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Sample records for altered radiation sensitivity

  1. Altered metaphase chromosome structure in xrs-5 cells is not related to its radiation sensitivity or defective DNA break rejoining

    International Nuclear Information System (INIS)

    The Chinese hamster ovary (CHO) cell line xrs-5 is a radiation-sensitive derivative of CHO-K1 cells. The xrs-5 cells have a defect in DNA double-strand break rejoining and show alterations in chromosome structure and nuclear morphology. The relationship between radiation sensitivity and metaphase chromosome morphology was examined in 12 'revertant' xrs-5 clones isolated following treatment with 5-azacytidine. Nine of the clones were radioresistant while the other three retained xrs-5-like radiation sensitivity. Chromosome morphology reverted to CHO-K1-like characteristics in three of the radioresistant clones and one of the radiosensitive clones suggesting that the over-condensed metaphase chromosome morphology of xrs-5 cells does not underlie its radiation sensitivity. Radiation sensitivity did correlate with DNA double-strand break rejoining ability. The radioresistant clones showing the over-condensed xrs-5-like chromosome morphology were also slightly more sensitive to the topoisomerase II inhibitor etoposide (VP-16) than CHO-K1, suggesting that the over-condensed morphology might be due to alterations in the phosphorylation of chromatin proteins

  2. X-ray survival characteristics and genetic analysis for nine Saccharomyces deletion mutants that show altered radiation sensitivity.

    Science.gov (United States)

    Game, John C; Williamson, Marsha S; Baccari, Clelia

    2005-01-01

    The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X rays, we are screening these mutants to identify additional genes that cause increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype cosegregates with the deletion allele and are obtaining multipoint survival-vs.-dose assays in at least one homozygous diploid and two haploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1, and VID21/EAF1 and discuss their potential roles in repair. Eight of these genes cause a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, results in at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultraviolet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino acids are also X-ray sensitive, which confirms that methylation of the lysine-79 residue is required for effective repair of radiation damage. PMID:15371366

  3. X-ray survival characteristics and genetic analysis for nine saccharomyces deletion mutants that show altered radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2004-01-07

    The availability of a genome-wide set of Saccharomyces deletion mutants provides a chance to identify all the yeast genes involved in DNA repair. Using X-rays, we are screening these mutants to identify additional genes that show increased sensitivity to the lethal effects of ionizing radiation. For each mutant identified as sensitive, we are confirming that the sensitivity phenotype co-segregates with the deletion allele and are obtaining multipoint survival-versus-dose assays in at least two haploid and one homozygous diploid strains. We present data for deletion mutants involving the genes DOT1, MDM20, NAT3, SPT7, SPT20, GCN5, HFI1, DCC1 and VID21/EAF1, and discuss their potential roles in repair. Eight of these genes have a clear radiation-sensitive phenotype when deleted, but the ninth, GCN5, has at most a borderline phenotype. None of the deletions confer substantial sensitivity to ultra-violet radiation, although one or two may confer marginal sensitivity. The DOT1 gene is of interest because its only known function is to methylate one lysine residue in the core of the histone H3 protein. We find that histone H3 mutants (supplied by K. Struhl) in which this residue is replaced by other amino-acids are also X-ray sensitive, seeming to confirm that methylation of the lysine-79 residue is required for effective repair of radiation damage.

  4. Radiation sensitive acrylate composition

    International Nuclear Information System (INIS)

    This application relates to radiation-sensitive compositions and more particularly to such compositions comprising acrylated esters. As used in this specification, the term acrylated esters refers to either acrylic or methacrylic acid resins. 3 tabs

  5. Individual radiation sensitivity (gender, age, genetic disposition). Consequences for radiation protection; Individuelle Strahlenempfindlichkeit (Geschlecht-Alter-genetische Disposition). Konsequenzen fuer den Strahlenschutz?

    Energy Technology Data Exchange (ETDEWEB)

    Streffer, C. [Universitaetsklinikum Essen (Germany)

    2013-07-01

    The effects of ionising radiation on human health is influenced by a number of physiological and molecular biological factors. This is also valid for the causation of stochastic radiation effects especially the causation of cancer. Several epidemiological studies have resulted with respect to the total rate of solid cancers that women are more sensitive than men by a factor of 1.6 to 2.0. For leukaemia this is not the case. The largest studies come from the investigations on the survivors of the atomic bombs in Hiroshima and Nagasaki. But also studies on the population of the Techa River (Southeast Urals) yield such data. The analyses of single cancer localizations come to different results with respect to the dependence on the sex. Secondary cancers after radiotherapy for cancer treatment show also higher rates in women than in men. A similar situation is observed with respect to the dependence of cancer rate on age. The total rate of solid cancers is highest with children and decreases with increasing age. The effects are very different again with single cancer localizations. An especially strong age dependence was observed for thyroid cancer. Increasingly individuals have been found who are especially radiosensitive on the basis of their genetic disposition also with respect to the causation of cancer. Mechanisms and possibilities to trace these individuals are discussed. It is also discussed whether and to which extent these data should have consequences for the practical radiological protection. (orig.)

  6. Radiation Sensitization in Cancer Therapy.

    Science.gov (United States)

    Greenstock, Clive L.

    1981-01-01

    Discusses various aspects of radiation damage to biological material, including free radical mechanisms, radiation sensitization and protection, tumor hypoxia, mechanism of hypoxic cell radiosensitization, redox model for radiation modification, sensitizer probes of cellular radiation targets, pulse radiolysis studies of free radical kinetics,…

  7. SEM probe of IC radiation sensitivity

    Science.gov (United States)

    Gauthier, M. K.; Stanley, A. G.

    1979-01-01

    Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

  8. DNA repair and radiation sensitivity in mammalian cells

    International Nuclear Information System (INIS)

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population

  9. Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

    OpenAIRE

    Lee, Kuei-Fang; Weng, Julia Tzu-Ya; Hsu, Paul Wei-Che; Chi, Yu-Hsiang; Chen, Ching-Kai; Liu, Ingrid Y.; CHEN, YI-CHENG; Wu, Lawrence Shih-Hsin

    2014-01-01

    Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from...

  10. Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Skiöld, Sara [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Azimzadeh, Omid [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Merl-Pham, Juliane [Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg (Germany); Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet [Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm (Sweden); Tapio, Soile [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden)

    2015-06-15

    Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.

  11. Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

    International Nuclear Information System (INIS)

    Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy

  12. Individual radiation sensitivity: implications in medical practice

    Energy Technology Data Exchange (ETDEWEB)

    Gisone, P.; Dubner, D.; Perez, M.D.R.; Michelin, S.; Di Giogio, M. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina); Bourguignon, M. [Direction Generale de la Surete Nucleaire et de la Radioprotection, Paris (France)

    2006-07-01

    Important advances in radiotherapy and nuclear medicine towards better treatment modalities and safer applications have taken place in recent years. Progress in medical imaging, better tumour targeting and optimization of radiation delivery have allowed for dose escalation and improved patient outcome. However, the tolerance of normal tissues constitutes the limiting factor for dose escalation in therapeutical uses of ionizing radiation (IR). Patients vary considerably in their normal tissue response to IR even after similar treatments. As many as 5% of cancer patients develop severe effects to external radiation therapy in normal tissues within the treatment field: they may include acute effects such as erythema and desquamation of the exposed skin and mucosa that appear during or directly after radiotherapy, late effects developed months or years later, such as fibrosis and telangiectasia and cancer induction. Several patient and treatment related factors are known to influence the variability of side effects, however up to a 70% of the total variance of normal tissue radiation response remained unexplained. Thus, individual sensitivity to IR, i.e. hypersensitivity to carcinogenic risks (stochastic effects) and hypersensitivity to deterministic effects, is becoming an important issue in oncology and raises questions regarding the underlying mechanisms. The mechanisms of DNA repair, the signalling pathways involved in radiation sensitivity and non-targeted effects are key aspects, essential to understanding radiation effects at genetic level. Moreover, human genetic diseases that combine higher incidence of cancer and hypersensitivity to IR are associated with defects in cell response to DNA damage. Therefore, much interest has raised during the last years in the developing of predictive tests capable to detect in advance such hypersensitive conditions. The goal of this presentation is to review the possible mechanisms involved in genetic and epigenetic

  13. Individual radiation sensitivity: implications in medical practice

    International Nuclear Information System (INIS)

    Important advances in radiotherapy and nuclear medicine towards better treatment modalities and safer applications have taken place in recent years. Progress in medical imaging, better tumour targeting and optimization of radiation delivery have allowed for dose escalation and improved patient outcome. However, the tolerance of normal tissues constitutes the limiting factor for dose escalation in therapeutical uses of ionizing radiation (IR). Patients vary considerably in their normal tissue response to IR even after similar treatments. As many as 5% of cancer patients develop severe effects to external radiation therapy in normal tissues within the treatment field: they may include acute effects such as erythema and desquamation of the exposed skin and mucosa that appear during or directly after radiotherapy, late effects developed months or years later, such as fibrosis and telangiectasia and cancer induction. Several patient and treatment related factors are known to influence the variability of side effects, however up to a 70% of the total variance of normal tissue radiation response remained unexplained. Thus, individual sensitivity to IR, i.e. hypersensitivity to carcinogenic risks (stochastic effects) and hypersensitivity to deterministic effects, is becoming an important issue in oncology and raises questions regarding the underlying mechanisms. The mechanisms of DNA repair, the signalling pathways involved in radiation sensitivity and non-targeted effects are key aspects, essential to understanding radiation effects at genetic level. Moreover, human genetic diseases that combine higher incidence of cancer and hypersensitivity to IR are associated with defects in cell response to DNA damage. Therefore, much interest has raised during the last years in the developing of predictive tests capable to detect in advance such hypersensitive conditions. The goal of this presentation is to review the possible mechanisms involved in genetic and epigenetic

  14. Albendazole sensitizes cancer cells to ionizing radiation

    International Nuclear Information System (INIS)

    Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage. ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted

  15. Radiation sensitivity of different citric pectins

    Energy Technology Data Exchange (ETDEWEB)

    Inamura, Patricia Y.; Mastro, Nelida L. del [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: patyoko@yahoo.com; nlmastro@ipen.br

    2007-07-01

    Pectic substances are important soluble polysaccharides of plant origin of considerable interest for food industry as gelling agent and stabilizer in jams, fruit jellies, yogurt drinks and lactic acid beverages. Polysaccharides can be degraded by ionizing radiation due to the free radical induced scission of the glycosidic bonds. Viscosity methods had been used to determine the efficiency of hydroxyl radical induced chain breaks generation in macromolecules. In the present work samples of pectin with different degree of methoxylation were employed in order to study their radiation sensitivity by means of viscosity measurements. Samples of citric pectin 1% solutions were irradiated with gamma rays at different doses, ranging from 0 to 15 kGy, using a {sup 60}Co Gammacell 220 (AECL), dose rate about 2 kGy/h. After irradiation the viscosity was measured on the viscometer Brookfield model LV-DVIII at 50, 60 and 70 deg C within a period of 48h. Pectin viscosity with high degree of methoxylation decreased sharply with the radiation dose remaining almost constant from 10 kGy. Pectin with low degree of methoxylation presented initially higher values of viscosity and the radiation induced decrease was also pronounced. Viscosity measurements decreased with the increase of the temperature applied for both kind of samples. The effect of radiation induced chain breaks generation in pectin molecules was evident through the viscosity reduction of irradiated pectin solutions although the viscosity presented diverse values depending of the degree of methoxylation of carboxyl groups in the backbone of polysaccharide macromolecules. (author)

  16. Radiation sensitivity of different citric pectins

    International Nuclear Information System (INIS)

    Pectic substances are important soluble polysaccharides of plant origin of considerable interest for food industry as gelling agent and stabilizer in jams, fruit jellies, yogurt drinks and lactic acid beverages. Polysaccharides can be degraded by ionizing radiation due to the free radical induced scission of the glycosidic bonds. Viscosity methods had been used to determine the efficiency of hydroxyl radical induced chain breaks generation in macromolecules. In the present work samples of pectin with different degree of methoxylation were employed in order to study their radiation sensitivity by means of viscosity measurements. Samples of citric pectin 1% solutions were irradiated with gamma rays at different doses, ranging from 0 to 15 kGy, using a 60Co Gammacell 220 (AECL), dose rate about 2 kGy/h. After irradiation the viscosity was measured on the viscometer Brookfield model LV-DVIII at 50, 60 and 70 deg C within a period of 48h. Pectin viscosity with high degree of methoxylation decreased sharply with the radiation dose remaining almost constant from 10 kGy. Pectin with low degree of methoxylation presented initially higher values of viscosity and the radiation induced decrease was also pronounced. Viscosity measurements decreased with the increase of the temperature applied for both kind of samples. The effect of radiation induced chain breaks generation in pectin molecules was evident through the viscosity reduction of irradiated pectin solutions although the viscosity presented diverse values depending of the degree of methoxylation of carboxyl groups in the backbone of polysaccharide macromolecules. (author)

  17. High sensitive radiation detector for radiology dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Valente, M.; Malano, F. [Instituto de Fisica Enrique Gaviola, Oficina 102 FaMAF - UNC, Av. Luis Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina); Molina, W.; Vedelago, J., E-mail: valente@famac.unc.edu.ar [Laboratorio de Investigaciones e Instrumentacion en Fisica Aplicada a la Medicina e Imagenes por Rayos X, Laboratorio 448 FaMAF - UNC, Ciudad Universitaria, 5000 Cordoba (Argentina)

    2014-08-15

    Fricke solution has a wide range of applications as radiation detector and dosimetry. It is particularly appreciated in terms of relevant comparative advantages, like tissue equivalence when prepared in aqueous media like gel matrix, continuous mapping capability, dose rate recorded and incident direction independence as well as linear dose response. This work presents the development and characterization of a novel Fricke gel system, based on modified chemical compositions making possible its application in clinical radiology. Properties of standard Fricke gel dosimeter for high dose levels are used as starting point and suitable chemical modifications are introduced and carefully investigated in order to attain high resolution for low dose ranges, like those corresponding to radiology interventions. The developed Fricke gel radiation dosimeter system achieves the expected typical dose dependency, actually showing linear response in the dose range from 20 up to 4000 mGy. Systematic investigations including several chemical compositions are carried out in order to obtain a good enough dosimeter response for low dose levels. A suitable composition among those studied is selected as a good candidate for low dose level radiation dosimetry consisting on a modified Fricke solution fixed to a gel matrix containing benzoic acid along with sulfuric acid, ferrous sulfate, xylenol orange and ultra-pure reactive grade water. Dosimeter samples are prepared in standard vials for its in phantom irradiation and further characterization by spectrophotometry measuring visible light transmission and absorbance before and after irradiation. Samples are irradiated by typical kV X-ray tubes and calibrated Farmer type ionization chamber is used as reference to measure dose rates inside phantoms in at vials locations. Once sensitive material composition is already optimized, dose-response curves show significant improvement regarding overall sensitivity for low dose levels. According to

  18. Directionally Sensitive Silicon Radiation Sensor (VCELL)

    Science.gov (United States)

    Cook, Koy B.

    2002-01-01

    Sensors are a mission critical element in many NASA programs and require some very unique properties such as small size, low power, high reliability, low weight. Low cost sensors offer the possibility of technology transfer to the public domain for commercial applications. One sensor application that is important to many NASA programs is the ability to point at a radiation source, such as the sun. Such sensors may be an integral part of the guidance and control systems in space platforms and in remote exploratory vehicles. Sun/solar pointing is also important for ground-based systems such as solar arrays. These systems are not required to be small and lightweight. However, if a sensor with a sun pointing capability was developed that is very small, rugged, lightweight and at the same time low cost, it certainly could be used in existing and perhaps many new ground based applications, The objective of the VCELL (Directionally Sensitive Silicon Radiation Sensor) research is to develop a new and very unique silicon based directionally sensitive radiation sensor which can be fabricated using conventional monolithic IC technologies and which will meet the above requirements. The proposed sensor is a novel silicon chip that is directionally sensitive to incident radiation, providing azimuth and elevation information on the incident radiation. The resulting sensor chip will be appropriate for integration into a silicon IC or useful in a hybrid structure to be interfaced with a standard IEEE 1451 bus interface IC to create an Intelligent Sensor. It is presently estimated that it will require about three man-years of effort to complete the VCELL research and development. This includes the optical, electrical, mechanical and silicon fabrication and testing as well as computer simulations and theoretical analysis and modeling including testing in simulated space environments, This report summarizes the sensor research completed this summer as part of the Summer Faculty

  19. Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Kuei-Fang Lee

    2014-01-01

    Full Text Available Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.

  20. Development of a radiation-sensitive indicator

    Science.gov (United States)

    Abdel-Fattah, A. A.; El-Kelany, M.; Abdel-Rehim, F.

    1996-10-01

    A poly(vinyl alcohol) (PVA) film containing acid-sensitive dye (bromophenol red, BPR) and water soluble chlorine-containing substance [CCl 3COONa or chloral hydrate (CCl 3CH(OH) 2, 2,2,2-trichloroethan-1,1-diol)] may be useful as a radiation-sensitive indicator. The acid-sensitive dye in the film changes its color from violet to pale yellow by irradiation due to the consequent lowering of the pH of the film caused by the HCl generated from the radiolysis of the Cl-containing substance. This film can be used as a dosimeter in a relatively low dose range up to 5 kGy. This response range makes this film useful in some food irradiation, pasteurization and water purification applications. The effects of temperature and relative humidity during irradiation and post-irradiation storage on the response of the film are discussed. It is inexpensive, does not require toxic solvents in preparation and easy to prepare in a laboratory.

  1. Stromal sensitivity to radiation and hyperthermia

    International Nuclear Information System (INIS)

    The influence on stroma of heat alone, X-rays alone or the combined treatment, has been studied using the tumour bed effect (TBE) as an assay. Ca NT cells have been implanted into previously treated subcutaneous sites as an angiogenic stimulus. The vascular damage is then assessed by the reduced tumour growth rate. A range of X-ray doses was used and large alterations in latent period for growth to 2 mm diameter were followed by smaller alterations in the growth rate of established tumours. A dose reponse relationship was seen for latency and for growth rate. A range of subcutaneous temperatures was obtained by immersion in a water bath for 60 minutes at 400 to 44.50C. A slight retardation of tumour growth was seen after 41.50C, but an unexpected acceleration resulted from 44.50C. Combined heat and X-ray treatments showed thermal sensitization of the X-ray induced TBE at 41.50C, with a reversal at higher temperatures. At 430C and 44.50C a mild thermal burn was induced and this appeared to elicit neovascularisation that could be utilized by the implanted tumour cells. Delayed implantation of tumour cells abolished this effect. (author)

  2. Sensitiveness of viruses to gamma radiation

    International Nuclear Information System (INIS)

    The sensitiveness of viruses to gamma rays was compared using eight viruses suspended with low concentration in drinking water, and four viruses present in high concentrations in tissue culture medium. The results show that the following factors are responsible for the resistance of viruses to gamma rays: 1. type of virus: the specific radiation resistance varied considerably; in general, there was a closer correlation with the general resistance of the virus to chemico-physical influences than with the type of nucleic acid of the virus examined; 2. medium of suspension and state of aggregation: high protein content and lyophilisation increased the resistance to gamma rays widely; 3. virus concentration: the virus reduction by a factor of 10 in suspensions with high virus concentration needed a higher radiation dose compared with suspensions of low virus content. All the results demonstrate the kinetics of inactivation to be a 1st order reaction. The increase of temperature to 410C did not show any significant influence. (orig.)

  3. Comparative study of different surrogate markers for individual radiation sensitivity

    International Nuclear Information System (INIS)

    Radiotherapy is an important part of therapeutic tumor treatment concept. The applied total dose is limited by the unavoidable radiation effect on the surrounding normal tissue and the risk of radiation induced acute or chronic side effects. The clinical radiation sensitivity, i.e. the risk of radiogenic side effects is strongly coupled to the cellular radiation sensitivity. The contribution is focused on the development of a predictive tool for the individual radiation sensitivity for individual radiotherapeutic planning using lymphocytes. Residual foci, i.e. accumulated repair associated proteins at the residual double strand break are supposed to be surrogate markers of the cellular radiation sensitivity. No relation between the foci detection and the G(0)/G(1) was found assay with respect to the individual radiation sensitivity.

  4. Radiation-induced motility alterations in medulloblastoma cells

    OpenAIRE

    Rieken, Stefan; Rieber, Juliane; Brons, Stephan; Habermehl, Daniel; Rief, Harald; Orschiedt, Lena; Lindel, Katja; Klaus J. Weber; Debus, Jürgen; Combs, Stephanie E

    2015-01-01

    Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metallop...

  5. Adaptive radiation-induced epigenetic alterations mitigated by antioxidants

    OpenAIRE

    Bernal, Autumn J.; Dolinoy, Dana C; Huang, Dale; Skaar, David A.; Weinhouse, Caren; Jirtle, Randy L

    2013-01-01

    Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (Avy) locus in a sex-specific man...

  6. Metal-containing radiation-sensitive polymers

    Energy Technology Data Exchange (ETDEWEB)

    Lee, A.Y.

    1986-01-01

    The copolymers of methyl methacrylate with alkali metal salts (Na, K, and Cs) of methacrylic acid have been prepared by saponification K, and Cs) of methylacrylic acid have been prepared by saponification of the homopolymer poly(methyl methacrylate), PMMA. Low degrees of hydrolysis have been achieved by a heterogeneous system, and from the infrared spectra it has been confirmed that the ester groups of the methyl methacrylates are directly converted to the metal salts of methacrylic acid. These ionomers exhibit pseudo high molecular weights in gel permeation chromatogram, but no appreciable increase in intrinsic viscosities is observed in comparison to PMMA. The coordinated inorganic polymers poly((dithio-2,2'-diacetato)bis(dimethylsulfoxide)dioxouranium(VI)) and poly()methylenebis(thio)-2,2'-bis(acetato))bis(dimethylsulfoxide)dioxouranium(VI))have been synthesized in dimethyl sulfoxide solution with about 90% yield. The degree of polymerization and the number of average molecular weights of these polymers have been assessed by high resolution nuclear magnetic resonance, with which the acetato end group to the bridging ligand group ratios have been determined. The polymers bridging ligand group ratios have been determined. The polymers have been characterized by employing various techniques: infrared spectra, thermal gravimetric analysis, /sup 13/C solid state nuclear magnetic resonance, and gel permeation chromatography. The prepared polymer samples have been subjected to various doses of /sup 137/Cs gamma radiation under which the polymers predominantly undergo chain scission. The radiation sensitivities of the polymers are assessed by G values which are obtained from gel permeation chromatograms. These uranyl polymers exhibit unusually high G values.

  7. Genetics of human sensitivity to ultraviolet radiation

    Science.gov (United States)

    Cleaver, James E.

    1994-07-01

    the major human health effects of solar and artificial UV light occur from the UVB and UVC wavelength ranges and involve a variety of short-term and long-term deleterious changes to the skin and eyes. the more important initial damage to cellular macromolecules involves dimerization of adjacent pyrimidines in DNA to produce cyclobutane pyrimidine dimes, (6-4) pyrimidine- pyrimidone, and (6-4) dewar photoproducts. these photoproducts can be repaired by a genetically regulated enzyme system (nucleotide excision repair) which removes oligonucleotides 29-30 nucleotides long that contain the photoproducts, and synthesizes replacement patches. At least a dozen gene products are involved in the process of recognizing photoproducts in DNA, altering local DNA helicity and cleaving the polynucleotide chain at defined positions either side of a photoproduct. Hereditary mutations in many of these genes are recognized in the human genetic disorders xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). Several of the gene products have other functions involving the regulation of gene transcription which accounts for the complex clinical presentation of repair deficient diseases that involve sensitivity of the skin and eyes to UV light, increased solar carcinogenesis (in XP), demyelination, and ganglial calcification (in CS), hair abnormalities (in TTD), and developmental and neurological abnormalities

  8. Radiation sensitivity of hyperthermal composting microorganisms

    Science.gov (United States)

    Choi, Jong-Il; Yoon, Min-Chul; Kim, Jae-Hun; Yamashita, Masamichi; Kim, Geun Joong; Lee, Ju-Woon

    In the space station and vehicles designed for long human mission, high-temperature compost is a promising technology for decomposing organic waste and producing the fertilizers. In space, the microorganisms could have the changed biological activities or even be mutated by ionizing irradiation. Therefore, in this study, the effect of gamma irradiation on the sensitivity of bacteria in hyperthermal composting was investigated. The sequence analysis of the amplified 16s rDNA genes and amoA gene were used for the identification of composting microorganisms. Viability of microorganisms in compost soil after gamma irradiation was directly visualized with LIVE/DEAD Baclight viability kit. The dominant bacterial genera are Weissella cibaria and Leuconostoc sp. and fungus genera are Metschnikowia bicuspidate and Pichia guilliermondii, respectively. By the gamma irradiation up to the dose of 1 kGy, the microbial population was not changed. Also, the enzyme activities of amylase and cellulose were sustained by the gamma irradiation. These results show that these hyperthermia microorganisms might have the high resistance to gamma radiation and could be used for agriculture in the Space Station.

  9. Thermal radiosensitization in radiation-sensitive mutant mouse leukemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Toshikazu (Hiroshima Univ. (Japan). School of Dentistry)

    1994-06-01

    This study investigated thermal, radiation, and combined thermal radiation sensitization of mouse leukemic cells, L5178Y, and radiation-sensitive mutant cells, LX830. Radiation sensitivity (D[sub 0]) values were 0.41 Gy for LX830 and 1.39 Gy for L5178Y, with the ratio of D[sub 0] values in LX830 to in L5178Y being 3.4. Thus, LX830 was more radiosensitive than L5178Y. LX830 showed no shouldered survival curves. Although sublethal damage (SLD) repair was seen to the almost same degree in both LX830 and L5178Y, potential lethal damage (PLD) repair was scarcely observed in LX830. Both cell lines were similar in thermal sensitivity (T[sub 0]). Eosine staining suggested that cell killing due to hyperthermia had occurred in the interphase in both LX830 and L5178Y. L5178Y showed thermal sensitivity low in the G1 phase and high in the S phase; on the contrary, LX830 showed it high in the G1 phase and low in the S phase. Thermal radiosensitization was similar in both cell lines, although there was a great difference in radiation sensitivity between the cell lines. The difference in radiation sensitivity (D[sub 0]) between L5178Y and LX830 became small when radiation was given at the time of the maximum thermal resistance. This seemed to contribute to a decrease in radiation sensitivity in LX830. It can be concluded that thermal radiosensitization depends on thermal sensitivity and that radiation sensitivity decreases in radiation-sensitive cells when exposed to irradiation at the time of thermal resistance. (N.K.).

  10. Hemochromatosis heterozygotes may constitute a radiation-sensitive subpopulation.

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, R G.(GEORGE A GRANT INC); Morris, James E.(BATTELLE (PACIFIC NW LAB)); Anderson, Larry E.(BATTELLE (PACIFIC NW LAB))

    1999-12-01

    A primary mechanism of radiation-induced DNA damage is by generation of free radicals. Chronically increased oxidative stress from elevated body iron may increase radiation sensitivity by decreasing cellular oxygen radical scavenging capability. Hemochromatosis heterozygotes have elevated body iron. Low-level radiation sensitization by iron may be particularly pertinent for risk of breast cancer. Since ten percent of the population appears to be heterozygous for the hemochromatosis gene, a radiosensitizing effect would have pervasive implications.

  11. Radiation-induced motility alterations in medulloblastoma cells.

    Science.gov (United States)

    Rieken, Stefan; Rieber, Juliane; Brons, Stephan; Habermehl, Daniel; Rief, Harald; Orschiedt, Lena; Lindel, Katja; Weber, Klaus J; Debus, Jürgen; Combs, Stephanie E

    2015-05-01

    Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-μm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV-coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α5. The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α5, which lead to increased cell adherence to extracellular matrix proteins. PMID:25736470

  12. On the instability effects in radiation-sensitive chalcogenide glasses

    International Nuclear Information System (INIS)

    The features of application of radiation-sensitive media based on chalcogenide glasses of As-Ge-S system for registration of high-energy γ-radiation are analysed. It is shown that compositional features of the observed time-instability effect should be taken into account in order to ensure a higher accuracy of the developed dosimeters

  13. On the instability effects in radiation-sensitive chalcogenide glasses

    Energy Technology Data Exchange (ETDEWEB)

    Balitska, V. [Lviv State University for Vital Activity Safety, 35 Kleparivska str., Lviv, UA-79007 (Ukraine); Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine); Kovalskiy, A. [Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine); International Materials Institute for New Functionality in Glass, Lehigh University, 5 East Packer Avenue, Bethlehem, PA 18015-3195 (United States); Shpotyuk, O. [Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine); International Materials Institute for New Functionality in Glass, Lehigh University, 5 East Packer Avenue, Bethlehem, PA 18015-3195 (United States)], E-mail: shpotyuk@novas.lviv.ua; Vakiv, M. [Lviv Institute of Materials of SRC ' Carat' , 202 Stryjska str., Lviv, UA-79031 (Ukraine)

    2007-04-15

    The features of application of radiation-sensitive media based on chalcogenide glasses of As-Ge-S system for registration of high-energy {gamma}-radiation are analysed. It is shown that compositional features of the observed time-instability effect should be taken into account in order to ensure a higher accuracy of the developed dosimeters.

  14. The Visualization of Infrared Radiation Using Thermal Sensitive Foils

    Science.gov (United States)

    Bochnícek, Zdenek

    2013-01-01

    This paper describes a set of demonstration school experiments where infrared radiation is detected using thermal sensitive foils. The possibility of using standard glass lenses for infrared imaging is discussed in detail. It is shown that with optic components made from glass, infrared radiation up to 2.5 µm of wavelength can be detected. The…

  15. Alterations induced in Escherichia Coli cells by gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kappke, J.; Schelin, H.R.; Paschuk, S.A.; Denyak, V.; Silva, E.R. da [Federal University of Technology of Parana (CPGEI/UTFPR), Curitiba, PR (Brazil)]. E-mails: jaquekap@yahoo.com.br; schelin@cpgei.cefetpr.br; sergei@utfpr.edu.br; Jesus, E.F.O. de; Lopes, R.T. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE). Lab. de Instrumentacao Nuclear]. E-mails: ricardo@lin.ufrj.br; edgar@lin.ufrj.br; Carlin, N.; Toledo, E.S. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Fisica]. E-mail: nelson.carlin@dfn.if.usp.br

    2007-07-01

    Modifications occurred in Escherichia coli cells exposed to gamma radiation ({sup 60}Co source) were investigated. The irradiations were done at the LIN-COPPE laboratory of the UFRJ and the analysis at the Biology Department of the UTFPR. The E. coli cells were irradiated with 30, 60, 90, 120, 150, 180, 210, 240, 300, 480, 600 e 750 Gy doses. The samples were analyzed with Gram-stain, biochemical tests in EPM, MIO and Lysine Broth, Simmons Cytrate Medium and Rhamnose Broth, antibiogram and isolation of auxotrophic mutants. It was observed that for the received doses the E. coli did not show morphological alterations in the tests. Some E. Coli cells showed to be able to deaminade the L-tryptophan or they changed their sensibility for amoxillin and cephaloonine after the irradiation. The existence of aauxotrophic mutants after irradiation was also verified. (author)

  16. Sensitivity of oysters (Crassostrea Brasiliana) to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mattiolo Marchese, S.R. [Brazilian Navy Technology Center, Sao Paulo (Brazil); Mastro, N.L. del [Inst. of Nuclear and Energy Researches IPEN-CNEN/SP, Sao Paulo (Brazil)

    1997-12-31

    Various foods including oysters, crabs and shrimps have been shown to be possible transmitters of Vibrio ssp. Irradiation of sea-foods is being considered an alternative to intervention measures in Public Health against food borne diseases. The aim of this work was to establish, the radiation resistance of the oysters Crassostrea brasiliana. The oysters were irradiated with Co-60 radiation with doses of 0, 1.5, 3 and 6 kGy. Survival curves as a function of time showed that 100% of the oysters irradiated with doses of 3 kGy survived at least 6 days. 100% those irradiated with 6 kGy survived 3 days. The obtained results are auspicious considering that a dose of 2 kGy is already effective in the diminishing of the microbial load on oysters. (author). 5 refs, 5 figs, 1 tab.

  17. Altered pulmonary epithelial permeability in canine radiation lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, I.H.; el-Khatib, E.; Logus, J.W.; Man, G.C.; Jacques, J.; Man, S.F.

    1986-09-01

    A radioaerosol scanning technique measuring regional clearance of sodium pertechnetate (99mTcO-4) and 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) was used to assess changes in canine pulmonary epithelial permeability following lung irradiation. Doses of 2000 cGy (11 dogs), 1000 cGy (2 dogs), and 500 cGy (2 dogs) were given in one fraction to either the entire right hemithorax (500 cGy) or the right lower lung (1000 and 2000 cGy). Radioaerosol scans, chest roentgenograms, and computerized tomograms (CT) were obtained before and serially after irradiation. A dose of 2000 cGy resulted in a decrease in regional pulmonary epithelial permeability to both 99mTcO4- and 99mTc-DTPA; both showed significant decreases from the 2nd wk postirradiation onward. In comparison, CT and chest roentgenogram did not become abnormal until 7.1 +/- 2.8 (SD) and 8.2 +/- 2.6 wk, respectively. Doses of 1,000 and 500 cGy produced reversible decreases in 99mTcO4- clearance. Lung morphology showed definite changes of radiation pneumonitis after 2000 and 1000 cGy but not after 500 cGy at approximately 9, 17, and 12 wk postirradiation, respectively. These results suggest that dose-dependent changes in pulmonary physiology may precede obvious structural alterations in radiation lung injury.

  18. Effect of troglitazone on radiation sensitivity in cervix cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    An, Zheng Zhe; Liu, Xian Guang; Song, Hye Jin; Choi, Chi Hwan; Kim, Won Dong; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of); Yu, Jae Ran [Konkuk University College of Medicine, Chungju (Korea, Republic of)

    2012-06-15

    Troglitazone (TRO) is a peroxisome proliferator-activated receptor {gamma} (PPAR{gamma} ) agonist. TRO has antiproliferative activity on many kinds of cancer cells via G1 arrest. TRO also increases Cu{sup 2+}/Zn{sup 2+} -superoxide dismutase (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer cells in vitro. Three human cervix cancer cell lines (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase, and catalase activities were measured at 2-10 {mu}M of TRO for 24 hours. Cell cycle was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate. Cell survival by radiation was measured with clonogenic assay. By 5 {mu}M TRO for 24 hours, the mRNA, protein expression and activity of catalase were increased in all three cell lines. G0- G1 phase cells were increased in HeLa and Me180 by 5 {mu}M TRO for 24 hours, but those were not increased in SiHa. By pretreatment with 5 {mu}M TRO radiation sensitivity was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2 {mu}M TRO which increased catalase but not increased G0-G1 cells, radiosensitization was not observed. ROS produced by radiation was decreased with TRO. TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation sensitivity through catalasemediated ROS scavenging according to TRO dose or cell types. The change of radiation sensitivity by combined with TRO is not dependent on the PPAR {gamma} expression level.

  19. Gadolinium nanoparticles and contrast agent as radiation sensitizers.

    Science.gov (United States)

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist(®) in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL(-1)), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly 'energy dependent' for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.

  20. Gadolinium nanoparticles and contrast agent as radiation sensitizers

    Science.gov (United States)

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F.; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist® in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL-1), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly ‘energy dependent’ for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.

  1. Characterization of UV radiation sensitive frog cell lines

    International Nuclear Information System (INIS)

    Twenty-one subclones of nine frog cell isolates were tested for sensitivity to a panel of DNA damaging agents. Two clones were identified which had a greater than wild type level of sensitivity to UV radiation but had a wild type level of sensitivity to the other agents. These clones were the haploid RRP602-7 and the diploid RRP802-1. RRP802-1 was found to be unstable with respect to UV sensitivity. The line was cloned in order to isolate stable sensitive and wild type derivatives. RRP802-1-16, a UV sensitive clone and RRP802-1-13, a clone with a wild type level of sensitivity to UV radiation, were isolated. The UV radiation sensitivity of RRP602-7, RRP802-1 and RRP802-1-16 did not correlate with cell size, cell shape, cell cycle distribution or ploidy. The cell cycle distribution after UV irradiation, the rate of DNA synthesis after UV-irradiation, the DNA polymerase α activity and the sister chromatid exchange frequency were all measured in RRP602-7, RRP802-1 and RRP802-1-16 in order to examine the DNA repair capacity. The presence of DNA repair pathways was examined directly in RRP602-7, RRP802-1 and RRP802-1-16. All were found to be proficient in photo-reactivation repair and postreplication repair of UV elicited DNA damage

  2. Radiation sensitive devices and systems for detection of radioactive materials and related methods

    Energy Technology Data Exchange (ETDEWEB)

    Kotter, Dale K

    2014-12-02

    Radiation sensitive devices include a substrate comprising a radiation sensitive material and a plurality of resonance elements coupled to the substrate. Each resonance element is configured to resonate responsive to non-ionizing incident radiation. Systems for detecting radiation from a special nuclear material include a radiation sensitive device and a sensor located remotely from the radiation sensitive device and configured to measure an output signal from the radiation sensitive device. In such systems, the radiation sensitive device includes a radiation sensitive material and a plurality of resonance elements positioned on the radiation sensitive material. Methods for detecting a presence of a special nuclear material include positioning a radiation sensitive device in a location where special nuclear materials are to be detected and remotely interrogating the radiation sensitive device with a sensor.

  3. Multipurpose High Sensitivity Radiation Detector: Terradex

    International Nuclear Information System (INIS)

    Terradex project aims to realise an accurate and programmable multiparametric tool which will measure relevant physical quantities such as observation time, energy and type of all decay products of three naturally occurring decay chains of uranium and thorium series present in nature as well as the decay products of man-made radioactivity. The measurements described in this work are based on the performance tests of the first version of an instrument that is designed to provide high counting accuracy, by introducing self-triggering, delayed time-coincidence technique, of products of a given decay chain. In order to qualify the technique and to calibrate the Terradex, a 222Rn source is used. The continuous and accurate monitoring of radon concentration in air is realised by observing the alpha and beta particles produced by the decay of 222Rn and its daughters and tag each of them with a precise occurrence time. The validity of delayed coincident technique by using the state of the art electronics with application of novel data sampling and analysis methods are discussed. The flexibility of sampling protocols and the advantages of online calibration capability to achieve the highest level of precision in natural and man-made radiation measurements are also described

  4. Multipurpose High Sensitivity Radiation Detector: Terradex

    Energy Technology Data Exchange (ETDEWEB)

    Alpat, Behcet [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy)]. E-mail: behcet.alpat@pg.infn.it; Aisa, Damiano [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Bizzarri, Marco [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Blasko, Sandor [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Esposito, Gennaro [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Farnesini, Lucio [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Fiori, Emmanuel [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Papi, Andrea [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Postolache, Vasile [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Renzi, Francesca [Dipartimento di Fisica dell' Universita di Perugia and INFN Sezione di Perugia (Italy); Ionica, Romeo [Politecnica University of Bucarest, Splaiul Indipendentei, Bucharest (Romania); Manolescu, Florentina [Space Science Institute of Bucharest, Maugurele, Bucharest (Romania); Ozkorucuklu, Suat [Suleyman Demirel Universitesi, Isparta (Turkey); Denizli, Haluk [Abant Izzet Baysal Universitesi, Bolu (Turkey); Tapan, Ilhan [Uludag Universitesi, Bursa (Turkey); Ercan Pilicer [Uludag Universitesi, Bursa (Turkey); Egidi, Felice [SITE Technology, Carsoli (Italy); Moretti, Cesare [SITE Technology, Carsoli(AQ) (Italy); Dicola, Luca [SITE Technology, Carsoli(AQ) (Italy)

    2007-05-11

    Terradex project aims to realise an accurate and programmable multiparametric tool which will measure relevant physical quantities such as observation time, energy and type of all decay products of three naturally occurring decay chains of uranium and thorium series present in nature as well as the decay products of man-made radioactivity. The measurements described in this work are based on the performance tests of the first version of an instrument that is designed to provide high counting accuracy, by introducing self-triggering, delayed time-coincidence technique, of products of a given decay chain. In order to qualify the technique and to calibrate the Terradex, a {sup 222}Rn source is used. The continuous and accurate monitoring of radon concentration in air is realised by observing the alpha and beta particles produced by the decay of {sup 222}Rn and its daughters and tag each of them with a precise occurrence time. The validity of delayed coincident technique by using the state of the art electronics with application of novel data sampling and analysis methods are discussed. The flexibility of sampling protocols and the advantages of online calibration capability to achieve the highest level of precision in natural and man-made radiation measurements are also described.

