttranscriptional regulation of splice factors and early alternative splicing events. PMID:22702956

Bieler, Sven; Hammer, Elke; Gesell-Salazar, Manuela; Völker, Uwe; Stangl, Karl; Meiners, Silke

2012-08-01

215

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

216

Radiation induced oral mucositis  

Directory of Open Access Journals (Sweden)

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

Satheesh Kumar P

2009-01-01

217

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

International Nuclear Information System (INIS)

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

218

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

International Nuclear Information System (INIS)

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

219

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

International Nuclear Information System (INIS)

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

220

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

Science.gov (United States)

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

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

2014-10-01

 
 
 
 
221

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)

222

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

223

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

Science.gov (United States)

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

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

2011-05-10

224

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

International Nuclear Information System (INIS)

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

225

Radiation induced effects in the developing central nervous system  

International Nuclear Information System (INIS)

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

226

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

227

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

228

Hormesis effect of low dose radiation on cellular DNA repair  

International Nuclear Information System (INIS)

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

229

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)

230

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

Science.gov (United States)

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

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

2010-04-01

231

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

International Nuclear Information System (INIS)

ing 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)

232

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

International Nuclear Information System (INIS)

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

233

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2005-12-11

234

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

235

Low-dose radiation: a cause of breast cancer  

International Nuclear Information System (INIS)

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

236

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

237

Contribution of bystander effects in radiation induced genotoxicity  

International Nuclear Information System (INIS)

The controversial use of a linear, no threshold extrapolation model for low dose risk assessment is based on the accepted dogma that the deleterious effects of ionizing radiation such as mutagenesis and carcinogenesis are attributable mainly to direct damage to DNA. However, this extrapolation was challenged by the recent reports on the bystander phenomenon. The bystander effect contributes to this debate by implying that the biological effects of low doses, where not all cells are traversed by a charged particle, are amplified by the transfer of factors to un-irradiated neighbors. This interested phenomenon implies that a linear extrapolation of risks from high to low doses may underestimate rather than over estimate low dose risks. Together with some radiation-induced phenomena such as adaptive response and genomic instability, the radiobiological response at low doses is likely to be a complex interplay among many factors. (author)

238

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)

239

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

Energy Technology Data Exchange (ETDEWEB)

Possible protective effects of the agonist (D-Trp/sup 6/)LH-RH and antagonist N-Ac(D-Phe(pCl)/sup 1,2/,D-Trp/sup 3/,D-Arg/sup 6/,D-Ala/sup 10/)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-Trp/sup 6/)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-Trp/sup 6/)LH-RH did not protect the rat testes exposed to 622 rads and, 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.

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

1987-02-01

240

Serotonin precursor 5-hydroxytryptophan disturbs the protective effect of low doses of antibodies to S100B protein during the formation of long-term sensitization.  

Science.gov (United States)

We studied the effect of ultralow doses of antibodies to calcium-binding protein S-100B and 5-hydroxytryptophan, a metabolic precursor of serotonin, on the formation of long-term sensitization as a neurobiological model of anxiety and depression. Daily administration of antibodies to S-100B to edible snail before the formation of long-term sensitization prevents its development. 5-Hydroxytryptophan administered before the formation of long-term sensitization abolished the protective effect of antibodies to S-100B protein. PMID:20396741

Tagirova, R R; Timoshenko, A Kh; Gainutdinov, Kh L; Shtark, M B; Epshtein, O I

2009-09-01

 
 
 
 
241

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 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

242

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

243

Effect of low dose radiation on the immune system  

International Nuclear Information System (INIS)

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

244

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

International Nuclear Information System (INIS)

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

245

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

246

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.)

247

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

International Nuclear Information System (INIS)

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

248

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

International Nuclear Information System (INIS)

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

249

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

International Nuclear Information System (INIS)

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

250

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)

251

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

International Nuclear Information System (INIS)

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

252

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 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

253

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

254

Ionizing radiation induced cataract  

International Nuclear Information System (INIS)

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

255

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 ( Ptopical 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

256

Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells.  

Science.gov (United States)

Ionizing radiation (IR) can generate reactive oxygen species (ROS). Excessive ROS have the potential to damage cellular macromolecules including DNA, proteins, and lipids and eventually lead to cell death. In this study, we evaluated the potential of arbutin, a drug chosen from a series of traditional herbal medicine by measuring intracellular hydroxyl radical scavenging ability in X-irradiated U937 cells. Arbutin (hydroquinone-?-D-glucopyranoside), a naturally occurring glucoside of hydroquinone, has been traditionally used to treat pigmentary disorders. However, there are no reports describing the effect of arbutin on IR-induced apoptosis. We confirmed that arbutin can protect cells from apoptosis induced by X-irradiation. The combination of arbutin and X-irradiation could reduce intracellular hydroxyl radical production and prevent mitochondrial membrane potential loss. It also could down-regulate the expression of phospho-JNK, phospho-p38 in whole cell lysate and activate Bax in mitochondria. Arbutin also inhibits cytochrome C release from mitochondria to cytosol. To verify the role of JNK in X-irradiation-induced apoptosis, the cells were pretreated with a JNK inhibitor, and found that JNK inhibitor could reduce apoptosis induced by X-irradiation. Taken together, our data indicate that arbutin plays an anti-apoptotic role via decreasing intracellular hydroxyl radical production, inhibition of Bax-mitochondria pathway and activation of the JNK/p38 MAPK pathway. PMID:25187044

Wu, Li-Hua; Li, Peng; Zhao, Qing-Li; Piao, Jin-Lan; Jiao, Yu-Fei; Kadowaki, Makoto; Kondo, Takashi

2014-11-01

257

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

International Nuclear Information System (INIS)

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

258

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

259

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)

260

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

 
 
 
 
261

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

Energy Technology Data Exchange (ETDEWEB)

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.)

Averbeck, D. [IRSN, Fontenay-aux-Roses (France); Lloyd, D. [Health Protection Agency, Chilton (United Kingdom); O' Neill, P. [Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

2010-10-11

262

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

263

Two pediatric cases of high dose radiation-induced meningiomas  

Energy Technology Data Exchange (ETDEWEB)

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)

Nagai, Miho [National Yokosuka Hospital, Kanagawa (Japan); Nagashima, Goro; Fujimoto, Tsukasa; Aoyagi, Masaru; Takasato, Yoshio

2001-10-01

264

Cellular responses to low doses of ionizing radiation: radioadaptive response  

International Nuclear Information System (INIS)

Various kinds of modulating effects on the activities of organisms have been observed to be produced by low doses of ionizing radiation, contrasting markedly with detrimental effects that predominate at higher dose level. Radioadaptive response is one of the most interesting and ubiquitous phenomena. Following the pioneer studies by Wolff et al. in human lymphocytes, we demonstrated that Chinese hamster cells pre-exposed to a low 'priming' dose of radiation showed the reduced frequencies of micronuclei and sister chromatid exchanges by a subsequent 'challenge' dose (1987). Further to elucidate the mechanism behind radioadaptive response, we have performed a series of experiments and revealed several important characteristics: (1) Radioadaptive response is caused by a narrow window of low doses (cGy level) for the full expression. (2) Gamma rays and X-rays elicit radioadaptive response like tritium beta-rays. (3) A 4-h interval is required for the full expression of the response, which decays rather rapidly with the progression of cell proliferation. (4) The expression of adaptive response is suppressed by the treatments with metabolic inhibitors of poly(ADP-ribose) polymerase, cytosolic protein synthesis, RNA polymerase II and protein kinase C. (5) Radioadaptive response cross-react to clastogenic lesions induced by other physical and chemical DNA-damaging agents. (6) Several proteins are newly synthesized concurrently with the expression of radioadaptive response after low doses, viewed by two-dimensional gel-electrophoresis of cellular proteins. (7) The repair of radiation-induced DNA double-strand breaks is apparently stimulated, especially during the early stage of their repair, in adapted cells but not in non-adapted cells. (8) The telomerase activity is hormetically induced by low-dose exposure. These observations suggest that radioadaptive response may be described as the induction of DNA damage repair mediated by a low-dose activated signaling pathway. A possible chain of molecular events in the process of radioadaptive response will be discussed. (author)

265

Molecular Tools and the Biology of Low-dose Effects  

Science.gov (United States)

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

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

2009-09-01

266

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

International Nuclear Information System (INIS)

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

267

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

268

Low dose of oleanolic acid protects against lithocholic acid-induced cholestasis in mice: potential involvement of nuclear factor-E2-related factor 2-mediated upregulation of multidrug resistance-associated proteins.  

Science.gov (United States)

Oleanolic acid (OA) is a natural triterpenoid and has been demonstrated to protect against varieties of hepatotoxicants. Recently, however, OA at high doses was reported to produce apparent cholestasis in mice. In this study, we characterized the protective effect of OA at low doses against lithocholic acid (LCA)-induced cholestasis in mice and explored further mechanisms. OA cotreatment (5, 10, and 20 mg/kg, i.p.) significantly improved mouse survival rate, attenuated liver necrosis, and decreased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase; more importantly, serum total bile acids and bilirubin, as well as hepatic total bile acids were also remarkably reduced. Gene and protein expression analysis showed that hepatic expression of multidrug resistance-associated protein 2 (Mrp2), Mrp3, and Mrp4 was significantly increased by OA cotreatment, whereas other bile acid metabolism- and transport-related genes, including Na+/taurocholate cotransporter, organic anion transporter 1b2, bile salt export pump, multidrug resistance protein 3, Cyp3a11, Cyp2b10, Sulfotransferase 2a1 (Sult2a1), and UDP-glucuronosyltransferase 1a1 (Ugt1a1), were only slightly changed. OA also caused increased nuclear factor-E2-related factor (Nrf2) mRNA expression and nuclear protein accumulation, whereas nuclear receptors farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive androstane receptor were not significantly influenced by OA. Luciferase (Luc) assays performed in HepG2 cells illustrated that OA was a strong Nrf2 agonist with moderate PXR and weak FXR agonism. Finally, in mouse primary cultured hepatocytes, OA dose- and time-dependently induced expression of Mrp2, Mrp3, and Mrp4; however, this upregulation was abrogated when Nrf2 was silenced. In conclusion, OA produces a protective effect against LCA-induced hepatotoxicity and cholestasis, possibly due to Nrf2-mediated upregulation of Mrp2, Mrp3, and Mrp4. PMID:24510383

Chen, Pan; Zeng, Hang; Wang, Yongtao; Fan, Xiaomei; Xu, Chenshu; Deng, Rongrong; Zhou, Xunian; Bi, Huichang; Huang, Min

2014-05-01

269

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

International Nuclear Information System (INIS)

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

270

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)

271

Low and very low doses, new recommendations?  