  5. Radiation-sensitive genetically susceptible pediatric sub-populations

    Energy Technology Data Exchange (ETDEWEB)

    Kleinerman, Ruth A. [National Cancer Institute, NIH, DHHS, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Rockville, MD (United States)

    2009-02-15

    Major advances in pediatric cancer treatment have resulted in substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft-tissue sarcomas has been observed in hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks of developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to ionizing radiation. (orig.)

  6. Radiation and cadmium induced histological alteration in the mice liver

    International Nuclear Information System (INIS)

    radiation and cadmium induced changes at histological level. Alterations in the histological changes were found dose dependent. More pronounced histopathological changes were registered after the combined exposure of cadmium chloride and gamma rays. (author)

  7. Polyploidy in aspen alters plant physiology and drought sensitivity

    Science.gov (United States)

    Greer, B.; Still, C. J.; Brooks, J. R.; Meinzer, F. C.

    2015-12-01

    Polyploids of quaking aspen (Populus tremuloides) may be better suited to dry climatic conditions than diploids. However, the expression of diploid and polyploid functional traits, including water use efficiency, an important component of drought avoidance and tolerance, are not well understood in quaking aspen. In this study diploid and triploid aspen clones' leaf, ramet, and stand functional traits were measured near the Rocky Mountain Biological Laboratory in Gothic, Colorado. The physiology of diploid and triploid aspen, including leaf size, chlorophyll content, stomatal size and density and stomatal conductance, as well as growth rates and carbon isotope discrimination in response to climate (measured in tree rings), were found to be significantly different between ploidy levels. These findings demonstrate different sensitivities of diploid and triploid clones to drought related climate stressors which may impact strategies for aspen forest management and conservation.

  8. Protection Strategy of Sensitive Body Organs in Radiation Therapy

    CERN Document Server

    Abolfath, Ramin M

    2009-01-01

    In this paper, we investigate protection strategies of sensitive body anatomy against the irradiation to the cancerous moving tumors in intensity modulated radiation therapy. Inspired by optimization techniques developed in statistical physics and dynamical systems, we deploy a method based on variational principles and formulate an efficient genetic algorithm which enable us to search for global minima in a complex landscape of irradiation dose delivered to the radiosensitive organs at risk. We take advantage of the internal motion of body anatomy during radiation therapy to reduce the unintentional delivery of the radiation to sensitive organs. We show that the accurate optimization of the control parameters, compare to the conventional IMRT and widely used delivery based on static anatomy assumption, leads to a significant reduction of the dose delivered to the organs at risk.

  9. Bio-molecular alterations induced by a chemical or radiating stress in isolated human cells

    International Nuclear Information System (INIS)

    After having recalled some aspects of radiobiology (effects of ionizing radiations, molecular targets of radiations, cellular responses with respect to the radiation), the author discusses various aspects of radio-sensitivity: intrinsic radio-sensitivity of tumoral and normal cells, DNA injuries and in vitro radio-sensitivity, genes of susceptibility to ionizing radiations, clustered injuries. Then she reports investigations performed by infrared micro-spectroscopy: characterization of pathological lines, of biological processes, of oxidative injuries induced by xenobiotics, of injuries induced by ionizing radiations

  10. Sensitivity to Radiation-Induced Cancer in Hemochromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Bull. Richard J.; Anderson, Larry E.

    2000-06-01

    The objectives of this pilot project using HFE-knockout homozygotes and heterozygotes are to (1) determine whether the knock-out mice have greater sensitivity to radiation-induced cancer of the colon, liver and breast, (2) establish the dependence of this sensitivity on the accumulation of iron, (3) determine the extent to which cell replication and apoptosis occur in these target tissues with varying iron load, and (4) correlate the increases in sensitivity with changes in insulin-related signaling in tumors and normal tissue from each target organ. Three experimental designs will be used in the pilot project. The sequence of experiments is designed to first explore the influence of iron load on the response and demonstrate that HFE knockout mice are more sensitive than the wild type to radiation-induced cancer in one or more of three target tissues (liver, colon and breast). The dose response relationships with a broader set of radiation doses will be explored in the second experiment. The final experiment is designed to explore the extent to which heterozygotes display the increased susceptibility to cancer induction and to independently assess the importance of iron load to the initiation versus promotion of tumors.

  11. Multi-Scale Distributed Sensitivity Analysis of Radiative Transfer Model

    Science.gov (United States)

    Neelam, M.; Mohanty, B.

    2015-12-01

    Amidst nature's great variability and complexity and Soil Moisture Active Passive (SMAP) mission aims to provide high resolution soil moisture products for earth sciences applications. One of the biggest challenges still faced by the remote sensing community are the uncertainties, heterogeneities and scaling exhibited by soil, land cover, topography, precipitation etc. At each spatial scale, there are different levels of uncertainties and heterogeneities. Also, each land surface variable derived from various satellite mission comes with their own error margins. As such, soil moisture retrieval accuracy is affected as radiative model sensitivity changes with space, time, and scale. In this paper, we explore the distributed sensitivity analysis of radiative model under different hydro-climates and spatial scales, 1.5 km, 3 km, 9km and 39km. This analysis is conducted in three different regions Iowa, U.S.A (SMEX02), Arizona, USA (SMEX04) and Winnipeg, Canada (SMAPVEX12). Distributed variables such as soil moisture, soil texture, vegetation and temperature are assumed to be uncertain and are conditionally simulated to obtain uncertain maps, whereas roughness data which is spatially limited are assumed a probability distribution. The relative contribution of the uncertain model inputs to the aggregated model output is also studied, using various aggregation techniques. We use global sensitivity analysis (GSA) to conduct this analysis across spatio-temporal scales. Keywords: Soil moisture, radiative transfer, remote sensing, sensitivity, SMEX02, SMAPVEX12.

  12. Modulation of MOS device radiation sensitivity by gate induced strain

    Energy Technology Data Exchange (ETDEWEB)

    Zekeriya, V.

    1986-01-01

    To correlate the radiation sensitivity of MOS devices with the bond strain at the SiO/sub 2/-Si interface, a series of experiments was performed to systematically modulate this strain by subjecting the samples to external mechanical stress. The interfacial strain distribution was changed by varying some of the parameters related to the processing of the gate electrode, and the radiation sensitivity for each case was determined. In particular, the strain distribution was varied by (1) subjecting the samples to PMA treatment, (2) using different gate Al thicknesses, (3) making use of a gate Al related stress relaxation effect, (4) using various gate electrode materials with different thermal constants, and (5) using the large stress changes produced at the gate edges of the devices. Results show a strong correlation between interfacial stress distribution and radiation-induced interface trap generation. The generation of positive oxide charge follows the same pattern, although the dependence is not as strong. The trend is such that one can obtain radiation-harder devices by increasing the amount of compressive stress exerted by the gate electrode on the underlying oxide and its silicon interface. In addition to these results, which were obtained by deliberately varying the stress distribution, it was observed that the interface tap density kept increasing with time after irradiation.

  13. Mechanisms of alteration of the immune system by ionizing radiations: a basis for radiation protection

    International Nuclear Information System (INIS)

    Full text of publication follows: Alterations of the immune system appear in relationship with exposure to ionizing radiation (IR) in different situations, e.g., accidents, radiation therapy of cancer, prenatal irradiation, some human diseases with hypersensitivity to IR and aging. Thus, the comprehension of the mechanisms of the alterations of the immune system by IR is necessary to elaborate strategies of protection and to pave the way for future possible therapies. At least 9 mechanisms of alterations can be identified: 1- Apoptosis. Apoptosis is a key mechanism of the natural regulation of the immune system and plays also a key role in the response to IR: lymphocytes die rapidly by apoptosis after exposure. Different pathways of induction of apoptosis have been identified, and include p53 dependent and mitochondria mediated pathways, as well as CD95 and ROS initiation; 2- TCR mutations. The T cell antigen receptor is responsible to discriminate between self and non self. Mutations of the TCR may result from exposure to IR; 3- Modification of the Th1-Th2 balance. T helper cells may express 2 distinct secretion patterns: Th1 cytokines promote cell-mediated immunity while Th2 cytokines favor humoral immunity. Although the effects of IR on the Th1/Th2 balance remains controversial, an imbalance towards a Th2 profile is likely and patients with cancer and systemic auto-immune disease often present a switch from Th1 to Th2; 4- Bystander effects and genetic instability. Stimulatory effect or genomic instability have been observed in haematopoietic cells exposed to IR and related to a bystander mechanism. 5- Shift toward an inflammatory profile. Ionizing radiation may induce a persistent inflammatory profile as a result of dis-regulation of cytokine production; such a status of persistent inflammation has been observed in Hiroshima and Nagasaki survivors. 6- Modification of antigen presentation. Antigen presentation by dendritic cells is an essential function preceding

  14. Altered radiation recovery by DNA double-strand break inducers

    International Nuclear Information System (INIS)

    Identical biphasic time-dependent profiles of cell survival were obtained in V79 fibroblasts exposed to a split-dose protocol consisting of a fixed dose of γ-rays followed, at a variable time interval, either by a second exposure to radiation, or by contact with an equi-toxic amount of antitumor drugs acting to produce DNA double-strand breaks. The drugs used in this context were the neocarcinostatin antibiotic (NCS), which preferentially cleaves DNA in the linker region of nucleosomes, and etoposide (VP), whose major target is topoisomerase IIα, a nuclear matrix fraction-linked enzyme acting to relieve topological constraints in replicating DNA and mitotic chromosomes. Radiation-induced DNA strand break rejoining was not inhibited by either drug. The initial number of DNA strand breaks was consistently found o depend only on the radiation dose and/or on the drug concentration. However, the cytotoxicity they induced in combined treatment was determined in essence by the time elapsed after the first radiation exposure. While resistance to NCS and VP in non-irradiated, synchronized cells peaks in G2 phase of the cell cycle, enhanced drug susceptibility was observed within the radiation-induced G2 block. Concomitant exposure to drug and radiation also resulted in supra-additive cytotoxic interaction. Our data suggest that impaired split-dose radiation recovery dose not proceed from inhibition of DNA damage repair, but rather from additional double-strand breaks produced by drug or radiation during the time cells are in the dynamic process of DNA repair; a time range characterized by a dynamic DNA fragility. (authors)

  15. Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Bourguignon, Michel H. [Direction Generale de la Surete Nucleaire et de la Radioprotection, Paris Cedex 12 (France); CEA-DSV-DRM Hopital, Service de Recherches en Hemato-Immunologie, Saint Louis, Paris (France); Gisone, Pablo A.; Perez, Maria R.; Michelin, Severino; Dubner, Diana; Giorgio, Marina di [Autoridad Regulatoria Nuclear, Laboratorio de Radiopatologia, Buenos Aires (Argentina); Carosella, Edgardo D. [CEA-DSV-DRM Hopital, Service de Recherches en Hemato-Immunologie, Saint Louis, Paris (France)

    2005-03-01

    Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are ''hypersensitive'' to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed. (orig.)

  16. Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection.

    Science.gov (United States)

    Bourguignon, Michel H; Gisone, Pablo A; Perez, Maria R; Michelin, Severino; Dubner, Diana; Giorgio, Marina Di; Carosella, Edgardo D

    2005-03-01

    Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation, offering a better likelihood of cure for malignant tumours. Although only a small percentage of individuals are "hypersensitive" to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed. PMID:15692806

  17. The effects of polaprezinc on radiation-induced taste alterations

    International Nuclear Information System (INIS)

    The effects of polaprezinc (an insoluble zinc complex of L-carnosine) on taste abnormalities were investigated in 22 patients receiving radiation therapy to head and neck malignancies. The total doses to the tongue were 25.5-46.0 Gy (mean, 37.9 Gy). All patients received 75 mg of polaprezinc two times a day with an interval of 0-1,561 days (mean, 305.3 days) after the completion of radiation therapy. The duration of the drug administration was 25-353 days (mean, 96.9 days). Twenty patients (90.9%) were aware of an improvement of a partial or complete loss of taste. Polaprezinc is effective in improving loss of taste after radiation therapy. (author)

  18. The effects of polaprezinc on radiation-induced taste alterations

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Katsumasa; Togao, Osamu [Kyushu Univ., Fukuoka (Japan). Graduate School of Medical Sciences; Shikama, Naoto (and others)

    2001-06-01

    The effects of polaprezinc (an insoluble zinc complex of L-carnosine) on taste abnormalities were investigated in 22 patients receiving radiation therapy to head and neck malignancies. The total doses to the tongue were 25.5-46.0 Gy (mean, 37.9 Gy). All patients received 75 mg of polaprezinc two times a day with an interval of 0-1,561 days (mean, 305.3 days) after the completion of radiation therapy. The duration of the drug administration was 25-353 days (mean, 96.9 days). Twenty patients (90.9%) were aware of an improvement of a partial or complete loss of taste. Polaprezinc is effective in improving loss of taste after radiation therapy. (author)

  19. Targeting Nucleophosmin 1 Represents a Rational Strategy for Radiation Sensitization

    International Nuclear Information System (INIS)

    Purpose: To test the hypothesis that small molecule targeting of nucleophosmin 1 (NPM1) represents a rational approach for radiosensitization. Methods and Materials: Wilde-type and NPM1-deficient mouse embryo fibroblasts (MEFs) were used to determine whether radiosensitization produced by the small molecule YTR107 was NPM1 dependent. The stress response to ionizing radiation was assessed by quantifying pNPM1, γH2AX, and Rad51 foci, neutral comet tail moment, and colony formation. NPM1 levels in a human-derived non-small-cell lung cancer (NSCLC) tissue microarray (TMA) were determined by immunohistochemistry. YTR107-mediated radiosensitization was assessed in NSCLC cell lines and xenografts. Results: Use of NPM1-null MEFs demonstrated that NPM1 is critical for DNA double- strand break (DSB) repair, that loss of NPM1 increases radiation sensitivity, and that YTR107-mediated radiosensitization is NPM1 dependent. YTR107 was shown to inhibit NPM1 oligomerization and impair formation of pNPM1 irradiation-induced foci that colocalized with γH2AX foci. Analysis of the TMA demonstrated that NPM1 is overexpressed in subsets of NSCLC. YTR107 inhibited DNA DSB repair and radiosensitized NSCLC lines and xenografts. Conclusions: These data demonstrate that YTR107-mediated targeting of NPM1 impairs DNA DSB repair, an event that increases radiation sensitivity

  20. Targeting Nucleophosmin 1 Represents a Rational Strategy for Radiation Sensitization

    Energy Technology Data Exchange (ETDEWEB)

    Sekhar, Konjeti R. [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Benamar, Mouadh [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Venkateswaran, Amudhan; Sasi, Soumya [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Penthala, Narsimha R.; Crooks, Peter A. [Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hann, Stephen R. [Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Geng, Ling [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Balusu, Ramesh [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas (United States); Abbas, Tarek [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Freeman, Michael L., E-mail: michael.freeman@vanderbilt.edu [Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States)

    2014-08-01

    Purpose: To test the hypothesis that small molecule targeting of nucleophosmin 1 (NPM1) represents a rational approach for radiosensitization. Methods and Materials: Wilde-type and NPM1-deficient mouse embryo fibroblasts (MEFs) were used to determine whether radiosensitization produced by the small molecule YTR107 was NPM1 dependent. The stress response to ionizing radiation was assessed by quantifying pNPM1, γH2AX, and Rad51 foci, neutral comet tail moment, and colony formation. NPM1 levels in a human-derived non-small-cell lung cancer (NSCLC) tissue microarray (TMA) were determined by immunohistochemistry. YTR107-mediated radiosensitization was assessed in NSCLC cell lines and xenografts. Results: Use of NPM1-null MEFs demonstrated that NPM1 is critical for DNA double- strand break (DSB) repair, that loss of NPM1 increases radiation sensitivity, and that YTR107-mediated radiosensitization is NPM1 dependent. YTR107 was shown to inhibit NPM1 oligomerization and impair formation of pNPM1 irradiation-induced foci that colocalized with γH2AX foci. Analysis of the TMA demonstrated that NPM1 is overexpressed in subsets of NSCLC. YTR107 inhibited DNA DSB repair and radiosensitized NSCLC lines and xenografts. Conclusions: These data demonstrate that YTR107-mediated targeting of NPM1 impairs DNA DSB repair, an event that increases radiation sensitivity.

  1. Alterations of nutritional status: impact of chemotherapy and radiation therapy

    International Nuclear Information System (INIS)

    The nutritional status of a cancer patient may be affected by the tumor, the chemotherapy and/or radiation therapy directed against the tumor, and by complications associated with that therapy. Chemotherpay-radiotherapy is not confined exclusively to malignant cell populations; thus, normal tissues may also be affected by the therapy and may contribute to specific nutritional problems. Impaired nutrition due to anorexia, mucositis, nausea, vomiting, and diarrhea may be dependent upon the specific chemotherapeutic agent, dose, or schedule utilized. Similar side effects from radiation therapy depend upon the dose, fractionation, and volume irradiated. When combined modality treatment is given the nutritional consequences may be magnified. Prospective, randomized clinical trials are underway to investigate the efficacy of nutritional support during chemotherapy-radiotherapy on tolerance to treatment, complications from treatment, and response rates to treatment. Preliminary results demonstrate that the administration of total parenteral nutrition is successful in maintaining weight during radiation therapy and chemotherapy, but that weight loss occurs after discontinuation of nutritional support. Thus, longterm evaluation is mandatory to learn the impact of nutritional support on survival, diease-free survival, and complication rates, as well as on the possible prevention of morbidity associated with aggressive chemotherapy-radiation therapy

  2. Radiation Exposure Alters Expression of Metabolic Enzyme Genes in Mice

    Science.gov (United States)

    Wotring, V. E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2011-01-01

    Most administered pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand the effects of spaceflight on the enzymes of the liver and exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. Additionally, it has been previous noted that pre-exposure to small radiation doses seems to confer protection against later and larger radiation doses. This protective power of pre-exposure has been called a priming effect or radioadaptation. This study is an effort to examine the drug metabolizing effects of radioadaptation mechanisms that may be triggered by early exposure to low radiation doses.

  3. Construction and isolation of radiation sensitive mutants of Escherichia Coli

    International Nuclear Information System (INIS)

    Damage to DNA by ionizing radiation consists mainly of single (SSB) and double (DSB) strand breaks as well as several types of base alterations, all of which may be removed by different repair mechanisms. Radiation also induces the SOS response, a set of repair and/or damage tolerance genes involved in functions such as replication arrest, excision and recombination repair, increase of both spontaneous and induced mutation and prophage induction, among others. The degree of SOS induction is related to the type and amount of damage and may be easily determined by a simple colorimetric assay, the SOS chromo test. In order to investigate the role of protection and/or repair genes on bacterial radiosensitivity, E. coli strains defective in either oxyR, recJ or recO genes were constructed and their respective SOS response to radiation, duly examined. The results show that although lack of regulatory gene oxyR increases radiosensitivity, it is the deficiencies in recJ and recO which seem to be more important. Both genes appear to take part in the repair of DSB and according to SOS measurements, their role is related also to damage processing conducent to the SOS triggering signal. A hypothetical working mechanism for the purpose, partially supported by the data is proposed. (Author)

  4. Sensitization of radiation-induced cell death by genistein

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Rim; Kim, In Gyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2010-03-15

    A number of epidemiological studies as well as biological experiments, showed that genistein, one of the isoflavone, prevents prostate cancer occurrence. In this study, we showed that genistein inhibited the cell proliferation of human promyeoltic leukemia HL-60 cells and induced G2/M phase arrest. In addition, combination of genistein treatment and {gamma}-irradiation displayed synergistic effect in apoptotic cell death of HL-60 cells. This means that the repair of genistein-induced DNA damage was hindered by {gamma}-irradiation and thus cell death was increased. In conclusion, genistein is one of the important chemicals that sensitize radiation-induced cell death.

  5. Analysis of radiation-induced genome alterations in Vigna unguiculata

    Directory of Open Access Journals (Sweden)

    van der Vyver C

    2011-09-01

    Full Text Available Christell van der Vyver1, B Juan Vorster2, Karl J Kunert3, Christopher A Cullis41Institute for Plant Biotechnology, Department of Genetics, University of Stellenbosch, Stellenbosch, South Africa; 2Department of Plant Production and Soil Science, and 3Department of Plant Science, Forestry and Agricultural Biotechnology Institute, University of Pretoria, Pretoria, South Africa; 4Case Western Reserve University, Department of Biology, Cleveland, OH, USAAbstract: Seeds from an inbred Vigna unguiculata (cowpea cultivar were gamma-irradiated with a dose of 180 Gy in order to identify and characterize possible mutations. Three techniques, ie, random amplified polymorphic DNA, microsatellites, and representational difference analysis, were used to characterize possible DNA variation among the mutants and nonirradiated control plants both immediately after irradiation and in subsequent generations. A large portion of putative radiation-induced genome changes had significant similarities to chloroplast sequences. The frequency of mutation at three of these isolated polymorphic regions with chloroplast similarity was further determined by polymerase chain reaction screening using a large number of individual parental, M1, and M2 plants. Analysis of these sequences indicated that the rate at which various regions of the genome is mutated in irradiation experiments differs significantly and also that mutations have variable “repair” rates. Furthermore, regions of the nuclear DNA derived from the chloroplast genome are highly susceptible to modification by radiation treatment. Overall, data have provided detailed information on the effects of gamma irradiation on the cowpea genome and about the ability of the plant to repair these genome changes in subsequent plant generations.Keywords: mutation breeding, gamma radiation, genetic mutations, cowpea, representational difference analysis

  6. The sensitivity of human mesenchymal stem cells to ionizing radiation

    International Nuclear Information System (INIS)

    Purpose: Recent studies have shown that mesenchymal stem cells (MSCs) obtained from bone marrow transplantation patients originate from the host. This clinical observation suggests that MSCs in their niches could be resistant to irradiation. However, the biologic responses of bone marrow MSCs to irradiation have rarely been described in the literature. Methods and Materials: In this study, human bone marrow-derived, clonally expanded MSCs were used to investigate their sensitivity to irradiation in vitro, and the cellular mechanisms that may facilitate resistance to irradiation. The human lung cancer cell line A549 and the breast cancer cell line HCC1937 were used as controls for radiosensitivity; the former line has been shown to be radioresistant and the latter radiosensitive. We then examined their in vitro biologic changes and sensitivities to radiation therapy. Results: Our results suggest that MSCs are characterized as resistant to irradiation. Several cellular mechanisms were demonstrated that may facilitate resistance to irradiation: ATM protein phosphorylation, activation of cell-cycle checkpoints, double-strand break repair by homologous recombination and nonhomologous end joining (NHEJ), and the antioxidant capacity for scavenging reactive oxygen species. Conclusions: As demonstrated, MSCs possess a better antioxidant reactive oxygen species-scavenging capacity and active double-strand break repair to facilitate their radioresistance. These findings provide a better understanding of radiation-induced biologic responses in MSCs and may lead to the development of better strategies for stem cell treatment and cancer therapy

  7. Radiation sensitivity basidiospore and mycelium in pleurotus ostreatus

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Keun; Chang, Hwa Hyoung [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1999-06-01

    To assess the effects of gamma-ray (Co-60) on radiation sensitivity and genetic similarity of the vasidiospore and mycelium in oyster mushroom, Pleurotus ostreatus, the D{sub 10} values and RAPD patterns were analysed. Three strains were isolated from basidiospores (PO-B1, -B2, and -B3 from 2 kGy irradiation group0 and five strains from mycelia (PO-M1, -M2 from 1 kGy, PO-M3 from 2 kGy, and PO-M4 and -M5 from 2+1 kGy irradiation group). The D{sub 10} values of extracellular chitinases of them were generally higher than those of the control. By the gamma-ray radiation, 22-25% of genetic similarities were changed in the basidiospore strains and 23-36% of them in the mycelium strains. From these results, it seems that the basidiospore could be more radio-resistant than the mycelium of P. ostreatus and that the genetic similarity of the mycelium of P. ostreatus could be changed easier than that of the basidiospore by the gamma-ray radiation. (author). 22 refs., 2 figs., 3 tabs.

  8. Alteration of dopamine receptor sensitivity by opiates and the subsequent effect of this alteration on opiate tolerance and dependence

    Energy Technology Data Exchange (ETDEWEB)

    Martin, J.R.

    1985-01-01

    The present study was undertaken to determine whether there is an alteration of dopamine receptor sensitivity following opiate administration, and whether this alteration has any influence on the development of opiate tolerance and dependence. Behavioral hypersensitivity to direct-acting dopamine agonists was observed in mice following acute or chronic morphine administration. Acute levorphanol administration also resulted in potentiation of dopamine agonist-induced behaviors. An increase in density of dopamine receptors, as measured by (/sup 3/H)butyrophenone binding accompanied the development of behavioral hypersensitivity. This increase was localized to the striatum, an area important in the mediation of dopamine-agonist induced behaviors. Naloxone or LiCl coadministered with the opiates prevented the development of hypersensitivity and the increase in density of dopamine receptors. Coadministration of lithium enhanced the development of acute and chronic tolerance. Lithium enhanced the development of dependence as determined by naloxone-induced hypothermia in chronically morphine-treated mice. Apomorphine enhanced naloxone-induced withdrawal in acutely dependent mice. This enhancement was blocked by coadministration of lithium with the opiates. These results suggest that dopamine receptor supersensitivity influences the degree of tolerance and dependence.

  9. Radiation-induced alterations of histone post-translational modification levels in lymphoblastoid cell lines

    International Nuclear Information System (INIS)

    Radiation-induced alterations in posttranslational histone modifications (PTMs) may affect the cellular response to radiation damage in the DNA. If not reverted appropriately, altered PTM patterns may cause long-term alterations in gene expression regulation and thus lead to cancer. It is therefore important to characterize radiation-induced alterations in PTM patterns and the factors affecting them. A lymphoblastoid cell line established from a normal donor was used to screen for alterations in methylation levels at H3K4, H3K9, H3K27, and H4K20, as well as acetylation at H3K9, H3K56, H4K5, and H4K16, by quantitative Western Blot analysis at 15 min, 1 h and 24 h after irradiation with 2 Gy and 10 Gy. The variability of alterations in acetylation marks was in addition investigated in a panel of lymphoblastoid cell lines with differing radiosensitivity established from lung cancer patients. The screening procedure demonstrated consistent hypomethylation at H3K4me3 and hypoacetylation at all acetylation marks tested. In the panel of lymphoblastoid cell lines, however, a high degree of inter-individual variability became apparent. Radiosensitive cell lines showed more pronounced and longer lasting H4K16 hypoacetylation than radioresistant lines, which correlates with higher levels of residual γ-H2AX foci after 24 h. So far, the factors affecting extent and duration of radiation-induced histone alterations are poorly defined. The present work hints at a high degree of inter-individual variability and a potential correlation of DNA damage repair capacity and alterations in PTM levels

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

    International Nuclear Information System (INIS)

    The in vitro cytokinesis-block (CB) micronucleus (MN) assay for human peripheral blood has been used extensively for the assessment of chromosomal damage induced by ionizing radiation and chemicals and considered a suitable biological dosimeter for estimating in vivo whole body exposures, particularly in the case of large scale radiation accidents. One of the major drawbacks of the MN assay is its reduced sensitivity for the detection of damage induced by low doses of low LET radiation, due to the high variability among the spontaneous MN frequencies. It is suggested that age, smoking habit and sex are the main confounding factors that contribute to the observed variability. Previous work in our laboratory, shows a significant positive correlation of the spontaneous and radiation induced MN frequencies with age and smoking habit, the latter being the strongest confounder. These findings led to in vitro studies of the dose-response relationships for smoking and non smoking donors evaluated separately, using 60Co γ rays. The objectives of the present work are: 1-To increase the amount of data of the dose-response relationships, using γ rays from a 60Co source, for smoking and non smoking donors, in order to find, if applicable, a correction factor for the calibration curve that takes into account the smoking habit of the individual in the case of accidental overexposure dose assessment, particularly in the low dose range. 2-To establish general conclusions on the current state of the technique. The sample for smoking and non smoking calibration curves was enlarged in the range of 0Gy to 2Gy. The fitting of both curves, performed up to the 2Gy dose, resulted in a linear quadratic model. MN distribution among bi nucleated cells was found to be over dispersed with respect to Poisson distribution, the average ratio of variance to mean being 1.13 for non smokers and 1.17 for smokers. Each fitted calibration curve, for smoking and non smoking donors, fell within the 95

  11. Intervention of oxygen-control ability to radiation sensitivity, cell aging and cell transformation

    International Nuclear Information System (INIS)

    Oxygen is essential for life, and cells have therefore developed numerous adaptive responses to oxygen change. Here, we examined the difference in oxygen-control functions of human (HE), mouse (ME), and Syrian hamster embryo (SHE) cells cultured under different oxygen conditions (0.5%, 2% and 20%), and also examined whether oxygen tensions contributed to cellular lifespan and transformation. HE cells had their replicative lifespan slightly extended under hypoxic (0.5% and 2% oxygen) conditions, but were not immortalized under any of the oxygen concentrations. On the other hand, although ME cells cultured under 20% oxygen tension decreased their proliferation potency temporarily at early stage, all rodent cells were immortalized and acquired anchorage-independency, regardless of oxygen tension. These results suggest that cellular oxygen control function is related to sensitivities cellular immortalization and transformation. To understand intervention of oxygen control ability on cellular immortalization and transformation, we examined the intracellular oxidative level, mitochondria functions and radiation sensitivity. Intracellular oxidative levels of hypoxically cultured rodent cells were significantly enhanced. Mitochondrial membrane potential was altered depend on oxygen tensions, but the change was not parallel to mitochondria number in rodent cells. ME cells were particularly sensitive to oxygen change, and showed a clear oxygen effect on the X-ray survival. However, there was no difference in frequency of radiation-induced micronuclei between HE and ME cells. These results suggest that the response to oxygen change differs markedly in HE and rodent cells. (author)

  12. MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Kuei-Fang Lee

    2014-01-01

    Full Text Available Various biological effects are associated with radiation exposure. Irradiated cells may elevate the risk for genetic instability, mutation, and cancer under low levels of radiation exposure, in addition to being able to extend the postradiation side effects in normal tissues. Radiation-induced bystander effect (RIBE is the focus of rigorous research as it may promote the development of cancer even at low radiation doses. Alterations in the DNA sequence could not explain these biological effects of radiation and it is thought that epigenetics factors may be involved. Indeed, some microRNAs (or miRNAs have been found to correlate radiation-induced damages and may be potential biomarkers for the various biological effects caused by different levels of radiation exposure. However, the regulatory role that miRNA plays in this aspect remains elusive. In this study, we profiled the expression changes in miRNA under fractionated radiation exposure in human peripheral blood mononuclear cells. By utilizing publicly available microRNA knowledge bases and performing cross validations with our previous gene expression profiling under the same radiation condition, we identified various miRNA-gene interactions specific to different doses of radiation treatment, providing new insights for the molecular underpinnings of radiation injury.

  13. Sensitivity and Acclimation of Three Canopy-Forming Seaweeds to UVB Radiation and Warming

    KAUST Repository

    Xiao, Xi

    2015-12-02

    Canopy-forming seaweeds, as primary producers and foundation species, provide key ecological services. Their responses to multiple stressors associated with climate change could therefore have important knock-on effects on the functioning of coastal ecosystems. We examined interactive effects of UVB radiation and warming on juveniles of three habitat-forming subtidal seaweeds from Western Australia–Ecklonia radiata, Scytothalia dorycarpa and Sargassum sp. Fronds were incubated for 14 days at 16–30°C with or without UVB radiation and growth, health status, photosynthetic performance, and light absorbance measured. Furthermore, we used empirical models from the metabolic theory of ecology to evaluate the sensitivity of these important seaweeds to ocean warming. Results indicated that responses to UVB and warming were species specific, with Sargassum showing highest tolerance to a broad range of temperatures. Scytothalia was most sensitive to elevated temperature based on the reduced maximum quantum yields of PSII; however, Ecklonia was most sensitive, according to the comparison of activation energy calculated from Arrhenius’ model. UVB radiation caused reduction in the growth, physiological responses and thallus health in all three species. Our findings indicate that Scytothalia was capable of acclimating in response to UVB and increasing its light absorption efficiency in the UV bands, probably by up-regulating synthesis of photoprotective compounds. The other two species did not acclimate over the two weeks of exposure to UVB. Overall, UVB and warming would severely inhibit the growth and photosynthesis of these canopy-forming seaweeds and decrease their coverage. Differences in the sensitivity and acclimation of major seaweed species to temperature and UVB may alter the balance between species in future seaweed communities under climate change.

  14. Sensitivity and Acclimation of Three Canopy-Forming Seaweeds to UVB Radiation and Warming.

    Science.gov (United States)

    Xiao, Xi; de Bettignies, Thibaut; Olsen, Ylva S; Agusti, Susana; Duarte, Carlos M; Wernberg, Thomas

    2015-01-01

    Canopy-forming seaweeds, as primary producers and foundation species, provide key ecological services. Their responses to multiple stressors associated with climate change could therefore have important knock-on effects on the functioning of coastal ecosystems. We examined interactive effects of UVB radiation and warming on juveniles of three habitat-forming subtidal seaweeds from Western Australia-Ecklonia radiata, Scytothalia dorycarpa and Sargassum sp. Fronds were incubated for 14 days at 16-30°C with or without UVB radiation and growth, health status, photosynthetic performance, and light absorbance measured. Furthermore, we used empirical models from the metabolic theory of ecology to evaluate the sensitivity of these important seaweeds to ocean warming. Results indicated that responses to UVB and warming were species specific, with Sargassum showing highest tolerance to a broad range of temperatures. Scytothalia was most sensitive to elevated temperature based on the reduced maximum quantum yields of PSII; however, Ecklonia was most sensitive, according to the comparison of activation energy calculated from Arrhenius' model. UVB radiation caused reduction in the growth, physiological responses and thallus health in all three species. Our findings indicate that Scytothalia was capable of acclimating in response to UVB and increasing its light absorption efficiency in the UV bands, probably by up-regulating synthesis of photoprotective compounds. The other two species did not acclimate over the two weeks of exposure to UVB. Overall, UVB and warming would severely inhibit the growth and photosynthesis of these canopy-forming seaweeds and decrease their coverage. Differences in the sensitivity and acclimation of major seaweed species to temperature and UVB may alter the balance between species in future seaweed communities under climate change. PMID:26630025

  15. Sensitivity and Acclimation of Three Canopy-Forming Seaweeds to UVB Radiation and Warming.

    Directory of Open Access Journals (Sweden)

    Xi Xiao

    Full Text Available Canopy-forming seaweeds, as primary producers and foundation species, provide key ecological services. Their responses to multiple stressors associated with climate change could therefore have important knock-on effects on the functioning of coastal ecosystems. We examined interactive effects of UVB radiation and warming on juveniles of three habitat-forming subtidal seaweeds from Western Australia-Ecklonia radiata, Scytothalia dorycarpa and Sargassum sp. Fronds were incubated for 14 days at 16-30°C with or without UVB radiation and growth, health status, photosynthetic performance, and light absorbance measured. Furthermore, we used empirical models from the metabolic theory of ecology to evaluate the sensitivity of these important seaweeds to ocean warming. Results indicated that responses to UVB and warming were species specific, with Sargassum showing highest tolerance to a broad range of temperatures. Scytothalia was most sensitive to elevated temperature based on the reduced maximum quantum yields of PSII; however, Ecklonia was most sensitive, according to the comparison of activation energy calculated from Arrhenius' model. UVB radiation caused reduction in the growth, physiological responses and thallus health in all three species. Our findings indicate that Scytothalia was capable of acclimating in response to UVB and increasing its light absorption efficiency in the UV bands, probably by up-regulating synthesis of photoprotective compounds. The other two species did not acclimate over the two weeks of exposure to UVB. Overall, UVB and warming would severely inhibit the growth and photosynthesis of these canopy-forming seaweeds and decrease their coverage. Differences in the sensitivity and acclimation of major seaweed species to temperature and UVB may alter the balance between species in future seaweed communities under climate change.

  16. Altered thermal sensitivity in facial skin in chronic whiplash-associated disorders

    Institute of Scientific and Technical Information of China (English)

    Birgitta Haggman-Henrikson; Ewa Lampa; Erik Nordh

    2013-01-01

    There is a close functional relationship between the jaw and neck regions and it has been suggested that trigeminal sensory impairment can follow whiplash injury. Inclusion of manageable routines for valid assessment of the facial sensory capacity is thus needed for comprehensive evaluations of patients exposed to such trauma. The present study investigated facial thermal thresholds in patients with chronic whiplash-associated disorders (WADs) with both a qualitative method and quantitative sensory testing (QST). Ten women with pain and dysfunction following a whiplash injury were compared to 10 healthy age-matched women. Thermal detection thresholds were assessed by qualitative chair-side testing and by QST according to the method-of-limits. Seven test sites in the facial skin (overlying each trigeminal branch bilaterally, and the midpoint of the chin) were examined. The detection warm and cold thresholds were defined as the mean values of 10 individual thresholds. For the WAD patients, the qualitative assessment demonstrated both reduced and increased sensitivity compared to the healthy, whereas QST systematically showed significantly higher detection thresholds (i.e., decreased sensitivity) for both cold and warm stimuli. For the individuals who were assessed as having increased sensitivity in the qualitative assessment, the QST displayed either normal or higher thresholds, i.e., decreased sensitivity. The results suggest that QST is more sensitive for detecting thermal sensory disturbances in the face than a qualitative method. The impaired thermal sensitivity among the patients corroborates the notion of altered thermal detection capacity induced by WAD-related pain.