International Nuclear Information System (INIS)

The topic of the seminar organized by the world council of nuclear workers (WONUC) was the effects of low or very low doses on human health. Discussions centred round the linearity of the relation between dose and effect in the evaluation and management of the health hazard. The recommendations proposed by ICPR (international commission for radiological protection) are based on this linearity as a precaution. On the one hand it is remembered that low dose irradiation might be beneficial. It has been proved that the irradiation of the whole body is efficient in case of Hodgkin lymphoma. On the other hand it is remembered that doses as low as 10 mSv in utero have led to an excess of cancer in children. Studies based on experimentally radio-induced cancers have been carried out in Japan, China, Canada and France.Their results seem to be not consistent with the hypothesis of linearity. During the last decade a lot of work has been made but a conclusion is far to be reached, it is said that the American department of energy (DOE) has invited bids in 1999 to launch research programs in order to clarify the situation. (A.C.)

272

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

273

Radiation-induced apoptosis  

Energy Technology Data Exchange (ETDEWEB)

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

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

1999-03-01

274

Radiation-induced pneumothorax  

International Nuclear Information System (INIS)

Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis

275

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)

276

Biological Effects of Low-Dose Exposure  

CERN Document Server

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

Komochkov, M M

2000-01-01

277

Radiation induced oral mucositis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2009-01-01

278

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.)

279

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

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

2007-01-01

280

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

 
 
 
 
281

Low dose response analysis through a cytogenetic end-point  

International Nuclear Information System (INIS)

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

282

The effects of chronic low dose irradiation on drosophila melanogaster  

International Nuclear Information System (INIS)

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

283

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)

284

Association between stochastic and non-stochastic effects and cellular damage. Low-dose implications  

International Nuclear Information System (INIS)

Stochastic effects have been defined as those for which the probability increases with dose without a threshold. Non-stochastic effects are those for which severity depends on dose and for which a threshold may occur. The difference in the definition of the types of effect suggests that the two are not related. In this paper it is shown that it is possible to interpret at least some non-stochastic effects as a consequence of a stochastic effect and that both types of effect can be related to a common cellular damage. It is assumed that at least some non-stochastic effects arise as a result of impairment of the function of a critical number of cells and animal mortality has been chosen as a typical example of a non-stochastic effect. Using this end-point the effects of dose rate, fractionation and radiation quality are considered to demonstrate the method of interpretation which has been chosen. It is proposed that radiation-induced DNA double-strand breaks are the crucial cellular lesions and that stochastic effects arise because each DNA double-strand break induced in a cell has a certain probability of causing a specific effect, such as mutation to a pre-malignant state. The dose relationships are linear quadratic in general and at low dose rates the relationships become linear, ??zero and the linear coefficient ? is strongly dependent on radiation quality. Non-stochastic effects are considered to arise, in some cases, because the function of a critical number of cells is impaired; animal mortality may occur because a critical number of bone marrow cells are killed. Using this concept an equation is derived for animal mortality based on the equation for cell killing which contains, in turn, the linear-quadratic dose relationship for the induction of DNA double-strand breaks. The implications of the analytical approach for both stochastic effects at low doses are discussed with special reference to radiological protection. (author)

285

Human Mesenchymal Stem Cells Provide Protection against Radiation-Induced Liver Injury by Antioxidative Process, Vasculature Protection, Hepatocyte Differentiation, and Trophic Effects  

Science.gov (United States)

To evaluate the potential therapeutic effect of the infusion of hMSCs for the correction of liver injuries, we performed total body radiation exposure of NOD/SCID mice. After irradiation, mir-27b level decreases in liver, increasing the directional migration of hMSCs by upregulating SDF1?. A significant increase in plasmatic transaminases levels, apoptosis process in the liver vascular system, and in oxidative stress were observed. hMSC injection induced a decrease in transaminases levels and oxidative stress, a disappearance of apoptotic cells, and an increase in Nrf2, SOD gene expression, which might reduce ROS production in the injured liver. Engrafted hMSCs expressed cytokeratin CK18 and CK19 and AFP genes indicating possible hepatocyte differentiation. The presence of hMSCs expressing VEGF and Ang-1 in the perivascular region, associated with an increased expression of VEGFr1, r2 in the liver, can confer a role of secreting cells to hMSCs in order to maintain the endothelial function. To explain the benefits to the liver of hMSC engraftment, we find that hMSCs secreted NGF, HGF, and anti-inflammatory molecules IL-10, IL1-RA contributing to prevention of apoptosis, increasing cell proliferation in the liver which might correct liver dysfunction. MSCs are potent candidates to repair and protect healthy tissues against radiation damages. PMID:24369528

Francois, Sabine; Mouiseddine, Moubarak; Allenet-Lepage, Bénédicte; Voswinkel, Jan; Douay, Luc; Benderitter, Marc; Chapel, Alain

2013-01-01

286

Human mesenchymal stem cells provide protection against radiation-induced liver injury by antioxidative process, vasculature protection, hepatocyte differentiation, and trophic effects.  

Science.gov (United States)

To evaluate the potential therapeutic effect of the infusion of hMSCs for the correction of liver injuries, we performed total body radiation exposure of NOD/SCID mice. After irradiation, mir-27b level decreases in liver, increasing the directional migration of hMSCs by upregulating SDF1 ? . A significant increase in plasmatic transaminases levels, apoptosis process in the liver vascular system, and in oxidative stress were observed. hMSC injection induced a decrease in transaminases levels and oxidative stress, a disappearance of apoptotic cells, and an increase in Nrf2, SOD gene expression, which might reduce ROS production in the injured liver. Engrafted hMSCs expressed cytokeratin CK18 and CK19 and AFP genes indicating possible hepatocyte differentiation. The presence of hMSCs expressing VEGF and Ang-1 in the perivascular region, associated with an increased expression of VEGFr1, r2 in the liver, can confer a role of secreting cells to hMSCs in order to maintain the endothelial function. To explain the benefits to the liver of hMSC engraftment, we find that hMSCs secreted NGF, HGF, and anti-inflammatory molecules IL-10, IL1-RA contributing to prevention of apoptosis, increasing cell proliferation in the liver which might correct liver dysfunction. MSCs are potent candidates to repair and protect healthy tissues against radiation damages. PMID:24369528

Francois, Sabine; Mouiseddine, Moubarak; Allenet-Lepage, Bénédicte; Voswinkel, Jan; Douay, Luc; Benderitter, Marc; Chapel, Alain

2013-01-01

287

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

Science.gov (United States)

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

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

2002-01-01

288

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)

289

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.)

290

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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

291

Differentially Expressed Genes Associated with Low-Dose Gamma Radiation  

Science.gov (United States)

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

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

292

Radiation-induced myelopathy  

International Nuclear Information System (INIS)

12 cases of radiation-induced myelopathy after 60Co teletherapy are reported on. Among these were 10 thoracal lesions, one cerviothoracal lesion, and one lesion of the medulla oblongata. In 9 cases, Hodgkin's disease had been the primary disease, tow patients had been irradiated because of suspected vertebral metastases of cancer of the breast, and one patient had suffered from a glomus tumour of the petrous bone. The spinal doses had exceeded the tolerance doses recommended in the relevant literature. There was no close correlation between the radiation dose and the course of the disease. The latency periods between the end of the radiotherapy and the onset of the neurological symptons varied from 6-16 mouths and were very constant in 7 cases with 6-9 months. The segmental height of the lesion corresponded to the level of irradiation. The presenting symptons of radiation-induced myelopathy are buruing dysaesthesias and Brown-Sequard's paralysis which may develop into transverse lesion of the cord with paraplegia still accompanied by dissociated perception disorders. The disease develos intermittently. Disturbances of the bladder function are frequent. The fluid is normal in most cases. Myelographic examinations were made in 8 cases. 3 cases developed into stationary cases exhibiting. Brown-Sequard syndrome, while 9 patients developed transverse lesion of the cord with paraplegia. 3 patients have died; antopsy findings are given for two of these. In the patngs are given for two of these. In the pathogenesis of radiation-induced myelopathy, the vascular factor is assumed to be of decisive importance. (orig./AK)

293

Low Dose Risk, Decisions, and Risk Communication  

International Nuclear Information System (INIS)

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

294

Transcriptional regulation of the low dose ionizing radiation induced protein clusterin  

International Nuclear Information System (INIS)

Full text: Radiation therapy using ionizing radiation (IR), along with chemotherapy, are common treatments for many different cancers. Therefore, it is vital to understand the cellular responses to these treatments in malignant cells, as well as the surrounding normal tissues for optimizing the efficacy of these treatments. Clusterin (CLU) has been implicated in many normal and pathological disease processes, although the function of clusterin still remains to be elucidated. Additionally, a correlation between increased CLU expression and increased tumor malignancy has been noted. It has been suggested that secretory clusterin (sCLU), the fully processed and glycosylated form of CLU, plays a role in cytoprotection after cellular stress, possibly due to its ability to act as a chaperone and clear cell debris after damage. Our laboratory identified clusterin as an x-ray inducible protein/transcript. We have shown that doses of IR as low as 2 cGy, which do not cause DNA damage, induce sCLU transcript and protein suggesting a potential role for sCLU in adaptive survival responses and bystander effects. The regulatory mechanisms underlying sCLU expression following IR are unknown. Recent data generated by our laboratory suggest that the tumor suppressor protein, p53, may play a major role in the regulation of this protein. p53 is found mutated in over 50% of all human cancers. MCF-7 human breast cancer cells containing the HPV-16 E6 protein have high basal levels of sCLU a6 protein have high basal levels of sCLU as compared to parental MCF-7 cells. Additionally, p53 null HCT116 human colon cancer cells show a greatly enhanced induction of sCLU after IR, compared to parental HCT116 cells containing wild-type p53. Current work is focused on better understanding the mechanisms underlying p53 suppression of this gene, as well as transcription factors needed for IR induction