  17. Altered sensitization patterns to sweet food stimuli in patients recovered from anorexia and bulimia nervosa.

    Science.gov (United States)

    Wagner, Angela; Simmons, Alan N; Oberndorfer, Tyson A; Frank, Guido K W; McCurdy-McKinnon, Danyale; Fudge, Julie L; Yang, Tony T; Paulus, Martin P; Kaye, Walter H

    2015-12-30

    Recent studies show that higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa (AN) and overeating in bulimia nervosa (BN). The purpose of this study was to determine whether sensitization effects might underlie pathologic eating behavior when a taste stimulus is administered repeatedly. Recovered AN (RAN, n=14) and BN (RBN, n=15) subjects were studied in order to avoid the confounding effects of altered nutritional state. Functional magnetic resonance imaging (fMRI) measured higher-order brain response to repeated tastes of sucrose (caloric) and sucralose (non-caloric). To test sensitization, the neuronal response to the first and second administration was compared. RAN patients demonstrated a decreased sensitization to sucrose in contrast to RBN patients who displayed the opposite pattern, increased sensitization to sucrose. However, the latter was not as pronounced as in healthy control women (n=13). While both eating disorder subgroups showed increased sensitization to sucralose, the healthy controls revealed decreased sensitization. These findings could reflect on a neuronal level the high caloric intake of RBN during binges and the low energy intake for RAN. RAN seem to distinguish between high energy and low energy sweet stimuli while RBN do not.

  18. An investigation of gamma-radiation sensitivity on in vitro study of Hordeum vulgare L.

    Directory of Open Access Journals (Sweden)

    Pinaki Chaudhuri

    2014-02-01

    Full Text Available Gamma-radiation sensitivity was studied on in vitro condition in Hordeum vulgare L. The variation of callusing response assessed with the increasing level of gamma-radiation treatment and regeneration delayed at higher dose level.

  19. Interleukin 1 beta initially sensitizes and subsequently protects murine intestinal stem cells exposed to photon radiation

    International Nuclear Information System (INIS)

    Interleukin 1 (IL-1) has been shown to prevent early bone marrow-related death following total-body irradiation, by protecting hematopoietic stem cells and speeding marrow repopulation. This study assesses the effect of IL-1 on the radiation response of the intestinal mucosal stem cell, a nonhematopoietic normal cell relevant to clinical radiation therapy. As observed with bone marrow, administration of human recombinant IL-1 beta (4 micrograms/kg) to C3H/Km mice 20 h prior to total-body irradiation modestly protected duodenal crypt cells. In contrast to bone marrow, IL-1 given 4 or 8 h before radiation sensitized intestinal crypt cells. IL-1 exposure did not substantially alter the slope of the crypt cell survival curve but did affect the shoulder: the X-ray survival curve was offset to the right by 1.01 +/- 0.06 Gy when IL-1 was given 20 h earlier and by 1.28 +/- 0.08 Gy to the left at the 4-h interval. Protection was greatest when IL-1 was administered 20 h before irradiation, but minimal effects persisted as long as 7 days after a single injection. The magnitude of radioprotection at 20 h or of radiosensitization at 4 h increased rapidly as IL-1 dose increased from 0 to 4 micrograms/kg. However, doses ranging from 10 to 100 micrograms/kg produced no further difference in radiation response. Animals treated with saline or IL-1 had similar core temperatures from 4 to 24 h after administration, suggesting that thermal changes were not responsible for either sensitization or protection. Mice irradiated 20 h after IL-1 had significantly greater crypt cell survival than saline-treated irradiated controls at all assay times, which ranged from 54 to 126 h following irradiation. The intervals to maximum crypt depopulation and initiation of repopulation were identical in both saline- and IL-1-treated groups

  20. Effect of pre-existing thermal sensitization on the radiation induced sensitization in type 304 stainless steels

    International Nuclear Information System (INIS)

    It is generally recognized that radiation induced sensitization plays an important role in initiating irradiation assisted stress corrosion cracking (IASCC) of austenitic stainless steels in reactor core internal of light water reactor. However, the synergism between radiation sensitization and prior thermal sensitization is unclear. This situation is likely to occur in most welded core internal structures subjected to neutron irradiation. In this study, the effect of prior thermal treatment on radiation sensitization were investigated on proton irradiated Type 304 stainless steel (SS) of initially as-received (AR) and thermal-sensitized (SEN) conditions. The Cr depletion profiles were measured by field emission gun transmission electron microscopy/energy dispersive spectroscopy (FEGTEM/EDS), and were calculated by a radiation induced segregation (RIS) model. The different initial conditions were input in the RIS model calculations. For the as-received condition, the initial Cr profile was modeled by a uniform concentration distribution. For the initially thermal-sensitized condition, the wider Cr depletion profile measured by FEGTEM/EDS was input as the initial condition. The results showed that radiation sensitization is characterized by a very narrow Cr depleted zone. The Cr content at grain boundary tends to be lower as radiation dose increases. Comparing with the non-sensitized (as-received) specimens with the same dosage, the grain boundary Cr content without prior sensitization is higher than that with sensitization pre-treatment. The deeper grain boundary Cr concentration of irradiated thermally sensitized sample is induced not only from proton irradiation effect, but also resulted from pre-existing Cr depletion

  1. Are biological effects of space radiation really altered under the microgravity environment?

    Science.gov (United States)

    Yatagai, Fumio; Ishioka, Noriaki

    2014-10-01

    Two major factors of space environment are space radiation and microgravity. It is generally considered that a high level of ionizing radiation (IR) in space has an influence on living organisms including humans; therefore, the possible alteration of space-radiation influences by the microgravity environment is of great concern. In fact, examination of such a possibility has been extensively conducted since the early days of space experiments, suggesting a possible synergistic effect of radiation and microgravity in some experiments but a negative observation in others. Because these complicated results remain not well understood, we propose a solution to this problem. Gene expression analysis is one of the solutions to the problem. In fact, gene expression may be changed by microgravity, and further modification may be possible through IR. This result could reveal an interactive effect of both factors on the cellular responses, which could in turn reveal whether the human-health abnormalities expected under the microgravity environment can be altered by space radiation. We believe that this is a new aspect in the study of the interactive effect of radiation and microgravity. However, further improvements in space experimental technologies are required for future studies.

  2. Chronic Intake of Japanese Sake Mediates Radiation-Induced Metabolic Alterations in Mouse Liver.

    Directory of Open Access Journals (Sweden)

    Tetsuo Nakajima

    Full Text Available Sake is a traditional Japanese alcoholic beverage that is gaining popularity worldwide. Although sake is reported to have beneficial health effects, it is not known whether chronic sake consumption modulates health risks due to radiation exposure or other factors. Here, the effects of chronic administration of sake on radiation-induced metabolic alterations in the livers of mice were evaluated. Sake (junmai-shu was administered daily to female mice (C3H/He for one month, and the mice were exposed to fractionated doses of X-rays (0.75 Gy/day for the last four days of the sake administration period. For comparative analysis, a group of mice were administered 15% (v/v ethanol in water instead of sake. Metabolites in the liver were analyzed by capillary electrophoresis-time-of-flight mass spectrometry one day following the last exposure to radiation. The metabolite profiles of mice chronically administered sake in combination with radiation showed marked changes in purine, pyrimidine, and glutathione (GSH metabolism, which were only partially altered by radiation or sake administration alone. Notably, the changes in GSH metabolism were not observed in mice treated with radiation following chronic administration of 15% ethanol in water. Changes in several metabolites, including methionine and valine, were induced by radiation alone, but were not detected in the livers of mice who received chronic administration of sake. In addition, the chronic administration of sake increased the level of serum triglycerides, although radiation exposure suppressed this increase. Taken together, the present findings suggest that chronic sake consumption promotes GSH metabolism and anti-oxidative activities in the liver, and thereby may contribute to minimizing the adverse effects associated with radiation.

  3. Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.

    Science.gov (United States)

    Musial, Barbara; Fernandez-Twinn, Denise S; Vaughan, Owen R; Ozanne, Susan E; Voshol, Peter; Sferruzzi-Perri, Amanda N; Fowden, Abigail L

    2016-04-01

    In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species. PMID:26740602

  4. Analysis of unstable chromosome alterations frequency induced by neutron-gamma mixed field radiation

    International Nuclear Information System (INIS)

    Nowadays monitoring chromosome alterations in peripheral blood lymphocytes have been used to access the radiation absorbed dose in individuals exposed accidental or occupationally to gamma radiation. However there are not many studies based on the effects of mixed field neutron-gamma. The radiobiology of neutrons has great importance because in nuclear factories worldwide there are several hundred thousand individuals monitored as potentially receiving doses of neutron. In this paper it was observed the frequencies of unstable chromosome alterations induced by a gamma-neutron mixed field. Blood was obtained from one healthy donor and exposed to mixed field neutron-gamma sources 241AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphases were analyzed for the presence of chromosome alterations by two experienced scorers. The results suggest that there is the possibility of a directly proportional relationship between absorbed dose of neutron-gamma mixed field radiation and the frequency of unstable chromosome alterations analyzed in this paper. (author)

  5. Radiation sensitivity of memory chip module of an ID card

    Energy Technology Data Exchange (ETDEWEB)

    Mathur, V.K. [Naval Surface Warfare Center, Carderock Division, Bethesda MD 20817 (United States)]. E-mail: veerendra.mathur@navy.mil; Barkyoumb, J.H. [Naval Surface Warfare Center, Carderock Division, Bethesda MD 20817 (United States); Yukihara, E.G. [Department of Physics, Oklahoma State University, Stillwater, OK 74078 (United States); Goeksu, H.Y. [GSF- National Research Center for Environment and Health, D-85764 Neuherberg (Germany)

    2007-01-15

    The utility of ID card chip modules to function as a radiation dosimeter is investigated. Specifically the thermoluminescence (TL) and optically stimulated luminescence (OSL) of a sampling of chip modules are measured over the range of 0.4-12Gy. Both infrared (830nm) from a laser diode and blue light (470nm) from LEDs were used to perform the OSL measurements. The TL measurements showed a linear dose-response relationship, but the TL suffered from a large zero-dose signal in the unirradiated samples and dose regeneration with time after heating the chip modules. The OSL measurements also showed a linear dose-response, but did not exhibit a zero-dose signal or regeneration. Performing the infrared OSL measurements at a temperature of 140{sup -}bar C may improve the dose sensitivity to 0.15Gy, but the dose-response is supralinear in the dose range investigated. Curve fitting of infrared and blue stimulated luminescence curves showed that both exhibit a fast and a slow component. Thermal stability studies indicates the presence of a component that decays in the first hour of irradiation, and a component that is stable at least during the period of investigation (up to 10h). This stable component is more appropriate for dosimetry purposes.

  6. Ultraviolet-B radiation alters phenolic salicylate and flavenoid composition of Populus trichocarpa leaves

    Energy Technology Data Exchange (ETDEWEB)

    Warren, J. M. [USDA Forest Service, Forestry Science Laboratory, Corwallis, OR (United States); Bassman, J. H. [Washington State Univ., Dept. of Natural Resources Sciences, Pullman, WA (United States); Fellman, J. K.; Mattinson, D. S. [Washington State Univ., Dept. of Horticulture and Landscape Architecture, Pullman, WA (United States); Eigenbrode, S. [Idaho Univ., Dept. of Plant, Soil and Entomological Sciences, Moscow, ID (United States)

    2003-06-01

    Foliar phenolic composition of field- and greenhouse-grown black cottonwood was studied by subjecting samples to near zero, ambient and twice-ambient concentrations of biologically effective ultraviolet-B radiation. Phenolic compounds were extracted after three months, separated by liquid chromatography and identified and quantified by diode-array spectrometry and mass spectrometry. Phenolic compounds that were found to have increased in response to UV-B radiation were flavonoids, although increasing the level of radiation to ambient and twice ambient levels did not result in further flavonoid accumulation in either greenhouse or field samples. There was, however, an increase in salicortin, a non-flavonoid glycoside, and a salicylates that is important in plant-herbivore-predator relationships. It was concluded that enhanced solar UV-B radiation has the capacity to significantly alter trophic structure in some ecosystems by stimulating specific phenolic compounds. 74 refs., 1 tab., 6 figs.

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

    International Nuclear Information System (INIS)

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

  8. Radiation-induced alterations in the distribution of lysosomal hydrolases in rat spleen homogenates. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, S.L.; Eklund, S.K.

    1978-07-01

    Whole-body exposure of rats to /sup 60/Co-..gamma.. radiation results in increases in the activities of two lysosomal hydrolases, ..beta..-glucuronidase and ..cap alpha..-fucosidase, found in the supernatant fraction of spleen homogenates. The redistribution of these enzymes from the ''particulate-bound'' to the ''free-supernatant'' fraction of spleen homogenates has been studied as a function of radiation dose. The response curves for the ratio of free/bound enzyme versus dose sigmoidal with maximum occurring at 300 to 400 rad.

  9. Nerve growth factor alters the sensitivity of rat masseter muscle mechanoreceptors to NMDA receptor activation.

    Science.gov (United States)

    Wong, Hayes; Dong, Xu-Dong; Cairns, Brian E

    2014-11-01

    Intramuscular injection of nerve growth factor (NGF) into rat masseter muscle induces a local mechanical sensitization that is greater in female than in male rats. The duration of NGF-induced sensitization in male and female rats was associated with an increase in peripheral N-methyl-d-aspartate (NMDA) receptor expression by masseter muscle afferent fibers that began 3 days postinjection. Here, we investigated the functional consequences of increased NMDA expression on the response properties of masseter muscle mechanoreceptors. In vivo extracellular single-unit electrophysiological recordings of trigeminal ganglion neurons innervating the masseter muscle were performed in anesthetized rats 3 days after NGF injection (25 μg/ml, 10 μl) into the masseter muscle. Mechanical activation threshold was assessed before and after intramuscular injection of NMDA. NMDA injection induced mechanical sensitization in both sexes that was increased significantly following NGF injection in the male rats but not in the female rats. However, in female but not male rats, further examination found that preadministration of NGF induced a greater sensitization in slow Aδ-fibers (2-7 m/s) than fast Aδ-fibers (7-12 m/s). This suggests that preadministration of NGF had a different effect on slowly conducting mechanoreceptors in the female rats compared with the male rats. Although previous studies have found an association between estrogenic tone and NMDA activity, no correlation was observed between NMDA-evoked mechanical sensitization and plasma estrogen level. This study suggests NGF alters NMDA-induced mechanical sensitization in the peripheral endings of masseter mechanoreceptors in a sexually dimorphic manner.

  10. Altered ATP-sensitive potassium channels may underscore obesity-triggered increase in blood pressure

    Institute of Scientific and Technical Information of China (English)

    Li-hong FAN; Hong-yan TIAN; Ai-qun MA; Zhi HU; Jian-hua HUO; Yong-xiao CAO

    2008-01-01

    Aim:To determine whether ATP-sensitive potassium channels are altered in VSMC from arotas and mesenteric arteries of obese rat,and their association with obesity-triggered increase in blood pressure.Methods:Obesity was induced by 24 weeks of high-fat diet feeding in male Sprague-Dawley rats.Control rats were fed with standard laboratory rat chow.Blood pressure and body weight of these rats were measured every 4 weeks.At the end of 24 weeks,KATP channel-mediated relaxation responses in the aortas and mesenteric arteries,KATP channel current,and gene expression were examined,respectively.Results:Blood pres-sure and body weight were increased in rats fed with high-fat diet.KATP channel-mediated relaxation responses,currents,and KATP expression in VSMC of both aortas and mesenteric arteries were inhibited in these rats.Conclusion:Altered ATP-sensitive potassium channels in obese rats may underscore obesity-triggered increase in blood pressure.

  11. Altered zinc sensitivity of NMDA receptors harboring clinically-relevant mutations.

    Science.gov (United States)

    Serraz, Benjamin; Grand, Teddy; Paoletti, Pierre

    2016-10-01

    Recent human genetic studies have identified a surprisingly high number of alterations in genes encoding NMDA receptor (NMDAR) subunits in several common brain diseases. Among NMDAR subunits, the widely-expressed GluN2A subunit appears particularly affected, with tens of de novo or inherited mutations associated with neurodevelopmental conditions including childhood epilepsies and cognitive deficits. Despite the increasing identification of NMDAR mutations of clinical interest, there is still little information about the effects of the mutations on receptor and network function. Here we analyze the impact on receptor expression and function of nine GluN2A missense (i.e. single-point) mutations targeting the N-terminal domain, a large regulatory region involved in subunit assembly and allosteric signaling. While several mutations produced no or little apparent effect on receptor expression, gating and pharmacology, two showed a drastic expression phenotype and two resulted in marked alterations in the sensitivity to zinc, a potent allosteric inhibitor of GluN1/GluN2A receptors and modulator of excitatory synaptic transmission. Surprisingly, both increase (GluN2A-R370W) and decrease (GluN2A-P79R) of zinc sensitivity were observed on receptors containing either one or two copies of the mutated subunits. Overexpression of the mutant subunits in cultured rat neurons confirmed the results from heterologous expression. These results, together with previously published data, indicate that disease-causing mutations in NMDARs produce a wide spectrum of receptor alterations, at least in vitro. They also point to a critical role of the zinc-NMDAR interaction in neuronal function and human health. PMID:27288002

  12. Solar Radiation Alters Toxicity of Carbofuran: Evidence from Empirical Trials with Duttaphyrnus melanostictus

    OpenAIRE

    M. R. Wijesinghe; B.A.D.M.C. Jayatillake; W. D. Ratnassoriya

    2011-01-01

    In the present study we investigated the potential of natural solar radiation to alter the toxicity of a commonly used carbamate pesticide, carbofuran, on tadpoles of the Common Asian Toad Duttaphrynus melanostictus. A single exposure trial was conducted over 96 hrs with three concentrations (150, 250 and 500 µgl-1) of photo-irradiated and non-irradiated carbofuran. Results show that photo-irradiation markedly reduced the toxicity of carbofuran as evident by its effects on three end points, i...

  13. Impact of Stromal Sensitivity on Radiation Response of Tumors Implanted in SCID Hosts Revisited

    Science.gov (United States)

    García-Barros, Mónica; Thin, Tin Htwe; Maj, Jerzy; Cordon-Cardo, Carlos; Haimovitz-Friedman, Adriana; Fuks, Zvi; Kolesnick, Richard

    2010-01-01

    Severe combined immunodeficient (SCID) mice carry a germ-line mutation in DNA-PK, associated with deficiency in recognition and repair DNA double strand breaks. Thus, SCID cells and tissues display increased sensitivity to radiation-induced post-mitotic (clonogenic) cell death. Nonetheless, the single radiation doses required for 50% permanent local control (TCD50) of tumors implanted in SCID mice are not significantly different from the TCD50 values of the same tumors in wild-type hosts. Whereas the tumor stroma is derived from the host, the observation that tumors implanted in SCID mice do not exhibit hypersensitivity to radiation might imply that stromal endothelial elements do not contribute substantially to tumor cure by ionizing radiation. Here we challenge this notion, testing the hypothesis that acid sphingomyelinase (ASMase)-mediated endothelial apoptosis, which results from plasma membrane alterations, not DNA damage, is a crucial element in the cure of tumors in SCID mice by single dose radiotherapy (SDRT). We show that endothelium in MCA/129 fibrosarcomas and B16 melanomas exhibit a wild-type apoptotic phenotype in SCID hosts, abrogated in tumors in SCIDasmase−/− littermates, which also acquire resistance to SDRT. Conversion into a radioresistant tumor phenotype when implanted in SCIDasmase−/− hosts provides compelling evidence that cell membrane ASMase-mediated microvascular dysfunction, rather than DNA damage-mediated endothelial clonogenic lethality, plays a mandatory role in the complex pathophysiologic mechanism of tumor cure by SDRT, and provides an explanation for the wild-type SDRT responses reported in tumors implanted in SCID mice. PMID:20924105

  14. Postnatal manganese exposure does not alter dopamine autoreceptor sensitivity in adult and adolescent male rats.

    Science.gov (United States)

    McDougall, Sanders A; Mohd-Yusof, Alena; Kaplan, Graham J; Abdulla, Zuhair I; Lee, Ryan J; Crawford, Cynthia A

    2013-04-15

    Administering manganese chloride (Mn) to rats on postnatal day (PD) 1-21 causes long-term reductions in dopamine transporter levels in the dorsal striatum, as well as a persistent increase in D1 and D2 receptor concentrations. Whether dopamine autoreceptors change in number or sensitivity is uncertain, although D2S receptors, which may be presynaptic in origin, are elevated in Mn-exposed rats. The purpose of this study was to determine if early Mn exposure causes long-term changes in dopamine autoreceptor sensitivity that persist into adolescence and adulthood. To this end, male rats were exposed to Mn on PD 1-21 and autoreceptor functioning was tested 7 or 70 days later by measuring (a) dopamine synthesis (i.e., DOPA accumulation) in the dorsal striatum after quinpirole or haloperidol treatment and (b) behavioral responsiveness after low-dose apomorphine treatment. Results showed that low doses (i.e., "autoreceptor" doses) of apomorphine (0.06 and 0.12 mg/kg) decreased the locomotor activity of adolescent and adult rats, while higher doses increased locomotion. The dopamine synthesis experiment also produced classic autoreceptor effects, because quinpirole decreased dorsal striatal DOPA accumulation; whereas, haloperidol increased DOPA levels in control rats, but not in rats given the nerve impulse inhibitor γ-butyrolactone. Importantly, early Mn exposure did not alter autoreceptor sensitivity when assessed in early adolescence or adulthood. The lack of Mn-induced effects was evident in both the dopamine synthesis and behavioral experiments. When considered together with past studies, it is clear that early Mn exposure alters the functioning of various dopaminergic presynaptic mechanisms, while dopamine autoreceptors remain unimpaired. PMID:23458069

  15. Toward the elucidation of factors concerning the individual difference of radiation sensitivity, and the reduction of radiation risks

    International Nuclear Information System (INIS)

    This article describes studies aiming at the title subject and contains 2 topics of genetic and non-genetic factors modifying the radiation sensitivity. The ultimate purposes of those studies are the introduction of individual weighting factor to correct the individual differences of the sensitivity (IDS) and the practical control of the sensitivity-concerned factors, in the field of medical exposure. For genetic factors, described are studies on factors modifying the sensitivity at DNA repair and on the control of the sensitivity through the DNA repairing factors. The former, using cultured cells, aims at identifying protein (gene) of possible biomarker for IDS in non-homologous end-joining (NHEJ), an important mechanism in repairing the double strand break of DNA. Ku protein is found as the candidate. The latter has revealed that cells lacking Artemis, XRCC4 or MDC1 gene are highly sensitive, and are planning to suppress Artemis activity artificially, which may lead to the reduction of radiation cancer formation due to the death of highly sensitive cells. For non-genetic factors, described are studies on the life habits modifying the sensitivity, on the control of the sensitivity through the radiation-induced adaptive response and with steroid hormone. In the first, in mice treated with high-calorie diet and X-irradiation, a possible radiation response is suggested in the hepatic DNA-methylation and micro-RNA. Second, the combination of radiation adaptive response in the genome damage and restriction of diet ingestion is shown to lower the sensitivity of mice with use of C, Ne ion or X-ray irradiation. Third, in studies on the radiation-induced formation and condensation of breast cancer stem cells in the presence of progesterone, the hormone is found to produce micro-RNA molecules relating with the suppression of cellular senescence and repressed carcinogenesis with over-expression of apoptosis inhibitory molecules. (T.T.)

  16. Initial impacts of altered UVB radiation on plant growth and decomposition in shortgrass steppe

    Science.gov (United States)

    King, Jennifer Y.; Milchunas, Daniel G.; Mosier, Arvin R.; Moore, John C.; Quirk, Meghan H.; Morgan, Jack A.; Slusser, James R.

    2003-11-01

    We initiated a study in winter 2000 in a Colorado shortgrass steppe to investigate effects of altered ultraviolet-B (UVB) radiation and altered precipitation on plant growth, plant tissue decomposition, and litter faunal activity. In the field, open-air structures were constructed of solid plastic sheet material that either passed all wavelengths of solar radiation or passed only wavelengths greater than 400 nm (UVB =280-315 nm). Preliminary results indicate decreases in warm-season grass production under UVB radiation and drought conditions. Analysis of fiber constituents shows some significant seasonal and UVB treatment effects. The results of in vitro digestible dry matter analyses show significantly higher digestibility with UVB. Simulated grazing increased plant production, but there were no UVB by grazing interactions. Litter decomposition was affected by UVB exposure, the CO2 growing conditions, and precipitation level. Under dry conditions, UVB radiation tended to increase litter decomposition, as measured by mass loss. There were no clear initial effects of UVB treatment on soluble and fiber constituents of litter. Exclusion of UVB resulted in reduced fungal hyphae counts in ambient CO2-grown litter collected in fall 2002. Preliminary results indicate that litter arthropod density was lower with exposure to UVB and also lower under drought conditions.

  17. Calcitonin gene-related peptide alters the firing rates of hypothalamic temperature sensitive and insensitive neurons

    Directory of Open Access Journals (Sweden)

    Grimm Eleanor R

    2008-07-01

    Full Text Available Abstract Background Transient hyperthermic shifts in body temperature have been linked to the endogenous hormone calcitonin gene-related peptide (CGRP, which can increase sympathetic activation and metabolic heat production. Recent studies have demonstrated that these centrally mediated responses may result from CGRP dependent changes in the activity of thermoregulatory neurons in the preoptic and anterior regions of the hypothalamus (POAH. Results Using a tissue slice preparation, we recorded the single-unit activity of POAH neurons from the adult male rat, in response to temperature and CGRP (10 μM. Based on the slope of firing rate as a function of temperature, neurons were classified as either warm sensitive or temperature insensitive. All warm sensitive neurons responded to CGRP with a significant decrease in firing rate. While CGRP did not alter the firing rates of some temperature insensitive neurons, responsive neurons showed an increase in firing rate. Conclusion With respect to current models of thermoregulatory control, these CGRP dependent changes in firing rate would result in hyperthermia. This suggests that both warm sensitive and temperature insensitive neurons in the POAH may play a role in producing this hyperthermic shift in temperature.

  18. Alteration of radiation response by two tyrosine kinase inhibitors: STI571 (Glivec) and BIBW 2992

    International Nuclear Information System (INIS)

    Concurrent chemo-radiation is one of the main weapon in the treatment of cancer. The targeted therapies may act on the mechanisms of tumor resistance to radiation and are therefore very promising in combination with radiotherapy. The STI571 (imatinib or Gleevec) inhibits specifically the Bcr-Abl tyrosine kinase. It leads to radiosensitization in K562 chronic myeloid leukemia cell line by alterations of the cell cycle. The BIBW2992 is a selective inhibitor of EGFR and HER2. The BIBW 2992 shows cytotoxic and radiosensitizing effects on pancreatic adenocarcinoma cells BxPC3 and Capan-2, regardless of KRAS status. The mechanism underlying this radiosensitization is not unequivocal, involving both changes in the cell cycle and induction of mitotic death. Our results show that the combination of an inhibitor of tyrosine kinase with ionizing radiation may lead to a radiosensitization in vitro with mechanisms depending on the type of cell line. (author)

  19. A Modular High Sensitive Radiation Detector for Homel and Security and Post Event Applications

    International Nuclear Information System (INIS)

    A modular, high sensitive radiation monitoring system designed for the homeland security radiological requirements and radiological post event applications is presented. The prevention of undocumented and potentially threatening shipment of radioactive and nuclear materials is a problem at seaports, border crossings, rail yards, airports and similar locations that requires the use of sensitive radiation detectors. Furthermore; radiological events such as the Fukushima nuclear incident emphasize the need for sensitive detector for monitoring food and commercial products

  20. Carcinogenic alterations in murine liver, lung, and uterine tumors induced by in utero exposure to ionizing radiation.

    Science.gov (United States)

    Lumniczky, K; Antal, S; Unger, E; Wunderlich, L; Hidvégi, E J; Sáfrány, G

    1998-02-01

    The atomic bombing of Hiroshima and Nagasaki and the nuclear accident at Chernobyl raised the question of prenatal sensitivity to ionizing radiation-induced cancer. In this study, mice were exposed to single doses of gamma-radiation (0.2-2.0 Gy) at different embryonic stages. The tumor incidence increased with dose from 15% in control mice to 35% in mice irradiated with 2.0 Gy on 18 d of prenatal life. Various oncogenic events were investigated in lymphoid, liver, lung, and uterine tumors. We observed threefold to fivefold increases in myc expression in 25% of the lymphomas, and the expression of Ha-ras and p53 genes decreased in 40% and 60% of the lung tumors by twofold to fivefold. Point mutations were tissue specific: Ha-ras codon 61 mutations were found in about 40% of the liver adenocarcinomas, Ki-ras codon 12 mutations in about 17% of lung tumors, and p53 mutations in about 15% of the lymphomas. Amplification and rearrangement of the p53, myc, and Ha-, Ki- and N-ras genes were not detected. Loss of heterozygosity on chromosome 4 at the multiple tumor suppressor 1 and 2 genes was observed in all types of malignancies. Allelic losses on chromosome 11 at the p53 locus were found in lymphoid, liver, and lung tumors, but they were absent from uterine tumors. Multiple oncogenic changes were often detected. The frequency of carcinogenic alterations was similar in spontaneous and radiation-induced lymphoid, liver, and uterine tumors. In radiation-induced lung adenocarcinomas, however, the incidences of many oncogenic changes were different from those found in their spontaneous counterparts. This suggests that different oncogenic pathways are activated during spontaneous and in utero gamma-radiation-induced murine lung carcinogenesis. PMID:9496910

  1. Mesenchymal stem cells are sensitive to treatment with kinase inhibitors and ionizing radiation

    International Nuclear Information System (INIS)

    Mesenchymal stem cells (MSCs) can regenerate damaged tissues and may therefore be of importance for normal tissue repair after cancer treatment. Small molecule receptor kinase inhibitors (RKIs) have recently been introduced into cancer treatment. However, the influence of these drugs - particularly in combination with radiotherapy - on the survival of MSCs is largely unknown. The sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells to small molecule kinase inhibitors of the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) receptors, as well to inhibitors of c-Kit, was examined in combination with ionizing radiation (IR); cell survival and proliferation were assessed. Expression patterns of different kinase receptors and ligands were investigated using gene arrays. MSCs were highly sensitive to the tyrosine kinase inhibitors SU14816 (imatinib) and SU11657 (sunitinib), but showed only moderate sensitivity to the selective TGFβ receptor 1 inhibitor LY2109761. Primary adult human fibroblasts were comparably resistant to all three inhibitors. The addition of IR had an additive or supra-additive effect in the MSCs, but this was not the case for differentiated fibroblasts. Proliferation was markedly reduced in MSCs following kinase inhibition, both with and without IR. Gene expression analysis revealed high levels of the PDGF α and β receptors, and lower levels of the TGFβ receptor 2 and Abl kinase. IR did not alter the expression of kinase receptors or their respective ligands in either MSCs or adult fibroblasts. These data show that MSCs are highly sensitive to RKIs and combination treatments incorporating IR. Expression analyses suggest that high levels of PDGF receptors may contribute to this effect. (orig.)

  2. Antiangiogenic Agent Might Upgrade tumor Cell Sensitivity to Ionizing Radiation

    International Nuclear Information System (INIS)

    The understanding of the fundamental role of angiogenesis and metastasis in cancer growth has led to tremendous interest in research regarding its regulatory mechanisms and clinical implications in the management of cancer. The present study was conducted to evaluate the influence of the angiogenic regulators modification on the tumor growth and the cell sensitivity to ionizing radiation targeting the improvement of cancer therapeutic protocols. Accordingly, the antiangiogenic activity of apigenin and selenium was tested in vitro via MTT assay. The action of Apigenin and or Selenium was examined in vivo by using a model of solid tumor carcinoma (EAC). The growth rate of solid tumor in all experimental groups was measured by Caliper. The irradiated mice were exposed to 6.5 Gy of gamma rays. Apigenin 50 mg/kg body weight and selenium 5 μg per mice were daily administrated for 14 consecutive days after tumor volume reached 1mm3. The angiogenic activators TNF-α (key cytokine) in spleen, serum MMP 2 and MMP 9, liver and tumor NO, the lipid peroxidation (LPx) and angiogenic inhibitor TIMP-1 in spleen as well as, antioxidant markers (CAT, SOD, GPX) in tumor and liver tissue and DNA fragmentation in splenocytes were estimated to monitor efficacy of Apigenin and selenium in cancer treatment strategy. All parameters were determined as a time course on days 16 and 22 after tumor volume reached 1mm3. The using of MTT assay on EAC cells shows inhibition in EAC cell proliferation after the incubation with apigenin and /or selenium. The administration of apigenin and /or selenium to mice bearing tumor and to irradiated mice bearing tumor reduce significantly the TNF-α expression, MMP 2,9 , NO , LPx level and increased the antioxidant enzymes (GPx , SOD and CAT) activities. The DNA fragmentation and the antiangiogenic factors TIMP-1 were significantly increased when compared with their values in mice bearing tumor or in irradiated mice bearing tumor. From the results obtained

  3. Ionizing radiation alters neuronal excitability in hippocampal slices of the guinea pig

    International Nuclear Information System (INIS)

    To investigate the effects of ionizing radiation on an isolated neuronal network without complicating systemic factors, slices of hippocampus from the guinea pig were isolated and studied in vitro. Slices were irradiated with a 60Co source and compared to paired, sham-irradiated controls. Electrophysiological activity in the CA 1 population of pyramidal cells was evoked by stimulation of the stratum radiatum. Analysis of the somatic and dendritic responses suggested sites of radiation damage. Orthodromically evoked activity was significantly decreased in slices receiving greater than 75 Gy gamma radiation. The effects were dose and dose-rate dependent. At 20 Gy/min, doses of 50 Gy and greater produced synaptic impairment while doses of 75 Gy and greater also produced postsynaptic damage (i.e., the ability of the synaptic response to generate an action potential). A lower dose rate, 5 Gy/min, reduced the sensitivity of synaptic damage to radiation exposure; synaptic impairment required a dose of 100 Gy or greater at the lower dose rate. In contrast, postsynaptic damage was not sensitive to dose rate. This study demonstrates that ionizing radiation can directly affect the integrated functional activity of neurons

  4. Role of Rosemary leaves extract against radiation-induced hematological and biochemical alterations in mice

    Directory of Open Access Journals (Sweden)

    Acharya Garima S.

    2008-01-01

    Full Text Available The present paper is a study of the modulatory effect of Rosmarinus officinalis leaves extract on radiation-induced hematological and biochemical changes in Swiss albino mice. The dose reduction factor for the Rosemary extract against gamma rays was calculated 1.53 from LD50/30 values. The Rosemary extract was administered orally for 5 consecutive days prior to radiation exposure. The hematological and biochemical parameters were assessed from day 1 to 30 post-irradiation intervals. The total erythrocyte count, total leucocytes count, hemoglobin, and hematocrit values in the experimental group were found to be elevated as compared to the control group of mice. Furthermore, the Rosemary extract treatment enhanced reduced glutathione content in the liver and blood against radiation-induced depletion. Treatment with the plant extract brought a significant fall in the lipid peroxidation level, suggesting rosemary's role in protection against radiation-induced membrane and cellular damage. The results from the present study suggest a radio-protective effect of the Rosemary extract against radiation-induced hematological and biochemical alterations in mice.

  5. Using synchrotron radiation angiography with a highly sensitive detector to identify impaired peripheral perfusion in rat pulmonary emphysema

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Hiromichi [University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Matsushita, Shonosuke, E-mail: shomatsu@md.tsukuba.ac.jp [University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Tsukuba University of Technology, Tsukuba, Ibaraki 305-8521 (Japan); Hyodo, Kazuyuki [High Energy Accelerator Research Organization, KEK, Tsukuba, Ibaraki 305-0801 (Japan); Sato, Yukio; Sakakibara, Yuzuru [University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)

    2013-03-01

    Synchrotron radiation angiography with a HARP detector made it possible to evaluate impaired pulmonary microcirculation in pulmonary emphysema by means of high sensitivity. Owing to limitations in spatial resolution and sensitivity, it is difficult for conventional angiography to detect minute changes of perfusion in diffuse lung diseases, including pulmonary emphysema (PE). However, a high-gain avalanche rushing amorphous photoconductor (HARP) detector can give high sensitivity to synchrotron radiation (SR) angiography. SR angiography with a HARP detector provides high spatial resolution and sensitivity in addition to time resolution owing to its angiographic nature. The purpose of this study was to investigate whether this SR angiography with a HARP detector could evaluate altered microcirculation in PE. Two groups of rats were used: group PE and group C (control). Transvenous SR angiography with a HARP detector was performed and histopathological findings were compared. Peak density of contrast material in peripheral lung was lower in group PE than group C (p < 0.01). The slope of the linear regression line in scattering diagrams was also lower in group PE than C (p < 0.05). The correlation between the slope and extent of PE in histopathology showed significant negative correlation (p < 0.05, r = 0.61). SR angiography with a HARP detector made it possible to identify impaired microcirculation in PE by means of its high spatial resolution and sensitivity.

  6. Using synchrotron radiation angiography with a highly sensitive detector to identify impaired peripheral perfusion in rat pulmonary emphysema

    International Nuclear Information System (INIS)

    Synchrotron radiation angiography with a HARP detector made it possible to evaluate impaired pulmonary microcirculation in pulmonary emphysema by means of high sensitivity. Owing to limitations in spatial resolution and sensitivity, it is difficult for conventional angiography to detect minute changes of perfusion in diffuse lung diseases, including pulmonary emphysema (PE). However, a high-gain avalanche rushing amorphous photoconductor (HARP) detector can give high sensitivity to synchrotron radiation (SR) angiography. SR angiography with a HARP detector provides high spatial resolution and sensitivity in addition to time resolution owing to its angiographic nature. The purpose of this study was to investigate whether this SR angiography with a HARP detector could evaluate altered microcirculation in PE. Two groups of rats were used: group PE and group C (control). Transvenous SR angiography with a HARP detector was performed and histopathological findings were compared. Peak density of contrast material in peripheral lung was lower in group PE than group C (p < 0.01). The slope of the linear regression line in scattering diagrams was also lower in group PE than C (p < 0.05). The correlation between the slope and extent of PE in histopathology showed significant negative correlation (p < 0.05, r = 0.61). SR angiography with a HARP detector made it possible to identify impaired microcirculation in PE by means of its high spatial resolution and sensitivity

  7. Differential sensitivity of Chironomus and human hemoglobin to gamma radiation.

    Science.gov (United States)

    Gaikwad, Pallavi S; Panicker, Lata; Mohole, Madhura; Sawant, Sangeeta; Mukhopadhyaya, Rita; Nath, Bimalendu B

    2016-08-01

    Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. PMID:27237970

  8. Alterations in the optic radiations of very preterm children—Perinatal predictors and relationships with visual outcomes

    Directory of Open Access Journals (Sweden)

    Deanne K. Thompson

    2014-01-01

    This study presents evidence for microstructural alterations in the optic radiations of VPT children, which are largely predicted by white matter abnormality or severe retinopathy of prematurity, and may partially explain the higher rate of visual impairments in VPT children.

  9. Radiation damage-controlled localization of alteration haloes in albite: implications for alteration types and patterns vis-à-vis mineralization and element mobilization

    Science.gov (United States)

    Pal, D. C.; Chaudhuri, T.