295

Radiation-induced micronucleus formation in mouse bone marrow after low dose exposures  

International Nuclear Information System (INIS)

The incidence of micronucleus formation was studied at 12, 24 and 36 h post-irradiation in the polychromatic (PCE) and normochromatic (NCE) erythrocytes of the bone marrow of mice whole-body exposed to 0, 3, 9, 18, 36, 54 and 72 cGy of 60Co ?-radiation. It was observed that the frequency of micronucleated polychromatic erythrocytes (MPCE) increased with the increase in exposure dose at all the post-irradiation time periods studied. Similarly, the frequency of micronucleated normochromatic erythrocytes (MNCE) also increased with the increase in exposure dose and the increase for both MPCE and MNCE was dose related. The dose-response relationship was linear-quadratic for both MPCE and MNCE. The study of mitotic index revealed that a dose as low as 9 cGy is capable of reducing the mitotic index significantly at 24 h post-irradiation and the dose response was linear-quadratic. However, no significant decline in the mitotic index was observed at 12 and 36 h post-irradiation

296

Protective effect of Adhatoda vascia Nees against radiation-induced damage at cellular, biochemical and chromosomal levels in Swiss albino mice.  

Science.gov (United States)

Extract of Adhatoda vasica (L) Nees leaves has been used for treatment of various diseases and disorders in Ayurved and Unani medicine. Modulatory effect of ethanolic extract of A. vasica (L) Nees against radiation-induced changes in terms of histological alterations in testis, reduced glutathione (GSH), lipid peroxidation (LPO), acid and alkaline phosphatases levels, and chromosomal alterations in Swiss albino mice was studied at various post-irradiation intervals between 1 and 30 days. Mice exposed to 8 Gy radiation showed radiation-induced sickness including marked changes in histology of testis and chromosomal aberrations in bone marrow cells with 100% mortality within 22 days. When ethanolic leaf extract of A. vasica was given orally at a dose of 800 mg kg(-1) body weight per mouse for 15 consecutive days and then exposed to radiation, death of Adhatoda-pretreated irradiated mice was reduced to 70% at 30 days. The radiation dose reduction factor was 1.43. There was significantly lesser degree of damage to testis tissue architecture and various cell populations including spermatogonia, spermatids and Leydig cells. Correspondingly, a significant decrease in the LPO and an increase in the GSH levels were observed in testis and liver of Adhatoda-pretreated irradiated mice. Similarly, a significant decrease in level of acid phosphatase and increase in level of alkaline phosphatase were observed. Adhatoda pretreatment significantly prevented radiation-induced chromosomal damage in bone marrow cells. The study suggests that Adhatoda plant extract has significant radioprotective effects on testis that warrants further mechanistic studies aimed at identifying the role of major ingredients in the extract. PMID:17965765

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

2007-09-01

297

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

International Nuclear Information System (INIS)

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

298

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

International Nuclear Information System (INIS)

Eight patients with esophageal cancer were treated by a new treatment schedule consisting of low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta. As monitored endoscopically, their therapeutic responses were satisfactory, and seven out of the eight survived for a range of 3 to 18 months and still active at work or ''cancer-free''. The seventh of the eight suffers from a second malignancy of adenocarcinoma of the cardia, different from the initial squamous cell carcinoma at the lower esophagus which had successfully been treated 3 months before. The present therapeutic design aims at treatment of lymphatic spreads in the adjacent structures as well as the original tumor in the esophagus and submucosal invasions. It is basically a consecutive, multimodal integration of selective concentration of therapeutic effects (extensive radiotherapy, topical application of bleomycin polyacrylate pasta, lymphatic chasing with colloidal bleomycin, and spatial concentration of cisplatin as the result of radiation-induced inflammations), perpetuation of the repairable DNA damage, and biological amplifications (protection against esophageal perforation with polyacrylate coating, and specific cancer cell recruitment). Application of the present therapeutic design is being expanded to treatment of cancer at other specific sites such as the head and neck tumors and rectal cancer with undeniable prospects. (author)

299

Molecular targets for radioprotection by low dose radiation exposure  

Energy Technology Data Exchange (ETDEWEB)

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

Seo, Hang Rhan; Lee, Yoon Jin; Cho, Chul Koo; Lee, Su Jae; Bae, Sang woo; Lee, Yun Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2004-07-01

300

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 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

 
 
 
 
301

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)

302

Radiation induced bladder carcinoma  

International Nuclear Information System (INIS)

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

303

[Radiation induced carcinogenesis].  

Science.gov (United States)

Intense research after Hiroshima and Nagasaki atomic bomb (A-bomb) tragedy and Chernobyl nuclear plant accident revealed that ionizing radiation (IR) more than 100 mSv induces cancers that are indistinguishable from sporadic tumors. It remains controversial whether low dose IR (less than 100 mSv) is oncogenic or not. Among IR-induced malignancies, leukemia (A-bomb) and thyroid cancers (Chernobyl), in which chimeric(fusion) oncogenes formed by chromosome translocations play a critical role, develop with relatively short latency. All other cancers develop after long latency. Age-related epigenetic changes, as well as additional genetic alterations, would contribute to IR-induced carcinogenesis. PMID:22514919

Inaba, Toshiya

2012-03-01

304

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

Energy Technology Data Exchange (ETDEWEB)

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.