    2016-07-01

    Uraninite, besides occurring in other modes, occurs as inclusions in albite in feldspathic schist in the Bagjata uranium deposits, Singhbhum shear zone, India. The feldspathic schist, considered the product of Na-metasomatism, witnessed multiple hydrothermal events, the signatures of which are preserved in the alteration halo in albite surrounding uraninite. Here we report radiation damage-controlled localization of alteration halo in albite and its various geological implications. Microscopic observation and SRIM/TRIM simulations reveal that the dimension of the alteration halo is dependent collectively on the zone of maximum cumulative α dose that albite was subjected to and by the extent of dissolution of uraninite during alteration. In well-preserved alteration haloes, from uraninite to the unaltered part of albite, the alteration minerals are systematically distributed in different zones; zone-1: K-feldspar; zone-2: chlorite; zone-3: LREE-phase/pyrite/U-Y-silicate. Based on textures of alteration minerals in the alteration microdomain, we propose a generalized Na+➔K+➔H+ alteration sequence, which is in agreement with the regional-scale alteration pattern. Integrating distribution of ore and alteration minerals in the alteration zone and their geochemistry, we further propose multiple events of U, REE, and sulfide mineralization/mobilization in the Bagjata deposit. The alteration process also involved interaction of the hydrothermal fluid with uraninite inclusions resulting in resorption of uraninite, redistribution of elements, including U and Pb, and resetting of isotopic clock. Thus, our study demonstrates that alteration halo is a miniature scale-model of the regional hydrothermal alteration types and patterns vis-à-vis mineralization/mobilization. This study further demonstrates that albite is vulnerable to radiation damage and damage-controlled fluid-assisted alteration, which may redistribute metals, including actinides, from radioactive minerals

  10. The alteration of pain sensitivity at disease-specific acupuncture points in premenstrual syndrome.

    Science.gov (United States)

    Chae, Younbyoung; Kim, Hee-Young; Lee, Hwa-Jin; Park, Hi-Joon; Hahm, Dae-Hyun; An, Kyungeh; Lee, Hyejung

    2007-04-01

    Acupuncture points (APs) are well known to be small regions of local or referred pain that are more sensitive than surrounding tissue. Based on bibliographical and clinical data, specific conditions are commonly believed to change the pain sensitivity at corresponding APs. The aim of the present study was to investigate whether the pressure pain threshold (PPT) of specific APs is associated with the severity of premenstrual syndrome. The 46 participants were female students attending a middle school. Premenstrual syndrome (PMS) was measured using a structured questionnaire, the menstruation distress questionnaire (MDQ). High PMS (HP) and low PMS (LP) groups were divided based on their MDQ scores. The PPTs at sites in the leg (the APs SP6, GB39, and LR3 and a non-AP 2-cm anterior to SP6) and in the arm (the APs PC6, TE5, and LI4 and a non-AP 2-cm proximal to PC6) were measured using an algometer. The PPT of the HP group at SP6 was significantly lower than that of the LP group (13.50 +/- 0.73 vs. 16.30 +/- 0.66 kilopascals, P < 0.05), but not at other APs or at non-APs. The findings of our study support the hypothesis that the alteration of pain threshold at specific APs is associated with the severity of corresponding diseases. Further studies are needed to determine whether an observation of pain sensitivity at the APs could be used as an adjunctive tool for the diagnosis of a clinical problem. PMID:17378970

  11. Appraisal of radio-protective potential of Tinospora cordifolia against radiation mediated biochemical alterations in intestine

    International Nuclear Information System (INIS)

    per oxidation level through out the period of study which suggests that it has a role in protection against radiation-induced membrane and cellular damage. Thus, the results from the present study demonstrate a radioprotective effect of the T.cordifolia root extract from radiation-induced biochemical alterations in intestine of mammals. (author)

  12. Radiation-induced alterations in murine lymphocyte homing patterns. I. Radiolabeling studies

    International Nuclear Information System (INIS)

    In vitro x-irradiation of 51Cr-labeled spleen, lymph node, bone marrow, or thymus cells was found to alter their subsequent in vivo distribution significantly in syngeneic BDF1 mice. Irradiated cells demonstrated an increased distribution to the liver and a significantly lower retention in the lungs. Cells going to the lymph nodes or Peyer's patches showed a significant exposure-dependent decrease in homing following irradiation. Irradiated lymph node cells homed in greater numbers to the spleen and bone marrow, while irradiated cells from other sources showed no preferential distribution to the same tissues. Sampling host tissues at various times after irradiation and injection did not demonstrate any return to normal patterns of distribution. The alterations in lymphocyte homing observed after in vitro irradiation appear to be due to the elimination of a selective population of lymphocytes or membrane alterations of viable cells, and the detection of these homing changes is in turn dependent upon the relative numbers of various lymphoid subpopulations which are obtained from different cell sources. Radiation-induced alterations in the normal homing patterns of lymphoid cells may thus be of considerable importance in the evaluation of subsequent functional assays in recipient animals

  13. Losartan sensitizes selectively prostate cancer cell to ionizing radiation.

    Science.gov (United States)

    Yazdannejat, H; Hosseinimehr, S J; Ghasemi, A; Pourfallah, T A; Rafiei, A

    2016-01-11

    Losartan is an angiotensin II receptor (AT-II-R) blocker that is widely used by human for blood pressure regulation. Also, it has antitumor property. In this study, we investigated the radiosensitizing effect of losartan on cellular toxicity induced by ionizing radiation on prostate cancer and non-malignant fibroblast cells. Human prostate cancer (DU-145) and human non-malignant fibroblast cells (HFFF2) were treated with losartan at different concentrations (0.5, 1, 10, 50 and 100 µM) and then these cells were exposed to ionizing radiation. The cell proliferation was determined using MTT assay. Our results showed that losartan exhibited antitumor effect on prostate cancer cells; it was reduced cell survival to 66% at concentration 1 µM. Losartan showed an additive killing effect in combination with ionizing radiation on prostate cancer cell. The cell proliferation was reduced to 54% in the prostate cancer cells treated with losartan at concentration 1 µM in combination with ionizing radiation. Losartan did not exhibit any toxicity on HFFF2 cell. This result shows a promising effect of losartan on enhancement of therapeutic effect of ionizing radiation in patients during therapy.

  14. Modulation of radiation induced alteration in the antioxidant status of mice by naringin

    International Nuclear Information System (INIS)

    The alteration of antioxidant status and lipid peroxidation by naringin, a citrus flavoglycoside, was investigated in Swiss albino mice treated with 2 mg/kg b. wt. naringin before exposure to 0.5, 1, 2, 3, and 4 Gy gamma radiation. Lipid peroxidation, glutathione, glutathione peroxidase, catalase and superoxide dismutase were determined in the liver and small intestine of mice treated or not with naringin at 0.5, 1, 2, 4 and 8 h post-irradiation. Whole-body irradiation of mice caused a dose dependent elevation in the lipid peroxidation while a dose dependent depletion was observed for glutathione, glutathione peroxidase, superoxide dismutase and catalase in both liver as well as small intestine. The study demonstrates that naringin protects mouse liver and intestine against the radiation-induced damage by elevating the antioxidant status and reducing the lipid peroxidation

  15. Simulated performance of a position sensitive radiation detecting system (COCAE)

    CERN Document Server

    Karafasoulis, K; Seferlis, S; Kaissas, I; Lambropoulos, C; Loukas, D; Poritiriadis, C

    2011-01-01

    Extensive simulations of a portable radiation detecting system have been performed in order to explore important performance parameters. The instrument consists of a stack of ten detecting layers made of pixelated Cadmium Telluride (CdTe) crystals. Its aim is to localize and identify radiation sources, by exploiting the Compton imaging technique. In this paper we present performance parameters based on simulation studies. Specifically the ratio of incompletely absorbed photons, the detector's absolute efficiency as well as its energy and angular resolution are evaluated in a wide range of incident photon energies.

  16. Sensitivity of aerosol direct radiative forcing to aerosol vertical profile

    OpenAIRE

    Chung, Chul E.; Choi, Jung-Ok

    2014-01-01

    Aerosol vertical profile significantly affects the aerosol direct radiative forcing at the TOA level. The degree to which the aerosol profile impacts the aerosol forcing depends on many factors such as presence of cloud, surface albedo and aerosol single scattering albedo (SSA). Using a radiation model, we show that for absorbing aerosols (with an SSA of 0.7–0.8) whether aerosols are located above cloud or below induces at least one order of magnitude larger changes of the aerosol forcing tha...

  17. Sensitivity to plant modelling uncertainties in optimal feedback control of sound radiation from a panel

    DEFF Research Database (Denmark)

    Mørkholt, Jakob

    1997-01-01

    of a rectangular baffled panel radiating into free field has been constructed. Secondary actuators have been modelled as vibrational inputs acting directly on the panel. A cost function proportional to the averaged radiated sound power and based on knowledge of the modal amplitudes of the panel has been derived...... in terms of a set of radiation filters modelling the radiation dynamics.Linear quadratic feedback control applied to the panel in order to minimise the radiated sound power has then been simulated. The sensitivity of the model based controller to modelling uncertainties when using feedback from actual...

  18. Leukocyte activity is altered in a ground based murine model of microgravity and proton radiation exposure.

    Directory of Open Access Journals (Sweden)

    Jenine K Sanzari

    Full Text Available Immune system adaptation during spaceflight is a concern in space medicine. Decreased circulating leukocytes observed during and after space flight infer suppressed immune responses and susceptibility to infection. The microgravity aspect of the space environment has been simulated on Earth to study adverse biological effects in astronauts. In this report, the hindlimb unloading (HU model was employed to investigate the combined effects of solar particle event-like proton radiation and simulated microgravity on immune cell parameters including lymphocyte subtype populations and activity. Lymphocytes are a type of white blood cell critical for adaptive immune responses and T lymphocytes are regulators of cell-mediated immunity, controlling the entire immune response. Mice were suspended prior to and after proton radiation exposure (2 Gy dose and total leukocyte numbers and splenic lymphocyte functionality were evaluated on days 4 or 21 after combined HU and radiation exposure. Total white blood cell (WBC, lymphocyte, neutrophil, and monocyte counts are reduced by approximately 65%, 70%, 55%, and 70%, respectively, compared to the non-treated control group at 4 days after combined exposure. Splenic lymphocyte subpopulations are altered at both time points investigated. At 21 days post-exposure to combined HU and proton radiation, T cell activation and proliferation were assessed in isolated lymphocytes. Cell surface expression of the Early Activation Marker, CD69, is decreased by 30% in the combined treatment group, compared to the non-treated control group and cell proliferation was suppressed by approximately 50%, compared to the non-treated control group. These findings reveal that the combined stressors (HU and proton radiation exposure result in decreased leukocyte numbers and function, which could contribute to immune system dysfunction in crew members. This investigation is one of the first to report on combined proton radiation and

  19. Motility alterations in celiac disease and non-celiac gluten sensitivity.

    Science.gov (United States)

    Pinto-Sanchez, Maria Ines; Bercik, Premysl; Verdu, Elena F

    2015-01-01

    Regulation of gut motility is complex and involves neuromuscular, immune and environmental mechanisms. It is well established that patients with celiac disease (CD) often display gut dysmotility. Studies have shown the presence of disturbed esophageal motility, altered gastric emptying, and dysmotility of the small intestine, gallbladder and colon in untreated CD. Most of these motor abnormalities resolve after a strict gluten-free diet, suggesting that mechanisms related to the inflammatory condition and disease process are responsible for the motor dysfunction. Motility abnormalities are also a hallmark of functional bowel disorders such as irritable bowel syndrome (IBS), where it has been proposed as underlying mechanism for symptom generation (diarrhea, constipation, bloating). Non-celiac gluten sensitivity (NCGS) is a poorly defined entity, mostly self-diagnosed, that presents clinically with IBS symptoms in the absence of specific celiac markers. Patients with NCGS are believed to react symptomatically to wheat components, and some studies have proposed the presence of low-grade inflammation in these patients. There is little information regarding the functional characterization of these patients before and after a gluten-free diet. A study suggested the presence of altered gastrointestinal transit in NCGS patients who also have a high prevalence of nonspecific anti-gliadin antibodies. Results of an ongoing clinical study in NCGS patients with positive anti-gliadin antibodies before and after a gluten-free diet will be discussed. Elucidating the mechanisms for symptom generation in NCGS patients is important to find new therapeutic alternatives to the burden of imposing a strict gluten-free diet in patients who do not have CD. PMID:25925923

  20. A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation

    Directory of Open Access Journals (Sweden)

    Shi HS

    2012-05-01

    Full Text Available Hua-shan Shi1,* Xiang Gao,1,3,* Dan Li,1,* Qiong-wen Zhang,1 Yong-sheng Wang,2 Yu Zheng,1 Lu-Lu Cai,1 Ren-ming Zhong,2 Ao Rui,1 Zhi-yong Li,1 Hao Zheng,1 Xian-cheng Chen,1 Li-juan Chen,11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 2State Key Laboratory of Biotherapy and Department of Thoracic Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China; 3Deparment of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People's Republic of China*These authors contributed equally to this workAbstract: Radiation pneumonitis (RP is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2 model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively

  1. Sensitivity study of cloud/radiation interaction using a second order turbulence radiative-convective model

    International Nuclear Information System (INIS)

    A high resolution one-dimensional version of a second order turbulence convective/radiative model, developed at the Los Alamos National Laboratory, was used to conduct a sensitivity study of a stratocumulus cloud deck, based on data taken at San Nicolas Island during the intensive field observation marine stratocumulus phase of the First International Satellite Cloud Climatology Program (ISCCP) Regional Experiment (FIRE IFO), conducted during July, 1987. Initial profiles for liquid water potential temperature, and total water mixing ratio were abstracted from the FIRE data. The dependence of the diurnal behavior in liquid water content, cloud top height, and cloud base height were examined for variations in subsidence rate, sea surface temperature, and initial inversion strength. The modelled diurnal variation in the column integrated liquid water agrees quite well with the observed data, for the case of low subsidence. The modelled diurnal behavior for the height of the cloud top and base show qualitative agreement with the FIRE data, although the overall height of the cloud layer is about 200 meters too high

  2. Radiation-Sensitive Indicator Based on m-Cresol Purple Dyed Poly (vinyl Butyral) for Possible Use in Radiation Dosimetry

    International Nuclear Information System (INIS)

    In the present work a PVB films containing different concentrations of m-cresol purple (ph indicator) and chloral hydrate were prepared. The chlorine containing (chIoral hydrate) polymer was dehydrochlorinated when the material irradiated thereby reducing ph and causing the acid-sensitive dye to change color. Such materials are not, however, reported to be sensitive. and quantitative at relatively low radiation doses. The useful dose ranges of this film ranges between 2 and 6 kGy. Radiation chemical yield was calculated. The effects of temperature and relative humidity during irradiation as well as pre and post irradiation stability on the response of films were described

  3. The sensitivity of Emiliania huxleyi (Prymnesiophycea) to ultraviolet-B radiation

    NARCIS (Netherlands)

    Buma, A.G.J.; van Oijen, T.; van de Poll, Willem; Veldhuis, M.J W; Gieskes, W.W C

    2000-01-01

    Emiliania huxleyi (Lohm.) Hay et Miller is an important component of the phytoplankton in open ocean waters. The sensitivity of this cosmopolitan alga to natural levels of UVB radiation has never been tested. Since DNA is believed to be a major target of natural UVB radiation (UVBR: 280-315 nm) in l

  4. Mobile Phone Radiation Induced Plasma Protein Alterations And Eye Pathology In Newly Born Mice

    Directory of Open Access Journals (Sweden)

    F. Eid*, M. Abou Zeid **, N Hanafi *** and A. El-Dahshan

    2013-07-01

    Full Text Available Abstract: The hazardous health effect of the exposure to 900-1800 MHz radiofrequency electromagnetic fields (RF-EMF which emitted from mobile phones was investigated on the plasma protein and eye of newly born mice. Twenty one newly born mice were divided into 3 groups, the 1st group served as control, the 2nd group exposed to mobile phone radiation daily for one month (45 min/day and the 3rd group remained one month following the end of exposure. The results showed deleterious changes in the plasma protein pattern by electrophoretic analysis. Also, the microscopic examination demonstrated numerous histopathological and histochemical changes in the eye mainly represented by degenerated, hemorrhagic areas and detachment in some layers of the eye with alteration in collagen, polysaccharides, total protein and marked increase in amyloid beta (β protein contents of newly born mice exposed to RF-EMF from mobile phone (45 min/day for one month as well as after one month following the end of exposure. It was concluded that the exposure to mobile phone radiation causes plasma proteins alterations and eye pathology in newly born mice.

  5. Radiation sensitivity of fungal microflora isolated from some pharmaceutical ingredients

    International Nuclear Information System (INIS)

    The total number of fungal microflora of D-glucose, NaCl, KCl and their solutions was determined. The fungal isolates were identified as Aspergillus fumigatus. Aspergillus niger; Spicaria divaricate and Spicaria silvatica and their response to γ-radiation was determined, the most predominant isolate Asp. fumigatus was also the most irradiation resistant. The Dio and the lethal dose were determined for each isolate in a pure spore suspension as well as in the presence of the other isolates. The higher lethal dose values obtained for pure spore suspension as compared to that obtained for the natural fungal flora a D-glucose are discussed in terms of spore clumping. The activity of amylase, protease and L-asparaginase of Asp. fumigatus was examined prior to and after exposure to different doses of γ-radiation. Though all were inhibited at high doses, the effect was not as drastic as it was on cell viability

  6. Andrographolide Sensitizes Ras-Transformed Cells to Radiation in vitro and in vivo

    International Nuclear Information System (INIS)

    Purpose: Increasing the sensitivity of tumor cells to radiation is a major goal of radiotherapy. The present study investigated the radiosensitizing effects of andrographolide and examined the molecular mechanisms of andrographolide-mediated radiosensitization. Methods and Materials: An H-ras-transformed rat kidney epithelial (RK3E) cell line was used to measure the radiosensitizing effects of andrographolide in clonogenic assays, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assays, and a xenograft tumor growth model. The mechanism of andrographolide-sensitized cell death was analyzed using annexin V staining, caspase 3 activity assays, and terminal transferase uridyl nick end labeling assays. The roles of nuclear factor kappa B (NF-κB) and Akt in andrographolide-mediated sensitization were examined using reporter assays, electrophoretic mobility shift assays, and Western blotting. Results: Concurrent andrographolide treatment (10 μM, 3 h) sensitized Ras-transformed cells to radiation in vitro (sensitizer enhancement ratio, 1.73). Andrographolide plus radiation (one dose of 300 mg/kg peritumor andrographolide and one dose of 6 Gy radiation) resulted in significant tumor growth delay (27 ± 2.5 days) compared with radiation alone (22 ± 1.5 days; p <.05). Radiation induced apoptotic markers (e.g., caspase-3, membrane reversion, DNA fragmentation), and andrographolide treatment did not promote radiation-induced apoptosis. However, the protein level of activated Akt was significantly reduced by andrographolide. NF-κB activity was elevated in irradiated Ras-transformed cells, and andrographolide treatment significantly reduced radiation-induced NF-κB activity. Conclusion: Andrographolide sensitized Ras-transformed cells to radiation both in vitro and in vivo. Andrographolide-mediated radiosensitization was associated with downregulation of Akt and NF-κB activity. These observations indicate that andrographolide is a novel radiosensitizing agent

  7. Repeated restraint stress alters sensitivity to the social consequences of ethanol differentially in early and late adolescent rats.

    OpenAIRE

    Varlinskaya, Elena I.; Truxell, Eric M.; Spear, Linda P.

    2013-01-01

    In rats, considerable differences in the social consequences of acute ethanol are seen across ontogeny, with adolescents being more sensitive to low dose ethanol-induced social facilitation and less sensitive to the social inhibition evident at higher ethanol doses relative to adults. Stressor exposure induces social anxiety-like behavior, indexed via decreases in social preference, and alters responsiveness to the social consequences of acute ethanol by enhancing ethanol-associated social fa...

  8. Sensitivity of the vibrios to ultraviolet-radiation

    International Nuclear Information System (INIS)

    The ultraviolet-inactivation kinetics of a number of strains of Vibrio cholerae (classical), Vibrio cholerae (el tor), NAG vibrios and Vibrio parahaemolyticus were investigated. Statistical analyses revealed significant differences between any two of the four types of vibrio in respect of their sensitivity to U.V. (author)

  9. Uncertainty and Sensitivity Analysis of Afterbody Radiative Heating Predictions for Earth Entry

    Science.gov (United States)

    West, Thomas K., IV; Johnston, Christopher O.; Hosder, Serhat

    2016-01-01

    The objective of this work was to perform sensitivity analysis and uncertainty quantification for afterbody radiative heating predictions of Stardust capsule during Earth entry at peak afterbody radiation conditions. The radiation environment in the afterbody region poses significant challenges for accurate uncertainty quantification and sensitivity analysis due to the complexity of the flow physics, computational cost, and large number of un-certain variables. In this study, first a sparse collocation non-intrusive polynomial chaos approach along with global non-linear sensitivity analysis was used to identify the most significant uncertain variables and reduce the dimensions of the stochastic problem. Then, a total order stochastic expansion was constructed over only the important parameters for an efficient and accurate estimate of the uncertainty in radiation. Based on previous work, 388 uncertain parameters were considered in the radiation model, which came from the thermodynamics, flow field chemistry, and radiation modeling. The sensitivity analysis showed that only four of these variables contributed significantly to afterbody radiation uncertainty, accounting for almost 95% of the uncertainty. These included the electronic- impact excitation rate for N between level 2 and level 5 and rates of three chemical reactions in uencing N, N(+), O, and O(+) number densities in the flow field.

  10. Radiation-induced epigenetic alterations after low and high LET irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut, E-mail: uaypa001@umaryland.edu [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Morgan, William F. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Baulch, Janet E. [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2011-02-10

    Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NF{kappa}B), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise

  11. Radiation effects in ultraviolet sensitive SiC photodiodes

    International Nuclear Information System (INIS)

    We tested SiC photodiodes with Co-60 gamma rays up to a total dose of 22 Mrad(SiC) and 32 MeV protons up to a fluence of 9 x 1012 cm-2. They showed a decrease in sensitivity of about 50% at a dose of 1 Mrad. The same decrease or somewhat less was observed during proton irradiations when the fluence is converted to an applied dose. (authors)

  12. Epicatechin stimulates mitochondrial activity and selectively sensitizes cancer cells to radiation.

    Directory of Open Access Journals (Sweden)

    Hosam A Elbaz

    Full Text Available Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (--epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (--epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and Western blot analyses. (--Epicatechin stimulated mitochondrial respiration and oxygen consumption in Panc-1 cells. Human normal fibroblasts were not affected. (--Epicatechin sensitized Panc-1, U87, and MIA PaCa-2 cells with an average radiation enhancement factor (REF of 1.7, 1.5, and 1.2, respectively. (--Epicatechin did not sensitize normal fibroblast cells to ionizing radiation with a REF of 0.9, suggesting cancer cell selectivity. (--Epicatechin enhanced Chk2 phosphorylation and p21 induction when combined with radiation in cancer, but not normal, cells. Taken together, (--epicatechin radiosensitized cancer cells, but not normal cells, and may be a promising candidate for pancreatic cancer treatment when combined with radiation.

  13. Gimeracil sensitizes cells to radiation via inhibition of homologous recombination

    International Nuclear Information System (INIS)

    Background and purpose: 5-Chloro-2,4-dihydroxypyridine (Gimeracil) is a component of an oral fluoropyrimidine derivative S-1. Gimeracil is originally added to S-1 to yield prolonged 5-FU concentrations in tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We found that Gimeracil by itself had the radiosensitizing effect. Methods and materials: We used various cell lines deficient in non-homologous end-joining (NHEJ) or homologous recombination (HR) as well as DLD-1 and HeLa in clonogenic assay. γ-H2AX focus formation and SCneo assay was performed to examine the effects of Gimeracil on DNA double strand break (DSB) repair mechanisms. Results: Results of γ-H2AX focus assay indicated that Gimeracil inhibited DNA DSB repair. It did not sensitize cells deficient in HR but sensitized those deficient in NHEJ. In SCneo assay, Gimeracil reduced the frequency of neo-positive clones. Additionally, it sensitized the cells in S-phase more than in G0/G1. Conclusions: Gimeracil inhibits HR. Because HR plays key roles in the repair of DSBH caused by radiotherapy, Gimeracil may enhance the efficacy of radiotherapy through the suppression of HR-mediated DNA repair pathways.

  14. Sensitive Detection of Cold Cesium Molecules by Radiative Feshbach Spectroscopy

    OpenAIRE

    Chin, Cheng; Kerman, Andrew J.; Vuletić, Vladan; Chu, Steven

    2002-01-01

    We observe the dynamic formation of $Cs_2$ molecules near Feshbach resonances in a cold sample of atomic cesium using an external probe beam. This method is 300 times more sensitive than previous atomic collision rate methods, and allows us to detect more than 20 weakly-coupled molecular states, with collisional formation cross sections as small as $\\sigma =3\\times 10^{-16}$cm$^2$. We propose a model to describe the atom-molecule coupling, and estimate that more than $2 \\times 10^5$ $Cs_2$ mo...

  15. Oyster radiation sensitivity; Sensibilidade de ostras a radiacao

    Energy Technology Data Exchange (ETDEWEB)

    Marchese, Sandra R.M. [Centro Tecnologico da Marinha em Sao Paulo (CTMSP), SP (Brazil); Mastro, Nelida L. del [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)

    1996-07-01

    Various food products like oysters, crabs and shrimps have been described as possible Vibrio spp. transmitting agents. Seafood irradiation is been presented as an alternative among the different public health intervention measures to control food borne diseases. The objective of this work was to establish, firstly, the radioresistance of Crassostrea brasiliana oysters. The oysters were irradiated with Co-60 radiation with doses of 0, 1.5,3 and 6 kGy. Survival curves a function of time showed that 100% of samples irradiated with 3 kGy survived at least 6 days; among those irradiated with 6 kGy, 100% survived 3 days. These results are encouraging since a dose of 2 kGy is already effective in diminishing oyster bioburden. (author)

  16. Alterations of CNS structure & function by charged particle radiation & resultant oxidative stress

    Science.gov (United States)

    Nelson, Gregory; Chang, Polly; Favre, Cecile; Fike, John; Komarova, Natalia; Limoli, Charles; Mao, Xiao-Wen; Obenaus, Andre; Raber, Jacob; Spigelman, Igor; Soltesz, Ivan; Song, Sheng-Kwei; Stampanoni, Marco; Vlkolinsky, Roman; Wodarz, Dominik

    The NSCOR program project is transitioning from establishing the existence of CNS responses to low doses of charged particles, to an investigation of mechanisms underlying these changes and extending the irradiation paradigm to more space-like exposures. In earlier experiments we examined radiation responses of the mouse brain (hippocampus) following exposure to 250 MeV protons and 600 MeV/n iron ions. Our key findings on structural changes were: 1) Significant dose and time dependent loss of en-dothelial cells and microvessel network remodeling occurs suggesting that vascular insufficiency is produced. 2) Significant dose dependent losses of neural precursor cells were observed in a lineage specific pattern which may be associated with cognitive impairment. 3) Evaluation of DNA damage showed dose and time dependent accumulation of mutations with region-specific mutation structures and gene expression profiling demonstrated activation of neurotrophic and adhesion factors as well as chemokine receptors associated with inflammation. Our key find-ings on functional changes were: 1) Time and dose dependent modifications to neural output expressed as enhanced excitability but reduced synaptic efficacy and plasticity (including long term potentiation). 2) Intrinsic membrane properties of neurons were not significantly modi-fied by radiation exposure but pharmacological treatments demonstrated changes in inhibitory synapses. 3) MRI imaging visualized brain structural changes based on altered water diffu-sion properties and patterns were consistent with demyelination or gliosis. Our key findings on neurodegeneration and fidelity of homeostasis were: 1) APP23 transgenic mice exhibited accelerated APP-type electrophysiological pathology over several months. 2) Microvessel net-work changes following irradiation were suggestive of poor tissue oxygenation. 3) The ability of the brain to respond a controlled septic shock was altered by irradiation; the septic shock reactions

  17. High-sensitivity observations of solar flare decimeter radiation

    CERN Document Server

    Benz, Arnold O; Monstein, C; Benz, Arnold O.; Messmer, Peter; Monstein, Christian

    2000-01-01

    A new acousto-optic radio spectrometer has observed the 1 - 2 GHz radio emission of solar flares with unprecedented sensitivity. The number of detected decimeter type III bursts is greatly enhanced compared to observations by conventional spectrometers observing only one frequency at the time. The observations indicate a large number of electron beams propagating in dense plasmas. For the first time, we report weak, reversed drifting type III bursts at frequencies above simultaneous narrowband decimeter spikes. The type III bursts are reliable signatures of electron beams propagating downward in the corona, apparently away from the source of the spikes. The observations contradict the most popular spike model that places the spike sources at the footpoints of loops. Conspicuous also was an apparent bidirectional type U burst forming a fish-like pattern. It occurs simultaneously with an intense U-burst at 600-370 MHz observed in Tremsdorf. We suggest that it intermodulated with strong terrestrial interference ...

  18. Synchrotron radiation X-ray fluorescence analysis on altered mineral muscovite in gold deposit

    Institute of Scientific and Technical Information of China (English)

    TANG Yun-Hui; YUAN Wan-Ming; WANG Li-Hua; HAN Chun-Ming; HUANG Yu-Ying; HE Wei

    2005-01-01

    Synchrotron radiation X-ray fluorescence (SRXRF) microprobe was used to ananlyse altered mineral muscovite and its surrounding feldspar in Yuerya gold deposit. The major, minor and trace elements of the two minerals were detected and analyzed. SRXRF analysis showed that the Yuerya muscovite had a complex chemical composition, containing K, Fe, Ca, Ti, Cr, Mn, Co, Cu, Zn and many trace or ultra-trace elements. Since muscovite resulted from the alteration of hydrothermal ore fluid acting on feldspar (plagioclase), the difference of chemical composition between the two minerals shows the components of ore fluid, which are characterized by the enrichment of alkaline and alkaline-earth metal elements K, Ca and ore-associated elements Fe, Cu, Zn. And gold, silver and platinum, invisible under microscope, were detected in some areas of muscovite, but not found in feldspar. Especially platinum, a mantle material, is rarely seen in the earth crust but now found in the gold deposit of magmatic sources; its appearance approves the idea of mantle flux participating in the gold mineralization, which suggests that the tectonic event controlling gold mineralization in the Yuerya district is a mantle phenomenon.

  19. Solar Radiation Alters Toxicity of Carbofuran: Evidence from Empirical Trials with Duttaphyrnus melanostictus

    Directory of Open Access Journals (Sweden)

    M.R.Wijesinghe

    2011-10-01

    Full Text Available In the present study we investigated the potential of natural solar radiation to alter the toxicity of a commonly used carbamate pesticide, carbofuran, on tadpoles of the Common Asian Toad Duttaphrynus melanostictus. A single exposure trial was conducted over 96 hrs with three concentrations (150, 250 and 500 µgl-1 of photo-irradiated and non-irradiated carbofuran. Results show that photo-irradiation markedly reduced the toxicity of carbofuran as evident by its effects on three end points, i.e. mortality, growth and swimming activity. The mortality of tadpoles exposed to irradiated carbofuran was significantly lower than those exposed to the non-irradiated pesticide. Both treatment and control tadpoles showed a hormetic response for mortality. Tadpoles in irradiated tanks were also larger and more active than those in the control tanks. Photo-altered toxicity was evident at all three tested concentrations. The results of this study therefore signals caution when directly linking results of empirical trials to field scenarios and highlight the necessity to evaluate toxic effects of compounds under variable environmental conditions.

  20. Solar Radiation Alters Toxicity of Carbofuran: Evidence from Empirical Trials with Duttaphyrnus melanostictus

    Directory of Open Access Journals (Sweden)

    M.R. Wijesinghe

    2011-10-01

    Full Text Available In the present study we investigated the potential of natural solar radiation to alter the toxicity of a commonly used carbamate pesticide, carbofuran, on tadpoles of the Common Asian Toad Duttaphrynus melanostictus. A single exposure trial was conducted over 96 hrs with three concentrations (150, 250 and 500 µgl-1 of photo-irradiated and non-irradiated carbofuran. Results show that photo-irradiation markedly reduced the toxicity of carbofuran as evident by its effects on three end points, i.e. mortality, growth and swimming activity. The mortality of tadpoles exposed to irradiated carbofuran was significantly lower than those exposed to the non-irradiated pesticide. Both treatment and control tadpoles showed a hormetic response for mortality. Tadpoles in irradiated tanks were also larger and more active than those in the control tanks. Photo-altered toxicity was evident at all three tested concentrations. The results of this study therefore signals caution when directly linking  results of empirical trials to field scenarios and highlight the necessity to evaluate toxic effects of compounds under variable environmental conditions.Keywords: Carbofuran, Duttaphrynus melanostictus, photo-degradation, tadpoles, toxicity

  1. Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Scanff, P.; Souidi, M.; Grison, S.; Griffiths, N.M.; Gourmelon, P. [Inst. de Radioprotection et de Surete Nucleaire, (IRSN), Direction de la RadioProtection de l' Homme, Service de Radiobiologie et d' Epidemiologie, Fontenay-aux-Roses, CEDEX (France)]. E-mail: pascale.scanff@irsn.fr

    2004-02-01

    The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed. (author)

  2. Singlet Oxygen-Mediated Oxidation during UVA Radiation Alters the Dynamic of Genomic DNA Replication.

    Directory of Open Access Journals (Sweden)

    Dany Graindorge

    Full Text Available UVA radiation (320-400 nm is a major environmental agent that can exert its deleterious action on living organisms through absorption of the UVA photons by endogenous or exogenous photosensitizers. This leads to the production of reactive oxygen species (ROS, such as singlet oxygen (1O2 and hydrogen peroxide (H2O2, which in turn can modify reversibly or irreversibly biomolecules, such as lipids, proteins and nucleic acids. We have previously reported that UVA-induced ROS strongly inhibit DNA replication in a dose-dependent manner, but independently of the cell cycle checkpoints activation. Here, we report that the production of 1O2 by UVA radiation leads to a transient inhibition of replication fork velocity, a transient decrease in the dNTP pool, a quickly reversible GSH-dependent oxidation of the RRM1 subunit of ribonucleotide reductase and sustained inhibition of origin firing. The time of recovery post irradiation for each of these events can last from few minutes (reduction of oxidized RRM1 to several hours (replication fork velocity and origin firing. The quenching of 1O2 by sodium azide prevents the delay of DNA replication, the decrease in the dNTP pool and the oxidation of RRM1, while inhibition of Chk1 does not prevent the inhibition of origin firing. Although the molecular mechanism remains elusive, our data demonstrate that the dynamic of replication is altered by UVA photosensitization of vitamins via the production of singlet oxygen.

  3. Evaluation of the morphological alteration of the root surface radiated with a diode laser

    International Nuclear Information System (INIS)

    The diode laser has been studied for periodontal therapy, as much for removal of calculus as for microbial reduction of periodontal pockets, as well as the visible analgesic effects and biomodulation capacity. For this reason the purpose of this study was to evaluate the morphological alteration of the root surface after radiation with the diode laser, 808 nm through analysis by scanning electron microscopy (SEM). Besides this, to verify the temperature variations caused during the radiation, a thermometer put into the dentinal wall of the root canal was used. In all, 18 teeth were used, 15 of which for the SEM study, and the other 3 were used to temperature variation analysis. The 25 samples were scraped on the root surface and planed with manual instruments. The other 5 were not subjected to any type of treatment. This, 6 groups of 5 samples each were formed. Control Group C whose samples had not received any treatment; Control Group C 1 was only scraped and polished conventionally with Hu-Friedy Gracey curettes 5 and 6; the other samples groups L1, L2, L3, L4 were radiated by diode laser using parameters of power 1,0 W; 1,2 W; 1,4 W; and 1,6 W respectively, 2 times for 10 seconds with 20 seconds intervals between each radiation in continuous mode. The results with relation to the increase of temperature in the interior of the root canal demonstrated that there was an increase of more than 5 degree Celsius. The results of the scanning electron microscope analysis of Control Group C demonstrated great irregularity and ridges on the root surface, with the presence of a dentine layer. Control Group C1 presented a similar aspect to Group L 1's, smoother and more homogeneous surface. Groups L2, L3, and L4 presented scratches alternating with smoother areas showing that fiber contacted the surface of the sample. The results reconfirmed the necessity of further studies using diode laser, with a beam of light emitted in an interrupted mode to improve the control of the

  4. High-sensitivity observations of solar flare decimeter radiation

    Science.gov (United States)

    Benz, A. O.; Messmer, P.; Monstein, C.

    2001-01-01

    A new acousto-optic radio spectrometer has observed the 1-2 GHz radio emission of solar flares with unprecedented sensitivity. The number of detected decimeter type III bursts is greatly enhanced compared to observations by conventional spectrometers observing only one frequency at the time. The observations indicate a large number of electron beams propagating in dense plasmas. For the first time, we report weak, reversed drifting type III bursts at frequencies above simultaneous narrowband decimeter spikes. The type III bursts are reliable signatures of electron beams propagating downward in the corona, apparently away from the source of the spikes. The observations contradict the most popular spike model that places the spike sources at the footpoints of loops. Conspicuous also was an apparent bidirectional type U burst forming a fish-like pattern. It occurs simultaneously with an intense U-burst at 600-370 MHz observed in Tremsdorf. We suggest that it intermodulated with strong terrestrial interference(cellular phones) causing a spurious symmetric pattern in the spectrogram at 1.4 GHz. Symmetric features in the 1-2 GHz range, some already reported in the literature, therefore must be considered with utmost caution.

  5. Novel computational methods for image analysis and quantification using position sensitive radiation detectors

    OpenAIRE

    Sanchez Crespo, Alejandro

    2005-01-01

    The major advantage of position sensitive radiation detector systems lies in their ability to non invasively map the regional distribution of the emitted radiation in real-time. Three of such detector systems were studied in this thesis, gamma-cameras, positron cameras and CMOS image sensors. A number of physical factors associated to these detectors degrade the qualitative and quantitative properties of the obtained images. These blurring factors could be divided into two groups. The first g...

  6. The application of comet- and micronucleus-assay for the determination of individual radiation sensitivity

    International Nuclear Information System (INIS)

    There are various fields in which different radiosensitivities of human beings play a crucial role: occupational exposure, radiation accidents, radiotherapy. Fast methods of analysis are required to determine individual radiation sensitivity. Two such methods are used in our institute since several years: micronuclei and comets. The comet assay, in particular, which does not require cell proliferation, was useful in the identification of radiosensitive individuals (e.g. ataxia telangiectasia patients or people who responded with severe side effects to radiotherapy). (orig.)