Ossenkopp, K.P.; Giugno, L. (Univ. of Western Ontario, London (Canada))

1989-10-01

305

Variability: The common factor linking low dose-induced genomic instability, adaptation and bystander effects  

International Nuclear Information System (INIS)

The characteristics of low dose radiation-induced genomic instability, adaptive responses, and bystander effects were compared in order to probe possible underlying mechanisms, and develop models for predicting response to in vivo low dose radiation exposures. While there are some features that are common to all three (e.g., absence of a true dose-response, the multiple endpoints affected by each), other characteristics appear to distinguish one from the other (e.g., TP53 involvement, LET response, influence of DNA repair). Each of the responses is also highly variable; not all cell and tissue models show the same response and there is much interindividual variation in response. Most of these studies have employed in vitro cell culture or tissue explant models, and understanding underlying mechanisms and the biological significance of these low dose-responses will require study of tissue-specific in vivo endpoints. The in vitro studies strongly suggest that modeling low dose radiation effects will be a complex process, and will likely require separate study of each of these low dose phenomena. Knowledge of instability responses, for example, may not aid in predicting other low dose effects in the same tissue

306

Shape of dose curve of cytogenetic damage in the low-dose range  

International Nuclear Information System (INIS)

Modification of cytogenetic damages yield in hamsters under low dose gamma radiation using caffeine and SH-protector is studied. It is shown that in the low dose range the same repair system functions which is triggered only after sufficient reorganization of chromatin caused by radiation-induced membrane permeability increase. In the low dose effect range it takes place in the range of dose rate ? 1 - (25-3) sGy/min, while in the plateau of dose curve it does not depen on the dose rate. When assessing carcinogenic risk the linear non-threshold concept may be used for extrapolation concerning only dose curve plotted under conditions of repair inhibition or absence

307

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

International Nuclear Information System (INIS)

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

308

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

309

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

Energy Technology Data Exchange (ETDEWEB)

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

Cheryl G. Burrell, Ph.D.

2012-05-14

310

Radiation-induced Proctitis.  

Science.gov (United States)

The incidence of chronic, radiation-induced proctitis is between 2% and 5 %. There is not a direct relationship between the incidence of acute radiation proctitis and the subsequent development of chronic proctitis. The treatment for this condition should proceed in a step-wise fashion from conservative therapy such as antidiarrhea medication, topical steroids, sucralfate enemas, and iron replacement to more aggressive treatment in those who do not respond. In the case of persistent rectal bleeding, laser therapy and formalin instillation should be tried prior to surgical intervention. If surgery is necessary, a transverse or descending colostomy should be tried. Aggressive surgery such as rectal resection and colo-anal anastomosis is associated with significant morbidity and mortality and should be reserved as a last resort measure. PMID:11096568

Ajlouni

1999-02-01

311

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

312

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

313

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

314

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

315

The risk to health from low doses of ionising radiation  

Energy Technology Data Exchange (ETDEWEB)

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

Wakeford, R.; Tawn, E.J

2005-05-15

316

Low Doses of Radiation Reduce Risk In Vivo  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The “Linear No Threshold” hypothesis, used in all radiation protection practices, assumes that all doses, no matter how low, increase the risk of cancer, birth defects and heritable mutations. In vitro cell based experiments show adaptive processes in response to low doses and dose rates of low LET radiation, and do not support the hypothesis. This talk will present cellular data and data from animal experiments that test the hypothesis in vivo for cancer risk. The data show that a single...

Mitchel, R. E. J.

2007-01-01

317

LOW DOSE MAGNESIUM SULPHATE REGIME FOR ECLAMPSIA  

Directory of Open Access Journals (Sweden)

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

318

SOD2-mediated effects induced by WR1065 and low-dose ionizing radiation on micronucleus formation in RKO human colon carcinoma cells.  

Science.gov (United States)

RKO36 cells exposed to either WR1065 or 10 cGy X rays show elevated SOD2 gene expression and SOD2 enzymatic activity. Cells challenged at this time with 2 Gy exhibit enhanced radiation resistance. This phenomenon has been identified as a delayed radioprotective effect or an adaptive response when induced by thiols or low-dose radiation, respectively. In this study we investigated the relative effectiveness of both WR1065 and low-dose radiation in reducing the incidence of radiation-induced micronucleus formation in binucleated RKO36 human colon carcinoma cells. The role of SOD2 in this process was assessed by measuring changes in enzymatic activity as a function of the inducing agent used, the level of protection afforded, and the inhibitory effects of short interfering RNA (SOD2 siRNA). Both WR1065 and 10 cGy X rays effectively induced a greater than threefold elevation in SOD2 activity 24 h after exposure. Cells irradiated at this time with 2 Gy exhibited a significant resistance to micronucleus formation (P < 0.05; Student's two-tailed t test). This protective effect was significantly inhibited in cells transfected with SOD2 siRNA. SOD2 played an important role in the adaptive/delayed radioprotective response by inhibiting the initiation of a superoxide anion-induced ROS cascade leading to enhanced mitochondrial and nuclear damages. PMID:21175348

Murley, Jeffrey S; Kataoka, Yasushi; Miller, Richard C; Li, Jian Jian; Woloschak, Gayle; Grdina, David J