  7. Increasing sensitivity of quasi-binary media analysis by spectral distribution of gamma-radiation albedo

    International Nuclear Information System (INIS)

    Full text: There has been suggested a method of increasing sensitivity of quasi-binary media analysis based on peculiarities of spectral distribution of gamma-radiation albedo. In quasi-binary media analysis in which there is observed close inter-connection between the effective coefficient of gamma-radiation weakening and heavy component content, it is necessary to obtain the maximum sensitivity of the analytical signal to the parameter being determined. The study showed that in certain geometrical parameters (source-detector distance, air gap between the probe and the medium surface) there is observed the spectrum displacement of the secondary radiation at the medium material composition change. The power distribution displacement of gamma-radiation albedo at the effective coefficient of gamma-radiation weakening change (the medium material composition) is explained by the adequate changing the length of free flight of primary quantum, angle characteristics of scattering and probability of photoelectric absorption of secondary radiation. The essence of the method suggested is in measuring the power corresponding to the maximum in the spectrum of the secondary radiation and the magnitude of gamma-radiation albedo. At the expense of these parameters change at the material composition of the medium analyzed variation there has been obtained the increase of the method contrast range. Depending on the type of the quasi-binary medium (coal, iron ore, carbonate raw materials) there have been determined optimal condition (primary radiation power, probe geometrical parameters) at which there is observed the maximum linear displacement of the power corresponding to the maximum in the secondary radiation spectrum and chosen the power intervals for normal magnitude of gamma-radiation albedo. The method is recommended to analyze raw and industrial materials of quasi-binary composition in which there is observed close correlation dependence between their effective atomic

  8. Gadolinium(III) texaphyrin: a tumor selective radiation sensitizer that is detectable by MRI.

    OpenAIRE

    Young, S W; Qing, F; Harriman, A; Sessler, J.L.; Dow, W C; Mody, T D; Hemmi, G W; Hao, Y.; Miller, R. A.

    1996-01-01

    Gadolinium(III) texaphyrin (Gd-tex2+) is representative of a new class of radiation sensitizers detectable by magnetic resonance imaging (MRI). This porphyrin-like complex has a high electron affinity [E1/2 (red.) approximately = -0.08 V versus normal hydrogen electrode] and forms a long-lived pi-radical cation upon exposure to hydrated electrons, reducing ketyl radicals, or superoxide ions. Consistent with these chemical findings, Gd-tex2+ was found to be an efficient radiation sensitizer in...

  9. Radiation dose-rate meter using an energy-sensitive counter

    International Nuclear Information System (INIS)

    A radiation dose-rate meter is described comprising: an energy-sensitive radiation detecting element which generates at an output thereof ionization current pulses having an amplitude proportional to the charge quanta deposited in the radiation detecting element by detected photons of ionizing radiation; a charge-sensitive preamplifier connected to the output of the radiation detecting element; a filter amplifier having a selected filter time constant for generating fixed width pulses at an output thereof in response to each of the step voltage pulses from the preamplifier having an amplitude proportional to the amplitude of each of the step voltage pulses applied to an input thereof; a multi-level discriminator means responsive to the voltage pulses at the output of the filter amplifier for generating a train of count pulses at an output thereof in response to each of the fixed width pulses; and a count rate meter means connected to the output of the multi-level discriminator means of registering the count pulses of each of the train of count pulses as a quantized measure of the radiation dose-rate per unit time of the detected photons of ionizing radiation

  10. Sensitivity of Escherichia coli acrA Mutants to Psoralen plus Near-Ultraviolet Radiation

    DEFF Research Database (Denmark)

    Hansen, M. Trier

    1982-01-01

    The sensitivity to psoralen plus near-ultraviolet radiation (PUVA) was compared in a pair of E. coli strains differing at the acrA locus. Survival was determined for both bacteria and phage λ. AcrA mutant cells were 40 times more sensitive than wild type to the lethal effect of PUVA. Free λ phage...... specifically in the environment of the cellular DNA so as to allow increased intercalation and photobinding of psoralens....

  11. Potential sensitivity of photosynthesis and isoprene emission to direct radiative effects of atmospheric aerosol pollution

    OpenAIRE

    2015-01-01

    A global Earth system model is applied to quantify the impacts of direct anthropogenic aerosol effective radiative forcing on gross primary productivity (GPP) and isoprene emission. The impacts of different pollution aerosol sources (all anthropogenic, biomass burning and non-biomass burning) are investigated by performing sensitivity experiments. On the global scale, our results show that land carbon fluxes (GPP and isoprene emission) are not sensitive to pollution aerosols...

  12. Effect of protein kinase C inhibitor (PKCI) on radiation sensitivity and c-fos transcription activity

    International Nuclear Information System (INIS)

    The human genetic disorder ataxia-telangiectasia (AT) is a multisystem disease characterized by extreme radiosensitivity. The recent identification of the gene mutated in AT, ATM, and the demonstration that it encodes a homologous domain of phosphatidylinositol 3-kinase (PI3-K), the catalytic subunit of an enzyme involved in transmitting signals from the cell surface to the nucleus, provide support for a role of this gene in signal transduction. Although ionizing radiation was known to induce c-fos transcription, nothing is known about how ATM or PKCI mediated signal transduction pathway modulates the c-fos gene transcription and gene expression. Here we have studied the effect of PKCI on radiation sensitivity and c-fos transcription in normal and AT cells. Normal (LM217) and AT (AT58IVA) cells were transfected with PKCI expression plasmid and the overexpression and integration of PKCI was evaluated by northern blotting and polymerase chain reaction, respectively. 5 Gy of radiation was exposed to LM and AT cells transfected with PKCI expression plasmid and cells were harvested 48 hours after radiation and investigated apoptosis with TUNEL method. The c-fos transcription activity was studied by performing CAT assay of reporter gene after transfection of c-fos CAT plasmid into AT and LM cells. Our results demonstrate for the first time a role of PKCI on. the radiation sensitivity and c-fos expression in LM and AT cells. PKCI increased radiation induced apoptosis in LM cells but reduced apoptosis in AT cells. The basal c-fos transcription activity is 70 times lower in AT cells than that in LM cells. The c-fos transcription activity was repressed by overexpression of PKCI in LM cells but not in AT cells. After induction of c-fos by Ras protein, overexpression of PKCI repressed c-fos transcription in LM cells but not in AT cells. Overexpression of PKCI increased radiation sensitivity and repressed c-fos transcription in LM cells but not in AT cells. The results may be a

  13. Sensitivity to Alternaria alternata toxin in citrus because of altered mitochondrial RNA processing

    OpenAIRE

    Ohtani, Kouhei; Yamamoto, Hiroyuki; Akimitsu, Kazuya

    2002-01-01

    Specificity in the interaction between rough lemon (Citrus jambhiri Lush.) and the fungal pathogen Alternaria alternata rough lemon pathotype is determined by a host-selective toxin, ACR-toxin. Mitochondria from rough lemon are sensitive to ACR-toxin whereas mitochondria from resistant plants, including other citrus species, are resistant. We have identified a C. jambhiri mitochondrial DNA sequence, designated ACRS (ACR-toxin sensitivity gene), that confers toxin sensitivity to Escherichia co...

  14. Radiation-Induced Epigenetic Alterations after Low and High LET Irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Aypar, Umut; Morgan, William F.; Baulch, Janet E.

    2011-02-01

    Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET x-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. MiRNA shown to be altered in expression level after x-ray irradiation are involved in chromatin remodeling and DNA methylation. Different and higher incidence of epigenetic changes were observed after exposure to low LET x-rays than high LET Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This study also shows that the irradiated cells acquire epigenetic changes even though they are chromosomally stable suggesting that epigenetic aberrations may arise in the cell without initiating RIGI.

  15. Altered patterns of gene expression underlying the enhanced immunogenicity of radiation-attenuated schistosomes.

    Directory of Open Access Journals (Sweden)

    Gary P Dillon

    Full Text Available BACKGROUND: Schistosome cercariae only elicit high levels of protective immunity against a challenge infection if they are optimally attenuated by exposure to ionising radiation that truncates their migration in the lungs. However, the underlying molecular mechanisms responsible for the altered phenotype of the irradiated parasite that primes for protection have yet to be identified. METHODOLOGY/PRINCIPAL FINDINGS: We have used a custom microarray comprising probes derived from lung-stage parasites to compare patterns of gene expression in schistosomula derived from normal and irradiated cercariae. These were transformed in vitro and cultured for four, seven, and ten days to correspond in development to the priming parasites, before RNA extraction. At these late times after the radiation insult, transcript suppression was the principal feature of the irradiated larvae. Individual gene analysis revealed that only seven were significantly down-regulated in the irradiated versus normal larvae at the three time-points; notably, four of the protein products are present in the tegument or associated with its membranes, perhaps indicating a perturbed function. Grouping of transcripts using Gene Ontology (GO and subsequent Gene Set Enrichment Analysis (GSEA proved more informative in teasing out subtle differences. Deficiencies in signalling pathways involving G-protein-coupled receptors suggest the parasite is less able to sense its environment. Reduction of cytoskeleton transcripts could indicate compromised structure which, coupled with a paucity of neuroreceptor transcripts, may mean the parasite is also unable to respond correctly to external stimuli. CONCLUSIONS/SIGNIFICANCE: The transcriptional differences observed are concordant with the known extended transit of attenuated parasites through skin-draining lymph nodes and the lungs: prolonged priming of the immune system by the parasite, rather than over-expression of novel antigens, could thus

  16. Impact of ultraviolet-B radiation on planktonic fish larvae: Alteration of the osmoregulatory function

    Energy Technology Data Exchange (ETDEWEB)

    Sucre, Elliott, E-mail: elliott.sucre@univ-montp2.fr [AEO Team (Adaptation Ecophysiologique et Ontogenese), UMR 5119 Ecosym UM2, CNRS, IRD, Ifremer, UM1, Universite Montpellier 2, cc092, Pl. Eugene Bataillon, 34095 Montpellier, Cx 05 (France); Vidussi, Francesca [RESEAUX Team (Reseaux Planctoniques et Changement Environnemental), UMR 5119 Ecosym UM2, CNRS, IRD, Ifremer, UM1, Universite Montpellier 2, cc093, Pl. Eugene Bataillon, 34095 Montpellier, Cx 05 (France); Mostajir, Behzad [RESEAUX Team (Reseaux Planctoniques et Changement Environnemental), UMR 5119 Ecosym UM2, CNRS, IRD, Ifremer, UM1, Universite Montpellier 2, cc093, Pl. Eugene Bataillon, 34095 Montpellier, Cx 05 (France); Centre d' ecologie marine experimentale MEDIMEER (Mediterranean centre for Marine Ecosystem Experimental Research), Universite Montpellier 2-CNRS (UMS 3301), Station Mediterraneenne de l' Environnement Littoral, MEDIMEER, 2 Rue des Chantiers, 34200 Sete (France); Charmantier, Guy; Lorin-Nebel, Catherine [AEO Team (Adaptation Ecophysiologique et Ontogenese), UMR 5119 Ecosym UM2, CNRS, IRD, Ifremer, UM1, Universite Montpellier 2, cc092, Pl. Eugene Bataillon, 34095 Montpellier, Cx 05 (France)

    2012-03-15

    Coastal marine ecosystems are submitted to variations of several abiotic and biotic parameters, some of them related to global change. Among them the ultraviolet-B (UV-B) radiation (UVBR: 280-320 nm) may strongly impact planktonic fish larvae. The consequences of an increase of UVBR on the osmoregulatory function of Dicentrarchus labrax larvae have been investigated in this study. In young larvae of D. labrax, as in other teleosts, osmoregulation depends on tegumentary ion transporting cells, or ionocytes, mainly located on the skin of the trunk and of the yolk sac. As early D. labrax larvae passively drift in the top water column, ionocytes are exposed to solar radiation. The effect of UVBR on larval osmoregulation in seawater was evaluated through nanoosmometric measurements of the blood osmolality after exposure to different UV-B treatments. A loss of osmoregulatory capability occured in larvae after 2 days of low (50 {mu}W cm{sup -2}: 4 h L/20 h D) and medium (80 {mu}W cm{sup -2}: 4 h L/20 h D) UVBR exposure. Compared to control larvae kept in the darkness, a significant increase in blood osmolality, abnormal behavior and high mortalities were detected in larvae exposed to UVBR from 2 days on. At the cellular level, an important decrease in abundance of tegumentary ionocytes and mucous cells was observed after 2 days of exposure to UVBR. In the ionocytes, two major osmoeffectors were immunolocalized, the Na{sup +}/K{sup +}-ATPase and the Na{sup +}/K{sup +}/2Cl{sup -} cotransporter. Compared to controls, the fluorescent immunostaining was lower in UVBR-exposed larvae. We hypothesize that the impaired osmoregulation in UVBR-exposed larvae originates from the lower number of tegumentary ionocytes and mucous cells. This alteration of the osmoregulatory function could negatively impact the survival of young larvae at the surface water exposed to UVBR.

  17. Impact of ultraviolet-B radiation on planktonic fish larvae: Alteration of the osmoregulatory function

    International Nuclear Information System (INIS)

    Coastal marine ecosystems are submitted to variations of several abiotic and biotic parameters, some of them related to global change. Among them the ultraviolet-B (UV-B) radiation (UVBR: 280–320 nm) may strongly impact planktonic fish larvae. The consequences of an increase of UVBR on the osmoregulatory function of Dicentrarchus labrax larvae have been investigated in this study. In young larvae of D. labrax, as in other teleosts, osmoregulation depends on tegumentary ion transporting cells, or ionocytes, mainly located on the skin of the trunk and of the yolk sac. As early D. labrax larvae passively drift in the top water column, ionocytes are exposed to solar radiation. The effect of UVBR on larval osmoregulation in seawater was evaluated through nanoosmometric measurements of the blood osmolality after exposure to different UV-B treatments. A loss of osmoregulatory capability occured in larvae after 2 days of low (50 μW cm−2: 4 h L/20 h D) and medium (80 μW cm−2: 4 h L/20 h D) UVBR exposure. Compared to control larvae kept in the darkness, a significant increase in blood osmolality, abnormal behavior and high mortalities were detected in larvae exposed to UVBR from 2 days on. At the cellular level, an important decrease in abundance of tegumentary ionocytes and mucous cells was observed after 2 days of exposure to UVBR. In the ionocytes, two major osmoeffectors were immunolocalized, the Na+/K+-ATPase and the Na+/K+/2Cl− cotransporter. Compared to controls, the fluorescent immunostaining was lower in UVBR-exposed larvae. We hypothesize that the impaired osmoregulation in UVBR-exposed larvae originates from the lower number of tegumentary ionocytes and mucous cells. This alteration of the osmoregulatory function could negatively impact the survival of young larvae at the surface water exposed to UVBR.

  18. Formates and dithionates: sensitive EPR-dosimeter materials for radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lund, E. [Department of Medicine and Care, Radiation Physics, Faculty of Health Sciences, University of Linkoeping, S-581 85 Linkoeping (Sweden)]. E-mail: eva.lund@imv.liu.se; Gustafsson, H. [Department of Medicine and Care, Radiation Physics, Faculty of Health Sciences, University of Linkoeping, S-581 85 Linkoeping (Sweden); Danilczuk, M. [Chemical Physics Laboratory, IFM, University of Linkoeping, S-581 83 Linkoeping (Sweden); Sastry, M.D. [Chemical Physics Laboratory, IFM, University of Linkoeping, S-581 83 Linkoeping (Sweden); Lund, A. [Chemical Physics Laboratory, IFM, University of Linkoeping, S-581 83 Linkoeping (Sweden); Vestad, T.A. [Department of Physics, University of Oslo, P.O. Box 1048 Blindern, N-0316 Oslo (Norway); Malinen, E. [Department of Physics, University of Oslo, P.O. Box 1048 Blindern, N-0316 Oslo (Norway); Hole, E.O. [Department of Physics, University of Oslo, P.O. Box 1048 Blindern, N-0316 Oslo (Norway); Sagstuen, E. [Department of Physics, University of Oslo, P.O. Box 1048 Blindern, N-0316 Oslo (Norway)

    2005-02-01

    Polycrystalline formates and dithionates are promising materials for EPR dosimetry, as large yields of radiation induced stable radicals are formed with a linear dose response. Rapid spin relaxation rates were detected in many of the substances, indicating that a high microwave power can be applied during EPR acquisition in order to improve sensitivity. Different techniques used to further improve the sensitivity, such as the replacement of {sup 7}Li with {sup 6}Li or exchange of protons with deuterons in the corresponding crystalline matrices and metal ion doping are discussed. It is concluded that formates and dithionates may be up to 10 times as sensitive as L-{alpha}-alanine.

  19. Differential sensitivity to natural ultraviolet radiation among phytoplankton species in Arctic lakes (Spitsbergen, Norway)

    NARCIS (Netherlands)

    Donk, van E.; Faafeng, B.A.; Lange, de H.J.

    2001-01-01

    Incubation experiments demonstrated a differential sensitivity to natural UV-radiation among the dominant phytoplankton species from three Arctic lakes, situated near Ny-Ålesund, Spitsbergen (79° N). The growth of small chlorophytes, diatoms and picocyanobacteria from two oligotrophic lakes was inhi

  20. Differential sensitivity to natural ultraviolet radiation among phytoplankton species in Arctic lakes (Spitsbergen, Norway)

    NARCIS (Netherlands)

    Van Donk, E.; Faafeng, B.A.; De Lange, H.J.; Hessen, D.O.

    2001-01-01

    Incubation experiments demonstrated a differential sensitivity to natural UV-radiation among the dominant phytoplankton species from three Arctic lakes, situated near Ny-Angstrom lesund, Spitsbergen (79 degrees N). The growth of small chlorophytes, diatoms and picocyanobacteria from two oligotrophic

  1. The WST survival assay: An easy and reliable method to screen radiation-sensitive individuals

    International Nuclear Information System (INIS)

    An easy, fast and reliable method was developed to screen hundreds of Epstein-Barr virus-transformed cell lines (lymphoblastoid cell lines, LCLs) for radiation sensitivity that were generated from lymphocytes isolated from young lung cancer patients. The WST-1 test explores the metabolic activity of the mitochondria as an indicator for the vital status of cells. Cell proliferation as well as indirect cell death can be quantified by this method on a large scale in microtiter plates. Cell survival was measured at 24- and 48-h post-irradiation with 10 Gy (137Cs source) by the WST-1 assay and Trypan blue staining. To set up the experimental screening conditions and to establish a positive and a negative control, an ATM-mutated cell line from a radiation-sensitive ATM patient and an ATM proficient cell line from a healthy brother were compared. An optimal differentiation between the two cell lines was demonstrated for 10 Gy and 24- and 48-h cell growth after irradiation. Upon screening 120 LCLs of young lung cancer patients under these conditions, 5 of them were found to be radiation sensitive to a high degree of statistical significance. The results have been confirmed by a second laboratory by means of Trypan blue testing. The WST-1 test represents an efficient and reliable method by means of screening for radiation-sensitive cell lines. (authors)

  2. Sensitivity to UV radiation in early life stages of the Mediterranean sea urchin Sphaerechinus granularis (Lamarck)

    Energy Technology Data Exchange (ETDEWEB)

    Nahon, Sarah [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); CNRS, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); Castro Porras, Viviana A. [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); Pruski, Audrey M. [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); CNRS, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); Charles, Francois [UPMC Univ Paris 06, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France); CNRS, UMR 7621, LOBB, Observatoire Oceanologique, F-66651, Banyuls/mer (France)], E-mail: charles@obs-banyuls.fr

    2009-03-01

    The sea urchin Sphaerechinus granularis was used to investigate the impact of relevant levels of UV-B radiation on the early life stages of a common Mediterranean free spawning benthic species. Sperm, eggs and embryos were exposed to a range of UV radiation doses. The resulting endpoints were evaluated in terms of fertilisation success, development and survival rates. Above a weighted UV radiation dose of 0.0029 kJ m{sup -2}, fertilisation capability of irradiated sperm decreased rapidly. The exposure of the eggs to 0.0175 kJ m{sup -2} and more led to delayed and inhibited development with ensuing embryonic morphological abnormalities. One-day old larvae remained strongly sensitive to UV radiation as shown by the 50% decrease of the larval survival rate for a dose of 0.025 kJ m{sup -2} UVR. The elevated sensitivity of embryos to experimental UVR went along with a lack of significant amount of sunscreen compounds (e.g., mycosporine-like amino acids) in the eggs. The present results demonstrated that gamete viability and embryonic development may be significantly impaired by solar UV radiation in S. granularis, compromising in this way the reproduction of the species. Unless adaptive behavioural reproductive strategies exist, the influence of ambient UV radiation appears as a selective force for population dynamics of broadcast spawners in the shallow benthic Mediterranean environment.

  3. Influence of Monosodium Glutamate on Radiation-Induced Biochemical Alterations in Male Albino Rats

    International Nuclear Information System (INIS)

    no effect on insulin resistance and their co-administration produces an additive effect compared to each single treatment. Regarding lipid profile, MSG as well as RAD-exposure induced hyperlipidaemia more noticeable in case of irradiation. Their co-administration had potentiated hyperlipidaemia compared to each single treatment. It is concluded that exposure to MSG together with RAD increased oxidative stress and neurotransmitter alteration in the brain and the risk of metabolic syndrome. It is thus recommended to limit the intake of MSG when human are at risk of overexposure to ionizing radiation.

  4. Effects of anesthesia-induced modest hypothermia on cellular radiation sensitivity

    Institute of Scientific and Technical Information of China (English)

    XIANG; Yingsong(项莺松); TANG; Gusheng(唐古生); XU; Xiongfei(许熊飞); YANG; Rujun(杨如俊); CAI; Jianming(蔡建明); ZHANG; Minghui(张明辉); CAO; Xuetao(曹雪涛)

    2002-01-01

    To assess the mechanisms of modest hypothermia(MH) and its effects on cellular radiation response, a model of anesthesia-induced modest hypothermia(AIMH) in the adult mice and a model of pure MH in the newborn mice were established. The survival rate of lethally irradiated mice was increased to 72% through AIMH before irradiation. Both apoptosis and necrosis of human fetal bone marrow CD34+ hematopoietic stem cells cultured under MH were significantly decreased as detected by MTT and flow cytometry, with three-color labeled by PE-CD34+/ FITC-AnnexinV /7AAD. The survival and proliferation of mouse bone marrow MNC treated with MH after irradiation were also increased. The MH exerted similar protective effects on the leukemia cell lines A20, HL60, K562 to the normal bone marrow cells, but it enhanced the radiation sensitivity of leukemia cell line FBL3 and mouse melanoma B16F10. No effects have been found on the radiation sensitivity of those cells treated with MH before irradiation. The results also showed that MH mediated the effects on radiation sensitivity, in addition to increasing the oxygen tension. These results show different effects of MH on different cells:(i) AIMH exerts a protective effect on the normal hematopoietic stem cells, some leukemia cell lines A20, HL60, K562, and some neoplasma 3LL, LOVO. And MH exhibits a synthetic effect with anesthetic.(ii) MH enhances the radiation sensitivity of another leukemia and neoplasma cell lines FBL3, B16F10 and CT26. Therefore, AIMH has a potential to enhance the effects of radiation-therapy and decrease side effects on some tumors.

  5. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

  6. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gazdzinski, Lisa M.; Cormier, Kyle [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Lu, Fred G. [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Lerch, Jason P. [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Wong, C. Shun [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Nieman, Brian J., E-mail: bjnieman@phenogenomics.ca [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

    2012-12-01

    Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

  7. Proteomic Alterations in B Lymphocytes of Sensitized Mice in a Model of Chemical-Induced Asthma

    OpenAIRE

    Steven Haenen; Jeroen A.J. Vanoirbeek; Vanessa De Vooght; Liliane Schoofs; Benoit Nemery; Elke Clynen; Hoet, Peter H. M.

    2015-01-01

    Introduction and Aim The role of B-lymphocytes in chemical-induced asthma is largely unknown. Recent work demonstrated that transferring B lymphocytes from toluene diisocyanate (TDI)-sensitized mice into naïve mice, B cell KO mice and SCID mice, triggered an asthma-like response in these mice after a subsequent TDI-challenge. We applied two-dimensional difference gel electrophoresis (2D-DIGE) to describe the “sensitized signature” of B lymphocytes comparing TDI-sensitized mice with control mi...

  8. Multiparametric assessment of radiation effects for the individual radiation sensitivity estimation; Multiparametrische Erfassung von Strahlenwirkungen zur Abschaetzung der individuellen Strahlenempfindlichkeit

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    The effects of low dose irradiation are highly relevant for radiation protection in the public. The sensitivity to clastogenic and tumorigenic effects of ionizing radiation (IR) varies considerably amongst individuals. Examples for genetically determined enhanced sensitivity are well known in some hereditary diseases: patients with chromosomal instability syndromes, Ataxia telangiectasia (A-T), Nijmegen Breakage Syndrome (NBS) and Bloom Syndrome (BS) show strongly enhanced sensitivity towards IR, severe immunodeficiencies, and a high incidence for developing leukemias and lymphomas. This obvious coincidence of enhanced radiosensitivity and tumor risk, and the frequently observed enhanced radiosensitivity of genetically non-defined tumor patients indicate that tumor patients may constitute a subpopulation with enriched genetical predisposition for enhanced radiosensitivity. Furthermore, a subpopulation of radiosensitive individuals may be part of the probably inconspicuous total population. For example, individuals heterozygous for the above mentioned genes (and possibly some other genes) show enhanced radiosensitivity if compared with the normal population. In general, heterozygous carriers of those hereditary deficiencies are clinically inconspicuous, but due an haploinsufficiency their tumour risk may be enhanced. This has been shown for mice carrying an heterozygous Nbs1 mutation (J.-Q. Wang, Lyon, pers. Communication). Our findings concerning enhanced radiation-induced chromosomal aberrations in heterozygous Nbs1 cell lines support this notion. The identification of high risk groups with enhanced radiosensitivity is therefore an important task for radioprotection. This project aimed at establishing a procedure which allows to test various cellular parameters as indicators for effects of radiation. A standard protocol for the isolation and cryoconservation of primary blood cells was developed. DNA repair analysis (Comet Assay) and radiation-induced apoptosis

  9. GAMMA RADIATION INTERACTS WITH MELANIN TO ALTER ITS OXIDATION-REDUCTION POTENTIAL AND RESULTS IN ELECTRIC CURRENT PRODUCTION

    Energy Technology Data Exchange (ETDEWEB)

    Turick, C.; Ekechukwu, A.; Milliken, C.

    2011-05-17

    The presence of melanin pigments in organisms is implicated in radioprotection and in some cases, enhanced growth in the presence of high levels of ionizing radiation. An understanding of this phenomenon will be useful in the design of radioprotective materials. However, the protective mechanism of microbial melanin in ionizing radiation fields has not yet been elucidated. Here we demonstrate through the electrochemical techniques of chronoamperometry, chronopotentiometry and cyclic voltammetry that microbial melanin is continuously oxidized in the presence of gamma radiation. Our findings establish that ionizing radiation interacts with melanin to alter its oxidation-reduction potential. Sustained oxidation resulted in electric current production and was most pronounced in the presence of a reductant, which extended the redox cycling capacity of melanin. This work is the first to establish that gamma radiation alters the oxidation-reduction behavior of melanin, resulting in electric current production. The significance of the work is that it provides the first step in understanding the initial interactions between melanin and ionizing radiation taking place and offers some insight for production of biomimetic radioprotective materials.

  10. Mesenchymal stem cells are sensitive to treatment with kinase inhibitors and ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nicolay, Nils H.; Debus, Juergen; Huber, Peter E. [Heidelberg University Hospital, Department of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (dkfz), Department of Molecular and Radiation Oncology, Heidelberg (Germany); Sommer, Eva; Lopez Perez, Ramon; Wirkner, Ute [German Cancer Research Center (dkfz), Department of Molecular and Radiation Oncology, Heidelberg (Germany); Bostel, Tilman [Heidelberg University Hospital, Department of Radiation Oncology, Heidelberg (Germany); Ho, Anthony D.; Saffrich, Rainer [Heidelberg University Hospital, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Lahn, Michael [Lilly Research Laboratories, Oncology Early Clinical Investigation, Indianapolis, IN (United States)

    2014-11-15

    Mesenchymal stem cells (MSCs) can regenerate damaged tissues and may therefore be of importance for normal tissue repair after cancer treatment. Small molecule receptor kinase inhibitors (RKIs) have recently been introduced into cancer treatment. However, the influence of these drugs - particularly in combination with radiotherapy - on the survival of MSCs is largely unknown. The sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells to small molecule kinase inhibitors of the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) receptors, as well to inhibitors of c-Kit, was examined in combination with ionizing radiation (IR); cell survival and proliferation were assessed. Expression patterns of different kinase receptors and ligands were investigated using gene arrays. MSCs were highly sensitive to the tyrosine kinase inhibitors SU14816 (imatinib) and SU11657 (sunitinib), but showed only moderate sensitivity to the selective TGFβ receptor 1 inhibitor LY2109761. Primary adult human fibroblasts were comparably resistant to all three inhibitors. The addition of IR had an additive or supra-additive effect in the MSCs, but this was not the case for differentiated fibroblasts. Proliferation was markedly reduced in MSCs following kinase inhibition, both with and without IR. Gene expression analysis revealed high levels of the PDGF α and β receptors, and lower levels of the TGFβ receptor 2 and Abl kinase. IR did not alter the expression of kinase receptors or their respective ligands in either MSCs or adult fibroblasts. These data show that MSCs are highly sensitive to RKIs and combination treatments incorporating IR. Expression analyses suggest that high levels of PDGF receptors may contribute to this effect. (orig.) [German] Mesenchymale Stammzellen (MSCs) koennen die Geweberegeneration unterstuetzen und haben daher moeglicherweise eine Rolle bei der Reparatur

  11. Sensitivity analysis of numerical weather prediction radiative schemes to forecast direct solar radiation over Australia

    Science.gov (United States)

    Mukkavilli, S. K.; Kay, M. J.; Taylor, R.; Prasad, A. A.; Troccoli, A.

    2014-12-01

    The Australian Solar Energy Forecasting System (ASEFS) project requires forecasting timeframes which range from nowcasting to long-term forecasts (minutes to two years). As concentrating solar power (CSP) plant operators are one of the key stakeholders in the national energy market, research and development enhancements for direct normal irradiance (DNI) forecasts is a major subtask. This project involves comparing different radiative scheme codes to improve day ahead DNI forecasts on the national supercomputing infrastructure running mesoscale simulations on NOAA's Weather Research & Forecast (WRF) model. ASEFS also requires aerosol data fusion for improving accurate representation of spatio-temporally variable atmospheric aerosols to reduce DNI bias error in clear sky conditions over southern Queensland & New South Wales where solar power is vulnerable to uncertainities from frequent aerosol radiative events such as bush fires and desert dust. Initial results from thirteen years of Bureau of Meteorology's (BOM) deseasonalised DNI and MODIS NASA-Terra aerosol optical depth (AOD) anomalies demonstrated strong negative correlations in north and southeast Australia along with strong variability in AOD (~0.03-0.05). Radiative transfer schemes, DNI and AOD anomaly correlations will be discussed for the population and transmission grid centric regions where current and planned CSP plants dispatch electricity to capture peak prices in the market. Aerosol and solar irradiance datasets include satellite and ground based assimilations from the national BOM, regional aerosol researchers and agencies. The presentation will provide an overview of this ASEFS project task on WRF and results to date. The overall goal of this ASEFS subtask is to develop a hybrid numerical weather prediction (NWP) and statistical/machine learning multi-model ensemble strategy that meets future operational requirements of CSP plant operators.

  12. Helicity sensitive terahertz radiation detection by dual-grating-gate high electron mobility transistors

    Energy Technology Data Exchange (ETDEWEB)

    Faltermeier, P.; Olbrich, P.; Probst, W.; Schell, L.; Ganichev, S. D. [Terahertz Center, University of Regensburg, 93040 Regensburg (Germany); Watanabe, T.; Boubanga-Tombet, S. A.; Otsuji, T. [Research Institute of Electrical Communication, Tohoku University, 980-8577 Sendai (Japan)

    2015-08-28

    We report on the observation of a radiation helicity sensitive photocurrent excited by terahertz (THz) radiation in dual-grating-gate (DGG) InAlAs/InGaAs/InAlAs/InP high electron mobility transistors (HEMT). For a circular polarization, the current measured between source and drain contacts changes its sign with the inversion of the radiation helicity. For elliptically polarized radiation, the total current is described by superposition of the Stokes parameters with different weights. Moreover, by variation of gate voltages applied to individual gratings, the photocurrent can be defined either by the Stokes parameter defining the radiation helicity or those for linear polarization. We show that artificial non-centrosymmetric microperiodic structures with a two-dimensional electron system excited by THz radiation exhibit a dc photocurrent caused by the combined action of a spatially periodic in-plane potential and spatially modulated light. The results provide a proof of principle for the application of DGG HEMT for all-electric detection of the radiation's polarization state.

  13. Adiponectin in mice with altered growth hormone action: links to insulin sensitivity and longevity?

    OpenAIRE

    Lubbers, Ellen R; List, Edward O.; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D.; Kineman, Rhonda D.; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J.; Berryman, Darlene E.

    2013-01-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high molecular weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered growth hormone (GH) signaling as these mice exhibit extremes in obesity that are positively associated with insulin sens...

  14. A novel high-throughput irradiator for in vitro radiation sensitivity bioassays

    Science.gov (United States)

    Fowler, Tyler L.

    Given the emphasis on more personalized radiation therapy there is an ongoing and compelling need to develop high-throughput screening tools to further examine the biological effects of ionizing radiation on cells, tissues and organ systems in either the research or clinical setting. Conventional x-ray irradiators are designed to provide maximum versatility to radiobiology researchers, typically accommodating small animals, tissue or blood samples, and cellular applications. This added versatility often impedes the overall sensitivity and specificity of an experiment resulting in a trade-off between the number of absorbed doses (or dose rates) and biological endpoints that can be investigated in vitro in a reasonable amount of time. Therefore, modern irradiator designs are incompatible with current high-throughput bioassay technologies. Furthermore, important dosimetry and calibration characteristics (i.e. dose build-up region, beam attenuation, and beam scatter) of these irradiators are typically unknown to the end user, which can lead to significant deviation between delivered dose and intended dose to cells that adversely impact experimental results. Therefore, the overarching goal of this research is to design and develop a robust and fully automated high-throughput irradiator for in vitro radiation sensitivity investigations. Additionally, in vitro biological validation of this system was performed by assessing intracellular reactive oxygen species production, physical DNA double strand breaks, and activation of cellular DNA repair mechanisms. Finally, the high-throughput irradiator was used to investigate autophagic flux, a cellular adaptive response, as a potential biomarker of radiation sensitivity.

  15. The effect of post-mastectomy radiation therapy on breast implants: Unveiling biomaterial alterations with potential implications on capsular contracture

    International Nuclear Information System (INIS)

    Post-mastectomy breast reconstruction with expanders and implants is recognized as an integral part of breast cancer treatment. Its main complication is represented by capsular contracture, which leads to poor expansion, breast deformation, and pain, often requiring additional surgery. In such a scenario, the debate continues as to whether the second stage of breast reconstruction should be performed before or after post-mastectomy radiation therapy, in light of potential alterations induced by irradiation to silicone biomaterial. This work provides a novel, multi-technique approach to unveil the role of radiotherapy in biomaterial alterations, with potential involvement in capsular contracture. Following irradiation, implant shells underwent mechanical, chemical, and microstructural evaluation by means of tensile testing, Attenuated Total Reflectance Fourier Transform InfraRed spectroscopy (ATR/FTIR), Scanning Electron Microscopy (SEM), high resolution stylus profilometry, and Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Our findings are consistent with radiation-induced modifications of silicone that, although not detectable at the microscale, can be evidenced by more sophisticated nanoscale surface analyses. In light of these results, biomaterial irradiation cannot be ruled out as one of the possible co-factors underlying capsular contracture. - Highlights: • The debate continues whether to perform breast reconstruction before or after PMRT. • Radiation therapy may alter implant material, concurring to capsular contracture. • In this work, irradiated implants were investigated by a multi-technique approach. • Radiation-induced alterations could be evidenced by ATR/FTIR and ToF-SIMS. • Reported alteration might represent a co-factor underlying capsular contracture

  16. The effect of post-mastectomy radiation therapy on breast implants: Unveiling biomaterial alterations with potential implications on capsular contracture

    Energy Technology Data Exchange (ETDEWEB)

    Ribuffo, Diego; Lo Torto, Federico [Department of Plastic Surgery, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Giannitelli, Sara M. [Tissue Engineering Unit, Department of Engineering, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128 Rome (Italy); Urbini, Marco; Tortora, Luca [Surface Analysis Laboratory, Department of Mathematics and Physics, University “Roma Tre”, Via della Vasca Navale 84, 00146 Rome (Italy); INFN — National Institute of Nuclear Physics, Section of Roma Tre, Via della Vasca Navale 84, 00146 Rome (Italy); Mozetic, Pamela; Trombetta, Marcella [Tissue Engineering Unit, Department of Engineering, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128 Rome (Italy); Basoli, Francesco; Licoccia, Silvia [Department of Chemical Science and Technologies, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00173 Rome (Italy); Tombolini, Vincenzo [Department of Radiation Oncology, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Spencer-Lorillard Foundation, Viale Regina Elena 291, 00161 Rome (Italy); Cassese, Raffaele [Department of Radiation Oncology, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Scuderi, Nicolò [Department of Plastic Surgery, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); and others

    2015-12-01

    Post-mastectomy breast reconstruction with expanders and implants is recognized as an integral part of breast cancer treatment. Its main complication is represented by capsular contracture, which leads to poor expansion, breast deformation, and pain, often requiring additional surgery. In such a scenario, the debate continues as to whether the second stage of breast reconstruction should be performed before or after post-mastectomy radiation therapy, in light of potential alterations induced by irradiation to silicone biomaterial. This work provides a novel, multi-technique approach to unveil the role of radiotherapy in biomaterial alterations, with potential involvement in capsular contracture. Following irradiation, implant shells underwent mechanical, chemical, and microstructural evaluation by means of tensile testing, Attenuated Total Reflectance Fourier Transform InfraRed spectroscopy (ATR/FTIR), Scanning Electron Microscopy (SEM), high resolution stylus profilometry, and Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Our findings are consistent with radiation-induced modifications of silicone that, although not detectable at the microscale, can be evidenced by more sophisticated nanoscale surface analyses. In light of these results, biomaterial irradiation cannot be ruled out as one of the possible co-factors underlying capsular contracture. - Highlights: • The debate continues whether to perform breast reconstruction before or after PMRT. • Radiation therapy may alter implant material, concurring to capsular contracture. • In this work, irradiated implants were investigated by a multi-technique approach. • Radiation-induced alterations could be evidenced by ATR/FTIR and ToF-SIMS. • Reported alteration might represent a co-factor underlying capsular contracture.

  17. Radiation sensitivity and gene expression in Enchytraeus japonensis, a species of earth worm

    International Nuclear Information System (INIS)

    The importance of radiological protection of the environment based on scientific principles is gaining international recognition as environment issues garner more attention. Earthworm (annelids) is a ubiquitous soil invertebrate known to play an important role in the maintenance of the soil ecosystem and thus selected as one of 12 kinds of reference animals and plants by the ICRP. In the present study, radiation sensitivity and gene expression in a recently described terrestrial oligochaete, Enchytraeus japonensis (E. japonensis) were studied. E. japonensis worms were acutely irradiated at increasing doses of gamma radiation, and the number of worms after 30 days of radiation was examined. The dose effectively inhibiting 50% of proliferation was approximately 22 Gy, which was comparable to the dose required to elicit growth inhibition in other earthworm species. In order to seek other biological endpoints for more sensitive and/or quicker assessment of radiation effects, gene expression profiling in E. japonensis was also performed, and poly (ADP-ribose) polymerase I (PARP I) was identified as a radiation-responsive gene. PARP I transcript level increased dose-dependently. (author)

  18. Biochemical reasoning for radiation protection and screening methods for radiation sensitivity and potential carcinogenicity

    International Nuclear Information System (INIS)

    Cells of different genetic characteristics respond differently to agents that modify radiation effects. When the modification is a result of chemical repair, reduction of the amount of damage by radical scavenging, production of hypoxia, or any other such mechanism, then the modification of the response will be the same for all types of cells, but not the same when biological or biochemical parameters are involved, because the differences between the cells affect the final outcome, and the genetic traits obviously become affected by chemical modifying agents. Some of these agents directly affect the repair of deoxyribonucleic acid (DNA) by mechanisms not yet understood. Another agent nicotinamide (NA), is directly linked to a repair pathway. Thus, a system that uses NA as a precursor of nicotinamide adenine dinucleotide (NAD)+, and uses NAD+ to produce the polymer polyadenosine diphosphate ribose (PADPR) appears to be an interesting and important factor in the biochemical events that may be linked to improved radioprotection. (author). 36 refs., 5 figs

  19. Identification of sensitive serum microRNA biomarkers for radiation biodosimetry.

    Directory of Open Access Journals (Sweden)

    Naduparambil Korah Jacob

    Full Text Available Exposure to ionizing radiation through environmental, occupational or a nuclear reactor accident such as the recent Fukushima Daiichi incident often results in major consequences to human health. The injury caused by radiation can manifest as acute radiation syndromes within weeks in organs with proliferating cells such as hematopoietic and gastrointestinal systems. Cancers, fibrosis and degenerative diseases are also reported in organs with differentiated cells, months or years later. Studies conducted on atom bomb survivors, nuclear reactor workers and animal models have shown a direct correlation of these effects with the absorbed dose. Physical dosimeters and the available radio-responsive biologics in body fluids, whose responses are rather indirect, have limitations to accurately evaluate the extent of post exposure damage. We have used an amplification-free, hybridization based quantitative assay utilizing the nCounter multiplex platform developed by nanoString Technologies to compare the levels of over 600 miRNAs in serum from mice irradiated at a range of 1 to 12 Gy at 24 and 48 hr time points. Development of a novel normalization strategy using multiple spike-in oligonucleotides allowed accurate measurement of radiation dose and time dependent changes in serum miRNAs. The response of several evolutionarily conserved miRNAs abundant in serum, were found to be robust and sensitive in the dose range relevant for medical triage and in patients who receive total body radiation as preparative regimen for bone marrow transplantation. Notably, miRNA-150, abundant in lymphocytes, exhibited a dose and time dependent decrease in serum, which we propose as a sensitive marker indicative of lymphocyte depletion and bone marrow damage. Our study has identified several markers useful for evaluation of an individual's response by minimally invasive methods, relevant to triage in case of a radiation accident and evaluation of toxicity and response

  20. The sensitivity of convective aggregation to diabatic processes in idealized radiative-convective equilibrium simulations

    Science.gov (United States)

    Holloway, C. E.; Woolnough, S. J.

    2016-03-01

    Idealized explicit convection simulations of the Met Office Unified Model exhibit spontaneous self-aggregation in radiative-convective equilibrium, as seen in other models in previous studies. This self-aggregation is linked to feedbacks between radiation, surface fluxes, and convection, and the organization is intimately related to the evolution of the column water vapor field. Analysis of the budget of the spatial variance of column-integrated frozen moist static energy (MSE), following Wing and Emanuel (2014), reveals that the direct radiative feedback (including significant cloud longwave effects) is dominant in both the initial development of self-aggregation and the maintenance of an aggregated state. A low-level circulation at intermediate stages of aggregation does appear to transport MSE from drier to moister regions, but this circulation is mostly balanced by other advective effects of opposite sign and is forced by horizontal anomalies of convective heating (not radiation). Sensitivity studies with either fixed prescribed radiative cooling, fixed prescribed surface fluxes, or both do not show full self-aggregation from homogeneous initial conditions, though fixed surface fluxes do not disaggregate an initialized aggregated state. A sensitivity study in which rain evaporation is turned off shows more rapid self-aggregation, while a run with this change plus fixed radiative cooling still shows strong self-aggregation, supporting a "moisture-memory" effect found in Muller and Bony (2015). Interestingly, self-aggregation occurs even in simulations with sea surface temperatures (SSTs) of 295 and 290 K, with direct radiative feedbacks dominating the budget of MSE variance, in contrast to results in some previous studies.

  1. Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

    Science.gov (United States)

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna

    2015-10-01

    The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

  2. Highly sensitivity adhesion molecules detection in hereditary haemochromatosis patients reveals altered expression.

    LENUS (Irish Health Repository)

    Norris, S

    2012-02-01

    Several abnormalities in the immune status of patients with hereditary haemochromatosis (HH) have been reported, suggesting an imbalance in their immune function. This may include persistent production of, or exposure to, altered immune signalling contributing to the pathogenesis of this disorder. Adhesion molecules L-, E- and P-Selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) are some of the major regulators of the immune processes and altered levels of these proteins have been found in pathological states including cardiovascular diseases, arthritis and liver cancer. The aim of this study was to assess L-, E- and P-Selectin, ICAM-1 and VCAM-1 expression in patients with HH and correlate these results with HFE mutation status and iron indexes. A total of 139 subjects were diagnosed with HH (C282Y homozygotes = 87, C282Y\\/H63D = 26 heterozygotes, H63D homozygotes = 26), 27 healthy control subjects with no HFE mutation (N\\/N), 18 normal subjects heterozygous for the H63D mutation served as age-sex-matched controls. We observed a significant decrease in L-selectin (P = 0.0002) and increased E-selectin and ICAM-1 (P = 0.0006 and P = 0.0059) expression in HH patients compared with healthy controls. This study observes for the first time that an altered adhesion molecules profile occurs in patients with HH that is associated with specific HFE genetic component for iron overload, suggesting that differential expression of adhesion molecules may play a role in the pathogenesis of HH.

  3. Pain sensitivity and tactile spatial acuity are altered in healthy musicians as in chronic pain patients.

    Directory of Open Access Journals (Sweden)

    Anna M. eZamorano

    2015-01-01

    Full Text Available Extensive training of repetitive and highly skilled movements, as it occurs in professional classical musicians, may lead to changes in tactile sensitivity and corresponding cortical reorganization of somatosensory cortices. It is also known that professional musicians frequently experience musculoskeletal pain and pain-related symptoms during their careers. The present study aimed at understanding the complex interaction between chronic pain and music training with respect to somatosensory processing. For this purpose, tactile thresholds (mechanical detection, grating orientation, two-point discrimination and subjective ratings to thermal and pressure pain stimuli were assessed in 17 professional musicians with chronic pain, 30 pain-free musicians, 20 non-musicians with chronic pain, and 18 pain-free non-musicians. We found that pain-free musicians displayed greater touch sensitivity (i.e. lower mechanical detection thresholds, lower tactile spatial acuity (i.e., higher grating orientation thresholds and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. Moreover, we also found that musicians and non-musicians with chronic pain presented lower tactile spatial acuity and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. The significant increment of pain sensitivity together with decreased spatial discrimination in pain-free musicians and the similarity of results found in chronic pain patients, suggests that the extensive training of repetitive and highly skilled movements in classical musicians could be considered as a risk factor for developing chronic pain, probably due to use-dependent plastic changes elicited in somatosensory pathways.

  4. Radio sensitivity of rice genotypes to gamma radiations based on seedling traits and physiological indices

    International Nuclear Information System (INIS)

    Three Basmati rice genotypes viz., 00515, 99417 and Super Basmati were examined for varietal differences in radio sensitivity to gamma radiations. Dry healthy seeds were exposed to variable doses of gamma radiations i.e., 150- 400 Gy with 50 Gy intervals. Highly significant differences among the genotypes (p<0.01) for all traits were observed. The differences among radiation treatments were highly significant (p<0.01) for shoot and root length, shoot and root fresh weight, water uptake, chlorophyll contents (a, b), plant height and panicle fertility while non significant differences were observed for germination percentage only. The genotype X dose interactions were non significant for germination percentage, shoot length, root length, shoot fresh weight and plant height indicating stability of performance for characters across different radiation levels. In contrast, chlorophyll (a, b), root fresh weight, water uptake and panicle fertility exhibited significant differences for interactions. Mutagenic treatments shifted mean values towards negative direction for almost all traits but not in a definite pattern. However, water uptake of seeds increased with increasing gamma radiation doses. In general, genotypes displayed variable response towards gamma radiations. (author)

  5. Rapamycin-mediated mTOR inhibition attenuates survivin and sensitizes glioblastoma cells to radiation therapy

    Institute of Scientific and Technical Information of China (English)

    Arunkumar Anandharaj; Senthilkumar Cinghu; Woo-Yoon Park

    2011-01-01

    Survivin, an antiapoptotic protein, is elevated in most malignancies and attributes to radiation resistance in tumors including glioblastoma multiforme. The downregulation of survivin could sensitize glioblastoma ceils to radiation therapy. In this study, we investigated the effect of rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), in attenuating survivin and enhancing the therapeutic efficacy for glioblastoma cells, and elucidated the underlying mechanisms. Here we tested various concentrations of rapamycin (1-8 nM) in combination with radiation dose 4 Gy. Rapamycin effectively modulated the protein kinase B (Akt)/mTOR pathway by inhibiting the phosphorylation of Akt and mTOR proteins, and this inhibition was further enhanced by radiation. The expression level of survivin was decreased in rapamycin pre-treatment glioblastoma ceils followed by radiation; meanwhile, the phosphorylation of H2A histone family member X (H2AX) at serine-139 (γ-H2AX) was increased, p21 protein was also induce on radiation with rapamycin pre-treatment, which enhanced G1 arrest and the accumulation of cells at G0/subG1 phase. Furthermore, the clonogenic cell survival assay revealed a significant dose-dependent decrease in the surviving fraction for all three cell lines pre-treated with rapamycin. Our studies demonstrated that targeting survivin may be an effective approach for radiosensitization of malignant glioblastoma.

  6. Sensitivity coefficients for the stochastic estimation of the radiation damage to the reactor pressure vessel

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, C.M.; Hernandez Valle, S. [Centro de Investigaciones Tecnologicas, Nucleares y Ambientales, La Habana (Cuba). E-mail: calvarez@ctn.isctn.edu.cu; svalle@ctn.isctn.edu.cu

    2000-07-01

    The construction of the sensitivity matrix in the case of the vessel radiation damage estimation by Monte Carlo techniques poses new problems related to the uncertainties of the obtained responses. In the case of deterministic calculations, the sensitivity coefficient obtention is a straightforward procedure based on the perturbation formalism through the calculation of the adjoint fluxes. In the paper an alternative procedure implementation based on the differential operator method is described with the modifications needed to the used HEXANN-EVALU code for the response estimations in the VVER-440 pressure vessel. (author)

  7. Crustaceous lichens sensitive monitor of caesium-137 radiation level in terrestrial environment

    Institute of Scientific and Technical Information of China (English)

    Du Chunguang; Zhao Ye; Zhang Jing; Xu Cuihua

    2005-01-01

    The activity of caesium-137 (Bq/kg) in the crustaceous lichens and other samples was determined to prove the feasibility that crustaceous lichens work as a sensitive biology monitor to record the caesium-137 (Bq/kg) radiation levels of terrestrial environment. The measurements were performed with GEM series HPGe (high-purity Germanium) coaxial detector system (ADCAM -100) made by EC & GORTEC Company in USA. It was found that the activity of caesium-137 (Bq/kg) in the crustaceous lichens was one order of magnitude higher than that found in surface soil,and was over three orders of magnitude higher than those found in the familiar biological samples. These results proved that crustaceous lichens may be one of the most sensitive biological monitors about the remote transmission and environmental radiation levels of caesium-137.

  8. Microbial functional diversity alters the structure and sensitivity of oxygen deficient zones

    Science.gov (United States)

    Penn, Justin; Weber, Thomas; Deutsch, Curtis

    2016-09-01

    Oxygen deficient zones (ODZs) below the ocean surface regulate marine productivity by removing bioavailable nitrogen (N). A complex microbial community mediates N loss, but the interplay of its diverse metabolisms is poorly understood. We present an ecosystem model of the North Pacific ODZ that reproduces observed chemical distributions yet predicts different ODZ structure, rates, and climatic sensitivity compared to traditional geochemical models. An emergent lower O2 limit for aerobic nitrification lies below the upper O2 threshold for anaerobic denitrification, creating a zone of microbial coexistence that causes a larger ODZ but slower total rates of N loss. The O2-dependent competition for the intermediate nitrite produces gradients in its oxidation versus reduction, anammox versus heterotrophic denitrification, and the net ecological stoichiometry of N loss. The latter effect implies that an externally driven ODZ expansion should favor communities that more efficiently remove N, increasing the sensitivity of the N cycle to climate change.

  9. Can OCT be sensitive to nanoscale structural alterations in biological tissue?

    OpenAIRE

    Yi, Ji; Radosevich, Andrew J.; Rogers, Jeremy D.; Norris, Sam C.P.; Çapoğlu, İlker R.; Taflove, Allen; Backman, Vadim

    2013-01-01

    Exploration of nanoscale tissue structures is crucial in understanding biological processes. Although novel optical microscopy methods have been developed to probe cellular features beyond the diffraction limit, nanometer-scale quantification remains still inaccessible for in situ tissue. Here we demonstrate that, without actually resolving specific geometrical feature, OCT can be sensitive to tissue structural properties at the nanometer length scale. The statistical mass-density distributio...

  10. Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice

    OpenAIRE

    Musial, Babara; Fernandez-Twinn, Denise S.; Owen R Vaughan; Ozanne, Susan E.; Voshol, Peter; Sferruzzi-Perri, Amanda N.; Fowden, Abigail L.

    2016-01-01

    In late pregnancy, maternal insulin resistance occurs to support fetal growth but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy, day (D) 16, and near term, D19, (term 20.5D). Non-pregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by dual energy X-ray absorptiometry, tissue insulin signalling protein abundance by Western blotting, glucose tolerance and ut...

  11. Amphetamine sensitization alters reward processing in the human striatum and amygdala.

    Directory of Open Access Journals (Sweden)

    Owen G O'Daly

    Full Text Available Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

  12. Phloem-specific expression of a melon Aux/IAA in tomato plants alters auxin sensitivity and plant development

    Directory of Open Access Journals (Sweden)

    Guy eGolan

    2013-08-01

    Full Text Available Phloem sap contains a large repertoire of macromolecules in addition to sugars, amino acids, growth substances and ions. The transcription profile of melon phloem sap contains over 1,000 mRNA molecules, most of them associated with signal transduction, transcriptional control, and stress and defense responses. Heterografting experiments have established the long-distance trafficking of numerous mRNA molecules. Interestingly, several trafficking transcripts are involved in the auxin response, including two molecules coding for auxin/indole acetic acid (Aux/IAA. To further explore the biological role of the melon Aux/IAA transcript CmF-308 in the vascular tissue, a cassette containing the coding sequence of this gene under a phloem-specific promoter was introduced into tomato plants. The number of lateral roots was significantly higher in transgenic plants expressing CmF-308 under the AtSUC2 promoter than in controls. A similar effect on root development was obtained after transient expression of CmF-308 in source leaves of N. benthamiana plants. An auxin-response assay showed that CmF-308-transgenic roots are more sensitive to auxin than control roots. In addition to the altered root development, phloem-specific expression of CmF-308 resulted in shorter plants, a higher number of lateral shoots and delayed flowering, a phenotype resembling reduced apical dominance. In contrast to the root response, cotyledons of the transgenic plants were less sensitive to auxin than control cotyledons. The reduced auxin sensitivity in the shoot tissue was confirmed by lower relative expression of several Aux/IAA genes in leaves and an increase in the relative expression of a cytokinin-response regulator, TRR8/9b. The accumulated data suggest that expression of Aux/IAA in the phloem modifies auxin sensitivity in a tissue-specific manner, thereby altering plant development.

  13. Can OCT be sensitive to nanoscale structural alterations in biological tissue?

    Science.gov (United States)

    Yi, Ji; Radosevich, Andrew J; Rogers, Jeremy D; Norris, Sam C P; Çapoğlu, İlker R; Taflove, Allen; Backman, Vadim

    2013-04-01

    Exploration of nanoscale tissue structures is crucial in understanding biological processes. Although novel optical microscopy methods have been developed to probe cellular features beyond the diffraction limit, nanometer-scale quantification remains still inaccessible for in situ tissue. Here we demonstrate that, without actually resolving specific geometrical feature, OCT can be sensitive to tissue structural properties at the nanometer length scale. The statistical mass-density distribution in tissue is quantified by its autocorrelation function modeled by the Whittle-Mateŕn functional family. By measuring the wavelength-dependent backscattering coefficient μb(λ) and the scattering coefficient μs, we introduce a technique called inverse spectroscopic OCT (ISOCT) to quantify the mass-density correlation function. We find that the length scale of sensitivity of ISOCT ranges from ~30 to ~450 nm. Although these sub-diffractional length scales are below the spatial resolution of OCT and therefore not resolvable, they are nonetheless detectable. The sub-diffractional sensitivity is validated by 1) numerical simulations; 2) tissue phantom studies; and 3) ex vivo colon tissue measurements cross-validated by scanning electron microscopy (SEM). Finally, the 3D imaging capability of ISOCT is demonstrated with ex vivo rat buccal and human colon samples. PMID:23571994

  14. Behavioral sensitization and long-term neurochemical alterations associated with the fungicide triadimefon.

    Science.gov (United States)

    Reeves, Ruth; Thiruchelvam, Mona; Richfield, Eric K; Cory-Slechta, Deborah A

    2003-09-01

    Triadimefon (TDF), a widely used triazole fungicide, blocks reuptake of the neurotransmitter dopamine (DA), similarly to cocaine. Preliminary studies show that intermittent intraperitoneal injections of TDF increase ambulatory and vertical activity across repeated injections [Neurotoxicology (in press)] leading to the hypothesis tested here, that exposure to TDF may influence the development and expression of behavioral sensitization, a model of psychostimulant-induced psychosis. Exposure of adult male C57BL/6 mice to 75 mg/kg i.p. TDF (TDF75) twice a week for 7 weeks increased vertical activity at each injection. Following a 2-week withdrawal period, a TDF challenge to test for expression of behavioral sensitization revealed further increases in vertical activity levels relative to all other conditions. TDF induction/expression of behavioral sensitization was associated with long-term, perhaps permanent modulation of dopaminergic function that included increases in striatal dihydroxyphenylacetic acid (DOPAC) and DA turnover, increases in medial prefrontal cortex (mPFC) dopamine transporter (DAT) binding, as well as decreases in DA D1 and increases in DA D2 and DAT receptor binding that appeared to target the nucleus accumbens shell (NAs) subregion. Thus, TDF exposure may serve as an environmental risk factor for DA system dysfunctions. PMID:14592684

  15. Sensitivity of pathogenic and free-living Leptospira spp. to UV radiation and mitomycin C

    Energy Technology Data Exchange (ETDEWEB)

    Stamm, L.V.; Charon, N.W.

    1988-03-01

    The habitats for the two major Leptospira spp. differ. The main habitat of L. biflexa is soil and water, whereas L. interrogans primarily resides in the renal tubules of animals. We investigated whether these two species, along with L. illini (species incertae sedis), differ with respect to their sensitivity to UV radiation. The doses of UV resulting in 37, 10 and 1% survival were determined for representive serovars from each species. L. interrogans serovar pomona was 3.0 to 4.8 times more sensitive to UV than the other Leptospira species under the 37, 10, and 1% survival parameters. In comparison to other bacteria, L. interrogans serovar pomona is among the most sensitive to UV. In a qualitative UV sensitivity assay., L. interrogans serovars were found to be in general more sensitive than L. biflexa serovars. All three species were found to have a photoreactivation DNA repair mechanism. Since organisms that are resistant to UV are often resistant to the DNA cross-linking agent mitomycin C, we tested the relative sensitivity of several Leptospira serovars to this compound. With few exceptions, L. biflexa and L. illini serovars were considerably more resistant to mitomycin C than the L. interrogans serovars. The mitomycin C sensitivity assay could be a useful addition to current characterization tests used to differentiate the Leptospira species.

  16. Potential sensitivity of photosynthesis and isoprene emission to direct radiative effects of atmospheric aerosol pollution

    OpenAIRE

    Strada, Susanna; Unger, Nadine

    2016-01-01

    A global Earth system model is applied to quantify the impacts of direct anthropogenic aerosol effective radiative forcing on gross primary productivity (GPP) and isoprene emission. The impacts of different pollution aerosol sources (anthropogenic, biomass burning, and non-biomass burning) are investigated by performing sensitivity experiments. The model framework includes all known light and meteorological responses of photosynthesis, but uses fixed canopy structures and ph...

  17. Experimental study of variations in background radiation and the effect on Nuclear Car Wash sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Church, J; Slaughter, D; Norman, E; Asztalos, S; Biltoft, P

    2007-02-07

    Error rates in a cargo screening system such as the Nuclear Car Wash [1-7] depend on the standard deviation of the background radiation count rate. Because the Nuclear Car Wash is an active interrogation technique, the radiation signal for fissile material must be detected above a background count rate consisting of cosmic, ambient, and neutron-activated radiations. It was suggested previously [1,6] that the Corresponding negative repercussions for the sensitivity of the system were shown. Therefore, to assure the most accurate estimation of the variation, experiments have been performed to quantify components of the actual variance in the background count rate, including variations in generator power, irradiation time, and container contents. The background variance is determined by these experiments to be a factor of 2 smaller than values assumed in previous analyses, resulting in substantially improved projections of system performance for the Nuclear Car Wash.

  18. Radiation sensitivity of fibroblast strains from patients with Usher's syndrome, Duchenne muscular dystrophy, and Huntington's disease

    International Nuclear Information System (INIS)

    The colony-forming ability of 10 normal human fibroblast cell strains and of 10 strains representing 3 degenerative diseases of either nerve or muscle cells was determined after exposure of the cells to X-rays or β-particles from tritiated water. Both methods of irradiation yielded similar comparative results. The fibroblast strains from the 5 Usher's syndrome patients and from 1 of the 2 Huntington's disease patients were hypersensitive to radiation, while those from the 3 Duchenne muscular dystrophy patients and the second Huntington's disease patient had normal sensitivity to radiation. These results indicate both disease-specific and strain-specific differences in the survival of fibroblasts after exposure to ionizing radiation. 38 refs.; 2 figs.; 3 tabs

  19. Numerical Simulation of Sensitivities of Snow Melting to Spectral Composition of the Incoming Solar Radiation

    Institute of Scientific and Technical Information of China (English)

    LI Weiping; SUN Shufen; WANG Siao; LIU Xin

    2009-01-01

    Snow albedo is an important factor influencing the snow surface energy budget and snow melting,yet uncertainties remain in the calculation of spectrally resolved snow surface albedo because the spectral composition (visible versus near infrared) of the incident solar radiation is seldom available. The influence of the spectral composition of the incoming solar radiation on the snow surface albedo, snow surface energy budget, and final snow ablation is investigated through sensitivity experiments of four snow seasons at two open sites in the Alps by using a multi-layer Snow-Atmosphere-Soil-Transfer scheme (SAST). Since the snow albedo in the near infrared (NIR) spectral band is significantly lower than that in the visible (VIS) band, and almost the entire NIR part of the solar radiation is absorbed in the top layer of the snow pack, given a fixed amount of incoming solar radiation, a lower VIS/NIR ratio implies that more NIR radiation is reaching the ground surface and more is absorbed by the top layer of the snow pack, therefore, speeding up the snow melting and increasing the surface runoff, although a lesser part of the solar radiation in the visible band is transmitted into and trapped by the sub-layer of the snow pack. The above VIS/NIR ratio effect of the incoming solar radiation can result in a couple of days difference in the timing of snow ablation and it becomes more significant in late spring when the total solar radiation is intensified with seasonal evolution. Snow aging also slightly intensifies this VIS/NIR ratio effect.

  20. Nonlinear Quantitative Radiation Sensitivity Prediction Model Based on NCI-60 Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Chunying Zhang

    2014-01-01

    Full Text Available We proposed a nonlinear model to perform a novel quantitative radiation sensitivity prediction. We used the NCI-60 panel, which consists of nine different cancer types, as the platform to train our model. Important radiation therapy (RT related genes were selected by significance analysis of microarrays (SAM. Orthogonal latent variables (LVs were then extracted by the partial least squares (PLS method as the new compressive input variables. Finally, support vector machine (SVM regression model was trained with these LVs to predict the SF2 (the surviving fraction of cells after a radiation dose of 2 Gy γ-ray values of the cell lines. Comparison with the published results showed significant improvement of the new method in various ways: (a reducing the root mean square error (RMSE of the radiation sensitivity prediction model from 0.20 to 0.011; and (b improving prediction accuracy from 62% to 91%. To test the predictive performance of the gene signature, three different types of cancer patient datasets were used. Survival analysis across these different types of cancer patients strongly confirmed the clinical potential utility of the signature genes as a general prognosis platform. The gene regulatory network analysis identified six hub genes that are involved in canonical cancer pathways.

  1. Radiation Sensitivity of some Food Borne Bacterial Pathogens in Animal Foods and Minced Meat

    International Nuclear Information System (INIS)

    Bacteriological examination of 100 samples of animal food stuffs (fish meal and bone and meat meal; as models of dry food materials) and 50 samples of minced meat (as a model of moist food materials) revealed the isolation of different bacterial pathogens; Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Proteus spp., Staph. aureus and Salmonella species, in a decreasing order of occurrence. In the experiment; the dry food stuffs were sterilized in autoclave and the minced meat was sterilized by gamma irradiation at 10 kGy. The efficacy of gamma irradiation against the inoculated bacterial isolates (E coli 0157: H7, Salmonella enteritidis and Staph. aureus) in animal food stuffs and minced meat was investigated. Irradiated samples were stored at room temperature (25 degree C) for 2 weeks. The food borne pathogens used in this study showed a difference in radiation sensitivity. E. coli 0157: H7, Staphylococcus aureus and Salmonella enteritidis were eradicated at 1, 2 and 3 kGy, respectively. Also, inoculated pathogens in minced meat were more sensitive to ionizing radiation than dry animal food stuffs. It could be concluded that low doses of gamma irradiation are effective means of inactivating pathogenic bacteria. This radiation sensitivity is related to the bacterial isolates and the evaluated growth

  2. Phosphate availability alters architecture and causes changes in hormone sensitivity in the Arabidopsis root system.

    Science.gov (United States)

    López-Bucio, José; Hernández-Abreu, Esmeralda; Sánchez-Calderón, Lenin; Nieto-Jacobo, María Fernanda; Simpson, June; Herrera-Estrella, Luis

    2002-05-01

    The postembryonic developmental program of the plant root system is plastic and allows changes in root architecture to adapt to environmental conditions such as water and nutrient availability. Among essential nutrients, phosphorus (P) often limits plant productivity because of its low mobility in soil. Therefore, the architecture of the root system may determine the capacity of the plant to acquire this nutrient. We studied the effect of P availability on the development of the root system in Arabidopsis. We found that at P-limiting conditions (increase in auxin sensitivity in the roots of P-deprived Arabidopsis seedlings. It was also found that the axr1-3, axr2-1, and axr4-1 Arabidopsis mutants have normal responses to low P availability conditions, whereas the iaa28-1 mutant shows resistance to the stimulatory effects of low P on root hair and lateral root formation. Analysis of ethylene signaling mutants and treatments with 1-aminocyclopropane-1-carboxylic acid showed that ethylene does not promote lateral root formation under P deprivation. These results suggest that in Arabidopsis, auxin sensitivity may play a fundamental role in the modifications of root architecture by P availability. PMID:12011355

  3. Ascorbate-Glutathione Cycle Alteration in Cadmium Sensitive Rice Mutant cadB-1

    Institute of Scientific and Technical Information of China (English)

    SHEN Guo-ming; ZHU Cheng; DU Qi-zhen; SHANGGUAN Li-na

    2012-01-01

    A rice cadmium (Cd) sensitive mutant cadB-1 was obtained using Agrobacterium tumefaciens mediated system.After exposure of cadB-1 and wild type (WT) rice seedlings to a range of Cd concentrations for 10 d,Cd accumulated to higher levels in roots,stems and leaves of both cadB-1 and WT with increasing external Cd concentrations,and the inhibition of seedling growth in cadB-1 was more serious than in WT.Hydrogen peroxide accumulation was higher in leaves and roots of cadB-1.The ratios of reduced glutathione (GSH)/oxidized glutathione (GSSG),ascorbate (ASC)/dehydroascorbate (DHA) and reduced nicotinamide adenine dinucleotide phosphate (NADPH)/oxidized nicotinamide adenine dinucleotide phosphate (NADP+) were lower in cadB-1 than in WT both in leaves and roots under high Cd levels.The activities of ascorbate peroxidase (APX),glutathione peroxidase (GR),dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR) were also lower in cadB-1 than in WT both in leaves and roots under the treatment of high levels of Cd.Our results suggest that under Cd stress,the ASC-GSH cycle was more seriously inhibited in cadB-1 than in WT,indicating that the mutant cadB-1 is less able to scavenge reactive oxygen species and sensitive to Cd.

  4. Alterations of Mitochondrial Function and Insulin Sensitivity in Human Obesity and Diabetes Mellitus.

    Science.gov (United States)

    Koliaki, Chrysi; Roden, Michael

    2016-07-17

    Mitochondrial function refers to a broad spectrum of features such as resting mitochondrial activity, (sub)maximal oxidative phosphorylation capacity (OXPHOS), and mitochondrial dynamics, turnover, and plasticity. The interaction between mitochondria and insulin sensitivity is bidirectional and varies depending on tissue, experimental model, methodological approach, and features of mitochondrial function tested. In human skeletal muscle, mitochondrial abnormalities may be inherited (e.g., lower mitochondrial content) or acquired (e.g., impaired OXPHOS capacity and plasticity). Abnormalities ultimately lead to lower mitochondrial functionality due to or resulting in insulin resistance and type 2 diabetes mellitus. Similar mechanisms can also operate in adipose tissue and heart muscle. In contrast, mitochondrial oxidative capacity is transiently upregulated in the liver of obese insulin-resistant humans with or without fatty liver, giving rise to oxidative stress and declines in advanced fatty liver disease. These data suggest a highly tissue-specific interaction between insulin sensitivity and oxidative metabolism during the course of metabolic diseases in humans. PMID:27146012

  5. Tumor progression: analysis of the instability of the metastatic phenotype, sensitivity to radiation and chemotherapy

    International Nuclear Information System (INIS)

    The major complications for tumor therapy are 1) tumor spread (metastasis); 2) the mixed nature of tumors (heterogeneity); and 3) the capacity of tumors to evolve (progress). To study these tumor characteristics, the rat 13762NF mammary adenocarcinoma was cloned and studied for metastatic properties and sensitivities to therapy (chemotherapy, radiation and hyperthermia). The cell clones were heterogeneous and no correlation between metastatic potential and therapeutic sensitivities was observed. Further, these phenotypes were unstable during pasage in vitro; yet, the changes were clone dependent and reproducible using different cryoprotected cell stocks. To understand the phenotypic instability, subclones were isolated from low and high passage cell clones. The results demonstrated that 1) tumor cells are heterogeneous for multiple phenotypes; 2) tumor cells are unstable for multiple phenotypes; 3) the magnitude, direction and time of occurrence of phenotypic drift is clone dependent; 4) the sensitivity of cell clones to ionizing radiation (γ or heat) and chemotherapy agents is independent of their metastatic potential; 5) shifts in metastatic potential and sensitivity to therapy may occur simultaneously but are not linked; and 6) tumor cells independently diverge to form several subpopulations with unique phenotypic profiles

  6. Sphingosine analog fingolimod (FTY720) increases radiation sensitivity of human breast cancer cells in vitro.

    Science.gov (United States)

    Marvaso, Giulia; Barone, Agnese; Amodio, Nicola; Raimondi, Lavinia; Agosti, Valter; Altomare, Emanuela; Scotti, Valerio; Lombardi, Angela; Bianco, Roberto; Bianco, Cataldo; Caraglia, Michele; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

    2014-06-01

    Radiotherapy is one of the most effective therapeutic strategies for breast cancer patients, although its efficacy may be reduced by intrinsic radiation resistance of cancer cells. Recent investigations demonstrate a link between cancer cell radio-resistance and activation of sphingosine kinase (SphK1), which plays a key role in the balance of lipid signaling molecules. Sphingosine kinase (SphK1) activity can alter the sphingosine-1-phosphate (S1P)/ceramide ratio leading to an imbalance in the sphingolipid rheostat. Fingolimod (FTY720) is a novel sphingosine analog and a potent immunosuppressive drug that acts as a SphK1 antagonist, inhibits the growth, and induces apoptosis in different human cancer cell lines. We sought to investigate the in vitro radiosensitizing effects of FTY720 on the MDA-MB-361 breast cancer cell line and to assess the effects elicited by radiation and FTY720 combined treatments. We found that FTY720 significantly increased anti-proliferative and pro-apoptotic effects induced by a single dose of ionizing radiation while causing autophagosome accumulation. At the molecular level, FTY720 significantly potentiated radiation effects on perturbation of signaling pathways involved in regulation of cell cycle and apoptosis, such as PI3K/AKT and MAPK. In conclusion, our data highlight a potent radiosensitizing effect of FTY720 on breast cancer cells and provide the basis of novel therapeutic strategies for breast cancer treatment. PMID:24657936

  7. Protective efficacy of Emblica officinalis Linn. against radiation and cadmium induced biochemical alterations in the liver of Swiss albino mice

    International Nuclear Information System (INIS)

    All organisms living on earth are being perpetually exposed to some amount of radiation originating from a variety of sources. Radiation causes deleterious effects in all forms of life due to increasing utilization and production of modern technology, a simultaneous exposure of organisms to heavy metals is also unavoidable. These heavy metals become toxic when present in large quantities, with increasing the industrial revolution and industrial waste, the emission of cadmium has increased into the environment. Thus concomitant exposure to cadmium chloride and ionizing radiation might produce deleterious effect upon biological system. The total environmental burden of toxicants may have greater effect as against their individual impact as expected by their nature. So interaction between radiation and other toxicants represents a field of great potential importance. In the recent years, immense interest has been developed in the field of chemoprotection against radiation and heavy metals induced changes. In view of the potential for practical application, a variety of compounds are being tested for their radioprotective activities. Among these, Emblica holds a great promise. In light of the above, the present study was aimed to evaluate the protective effect of Emblica against radiation and cadmium induced biochemical alterations in the liver of Swiss albino mice. The animals were exposed to 6.0 Gy of gamma rays with or without cadmium chloride treatment. The Emblica was administered seven days prior to irradiation or cadmium chloride treatment

  8. Soft x rays as a tool to investigate radiation-sensitive sites in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, D.J.; Zaider, M.

    1983-01-01

    It is now clear that the initial geometrical distribution of primary radiation products in irradiated biological matter is fundamental to the observed end point (cell killing, mutation induction, chromosome aberrations, etc.). In recent years much evidence has accumulated indicating that for all radiations, physical quantities averaged over cellular dimensions (micrometers) are not good predictors of biological effect, and that energy-deposition processes at the nanometer level are critical. Thus irradiation of cells with soft x rays whose secondary electrons have ranges of the order of nanometers is a unique tool for investigating different models for predicting the biological effects of radiation. We demonstrate techniques whereby the biological response of the cell and the physical details of the energy deposition processes may be separated or factorized, so that given the response of a cellular system to, say, soft x rays, the response of the cell to any other radiation may be predicted. The special advantages of soft x rays for eliciting this information and also information concerning the geometry of the radiation sensitive structures within the cell are discussed.

  9. Radiogenic male breast cancer with in vitro sensitivity to ionizing radiation and bleomycin

    International Nuclear Information System (INIS)

    A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis

  10. A new highly sensitive low-Z LiF-based OSL phosphor for radiation dosimetry

    International Nuclear Information System (INIS)

    A new low-Z lithium fluoride-based optical stimulated luminescent (OSL) phosphor is developed. The phosphor shows good OSL properties, and its sensitivity is comparable with that of the commercial Al2O3:C (Landauer, Inc.) phosphor. For the luminescence averaged over initial 3 s, blue stimulated luminescence (BSL) and green stimulated luminescence (GSL) sensitivities were found to be 0.27 and 4 times, respectively, than that of Al2O3:C (Landauer, Inc.). The BSL decay is fast, and the whole signal decays within 3 s; the GSL decay is relatively slow, and the signal decays in 25 s. The fast decay, good sensitivity, good linearity and its near tissue equivalence (Zeff ∼8.14) will make this phosphor suitable for radiation dosimetry particularly in personnel as well as in medical dosimetry. (authors)

  11. Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei

    International Nuclear Information System (INIS)

    Folic acid deficiency can lead to uracil incorporation into DNA, hypomethylation of DNA, inefficient DNA repair and increase chromosome malsegregation and breakage. Because ionising radiation increases demand for efficient DNA repair and also causes chromosome breaks we hypothesised that folic acid deficiency may increase sensitivity to radiation-induced chromosome breakage. We tested this hypothesis by using the cytokinesis-block micronucleus assay in 10 day WIL2-NS cell cultures at four different folic acid concentrations (0.2, 2, 20, and 200 nM) that span the 'normal' physiological range in humans. The study showed a significant dose-dependent increase in frequency of binucleated cells with micronuclei and/or nucleoplasmic bridges with decreasing folic acid concentration (P < 0.0001, P = 0.028, respectively). These biomarkers of chromosomal instability were also increased in cells irradiated (1.5 Gy γ-rays) on day 9 relative to un-irradiated controls (P < 0.05). Folic acid deficiency and γ-irradiation were shown to have a significant interactive effect on frequency of cells containing micronuclei (two-way ANOVA, interaction P 0.0039) such that the frequency of radiation-induced micronucleated cells (i.e. after subtracting base-line frequency of un-irradiated controls) increased with decreasing folic acid concentration (P-trend < 0.0001). Aneuploidy of chromosome 21, apoptosis and necrosis were increased by folic acid deficiency but not by ionising radiation. The results of this study show that folate status has an important impact on chromosomal stability and is an important modifying factor of cellular sensitivity to radiation-induced genome damage

  12. Studies on the Photoperiod Sensitive Characters of Male Fertility Alteration of Peiai64S' Main Male Genic Sterile Gene

    Institute of Scientific and Technical Information of China (English)

    ZENG Han-lai; ZHANG Duan-pin; ZHANG Zhi-yu; YI Wen-kai; ZHU Xin; MENG Hui-jun

    2002-01-01

    Peiai64S, an indica male sterile rice with a male fertility alteration under different environments, is selected from the offspring of indica rice crossed with Nongken58S. Nongken58S, a japonica photoperiod sensitive genic male sterile rice (PGMS), deriving from a natural mutant plant individual of normal japonica rice variety, Nongken58, is used as a male sterile gene donor of Peiai64S. But Peiai64S is not a typical PGMS rice, the male fertility is sensitive to temperature just as thermo-sensitive genic male sterile rice (TGMS). We have selected typical PGMS plants in F2 population of Peiai64S × Nongken58, whose ratio of fertile plants to sterile plants is nearly 3:1. The sterility inheritance conformed to one pair of gene segregation model. The result indicates the main male sterile gene in Peiai64S is not other than the PGMS gene, and comes from Nongken58S. The genetic background affects effective expression of the PGMS gene. This suggests that we ought to focus on optimizing the genetic background of the PGMS gene in PGMS rice breeding, and select an ideal genetic background as a transgenic background in molecular breeding.