2011-01-01

319

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

320

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

 
 
 
 
321

Accidental chronic exposure to low dose radiation in Taiwan  

Energy Technology Data Exchange (ETDEWEB)

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

Lebaron-Jacobs, L. [CEA Cadarache, 13 - Saint Paul lez Durance (France); Nenot, J.C. [Institut de Radioprotection et de Surete Nucleaire (IRSN), 92 - Fontenay aux Roses (France); Flury-Herard, A. [CEA Fontenay aux Roses, 92 (France)

2006-07-01

322

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

323

Accidental chronic exposure to low dose radiation in Taiwan  

International Nuclear Information System (INIS)

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

324

Effects of emitter junction and passive base region on low dose rate effect in bipolar devices  

International Nuclear Information System (INIS)

Low dose rate effect in bipolar devices consists in the increase of peripheral surface recombination current with dose rate decrease. This is due to the more rapid positive oxide charge and interface trap density build-up as the dose rate becomes lower. High dose rate elevated temperature irradiation is proposed for simulation if the low dose rate effect. In the present we tried to separate the effect of radiation-induced charge in the thick passivation oxide over the emitter junction and passive base regions of npn bipolar transistor. Its goal is to improve bipolar device design for use in space environments and nuclear installations. Three experiments were made during this work. 1. Experiment on radiation-induced charge neutralization (RICN) effect under elevated temperature was performed to show transistor degradation dependence on emitter-base bias. 2. High dose rate elevated and room temperature irradiation of bipolar transistors were performed to separate effects of emitter-junction and passive base regions. 3. Pre- and post- irradiation hydrogen ambient storage was used to investigate its effect on radiation-induced charge build-up over the passive base region. All experiments were performed with npn and pnp transistors. (authors)

325

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.)

326

Low dose irradiation reduces cancer mortality rates  

International Nuclear Information System (INIS)

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)

327

Dose rate effectiveness in radiation-induced teratogenesis in mice  

Energy Technology Data Exchange (ETDEWEB)

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 {gamma}-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)

Kato, F.; Ootsuyama, A.; Norimura, T. [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

2000-05-01

328

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)

329

Caffeine Markedly Enhanced Radiation-Induced Bystander Effects  

Science.gov (United States)

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

Jiang, Erkang; Wu, Lijun

2009-04-01

330

Caffeine Markedly Enhanced Radiation-Induced Bystander Effects  

International Nuclear Information System (INIS)

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

331

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.)

332

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

333

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

334

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)

335

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)

336

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

International Nuclear Information System (INIS)

med 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.)

337

Measurements of growth and decay of radiation induced attenuation during the irradiation and recovery of plastic optical fibres  

Science.gov (United States)

In this work, we present the experimental study of the radiation-induced attenuation in step-index polymethyl-methacrylate based plastic optical fibre by exposure to low dose rate ionizing radiation. The low dose exposure has been found to induce significant permanent attenuation in plastic optical fibres. Based on the experimental results, the formula between radiation-induced attenuation and radiation dose is obtained accordingly. The recovery properties of plastic optical fibre also were investigated. The fibre begins to recover immediately after irradiation, but it does not fully recover, i.e. the irradiation leads to permanent damage of polymer.

Kova?evi?, M. S.; Savovi?, S.; Djordjevich, A.; Baji?, J.; Stupar, D.; Kova?evi?, M.; Simi?, S.

2013-04-01

338

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)

339

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

Science.gov (United States)

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

Belli, M; Salomaa, S; Ottolenghi, A

2011-02-01

340

MELODI: The 'Multidisciplinary European Low-Dose Initiative'  

International Nuclear Information System (INIS)

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

 
 
 
 
341

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

342

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

International Nuclear Information System (INIS)

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

343

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

344

Simulating threshold voltage shift of MOS devices due to radiation in the low-dose range  

CERN Document Server

An analytical MOSFET threshold voltage shift model due to radiation in the low-dose range has been developed for circuit simulations. Experimental data in the literature shows that the model predictions are in good agreement. It is simple in functional form and hence computationally efficient. It can be used as a basic circuit simulation tool for analysing MOSFET exposed to a nuclear environment up to about 1 Mrad(Si). In accordance with common believe, radiation induced absolute change of threshold voltage was found to be larger in irradiated PMOS devices. However, if the radiation sensitivity is defined in the way authors did it, the results indicated NMOS rather than PMOS devices are more sensitive, specially at low doses. This is important from the standpoint of their possible application in dosimetry

Wan Xin Heng; Gao Wen Yu; Huang Ru; Wang Yang Yuan

2002-01-01

345

Protection of mouse bone marrow against radiation-induced chromosome damage and stem cell death by the ocimum flavonoids orientin and vicenin.  