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

    International Nuclear Information System (INIS)

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

  14. High temperature, drought and their interaction induced protein alterations in sensitive and tolerant wheat varieties

    Directory of Open Access Journals (Sweden)

    Vikender Kaur, Reena Mahla And R.K.Behl

    2014-12-01

    Full Text Available Two contrasting wheat (Triticum aestivum L. cultivars WH730 (high temperature tolerant and UP2565 (high temperature sensitive were tested for differential response to combined and individually applied high temperature (HT and drought (D stress at seedling stage for peptide profile. Initial profile of the stress induced peptides was outlined via SDS electrophoresis of leaf extracts. Electrophoretic pattern of proteins revealed expression of new bands as well as disappearance of certain others in HT, D and interactive HT+D stress treated and revived samples in both wheat varieties relative to untreated control samples. Some of the bands that appeared in stress treated seedlings were also present after revival indicating their protective role, while some new peptides synthesized after stress but disappeared after revival period may be designated true stress proteins. However, all the plants from heat, drought and their interactive stress treatments continued to grow during recovery period. This suggests that these proteins and other newly synthesized proteins may have protective effects at high temperature (40°C and water scarcity and provide plants for healthy growth during the recovery period. Furthermore, elucidating the functions of proteins expressed by genes in stress tolerant and susceptible plants may provide important information for designing new strategies for crop improvement.

  15. Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

    Directory of Open Access Journals (Sweden)

    McIntyre Bradley W

    2005-04-01

    Full Text Available Abstract Background Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis in human osteosarcoma would result in resistance to chemotherapy. Methods Osteosarcoma cell lines (SAOS-2 and TE-85 obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining. Results Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended. Moreover, suspended anoikis resistant TE-85 cells (TE-85ar retained their sensitivity to chemotherapy as well. Conclusion Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.

  16. Studies on the Mechanism of Radiation Resistance in Micrococcus Radiodurans and its Sensitization

    International Nuclear Information System (INIS)

    Efficient and accurate repair of radiation-induced lesions in M. radiodurans was investigated as to the cause of its extreme radioresistance. The cells were made permeable to deoxyribonucleoside triphosphate by treatment with non-ionic detergent, Triton X-100. After irradiation with 2 krad gamma rays more than 80% of the single-strand scissions were rejoined in the permeable cells within 10 min at 37°C. This fast repair process requires the presence of deoxyribonucleoside triphosphates and NAD. However, rejoining of DNA strand scission was incomplete after prolonged incubation in the permeable cells. This suggests that alternate repair reaction(s) is necessary for complete recovery. The other type of radiation lesion was found by postirradiation incubation at non-permissive temperature, which markedly sensitizes this bacterium to radiation. Postincubation at this temperature also sensitizes the cells to chemicals that damage DNA. The extreme radioresistance of this bacterium was also lost by mutation and an isolated radiosensitive mutant showed almost the same radiosensitivity as E. coli K12 or B/r. These results are discussed in connection with the extreme radioresistance of M. radiodurans. (author)

  17. Radiation sensitivity of graphene field effect transistors and other thin film architectures

    Science.gov (United States)

    Cazalas, Edward

    An important contemporary motivation for advancing radiation detection science and technology is the need for interdiction of nuclear and radiological materials, which may be used to fabricate weapons of mass destruction. The detection of such materials by nuclear techniques relies on achieving high sensitivity and selectivity to X-rays, gamma-rays, and neutrons. To be attractive in field deployable instruments, it is desirable for detectors to be lightweight, inexpensive, operate at low voltage, and consume low power. To address the relatively low particle flux in most passive measurements for nuclear security applications, detectors scalable to large areas that can meet the high absolute detection efficiency requirements are needed. Graphene-based and thin-film-based radiation detectors represent attractive technologies that could meet the need for inexpensive, low-power, size-scalable detection architectures, which are sensitive to X-rays, gamma-rays, and neutrons. The utilization of graphene to detect ionizing radiation relies on the modulation of graphene charge carrier density by changes in local electric field, i.e. the field effect in graphene. Built on the principle of a conventional field effect transistor, the graphene-based field effect transistor (GFET) utilizes graphene as a channel and a semiconducting substrate as an absorber medium with which the ionizing radiation interacts. A radiation interaction event that deposits energy within the substrate creates electron-hole pairs, which modify the electric field and modulate graphene charge carrier density. A detection event in a GFET is therefore measured as a change in graphene resistance or current. Thin (micron-scale) films can also be utilized for radiation detection of thermal neutrons provided nuclides with high neutron absorption cross section are present with appreciable density. Detection in thin-film detectors could be realized through the collection of charge carriers generated within the

  18. Differential sensitivity of coral larvae to natural levels of ultraviolet radiation during the onset of larval competence.

    KAUST Repository

    Aranda, Manuel

    2011-07-01

    Scleractinian corals are the major builders of the complex structural framework of coral reefs. They live in tropical waters around the globe where they are frequently exposed to potentially harmful ultraviolet radiation (UVR). The eggs and early embryonic stages of some coral species are highly buoyant and remain near the sea surface for prolonged periods of time and may therefore be the most sensitive life stages with respect to UVR. Here, we analysed gene expression changes in five developmental stages of the Caribbean coral Montastraea faveolata to natural levels of UVR using high-density cDNA microarrays (10 930 clones). We found that larvae exhibit low sensitivity to natural levels of UVR during early development as reflected by comparatively few transcriptomic changes in response to UVR. However, we identified a time window of high UVR sensitivity that coincides with the motile planula stage and the onset of larval competence. These processes have been shown to be affected by UVR exposure, and the transcriptional changes we identified explain these observations well. Our analysis of differentially expressed genes indicates that UVR alters the expression of genes associated with stress response, the endoplasmic reticulum, Ca(2+) homoeostasis, development and apoptosis during the motile planula stage and affects the expression of neurogenesis-related genes that are linked to swimming and settlement behaviour at later stages. Taken together, our study provides further data on the impact of natural levels of UVR on coral larvae. Furthermore, our results might allow a better prediction of settlement and recruitment rates after coral spawning events if UVR climate data are taken into account.

  19. Competition and sensitivity of wheat and wild oat exposed to enhanced UV-B radiation at different densities under field conditions

    International Nuclear Information System (INIS)

    The influence of enhanced UV-B radiation (approximating a 15% ozone layer reduction) on competitive interaction between spring wheat (Triticum aestivum) and wild oat (Avena fatua) was examined in the field. The density-dependent mortality of both wheat and wild oat did not exhibit a significant difference between control and UV-B treatment conditions. A relatively high degree of competitive stress enhanced the effects of UV-B stress on biomass reduction. The relative competitive status of wheat in terms of total biomass increased under UV-B enhancement while it decreased when based upon grain production. Shifts in competitive balance occurred with significant changes in total biomass, especially when plants grew at higher densities in monocultures and mixtures. The sensitivity of wild oat to intensification of UV-B radiation at higher densities in mixtures was greater than that at lower densities. At all densities examined, wheat grown in mixture was significantly less sensitive to UV-B radiation than that in monoculture, and just the opposite for wild oat. The density of monocultures did not alter the response index (RI) of wheat and wild oat to enhanced UV-B radiation. (author)

  20. Colchicine sensitizes human hepatocellular carcinoma cells to damages caused by radiation

    Institute of Scientific and Technical Information of China (English)

    Chia-Yuan Liu; Hui-Fen Liao; Shou-Chuan Shih; Shee-Chan Lin; Wen-Hsiung Chang; Cheng-Hsin Chu; Tsang-En Wang; Yu-Jen Chen

    2005-01-01

    AIM: We studied the effect of colchicine combined with radiation on the survival of human hepatocellular carcinoma (HCC) HA22T/VGH cells.METHODS: Twenty-four hours after treatment with 0-8 ng/mL colchicine, HA22T/VGH cells were irradiated at various doses (0, 1, 2, 4, and 8 Gy). Colony assay was performed to assess the surviving cell fraction. Survival curves were fitted by using a linear-quadratic model to estimate the sensitizer enhancement ratio (SER). Flow cytometry was used for cell cycle analysis.RESULTS: Colchicine at lower concentrations (1 and 2 ng/mL) had obvious synergy with radiation to inhibit HCC cell growth, whereas higher concentrations (4 and 8 ng/mL) had only additive effect to radiation. Pretreatment with 1 and 2 ng/mL colchicine for 24-h enhanced cell killing by radiation with SERs of 1.21 and 1.53, respectively.G2/M arrest was only observed with higher colchicine doses (8 and 16 ng/mL) after 24-h treatment; this effect was neither seen with lower doses (1, 2, and 4 ng/mL)nor with any dose after only 1 h of treatment.CONCLUSION: Our results suggest that colchicine has potential as an adjunct to radiotherapy for HCC treatment.Lower doses of colchicine possess radiosensitizing effects via some mechanism other than G2/M arrest. Further study is necessary to elucidate the mechanism.

  1. Altered ratio of D1 and D2 dopamine receptors in mouse striatum is associated with behavioral sensitization to cocaine.

    Directory of Open Access Journals (Sweden)

    Dawn Thompson

    Full Text Available BACKGROUND: Drugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R availability in the brain. Such a decrease consequently alters the ratio of D1R:D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified. METHODS AND FINDINGS: ETHICS STATEMENT: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT and G protein coupled receptor associated sorting protein-1 (GASP-1 knock out (KO mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine. CONCLUSIONS: Together, our data suggests that changes in the ratio of the D1:D2R could contribute to cocaine-induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization.

  2. Variability of individual normal tissue radiation sensitivity. An international empirical evaluation of endogenous and exogenous

    International Nuclear Information System (INIS)

    Background: The variability of normal-tissue response is of major concern for radiation therapy. Multiple endogenous and exogenous factors are qualitatively known to alter the acute and late tissue response. Which of them are regarded most important by the European radiation oncologists and what is, empirically, their quantitative influence on the acute or late tissue tolerance? Methods: In August 1997, we sent a questionnaire to 255 European radiation oncology departments. Among others, the questionnaire asked for endogenous and exogenous factors modifying the tissue response to radiation therapy and their quantitative influence on the acute and late radiation morbidity (TD5/5). Fifty-five questionnaires (21.5%) were answered. Results: Empirically, the most important endogenous factors to modify the acute tissue tolerance are (a) metabolic/other diseases with macro- or microangiopathia (17 answers [a]/32% mean decrease of tissue tolerance), (b) collagen diseases (9 a/37%) and (c) immune diseases (5 a/53%). As endogenous response modifiers for the TD5/5 are recognized (a) metabolic or other diseases leading to marcro- or microangiopathia (15 a/31%), (b) collagen diseases (11 a/38%) and (c) immune diseases (2 a/50%). Inflammations from any reason are assumed to alter the acute tissue tolerance by (6 a/26%) and the TD5/5 by (10 a/24%). Exogenous modifiers of the acute tissue response mentioned are (a) smoking (34 a/44%), (b) alcohol (23 a/45%), (c) nutrition/diets (16 a/45%), (d) hygiene (9 a/26%) and (e) medical therapies (10 a/37%). Exogenous factors assumed to influence the TD5/5 are (a) smoking (22 a/40%), (b) alcohol (15 a/38%), (c) nutrition/diets (9 a/48%), (d) hygiene (5 a/34%) and (e) medical therapies (10 a/30%). Conclusions: Exogenous factors are regarded more important by number and extent on the acute and late tissue response than endogenous modifiers. Both may have an important influence on the individual expression of normal tissue response. (orig.)

  3. Medullary Endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression.

    Science.gov (United States)

    Schaich, Chris L; Grabenauer, Megan; Thomas, Brian F; Shaltout, Hossam A; Gallagher, Patricia E; Howlett, Allyn C; Diz, Debra I

    2016-01-01

    CB1 cannabinoid receptors are expressed on vagal afferent fibers and neurons within the solitary tract nucleus (NTS), providing anatomical evidence for their role in arterial baroreflex modulation. To better understand the relationship between the brain renin-angiotensin system (RAS) and endocannabinoid expression within the NTS, we measured dorsal medullary endocannabinoid tissue content and the effects of CB1 receptor blockade at this brain site on cardiac baroreflex sensitivity (BRS) in ASrAOGEN rats with low glial angiotensinogen, normal Sprague-Dawley rats and (mRen2)27 rats with upregulated brain RAS expression. Mass spectrometry revealed higher levels of the endocannabinoid 2-arachidonoylglycerol in (mRen2)27 compared to ASrAOGEN rats (2.70 ± 0.28 vs. 1.17 ± 0.09 ng/mg tissue; P system that influence cardiovagal BRS in animals with genetic alterations in the brain RAS.

  4. Radiation-induced DNA double-strand break frequencies in human squamous cell carcinoma cell lines of different radiation sensitivities

    International Nuclear Information System (INIS)

    DNA neutral (pH 9-6) filter elution was used to measure radiation-induced DNA double-strand break (dsb) frequencies in eight human squamous cell carcinoma cell lines with radiosensitivities (D0) ranging from 1.07 to 2.66 Gy and D-bar values ranging from 1.46 to 4.08 Gy. Elution profiles of unirradiated samples from more radiosensitive cell lines were all steeper in slope than profiles from resistant cells. The shapes of the dsb induction curves were curvilinear and there was some variability from cell line to cell line in the dose-response for the induction of DNA dsb after exposures to 5-100 Gy 60Co γ-rays. There was no relation between shapes of survival curves and shapes of the dose-responses for the induction of DNA dsb. At low doses (5-25 Gy), three out of four of the more sensitive cell lines (D-bar3.0 Gy). Although the low-dose (5-25 Gy) elution results were variable, they suggest that DNA neutral elution will detect differences between sensitive and resistant tumour cells in initial DNA dsb frequencies. (author)

  5. Plant Temperature for Sterile Alteration of a Temperature-Sensitive Genic Male Sterile Rice, Peiai64S

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The forecast of sterile alteration for the temperature-sensitive genic male sterile (TGMS) line in two-line hybrid rice seed production was traditionally based on screen temperature determined by weather station. The article put forward a new approach based on plant temperature, which was more exact and direct than the traditional method. The result of the simulation of the self-seeded setting rate of a widely used TGMS line, Peiai64S, by several temperature parameters and durations, showed that the fertility was directly affected by the plant temperature at a height of 20 cm or the air temperature around it in three days duration. Using the stem temperature of three days at a height of 20 cm as the simulation parameter,the fertility of Peiai64S had the maximum, minimum and optimum temperatures as 22.8, 21.7 and 22.5℃, respectively,whereas 23.2, 21.5 and 21.8℃ when using the air temperature of three days around the height of 20 cm as the parameter.Such temperature indices can be used to conclude the sterile alteration of TGMS for safeguarding seed production of twoline hybrid rice. The article also established a statistic model to conclude plant temperature by water temperatures at inflow and outflow, and air temperature and cloudage from weather station.

  6. Sensitization of prostate cancer to ionizing radiation by targeting poly(ADP-robose) polymerase: preclinical studies

    International Nuclear Information System (INIS)

    Poly(ADP-ribose) polymerase (PARP) is a DNA-binding enzyme which plays important roles in the maintenance of genome stability, immediate cellular responses to DNA damage, and apoptosis. A DNA-binding domain of PARP (PARP-DBD) acts as a dominant-negative mutant by binding to DNA strand breaks irreversibly and sensitizing mammalian cells to DNA-damaging agents (1, 2). To direct the expression of human PARP-DBD to prostate we developed recombinant plasmids expressing the PARP-DBD under the control of the 5'-flanking sequences of the human prostate-specific antigen (PSA) gene. In vitro studies revealed that PSA promoter driven expression of the PARP-DBD showed prostate tissue specificity and androgen responsiveness and sensitized LNCaP cells to DNA-damaging agents, such as ionizing radiation and etoposide (3). To assess the efficiency of this strategy in vivo, we developed a cationic liposome-mediated gene delivery of PARP-DBD plasmid in tumor xenografts of PSA producing and androgen sensitive prostate cancer cells (LNCaP and 22Rv1). Tumor bearing mice were treated with intratumoral liposome-complexed PARP-DBD (LE-PARP-DBD), ionizing radiation (IR) or a combination of LE-PARP-DBD and IR. Control groups received blank liposomes or were left untreated. Administration of LE-PARP-DBD resulted in expression of dominant-negative mutant of PARP in tumor cells and enhanced radiation-induced inhibition of tumor growth. These results provide a proof-of- principle for a novel therapeutic strategy to control prostate cancer. The study was supported in part by grants from the U.S. Army Medical Research and Development Command DAMD 17-00-1-0019 and DAMD 17-00-1-0276 (to V.S.). (1) J.Biol.Chem., 265:18721-18724, 1990; (2) Cancer Research, 58: 3495-3498, 1998; (3) Cancer Research, 62: 6879-6883, 2002

  7. Potential sensitivity of photosynthesis and isoprene emission to direct radiative effects of atmospheric aerosol pollution

    Science.gov (United States)

    Strada, Susanna; Unger, Nadine

    2016-04-01

    A global Earth system model is applied to quantify the impacts of direct anthropogenic aerosol effective radiative forcing on gross primary productivity (GPP) and isoprene emission. The impacts of different pollution aerosol sources (anthropogenic, biomass burning, and non-biomass burning) are investigated by performing sensitivity experiments. The model framework includes all known light and meteorological responses of photosynthesis, but uses fixed canopy structures and phenology. On a global scale, our results show that global land carbon fluxes (GPP and isoprene emission) are not sensitive to pollution aerosols, even under a global decline in surface solar radiation (direct + diffuse) by ˜ 9 %. At a regional scale, GPP and isoprene emission show a robust but opposite sensitivity to pollution aerosols in regions where forested canopies dominate. In eastern North America and Eurasia, anthropogenic pollution aerosols (mainly from non-biomass burning sources) enhance GPP by +5-8 % on an annual average. In the northwestern Amazon Basin and central Africa, biomass burning aerosols increase GPP by +2-5 % on an annual average, with a peak in the northwestern Amazon Basin during the dry-fire season (+5-8 %). The prevailing mechanism varies across regions: light scattering dominates in eastern North America, while a reduction in direct radiation dominates in Europe and China. Aerosol-induced GPP productivity increases in the Amazon and central Africa include an additional positive feedback from reduced canopy temperatures in response to increases in canopy conductance. In Eurasia and northeastern China, anthropogenic pollution aerosols drive a decrease in isoprene emission of -2 to -12 % on an annual average. Future research needs to incorporate the indirect effects of aerosols and possible feedbacks from dynamic carbon allocation and phenology.

  8. MiR-224 expression increases radiation sensitivity of glioblastoma cells

    International Nuclear Information System (INIS)

    Highlights: • MiR-224 expression in established glioblastoma cell lines and sporadic tumor tissues is low. • Exogenous miR-224 expression was found to increase radiation sensitivity of glioblastoma cells. • MiR-224 expression brought about 55–60% reduction in API5 expression levels. • Transfection with API5 siRNA increased radiation sensitivity of glioblastoma cells. • Low miR-224 and high API5 expression correlated with worse survival of GBM patients. - Abstract: Glioblastoma (GBM) is the most common and highly aggressive primary malignant brain tumor. The intrinsic resistance of this brain tumor limits the efficacy of administered treatment like radiation therapy. In the present study, effect of miR-224 expression on growth characteristics of established GBM cell lines was analyzed. MiR-224 expression in the cell lines as well as in primary GBM tumor tissues was found to be low. Exogenous transient expression of miR-224 using either synthetic mimics or stable inducible expression using doxycycline inducible lentiviral vector carrying miR-224 gene, was found to bring about 30–55% reduction in clonogenic potential of U87 MG cells. MiR-224 expression reduced clonogenic potential of U87 MG cells by 85–90% on irradiation at a dose of 6 Gy, a dose that brought about 50% reduction in clonogenic potential in the absence of miR-224 expression. MiR-224 expression in glioblastoma cells resulted in 55–65% reduction in the expression levels of API5 gene, a known target of miR-224. Further, siRNA mediated down-regulation of API5 was also found to have radiation sensitizing effect on glioblastoma cell lines. Analysis of the Cancer Genome Atlas data showed lower miR-224 expression levels in male GBM patients to correlate with poorer survival. Higher expression levels of miR-224 target API5 also showed significant correlation with poorer survival of GBM patients. Up-regulation of miR-224 or down-regulation of its target API5 in combination with radiation therapy

  9. MiR-224 expression increases radiation sensitivity of glioblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Upraity, Shailendra; Kazi, Sadaf; Padul, Vijay; Shirsat, Neelam Vishwanath, E-mail: nshirsat@actrec.gov.in

    2014-05-30

    Highlights: • MiR-224 expression in established glioblastoma cell lines and sporadic tumor tissues is low. • Exogenous miR-224 expression was found to increase radiation sensitivity of glioblastoma cells. • MiR-224 expression brought about 55–60% reduction in API5 expression levels. • Transfection with API5 siRNA increased radiation sensitivity of glioblastoma cells. • Low miR-224 and high API5 expression correlated with worse survival of GBM patients. - Abstract: Glioblastoma (GBM) is the most common and highly aggressive primary malignant brain tumor. The intrinsic resistance of this brain tumor limits the efficacy of administered treatment like radiation therapy. In the present study, effect of miR-224 expression on growth characteristics of established GBM cell lines was analyzed. MiR-224 expression in the cell lines as well as in primary GBM tumor tissues was found to be low. Exogenous transient expression of miR-224 using either synthetic mimics or stable inducible expression using doxycycline inducible lentiviral vector carrying miR-224 gene, was found to bring about 30–55% reduction in clonogenic potential of U87 MG cells. MiR-224 expression reduced clonogenic potential of U87 MG cells by 85–90% on irradiation at a dose of 6 Gy, a dose that brought about 50% reduction in clonogenic potential in the absence of miR-224 expression. MiR-224 expression in glioblastoma cells resulted in 55–65% reduction in the expression levels of API5 gene, a known target of miR-224. Further, siRNA mediated down-regulation of API5 was also found to have radiation sensitizing effect on glioblastoma cell lines. Analysis of the Cancer Genome Atlas data showed lower miR-224 expression levels in male GBM patients to correlate with poorer survival. Higher expression levels of miR-224 target API5 also showed significant correlation with poorer survival of GBM patients. Up-regulation of miR-224 or down-regulation of its target API5 in combination with radiation therapy

  10. Role of Rosemary leaves extract against radiation-induced hematological and biochemical alterations in mice

    OpenAIRE

    Acharya Garima S.; Goyal Pradeep K.

    2008-01-01

    The present paper is a study of the modulatory effect of Rosmarinus officinalis leaves extract on radiation-induced hematological and biochemical changes in Swiss albino mice. The dose reduction factor for the Rosemary extract against gamma rays was calculated 1.53 from LD50/30 values. The Rosemary extract was administered orally for 5 consecutive days prior to radiation exposure. The hematological and biochemical parameters were assessed from day 1 to 30 post-irradiation intervals. The total...

  11. NOXA-induced alterations in the Bax/Smac axis enhance sensitivity of ovarian cancer cells to cisplatin.

    Directory of Open Access Journals (Sweden)

    Chao Lin

    Full Text Available Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy.

  12. Sensitivity of the Planetary Boundary Layer simulation in RAMS meteorological model to the solar radiation input

    Science.gov (United States)

    Campo, Lorenzo

    2013-04-01

    The dynamics of the Planetary Boundary Layer is determined by the surface conditions, not only in terms of roughness, topography and land cover but also, and mainly, by the turbulent energy fluxes at the interface between the land and the atmosphere. In a vegetated area such fluxes, namely sensible heat and evapotranspiration, are part of the surface energy budget that is driven by the incoming solar radiation input. The modern LAM (Limited Area Model) meteorological models, the last years saw an increasing interest in the reconstruction of this surface balance, in order to provide, to the atmospheric simulation, more accurate conditions for the lower boundary. In particular, the meteorological model RAMS (Regional Atmospheric Modeling System, Colorado state University) employs a detailed SVAT model for the surface phenomena, LEAF-3, that includes vegetation dynamics, evapotranspiration, soil moisture, longwave and shortwave radiation budget, etc. An incorrect input in terms of solar radiation can lead to distortions in the simulation of the energy fluxes at the surface and, consequently, to the dynamics of the whole boundary layer. In this work a sensitivity analysis of a Large Eddy Simulation of the PBL was performed with respect to the available radiation schemes in RAMS, also comparing with the observations of a ground radiometer. The solar radiation input of the model was then replaced with the observations in order to study the changes in terms of dynamics of the PBL. The domain of the simulation was an area of 5 km2 in central Italy, in a period in Summer 2008. A discussion of the results is provided.

  13. On high-frequency radiation scattering sensitivity to surface roughness in particulate media

    Science.gov (United States)

    Zohdi, T. I.

    2016-06-01

    This paper analyzes the sensitivity of high-frequency radiation scattering in particulate media, to particle surface roughness. Ray-tracing theory and computation are employed. Since the magnitude of the Poynting vector ray, the irradiance, is the appropriate quantity to be tracked, the behavior of the reflectance, which controls the ratio of the reflected and incident Poynting vector magnitudes, is of primary concern. The reflectance is a highly nonlinear function of the refractive indices and angle of incidence. The present work first addresses the relationship between a single scatterer's sensitivity to its surface roughness and then the response of a large number of scatterers to the surface roughness. The analysis indicates that, for a single scatterer, the sensitivity of the response to roughness decreases, up to a point, and then increases again, i.e., it is nonmonotone. However, for a system of multiple scatterers, this effect vanishes, due to multiple internal reflections which dominate the overall response characteristics. While it was relatively straightforward to compute the overall sensitivity of a single scattering body, for example a sphere, when multiple reflecting bodies are considered, numerical simulations are necessary because the reflected rays from one "rough" body will, in turn, be reflected to another "rough" body, etc. Examples are given for a system of randomly distributed scatterers.

  14. Pomegranate Alleviates Oxidative Damage and Neurotransmitter Alterations in Rats Brain Exposed to Aluminum Chloride and/or Gamma Radiation

    International Nuclear Information System (INIS)

    Aluminum and gamma radiation, both are potent neurotoxins and have been implicated in many human neuro degenerative diseases. The present study was designed to investigate the role of pomegranate in alleviating oxidative damage and alteration of neurotransmitters in the brain of rats exposed to aluminum chloride (AlCl3), and/or gamma radiation (IR). The results revealed that rats whole body exposed to γ- rays, (1 Gy/week up to 4 Gy), and/or administered aluminum chloride (35 mg/kg body weight), via gavages for 4 weeks, resulted in brain tissue damage, featuring by significant increase of the level of thiobarbituric acid reactive substances (TBARS), and advanced oxidation protein products (AOPP), associated with significant decrease of superoxide dismutase (SOD) and catalase (CAT) activities, as well as glutathione (GSH) content indicating occurrence of oxidative stress. A significant decrease of serotonin (5-HT) level associated with a significant increase of 5-hydroxyindole acetic acid (5-HIAA), in addition to a significant decrease in dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents recorded at the 1st, 7th and 14th day post-irradiation, indicating alterations in the metabolism of brain monoamines. On the other hand, the results exhibited that, supplementation of rats with pomegranate, via gavages, at a dose of 3 ml /kg body weight/ day, for 4 weeks along with AlCl3 with or without radiation has significantly ameliorated the changes occurred in the mentioned parameters and the values returned close to the normal ones. It could be concluded that pomegranate, by its antioxidant constituents might antagonize brain oxidative damage and minimize the severity of aluminum (Al), and/or radiation-induced neurotransmitters disorders

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

    International Nuclear Information System (INIS)

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

  16. Radiation-induced Alterations in Immune Response to Staphylococcus aureus Infection

    International Nuclear Information System (INIS)

    In an age when medical advances and terrorist threats frequently make news headlines, exposure to radiation is quickly becoming an issue of public, private, and government interest. Radiotherapy is a common treatment modality for cancer and other diseases. However, there are also equally clear hazards, such as the use of radioactive materials in acts of terrorism or war. Concomitant accidental or terrorism-related exposure to sublethal gamma or mixed-field (gamma and neutron) radiation would inevitably increase morbidity among individuals exposed to microbes. Ionizing radiation damages the haematopoietic and gastrointestinal systems. Prompt, sublethal irradiation increases the susceptibility to bacterial infections by decreasing the number of circulating mature white blood cells in the intestine. The data presented herein represent the first results exploring the effects of whole-body irradiation on the ability of the immune system to respond to microbes. We utilized γ-ray radiation as a model for radiation exposure and then challenged the animals 4 days postexposure to investigate the immune response in the most vulnerable phase of the hematopoietic-immune system. We employed Stapylococcus aureus bacterial challenges, a Gram-positive bacterium that is a major cause of septic shock and death

  17. Radiation sensitivity of foodborne pathogens in meat byproducts with different packaging

    International Nuclear Information System (INIS)

    The aim of this study was to determine radiation sensitivity of Escherichia coli O157:H7 and Listeria monocytogenes in edible meat byproducts. Seven beef byproducts (heart, liver, lung, lumen, omasum, large intestine, and small intestine) and four pork byproducts (heart, large intestine, liver, and small intestine) were used. Electron beam irradiation significantly reduced the numbers of pathogenic microorganisms in meat byproducts and no viable cells were detected in both aerobically- and vacuum-packaged samples irradiated at 4 kGy. Meat byproducts packed under vacuum had higher D10 value than the ones packed aerobically. No significant difference was observed between the D10 values of E. coli O157:H7 and L. monocytogenes inoculated in either aerobically or vacuum packaged samples. These results suggest that low-dose electron beam irradiation can significantly decrease microbial numbers and reduce the risk of meat byproduct contamination by the foodborne pathogens. - Highlights: • Radiation sensitivities of pathogens in meat byproduct were tested. • Electron beam irradiation of 3 or 4 kGy reduced pathogens by> 9 log • The D10 values were lower in the aerobic-packaging than under vacuum condition

  18. Position-sensitive radiation monitoring (surface contamination monitor). Innovative technology summary report

    Energy Technology Data Exchange (ETDEWEB)

    1999-06-01

    The Shonka Research Associates, Inc. Position-Sensitive Radiation Monitor both detects surface radiation and prepares electronic survey map/survey report of surveyed area automatically. The electronically recorded map can be downloaded to a personal computer for review and a map/report can be generated for inclusion in work packages. Switching from beta-gamma detection to alpha detection is relatively simple and entails moving a switch position to alpha and adjusting the voltage level to an alpha detection level. No field calibration is required when switching from beta-gamma to alpha detection. The system can be used for free-release surveys because it meets the federal detection level sensitivity limits requires for surface survey instrumentation. This technology is superior to traditionally-used floor contamination monitor (FCM) and hand-held survey instrumentation because it can precisely register locations of radioactivity and accurately correlate contamination levels to specific locations. Additionally, it can collect and store continuous radiological data in database format, which can be used to produce real-time imagery as well as automated graphics of survey data. Its flexible design can accommodate a variety of detectors. The cost of the innovative technology is 13% to 57% lower than traditional methods. This technology is suited for radiological surveys of flat surfaces at US Department of Energy (DOE) nuclear facility decontamination and decommissioning (D and D) sites or similar public or commercial sites.

  19. The effects of altered levels of UV-B radiation on an Antarctic grass and lichen

    NARCIS (Netherlands)

    Lud, D.; Huiskes, A.H.L.; Moerdijk-Poortvliet, T.C.W.; Rozema, J.J.

    2001-01-01

    We report a long-term experiment on the photosynthetic response of natural vegetation of Deschampsia antarctica (Poaceae) and Turgidosculum complicatulum (Lichenes) to altered UV-B levels on Leonie Island, Antarctica. UV-B above the vegetation was reduced by filter screens during two seasons. Half o

  20. Alterations in biochemical and physiological characters in radiation-induced mutants of grain legumes

    International Nuclear Information System (INIS)

    Selected examples from different grain legumes are studied. The biochemically and physiologically detectable alterations in distintc characters as caused by the action of mutant genes are presented comparatively. The interactions between different mutant genes in order to evaluated the influence of the genotypic constitution on the expression of mutated genes are emphasized. (M.A.C.)

  1. Estimations of climate sensitivity based on top-of-atmosphere radiation imbalance

    Directory of Open Access Journals (Sweden)

    B. Lin

    2010-02-01

    Full Text Available Large climate feedback uncertainties limit the accuracy in predicting the response of the Earth's climate to the increase of CO2 concentration within the atmosphere. This study explores a potential to reduce uncertainties in climate sensitivity estimations using energy balance analysis, especially top-of-atmosphere (TOA radiation imbalance. The time-scales studied generally cover from decade to century, that is, middle-range climate sensitivity is considered, which is directly related to the climate issue caused by atmospheric CO2 change. The significant difference between current analysis and previous energy balance models is that the current study targets at the boundary condition problem instead of solving the initial condition problem. Additionally, climate system memory and deep ocean heat transport are considered. The climate feedbacks are obtained based on the constraints of the TOA radiation imbalance and surface temperature measurements of the present climate. In this study, the TOA imbalance value of 0.85 W/m2 is used. Note that this imbalance value has large uncertainties. Based on this value, a positive climate feedback with a feedback coefficient ranging from −1.3 to −1.0 W/m2/K is found. The range of feedback coefficient is determined by climate system memory. The longer the memory, the stronger the positive feedback. The estimated time constant of the climate is large (70~120 years mainly owing to the deep ocean heat transport, implying that the system may be not in an equilibrium state under the external forcing during the industrial era. For the doubled-CO2 climate (or 3.7 W/m2 forcing, the estimated global warming would be 3.1 K if the current estimate of 0.85 W/m2 TOA net radiative heating could be confirmed. With accurate long-term measurements of TOA radiation, the analysis method suggested by this study provides a great potential in the

  2. Enhanced radiation sensitivity and radiation recall dermatitis (RRD after hypericin therapy – case report and review of literature

    Directory of Open Access Journals (Sweden)

    Schäfer Christof

    2006-09-01

    Full Text Available Abstract Background Modern radiotherapy (RT reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a "recall phenomenon" imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of "radiation recall dermatitis" (RRD one year after RT as a result of taking hypericin (St. John's wort. Case report A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward. Conclusion Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially

  3. Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy – case report and review of literature

    International Nuclear Information System (INIS)

    Modern radiotherapy (RT) reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a 'recall phenomenon' imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of 'radiation recall dermatitis' (RRD) one year after RT as a result of taking hypericin (St. John's wort). A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward. Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially for complementary or alternative

  4. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Suk Chul [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Lee, Kyung-Mi [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kang, Yu Mi [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Kwanghee [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Chong Soon [Department of Nuclear Medicine, Haeundae Paik Hospital, Inje University, Busan 612-030 (Korea, Republic of); Kim, Hee Sun, E-mail: hskimdvm@khnp.co.kr [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of)

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  5. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    International Nuclear Information System (INIS)

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4+ T, CD8+ T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1α, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-γ. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose γ-radiation, which may be associated with the functional benefits observed in various experimental models.

  6. Etoposide sensitizes CT26 colorectal adenocarcinoma to radiation therapy in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    Chia-Yuan Liu; Hui-Fen Liao; Tsang-En Wang; Shee-Chan Lin; Shou-Chuan Shih; Wen-Hsuing Chang; Yuh-Cheng Yang; Ching-Chung Lin; Yu-Jen Chen

    2005-01-01

    AIM: To investigate the combined effect of etoposide and radiation on CT26 colorectal adenocarcinoma implanted into BALB/c mice.METHODS: We evaluated the radiosensitizing effect of etoposide on CT26 colorectal adenocarcinoma in a syngeneic animal model. BALB/c mice were subcutaneously implanted with CT26 cells and divided into four groups:control (intra-peritoneal salinex2) group, etoposide (5 mg/kgintra-peritoneallyx2) group, radiation therapy (RT 5 Gyx2fractions) group, and combination therapy with etoposide (5 mg/kg intra-peritoneally 1 h before radiation) group.RESULTS: Tumor growth was significantly inhibited by RT and combination therapy. The effect of combination therapy was better than that of RT. No significant changes were noted in body weight, plasma alanine aminotransferase,or creatinine in any group. The leukocyte count significantly but transiently decreased in the RT and combination therapy groups, but not in the etoposide and control groups. There was no skin change or hair loss in the RT and combination therapy groups.CONCLUSION: Etoposide can sensitize CT26 colorectal adenocarcinoma in BALB/c mice to RT without significant toxicity.

  7. Estimating option values of solar radiation management assuming that climate sensitivity is uncertain.

    Science.gov (United States)

    Arino, Yosuke; Akimoto, Keigo; Sano, Fuminori; Homma, Takashi; Oda, Junichiro; Tomoda, Toshimasa

    2016-05-24

    Although solar radiation management (SRM) might play a role as an emergency geoengineering measure, its potential risks remain uncertain, and hence there are ethical and governance issues in the face of SRM's actual deployment. By using an integrated assessment model, we first present one possible methodology for evaluating the value arising from retaining an SRM option given the uncertainty of climate sensitivity, and also examine sensitivities of the option value to SRM's side effects (damages). Reflecting the governance challenges on immediate SRM deployment, we assume scenarios in which SRM could only be deployed with a limited degree of cooling (0.5 °C) only after 2050, when climate sensitivity uncertainty is assumed to be resolved and only when the sensitivity is found to be high (T2x = 4 °C). We conduct a cost-effectiveness analysis with constraining temperature rise as the objective. The SRM option value is originated from its rapid cooling capability that would alleviate the mitigation requirement under climate sensitivity uncertainty and thereby reduce mitigation costs. According to our estimates, the option value during 1990-2049 for a +2.4 °C target (the lowest temperature target level for which there were feasible solutions in this model study) relative to preindustrial levels were in the range between $2.5 and $5.9 trillion, taking into account the maximum level of side effects shown in the existing literature. The result indicates that lower limits of the option values for temperature targets below +2.4 °C would be greater than $2.5 trillion. PMID:27162346

  8. Lung tumorigenic response of strain A mice exposed to hypoxic cell sensitizers alone and in combination with gamma-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Mian, T.A.; Theiss, J.C.; Grdina, D.J.

    1983-01-01

    The influence of metronidazole, misonidazole, and desmethylmisonidazole on the induction of lung adenomas in the strain A mouse was examined. Two dose levels of the hypoxic cell sensitizers, 0.2 and 0.6 mg/g, were used either alone or in combination with 900 rads of gamma-radiation in a fractionated dose schedule of twice a week for 3 weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased (p less than 0.10) in the group receiving the higher dose (0.6 mg/g) of misonidazole but was not significantly different from results for the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with that in the control group. Thus, under the experimental exposure conditions used in this investigation, which were somewhat similar to the exposure conditions occurring in clinical treatment, each of the hypoxic cell sensitizers tested failed to sensitize significantly the mice to the carcinogenic effects of gamma-radiation.

  9. Lung tumorigenic response of strain A mice exposed to hypoxic cell sensitizers alone and in combination with gamma-radiation.