Science.gov (United States)

In a previous study, orientin and vicenin, the water-soluble plant flavonoids, protected mice against radiation lethality (Uma Devi et al., Radiat. Res. 151, 74-78, 1999). To study bone marrow protection, adult Swiss mice were exposed to 0-6 Gy 60Co gamma rays 30 min after an intraperitoneal injection of 50 microg/ kg body weight of orientin/vicenin. Chromosomal aberrations in bone marrow were studied at 24 h postirradiation. Stem cell survival was studied using the exogenous spleen colony (CFU-S) assay. Radiation produced a dose-dependent increase in aberrant cells as well as in the yield of the different types of aberrations (breaks, fragments, rings and dicentrics) and a decrease in CFU-S. Pretreatment with either flavonoid significantly reduced the aberrant cells and different aberrations and increased the number of CFU-S compared to the respective radiation-alone groups. The dose modification factors for 50% reductions in the number of CFU-S were 1.6 for orientin and 1.7 for vicenin. The present finding that very low nontoxic doses of orientin and vicenin provide efficient protection against bone marrow damage at clinically relevant radiation doses suggests their potential for protection of normal tissues in radiotherapy. PMID:15658892

Nayak, V; Devi, P Uma

2005-02-01

346

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.

347

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

348

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

349

Effects of low-dose radiation  

Energy Technology Data Exchange (ETDEWEB)

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

Bunyard, P.; Searle, G.

1986-01-01

350

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

351

Low-Dose Computed Tomography Protocols  

International Nuclear Information System (INIS)

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

352

MIRD continuing education: Bystander and low dose-rate effects: are these relevant to radionuclide therapy?  

Science.gov (United States)

Bystander and low-dose-rate effects influence the dose-response relationship in a manner not predicted by current dosimetric methodologies. Radiation-induced bystander effects refer to biologic responses in cells that are not traversed by an ionizing radiation track and, thus, not subject to direct energy deposition; that is, the responses occur in nonirradiated cells. Low-dose-rate hypersensitivity effects have been documented as a reduction in the survival of cells irradiated at dose rates of 0.1-1.0 Gy/h, with total doses ranging from 1.5 to 5 Gy. For humans undergoing external radiotherapy, evidence of bystander events has been observed in the form of abscopal effects, wherein irradiation of one portion of the anatomy affects a portion outside the radiation field, whereas low-dose-rate hypersensitivity has not been described. In this report, the historical literature is briefly reviewed, key experiments are summarized, and current understanding of the factors thought to be involved in the bystander and low-dose-rate effects is conveyed. The mechanisms associated with these events are still being investigated, and questions remain on their impact in radionuclide therapy. Although current findings do not yet sufficiently justify changing traditional dose estimates used to predict the outcomes of radionuclide therapy, it is important to appreciate the potential importance of these effects and to begin revising methods to reflect the emerging empiric and mechanistic knowledge. PMID:17873139

Sgouros, George; Knox, Susan J; Joiner, Michael C; Morgan, William F; Kassis, Amin I

2007-10-01

353

Perspectives in low dose risk estimation  

International Nuclear Information System (INIS)

Currently, debate ranges from whether very low doses have disproportionately large consequences, to whether there is a practical threshold. Whilst epidemiology for low doses can achieve somewhat higher power from conflation of results, the uncertainties are such that advances in radiobiology are essential. Conceptually, deviations from low-dose linearity can arise from changes in the cell, or in neighbouring cells, such that subsequent insults from irradiation or other carcinogens are more likely (sensitisation) or less likely (desensitisation) to result in cancer. Such feedback changes are common in living organisms (allergies and homeostatic stabilisation). Bystander effects indicate that neighbouring cells may be influenced. The effects of conditioning doses at high doses indicate that in some circumstances cells can retain a memory of earlier damage. What is measured in epidemiology is the net excess of cancers from irradiation above the much higher rates of cancer from environmental and spontaneous causes. Epidemiological dose-response curves are 'dressed'. Memory and group influences provide mechanisms which enable the 'naked' dose-response curve for the cell alone to be clothed. Junk DNA and anonymous carcinogens are also discussed. (author)

354

Estimation of radiation risks at low dose  

International Nuclear Information System (INIS)

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

355

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

International Nuclear Information System (INIS)

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

356

Complex damage, low doses and Bystander effects  

International Nuclear Information System (INIS)

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

357

Targeted and nontargeted effects of low-dose ionizing radiation on delayed genomic instability in human cells.  

Science.gov (United States)

All humans receive some radiation exposure and the risk for radiation-induced cancer at low doses is based on the assumption that there is a linear non-threshold relationship between dose and subsequent effect. Consequently, risk is extrapolated linearly from high radiation doses to very low doses. However, adaptive responses, bystander effects, and death-inducing effect may influence health effects associated with low-dose radiation exposure. Adaptive response is the phenomenon by which cells irradiated with a sublethal radiation dose can become less susceptible to subsequent high-dose radiation exposure. Bystander effects are nontargeted effects observed in cells that were not irradiated but were either in contact with or received soluble signals from irradiated cells. These non-hit bystander cells can exhibit damage typically associated with direct radiation exposure. Death-inducing effect is a phenomenon whereby medium from human-hamster hybrid cells displaying radiation-induced chromosomal instability is toxic to unirradiated parental cells. In this study, we show that human RKO cells do not exhibit adaptive response, bystander effect, or death-inducing effect, as measured by cell killing, or delayed genomic instability in a stably transfected plasmid-based green fluorescent protein assay measuring homologous recombination and delayed mutation/deletion events. However, growth medium conditioned by some chromosomally unstable RKO derivatives induced genomic instability, indicating that these cells can secrete factor(s) that