    Science.gov (United States)

    Mian, T A; Theiss, J C; Grdina, D J

    1983-01-01

    The influence of metronidazole, misonidazole, and desmethylmisonidazole on the induction of lung adenomas in the strain A mouse was examined. Two dose levels of the hypoxic cell sensitizers, 0.2 and 0.6 mg/g, were used either alone or in combination with 900 rads of gamma-radiation in a fractionated dose schedule of twice a week for 3 weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased (p less than 0.10) in the group receiving the higher dose (0.6 mg/g) of misonidazole but was not significantly different from results for the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with that in the control group. Thus, under the experimental exposure conditions used in this investigation, which were somewhat similar to the exposure conditions occurring in clinical treatment, each of the hypoxic cell sensitizers tested failed to sensitize significantly the mice to the carcinogenic effects of gamma-radiation.

  10. Synergistic effects of ultraviolet radiation, thermal cycling and atomic oxygen on altered and coated Kapton surfaces

    Science.gov (United States)

    Dever, Joyce A.; Bruckner, Eric J.; Rodriguez, Elvin

    1992-01-01

    The photovoltaic (PV) power system for Space Station Freedom (SSF) uses solar array blankets which provide structural support for the solar cells and house the electrical interconnections. In the low earth orbital (LEO) environment where SSF will be located, surfaces will be exposed to potentially damaging environmental conditions including solar ultraviolet (UV) radiation, thermal cycling, and atomic oxygen. It is necessary to use ground based tests to determine how these environmental conditions would affect the mass loss and optical properties of candidate SSF blanket materials. Silicone containing, silicone coated, and SiO(x) coated polyimide film materials were exposed to simulated LEO environmental conditions to determine their durability and whether the environmental conditions of UV, thermal cycling and oxygen atoms act synergistically on these materials. A candidate PV blanket material called AOR Kapton, a polysiloxane polyimide cast from a solution mixture, shows an improvement in durability to oxygen atoms erosion after exposure to UV radiation or thermal cycling combined with UV radiation. This may indicate that the environmental conditions react synergistically with this material, and the damage predicted by exposure to atomic oxygen alone is more severe than that which would occur in LEO where atomic oxygen, thermal cycling and UV radiation are present together.

  11. The effect of post-mastectomy radiation therapy on breast implants: Unveiling biomaterial alterations with potential implications on capsular contracture.

    Science.gov (United States)

    Ribuffo, Diego; Lo Torto, Federico; Giannitelli, Sara M; Urbini, Marco; Tortora, Luca; Mozetic, Pamela; Trombetta, Marcella; Basoli, Francesco; Licoccia, Silvia; Tombolini, Vincenzo; Cassese, Raffaele; Scuderi, Nicolò; Rainer, Alberto

    2015-12-01

    Post-mastectomy breast reconstruction with expanders and implants is recognized as an integral part of breast cancer treatment. Its main complication is represented by capsular contracture, which leads to poor expansion, breast deformation, and pain, often requiring additional surgery. In such a scenario, the debate continues as to whether the second stage of breast reconstruction should be performed before or after post-mastectomy radiation therapy, in light of potential alterations induced by irradiation to silicone biomaterial. This work provides a novel, multi-technique approach to unveil the role of radiotherapy in biomaterial alterations, with potential involvement in capsular contracture. Following irradiation, implant shells underwent mechanical, chemical, and microstructural evaluation by means of tensile testing, Attenuated Total Reflectance Fourier Transform InfraRed spectroscopy (ATR/FTIR), Scanning Electron Microscopy (SEM), high resolution stylus profilometry, and Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Our findings are consistent with radiation-induced modifications of silicone that, although not detectable at the microscale, can be evidenced by more sophisticated nanoscale surface analyses. In light of these results, biomaterial irradiation cannot be ruled out as one of the possible co-factors underlying capsular contracture.

  12. Alterations of mtDNA number and 4977 bp deletion induced by ionizing radiation in human peripheral blood

    International Nuclear Information System (INIS)

    Alterations of mitochondria DNA (mtDNA) 4977 bp common deletion (CD) and mtDNA copy number induced by ionizing radiation were observed in human different cell lines and total body irradiation patients. However, only few experiments have evaluated the levels of the CD and mtDNA copy number in human peripheral blood exposed to ionizing radiation till now. The aim of this study is to analyze the mtDNA alterations in irradiated human peripheral blood from healthy donors as well as to explore their feasibility as biomarkers for constructing new biodosimeter. Peripheral blood samples were collected from six healthy donors, and exposed to 60Co gamma ray with the doses of 0 Gy, 1 Gy, 2 Gy, 3 Gy, 4 Gy and 5 Gy. Levels of the CD and mtDNA copy number in irradiated samples after 2h or 24 h incubation were detected using TaqMan real-time PCR, and the CD ratio was calculated. The results showed that the mean of the CD ratio and the CD copy number exhibited a dose-dependent increase 2 h in the dose range from 0-5 Gy, and of the mtDNA copy number significantly increased 24 h in irradiated groups compared with 0 Gy group after irradiation. It indicates that the parameters in human peripheral blood may be considered as molecular biomarkers to applying construction of new biodosimeter. (authors)

  13. Optical Coherence Tomography for Quantitative Assessment of Microstructural and Microvascular Alterations in Late Oral Radiation Toxicity

    Science.gov (United States)

    Davoudi, Bahar

    More than half of head-and-neck cancer patients undergo radiotherapy at some point during their treatment. Even though the use of conformed therapeutic beams has increased radiation dose localization to the tumor, resulting in more normal tissue sparing, still, in many head-and-neck cancer patients, the healthy tissue of the oral cavity still receives a sizeable amount of radiation. This causes acute and / or late complications in these patients. The latter occur as late as several months or even years after the completion of treatment and are typically associated with severe symptoms. Currently, the clinical method for diagnosing these complications is visual examination of the oral tissue surface. However, it has been well established that such complications originate in subsurface oral tissue layers including its microvasculature. Therefore, to better understand the mechanism of these complications and to be able to diagnose them earlier, there exists a need for subsurface monitoring of the irradiated oral tissue. Histology has been used as such a tool for research purposes; however, its use in clinical diagnosis is limited due to its invasive and hazardous nature. Therefore, in this thesis, I propose to use optical coherence tomography (OCT) as a subsurface, micron-scale resolution optical imaging tool that can provide images of oral tissue subsurface layers down to a depth of 1-2 mm (structural OCT), as well as images demonstrating vessel morphology (speckle variance OCT) and blood flow information (Doppler OCT). This thesis explains the development of an OCT setup and an oral probe to acquire images in-vivo. Moreover, it introduces a software-based quantification platform for extracting specific biologically-meaningful metrics from the structural and vascular OCT images. It then describes the application of the developed imaging and quantification platform in a feasibility clinical study that was performed on 15 late oral radiation toxicity patients and 5 age

  14. An Escherichia coli strain deficient for both exonuclease V and deoxycytidine triphosphate deaminase shows enhanced sensitivity to ionizing radiation.

    Science.gov (United States)

    Estèvenon, A M; Kooistra, J; Sicard, N

    1995-02-20

    An Escherichia coli mutant lacking deoxycytidine triphosphate deaminase (Dcd) activity and an unknown function encoded by a gene designated ior exhibits sensitivity to ionizing radiation whereas dcd mutants themselves are not sensitive. A DNA fragment from an E. coli genomic library that restores the wild type level of UV and gamma ray resistance to this mutant has been cloned in the multicopy vector pBR322. Comparison of its restriction map with the physical map of the E. coli chromosome revealed complete identity to the recBD genes. ior affects ATP-dependent exonuclease activity, suggesting that it is an allele of recB. This mutation alone does not confer sensitivity to UV and gamma radiation, indicating that lack of Dcd activity is also required for expression of radiation sensitivity.

  15. Differential Sensitivity of Cells to Radiation Mediated by p53 Pulses

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Kang, Mi Young; Kawala, Remigius A.; Ryu, Tae Ho; Kim, Jin-Hong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    Exposure of cells to ionizing radiation activates protein genes related cell cycle arrest and cell death (apoptosis or autophagy). The tumor suppressor p53 participates not only in regulation of apoptosis, but also in autophagy mechanism. Apoptosis (type I cell death) is characterized by the activation of caspases and the formation of apoptotic bodies, and plays essential roles in all multicellular organisms. On the other hand, autophagy (type II cell death) is characterized by the presence of cytoplasmic engulfing vesicles, alias autophagosomes, and is a major intracellular pathway for degradation and recycling of proteins, ribosomes and entire organelles. The purpose of this study was to determine whether ionizing radiation treatment induces autophagy depending on the p53 expression levels. RKO (wild-type p53) and RKO E6 (null-type p53) cells were used to evaluate the effects of p53 on the sensitivity of cells to ionizing radiation. In the RKO E6 cells, the function of p53 was disabled with human papillomavirus E6 oncoprotein. These results indicated that p53 and p21 were required to block apoptosis and induce autophagy in RKO cells. The expression of p21 by a p53-dependent mechanism is required to develop autophagic properties after DNA damage. Results in this study suggest that the radioresistance of the RKO cells was associated with the increased p21 expression, resulting in autophagy induction. The tumor suppressor p53 could regulate radiosensitivity by inhibiting autophagy and activating apoptosis; the ionizing radiation-induced expression of p53 in the RKO cells regulated autophagy, suggesting the significance of the level of p53 in determining the radiosensitivity by regulating autophagy and apoptosis.

  16. Radiation Sensitivity in a Preclinical Mouse Model of Medulloblastoma Relies on the Function of the Intrinsic Apoptotic Pathway.

    Science.gov (United States)

    Crowther, Andrew J; Ocasio, Jennifer K; Fang, Fang; Meidinger, Jessica; Wu, Jaclyn; Deal, Allison M; Chang, Sha X; Yuan, Hong; Schmid, Ralf; Davis, Ian; Gershon, Timothy R

    2016-06-01

    While treatments that induce DNA damage are commonly used as anticancer therapies, the mechanisms through which DNA damage produces a therapeutic response are incompletely understood. Here we have tested whether medulloblastomas must be competent for apoptosis to be sensitive to radiotherapy. Whether apoptosis is required for radiation sensitivity has been controversial. Medulloblastoma, the most common malignant brain tumor in children, is a biologically heterogeneous set of tumors typically sensitive to radiation and chemotherapy; 80% of medulloblastoma patients survive long-term after treatment. We used functional genetic studies to determine whether the intrinsic apoptotic pathway is required for radiation to produce a therapeutic response in mice with primary, Shh-driven medulloblastoma. We found that cranial radiation extended the survival of medulloblastoma-bearing mice and induced widespread apoptosis. Expression analysis and conditional deletion studies showed that Trp53 (p53) was the predominant transcriptional regulator activated by radiation and was strictly required for treatment response. Deletion of Bax, which blocked apoptosis downstream of p53, was sufficient to render tumors radiation resistant. In apoptosis-incompetent, Bax-deleted tumors, radiation activated p53-dependent transcription without provoking cell death and caused two discrete populations to emerge. Most radiated tumor cells underwent terminal differentiation. Perivascular cells, however, quickly resumed proliferation despite p53 activation, behaved as stem cells, and rapidly drove recurrence. These data show that radiation must induce apoptosis in tumor stem cells to be effective. Mutations that disable the intrinsic apoptotic pathways are sufficient to impart radiation resistance. We suggest that medulloblastomas are typically sensitive to DNA-damaging therapies, because they retain apoptosis competence. Cancer Res; 76(11); 3211-23. ©2016 AACR. PMID:27197166

  17. Characterization of dose-dependent Young's modulus for a radiation-sensitive polymer gel

    International Nuclear Information System (INIS)

    Radiation-sensitive polymer gels for clinical dosimetry have been intensively investigated with magnetic resonance imaging (MRI) because the transversal magnetic relaxation time is dependent on irradiation dose. MRI is expensive and not easily available in most clinics. For this reason, low-cost, quick and easy-to-use potential alternatives such as optical computed tomography (CT), x-ray CT or ultrasound attenuation CT have also been studied by others. Here, we instead evaluate the dose dependence of the elastic material property, Young's modulus and the dose response of the viscous relaxation of radiation-sensitive gels to discuss their potential for dose imaging. Three batches of a radiation-sensitive polymer gel (MAGIC gel) samples were homogeneously irradiated to doses from 0 Gy to 45.5 Gy. Young's modulus was computed from the measured stress on the sample surface and the strain applied to the sample when compressing it axially, and the viscous relaxation was determined from the stress decay under sustained compression. The viscous relaxation was found not to change significantly with dose. However, Young's modulus was dose dependent; it approximately doubled in the gels between 0 Gy and 20 Gy. By fitting a second-order polynomial to the Young's modulus-versus-dose data, 99.4% of the variance in Young's modulus was shown to be associated with the change in dose. The precision of the gel production, irradiation and Young's modulus measurement combined was found to be 4% at 2 Gy and 3% at 20 Gy. Potential sources of measurement error, such as those associated with the boundary conditions in the compression measurement, inhomogeneous polymerization, temperature (up to 1% error) and the evaporation of water from the sample (up to 1% error), were estimated and discussed. It was concluded that Young's modulus could be used for dose determination. Imaging techniques such as elastography may help to achieve this if they can provide a local measurement of Young

  18. Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells.

    Science.gov (United States)

    Canuto, K S; Sergio, L P S; Guimarães, O R; Geller, M; Paoli, F; Fonseca, A S

    2015-10-01

    Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia colicells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficientE. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

  19. Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells

    Directory of Open Access Journals (Sweden)

    K.S. Canuto

    2015-01-01

    Full Text Available Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia coli cells that were exposed to ultraviolet C (UVC radiation. Exponential and stationary wild-type and uvrA-deficient E. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC. Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out.

  20. Low-level red laser therapy alters effects of ultraviolet C radiation on Escherichia coli cells

    Energy Technology Data Exchange (ETDEWEB)

    Canuto, K.S.; Guimaraes, O.R.; Geller, M. [Centro Universitario Serra dos Orgaos, Teresopolis, RJ (Brazil). Centro de Ciencias da Saude; Sergio, L.P.S. [Instituto de Biologia Roberto Alcantara Gomes, Rio de Janeiro, RJ (Brazil). Departamento de Biofisica e Biometria; Paoli, F. [Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, MG (Brazil). Departamento de Morfologia; Fonseca, A.S., E-mail: adnfonseca@ig.com.br [Universidade Federal do Estado do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Departamento de Ciencias Fisiologicas

    2015-10-15

    Low-level lasers are used at low power densities and doses according to clinical protocols supplied with laser devices or based on professional practice. Although use of these lasers is increasing in many countries, the molecular mechanisms involved in effects of low-level lasers, mainly on DNA, are controversial. In this study, we evaluated the effects of low-level red lasers on survival, filamentation, and morphology of Escherichia coli cells that were exposed to ultraviolet C (UVC) radiation. Exponential and stationary wild-type and uvrA-deficient E. coli cells were exposed to a low-level red laser and in sequence to UVC radiation. Bacterial survival was evaluated to determine the laser protection factor (ratio between the number of viable cells after exposure to the red laser and UVC and the number of viable cells after exposure to UVC). Bacterial filaments were counted to obtain the percentage of filamentation. Area-perimeter ratios were calculated for evaluation of cellular morphology. Experiments were carried out in duplicate and the results are reported as the means of three independent assays. Pre-exposure to a red laser protected wild-type and uvrA-deficient E. coli cells against the lethal effect of UVC radiation, and increased the percentage of filamentation and the area-perimeter ratio, depending on UVC fluence and physiological conditions in the cells. Therapeutic, low-level red laser radiation can induce DNA lesions at a sub-lethal level. Consequences to cells and tissues should be considered when clinical protocols based on this laser are carried out. (author)

  1. Radioprotective potential of Emblica officinalis fruit extract against hematological alterations induced by gamma radiation

    International Nuclear Information System (INIS)

    In the era of expending nuclear energy program all over the world, the role of radiation biology has acquired greater relevance and significance in addressing the health issues in view of constant human exposure to various types of radiations. Radioprotective drugs hold immense promise for saving precious human lives in from irradiation in various situations. Currently available synthetic radiomudulators is fraught with their inherent toxicity at the optimum dose and hence the need to discover and develop new more effective less toxic radiomudulatory drugs from natural sources. In the present study, the protective effect of Emblica officinalis fruit extract (EOFE) has been assessed by estimating hematological constituents against irradiation. For this purpose, Swiss albino mice were divided into four groups. Group I was administered with double distilled water (DDW) volume equal to EOFE (100 mg./kg. body wt./animal/clay) by oral gavages to serve as normal. Group II was administered orally EOFE for 7 days once daily at a does of 100 mg./kg.b. wt./animal/day, Group Ill animals were exposed to 2.5 Gy gamma radiations to serve as irradiated control. Group IV mice were treated with EOFE, orally for consecutive days (as in Group II) and were exposed to 2.5 Gy gamma rays half an hr. after the last administration of EOFE on day 7th. The above animals were necropsied on 12 hr, 24 hr, 3 days, 5 days, 10 days, 20 days and 30 days post treatment intervals, and their blood was collected for estimation of blood constituents. A significant decline in RBC, hemoglobin (Hb) and hematocrit (Hct) contents from normal was observed in irradiated control animals (Group III). All these parameters were found to be significantly higher in EOFE pretreated irradiated animals (Group IV). From these results, it is concluded that Emblica officinalis fruit extract has the ability to protect the individuals from radiation-induced hematological injuries. (author)

  2. The effect of free radical inhibitor on the sensitized radiation crosslinking and thermal processing stabilization of polyurethane shape memory polymers

    International Nuclear Information System (INIS)

    The effects of free radical inhibitor on the electron beam crosslinking and thermal processing stabilization of novel radiation crosslinkable polyurethane shape memory polymers (SMPs) blended with acrylic radiation sensitizers have been determined. The SMPs in this study possess novel processing capabilities—that is, the ability to be melt processed into complex geometries as thermoplastics and crosslinked in a secondary step using electron beam irradiation. To increase susceptibility to radiation crosslinking, the radiation sensitizer pentaerythritol triacrylate (PETA) was solution blended with thermoplastic polyurethane SMPs made from 2-butene-1,4-diol and trimethylhexamethylene diisocyanate (TMHDI). Because the thermoplastic melt processing methods such as injection molding are often carried out at elevated temperatures, sensitizer thermal instability is a major processing concern. Free radical inhibitor can be added to provide thermal stabilization; however, inhibitor can also undesirably inhibit radiation crosslinking. In this study, we quantified both the thermal stabilization and radiation crosslinking inhibition effects of the inhibitor 1,4-benzoquinone (BQ) on polyurethane SMPs blended with PETA. Sol/gel analysis of irradiated samples showed that the inhibitor had little to no inverse effects on gel fraction at concentrations of 0–10,000 ppm, and dynamic mechanical analysis showed only a slight negative correlation between BQ composition and rubbery modulus. The 1,4-benzoquinone was also highly effective in thermally stabilizing the acrylic sensitizers. The polymer blends could be heated to 150 °C for up to 5 h or to 125 °C for up to 24 h if stabilized with 10,000 ppm BQ and could also be heated to 125 °C for up to 5 h if stabilized with 1000 ppm BQ without sensitizer reaction occurring. We believe this study provides significant insight into methods for manipulation of the competing mechanisms of radiation crosslinking and thermal stabilization of

  3. Gene expression profiling of human dermal fibroblasts exposed to bleomycin sulphate does not differentiate between radiation sensitive and control patients

    International Nuclear Information System (INIS)

    Gene expression profiling of the transcriptional response of human dermal fibroblasts to in vitro radiation has shown promise as a predictive test of radiosensitivity. This study tested if treatment with the radiomimetic drug bleomycin sulphate could be used to differentiate radiation sensitive patients and controls in patients who had previously received radiotherapy for early breast cancer. Eight patients who developed marked late radiation change assessed by photographic breast appearance and 8 matched patients without any change were selected from women entered in a prospective randomised trial of breast radiotherapy fractionation. Gene expression profiling of primary skin fibroblasts exposed in vitro to bleomycin sulphate and mock treated fibroblast controls was performed. 973 genes were up-regulated and 923 down-reguated in bleomycin sulphate treated compared to mock treated control fibroblasts. Gene ontology analysis revealed enriched groups were cellular localisation, apoptosis, cell cycle and DNA damage response for the deregulated genes. No transcriptional differences were identified between fibroblasts from radiation sensitive cases and control patients; subgroup analysis using cases exhibiting severe radiation sensitivity or with high risk alleles present in TGF β1 also showed no difference. The transcriptional response of human dermal fibroblasts to bleomycin sulphate has been characterised. No differences between clinically radiation sensitive and control patients were detected using this approach

  4. Hypoxia-reoxygenation differentially alters the thermal sensitivity of complex I basal and maximal mitochondrial oxidative capacity.

    Science.gov (United States)

    Onukwufor, John O; Kibenge, Fred; Stevens, Don; Kamunde, Collins

    2016-11-01

    Hypoxia-reoxygenation (H-R) transitions and temperature fluctuations occur frequently in biological systems and likely interact to alter cell function. To test how H-R modulates mitochondrial function at different temperatures we measured the effects of H-R on isolated fish liver mitochondrial oxidation rates over a wide temperature range (5-25°C). Subsequently, the mechanisms underlying H-R induced mitochondrial responses were examined. H-R inhibited the complex I (CI) maximal (state 3) and stimulated the basal (state 4) mitochondrial oxidation rates with temperature enhancing both effects. As a result, the thermal sensitivity (Q10) for CI maximal respiration was reduced while that for basal respiration was increased by H-R. H-R reduced both the coupling and phosphorylation efficiencies more profoundly at high temperature suggesting that mitochondria were more resistant to H-R at low temperature. The H-R induced mitochondrial impairments were associated with increased reactive oxygen species (ROS) production and proton leak, dissipation of membrane potential, and loss of structural integrity of the organelles. Overall, our study provides insight into the mechanisms of H-R induced mitochondrial morphofunctional disruption and shows that the moderation of effects of H-R on oxidative phosphorylation by temperature depends on the functional state. PMID:27387443

  5. Using satellites to investigate the sensitivity of longwave downward radiation to water vapor at high elevations

    Science.gov (United States)

    Naud, Catherine M.; Miller, James R.; Landry, Chris

    2012-03-01

    Many studies suggest that high-elevation regions may be among the most sensitive to future climate change. However, in situ observations in these often remote locations are too sparse to determine the feedbacks responsible for enhanced warming rates. One of these feedbacks is associated with the sensitivity of longwave downward radiation (LDR) to changes in water vapor, with the sensitivity being particularly large in many high-elevation regions where the average water vapor is often low. We show that satellite retrievals from the Moderate Resolution Imaging Spectroradiometer (MODIS) and Clouds and the Earth's Radiant Energy System (CERES) can be used to expand the current ground-based observational database and that the monthly averaged clear-sky satellite estimates of humidity and LDR are in good agreement with the well-instrumented Center for Snow and Avalanche Studies ground-based site in the southwestern Colorado Rocky Mountains. The relationship between MODIS-retrieved precipitable water vapor and surface specific humidity across the contiguous United States was found to be similar to that previously found for the Alps. More important, we show that satellites capture the nonlinear relationship between LDR and water vapor and confirm that LDR is especially sensitive to changes in water vapor at high elevations in several midlatitude mountain ranges. Because the global population depends on adequate fresh water, much of which has its source in high mountains, it is critically important to understand how climate will change there. We demonstrate that satellites can be used to investigate these feedbacks in high-elevation regions where the coverage of surface-based observations is insufficient to do so.

  6. Patterns of dioxin-altered mRNA expression in livers of dioxin-sensitive versus dioxin-resistant rats

    Energy Technology Data Exchange (ETDEWEB)

    Franc, Monique A. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Johnson and Johnson Pharmaceutical Research and Development, Department of Pharmacogenomics, 1000 Route 202 South, P.O. Box 300, Raritan, NJ (United States); Moffat, Ivy D.; Boutros, Paul C.; Okey, Allan B. [University of Toronto, Department of Pharmacology and Toxicology, Medical Sciences Building, Toronto, ON (Canada); Tuomisto, Jouni T.; Tuomisto, Jouko [National Public Health Institute, Department of Environmental Health, Centre for Environmental Health Risk Analysis, Kuopio (Finland); Pohjanvirta, Raimo [University of Helsinki, Department of Food and Environmental Hygiene, Faculty of Veterinary Medicine, Helsinki (Finland)

    2008-11-15

    Dioxins exert their major toxicologic effects by binding to the aryl hydrocarbon receptor (AHR) and altering gene transcription. Numerous dioxin-responsive genes previously were identified both by conventional biochemical and molecular techniques and by recent mRNA expression microarray studies. However, of the large set of dioxin-responsive genes the specific genes whose dysregulation leads to death remain unknown. To identify specific genes that may be involved in dioxin lethality we compared changes in liver mRNA levels following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in three strains/lines of dioxin-sensitive rats with changes in three dioxin-resistant rat strains/lines. The three dioxin-resistant strains/lines all harbor a large deletion in the transactivation domain of the aryl hydrocarbon receptor (AHR). Despite this deletion, many genes exhibited a ''Type-I'' response - that is, their responses were similar in dioxin-sensitive and dioxin-resistant rats. Several genes that previously were well established as being dioxin-responsive or under AHR regulation emerged as Type-I responses (e.g. CYP1A1, CYP1A2, CYP1B1 and Gsta3). In contrast, a relatively small number of genes exhibited a Type-II response - defined as a difference in responsiveness between dioxin-sensitive and dioxin-resistant rat strains. Type-II genes include: malic enzyme 1, ubiquitin C, cathepsin L, S-adenosylhomocysteine hydrolase and ferritin light chain 1. In silico searches revealed that AH response elements are conserved in the 5'-flanking regions of several genes that respond to TCDD in both the Type-I and Type-II categories. The vast majority of changes in mRNA levels in response to 100 {mu}g/kg TCDD were strain-specific; over 75% of the dioxin-responsive clones were affected in only one of the six strains/lines. Selected genes were assessed by quantitative RT-PCR in dose-response and time-course experiments and responses of some genes were

  7. Can climate sensitivity be estimated from short-term relationships of top-of-atmosphere net radiation and surface temperature?

    International Nuclear Information System (INIS)

    Increasing the knowledge in climate radiative feedbacks is critical for current climate studies. This work focuses on short-term relationships between global mean surface temperature and top-of-atmosphere (TOA) net radiation. The relationships may be used to characterize the climate feedback as suggested by some recent studies. As those recent studies, an energy balance model with ocean mixed layer and both radiative and non-radiative heat sources is used here. The significant improvement of current model is that climate system memories are considered. Based on model simulations, short-term relationship between global mean surface temperature and TOA net radiation (or the linear striation feature as suggested by previous studies) might represent climate feedbacks when the system had no memories. However, climate systems with the same short-term feedbacks but different memories would have a similar linear striation feature. This linear striation feature reflects only fast components of climate feedbacks and may not represent the total climate feedback even when the memory length of climate systems is minimal. The potential errors in the use of short-term relationships in estimations of climate sensitivity could be big. In short time scales, fast climate processes may overwhelm long-term climate feedbacks. Thus, the climate radiative feedback parameter obtained from short-term data may not provide a reliable estimate of climate sensitivity. This result also suggests that long-term observations of global surface temperature and TOA radiation are critical in the understanding of climate feedbacks and sensitivities.

  8. Food restriction alters pramipexole-induced yawning, hypothermia, and locomotor activity in rats: Evidence for sensitization of dopamine D2 receptor-mediated effects

    OpenAIRE

    Collins, Gregory T; Calinski, Diane M.; Newman, Amy Hauck; Grundt, Peter; Woods, James H.

    2008-01-01

    Food restriction enhances sensitivity to the reinforcing effects of a variety of drugs of abuse including opiates, nicotine, and psychostimulants. Food restriction has also been shown to alter a variety of behavioral and pharmacological responses to dopaminergic agonists including an increased sensitivity to the locomotor stimulatory effects of direct- and indirect-dopamine agonists, elevated extracellular dopamine levels in responses to psychostimulants, as well as suppression of agonist-ind...

  9. Radiation sensitivity of natural organic matter: Clay mineral association effects in the Callovo-Oxfordian argillite

    International Nuclear Information System (INIS)

    Clay-rich low-organic carbon formations (e.g., Callovo-Oxfordian argillite in France and Opalinus Clay in Switzerland) are considered as host rocks for radioactive waste disposal. The clay-organic carbon has a strong impact on the chemical stability of the clays. For this reason, the nature of the clay-organic carbon, the release of hydrophilic organic compounds, namely, humic (HA) and fulvic acids (FA) and the radiation sensitivity of the undisturbed host rock organics was investigated. The clay sample originates from Oxfordian argillite (447 m depth, borehole EST 104). HA and FA were extracted following the standard International Humic Substance Society (IHSS) isolation procedure. Synchrotron based (C-, K-, Ca-, O- and Fe-edge XANES) scanning transmission X-ray microscopy (STXM) and FT-IR microspectroscopy was used to identify under high spatial resolution the distribution of clay-organic matter with different functionality using principal component and cluster analysis. The results show that in this old (Jurassic) geological formation, small parts of the organic inventory (1-5%) keeps the structure/functionality and can be mobilized as hydrophilic humic substance type material (HA and FA). Target spectra analysis shows best correlation for isolated humic acids with organics found in smectite-rich regions, whereas the extractable FA has better spectral similarities with the illite mixed layer minerals (MLM) regions. After radiation of 1.7 GGy under helium atmosphere the same rock sample area was investigated for radiation damage. Radiation damage in the smectite and illite-MLM associated organic matter is comparably low with 20-30% total oxygen mass loss and 13-18% total carbon mass loss. A critical dose dc of 2.5 GGy and a optical density after infinite radiation (OD∝) of 54% was calculated under room temperature conditions. C(1s) XANES show a clear increase in C=C bonds especially in the illite-MLM associated organics. This results suggests a combination of

  10. Radiation sensitivity of foodborne pathogens in meat byproducts with different packaging

    Science.gov (United States)

    Yong, Hae In; Kim, Hyun-Joo; Nam, Ki Chang; Kwon, Joong Ho; Jo, Cheorun

    2015-10-01

    The aim of this study was to determine radiation sensitivity of Escherichia coli O157:H7 and Listeria monocytogenes in edible meat byproducts. Seven beef byproducts (heart, liver, lung, lumen, omasum, large intestine, and small intestine) and four pork byproducts (heart, large intestine, liver, and small intestine) were used. Electron beam irradiation significantly reduced the numbers of pathogenic microorganisms in meat byproducts and no viable cells were detected in both aerobically- and vacuum-packaged samples irradiated at 4 kGy. Meat byproducts packed under vacuum had higher D10 value than the ones packed aerobically. No significant difference was observed between the D10 values of E. coli O157:H7 and L. monocytogenes inoculated in either aerobically or vacuum packaged samples. These results suggest that low-dose electron beam irradiation can significantly decrease microbial numbers and reduce the risk of meat byproduct contamination by the foodborne pathogens.

  11. Radiation-sensitive mutant of hypertoxinogenic strain 569B of Vibro cholerae

    International Nuclear Information System (INIS)

    A radiation-sensitive mutant of the hypertoxinogenic strain 569B of Vibrio cholerae was isolated and characterized. The mutant, designated V. cholerae 569Bsub(s), lacks both excision- and medium-dependent dark-repair mechanisms of UV-induced DNA damage while retaining the wild-type photoreactivating capability. Analysis of the UV-irradiated cell DNA by velocity sedimentation in alkaline sucrose gradient suggests that UV-induced pyrimidine dimers may not be incised in these cells. In contrast to the wild-type cells, the mutant cell DNA was degraded after treatment with nalidixic acid. The mutant cells failed to produce any detectable amount of cholera toxin as measured by ileal-loop assay. (orig.)

  12. Radiation-sensitive mutant of hypertoxinogenic strain 569B of Vibro cholerae

    Energy Technology Data Exchange (ETDEWEB)

    Das, G.; Das, J. (Indian Inst. of Chemical Biology, Calcutta. Biophysics Div.)

    1983-04-01

    A radiation-sensitive mutant of the hypertoxinogenic strain 569B of Vibrio cholerae was isolated and characterized. The mutant, designated V. cholerae 569Bsub(s), lacks both excision- and medium-dependent dark-repair mechanisms of UV-induced DNA damage while retaining the wild-type photoreactivating capability. Analysis of the UV-irradiated cell DNA by velocity sedimentation in alkaline sucrose gradient suggests that UV-induced pyrimidine dimers may not be incised in these cells. In contrast to the wild-type cells, the mutant cell DNA was degraded after treatment with nalidixic acid. The mutant cells failed to produce any detectable amount of cholera toxin as measured by ileal-loop assay.

  13. Radiation-sensitive mutant of hypertoxinogenic strain 569B of Vibrio cholerae.

    Science.gov (United States)

    Das, G; Das, J

    1983-04-01

    A radiation-sensitive mutant of the hypertoxinogenic strain 569B of Vibrio cholerae was isolated and characterized. The mutant, designated V. cholerae 569Bs, lacks both excision- and medium-dependent dark-repair mechanisms of UV-induced DNA damage while retaining the wild-type photoreactivating capability. Analysis of the UV-irradiated cell DNA by velocity sedimentation in alkaline sucrose gradient suggests that UV-induced pyrimidine dimers may not be incised in these cells. In contrast to the wild-type cells, the mutant cell DNA was degraded after treatment with nalidixic acid. The mutant cells failed to produce any detectable amount of cholera toxin as measured by ileal-loop assay.

  14. The radiation sensitivity of the haemopoietic microenvironment - effect of dose rate on ectopic ossicle formation

    International Nuclear Information System (INIS)

    The haemopoietic microenvironment (HM) consists of a complex mixture of cellular types and extra-cellular matrix. It is essential for prolonged haemopoiesis in both the normal situation and after bone marrow transplantation. The competence of the HM can be assessed by ectopic grafting of femoral marrow. A complete haemopoietic organ develops at the site of implantation. Stem cells (CFU-S) which inhabit the ossicle formed after ectopic implantation can be measured, to assess the function of the engrafted HM to support haemopoiesis. Using this functional endpoint the radiation sensitivity of the HM has been examined at both high and low dose rates, and it is concluded that high doses of γ-irradiation delivered at 4 Gy/min or 0.016 Gy/min have widely different effects on the HM, the former proving much more damaging than the latter. 16 refs.; 2 figs

  15. Study of the sensitivity of the radiation transport problem in a scattering medium

    International Nuclear Information System (INIS)

    In this work, the system of differential equations obtained by the angular approach of the two-dimensional transport equation by the discrete ordinates method is solved through the formulation of finite elements with the objective of investigating the sensitivity of the outgoing flux of radiation with the incoming flux and the properties of absorption and scattering of the medium. The variational formulation for the system of differential equations of second order with the generalized boundary conditions of Neumann (third type) allows an easy implementation of the method of the finite elements with triangular mesh and approximation space of first order. The geometry chosen for the simulations is a circle with a non homogeneous circular form in its interior. The mapping of Dirichlet-Neumann is studied through various simulations involving the incoming flux, the outgoing flux and the properties of the medium. (author)

  16. Application of generalized estimating equations to a study in vitro of radiation sensitivity

    International Nuclear Information System (INIS)

    We describes an application of the generalized estimating equation (GEE) method (Liang K-Y, Zeger SL: Longitudinal data analysis using generalized linear models. Biometrika 73:13-22, 1986) for regression analyses of correlated Poisson data. As an alternative to the use of an arbitrarily chosen working correlation matrix, we demonstrate the use of GEE with a reasonable model for the true covariance structure among repeated observations within individuals. We show that, under such a split-plot design with large clusters, the asymptotic relative efficiency of GEE with simple (independence or exchangeable) working correlation matrices is rather low. We also illustrate the use of GEE with an empirically estimated model for overdispersion in a large study of radiation sensitivity where cluster size is small and a simple working correlation structure is sufficient. We conclude by summarizing issues and needs for further work concerning efficiency of the GEE parameter estimates in practice. (author)

  17. Radiation sensitive indicator based on tetrabromophenol blue dyed poly(vinyl alcohol)

    International Nuclear Information System (INIS)

    Radiation sensitive indicators based on dyed polyvinyl alcohol (PVA) containing acid- sensitive dye (tetrabromophenol blue, TBPB) and chloral hydrate (CCl3·CH·(OH)2, 2,2,2-trichloroethane-1,1-diol) have been developed. These plastic film dosimeters undergo color change from blue (the alkaline form of TBPB) to yellow (the acidic form of TBPB), indicating acid formation. The concentration of radiation formed acids in the films containing different concentrations of chloral hydrate was calculated at different doses. These films can be used as dosimeters for food irradiation applications where the maximum of the useful dose ranges are between 1 and 8 kGy depending on chloral hydrate concentration in the film. The films have the advantage of negligible humidity effects on response in the intermediate range of relative humidity from 0 to 70% as good post irradiation stability when stored in the dark at room temperature. The overall combined uncertainty (at 2σ) associated with measurement of response (ΔA mm−1) at 623 nm for dose range 1–8 kGy is 4.53%. - Highlights: ► On irradiating TBPB/PVA films the color change from blue to green and yellow. ► The amount of acid formed depends on dose and concentration of chloral hydrate. ► The dose range 1–8 kGy the film can be used for food irradiation applications. ► The response of these films has negligible humidity effects from 0 to 70%. ► The combined uncertainty at 2σ using TBPB/PVA films was found to be 4.53%

  18. Prevention of Radiation Induced Hematological Alterations by Medicinal Plant Rosmarinus Officinalis, in Mice

    OpenAIRE

    Sancheti, Garima; P.K. Goyal

    2006-01-01

    The modulatory influence of Rosmarinus officinalis (rosemary) leaves extract was investigated in Swiss albino mice at a dose of 3 Gy gamma radiation. For this purpose, adult Swiss albino mice were irradiated with 3 Gy gamma rays in the presence (experimental) or absence (control) of rosemary (1000 mg/kg body wt.). These animals were necropsied and their blood was collected at days 1, 3, 5, 10, 20 and 30 post-irradiation. A decrease in the number of erythrocyte and leucocyte counts, hemoglobin...

  19. Higher sensitivity of LEC strain rat in radiation-induced acute intestinal death.

    Science.gov (United States)

    Hayashi, M; Endoh, D; Kon, Y; Yamashita, T; Hashimoto, N; Sato, F; Kasai, N; Namioka, S

    1992-04-01

    LEC strain rats (LEC rats), which have been known to develop hereditarily spontaneous fulminant hepatitis 4-5 months after birth, were highly sensitive to whole-body X-irradiation as compared to WKAH strain rats (WKAH rats). Radiation-induced acute intestinal death occurred at doses higher than 6.5 Gy in LEC rats, and at doses higher than 12.8 Gy in WKAH rats, respectively. By the probit analysis of survival data, it was shown that the LD50/7 value of LEC rats was estimated to be 7.03 Gy which was significantly lower than that (12.99 Gy) of WKAH rats. Histopathological examinations of small intestines from LEC rats 2 days after irradiation at the dose of 8.5 Gy showed severe epithelial death together with edema, whereas little or no significant changes were noted in intestinal epithelium of 8.5 Gy-irradiated WKAH rats. These results suggest that the radiosensitivity of LEC rats to ionizing radiation appears to be higher than that of other strains of rats.

  20. A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids

    International Nuclear Information System (INIS)

    We have characterized some of the physiology of multicellular spheroids of different sizes grown from Chinese hamster lung fibroblast (V79) cells. Among the parameters studied were oxygen tension distributions within the spheroid. This was achieved using ultramicroelectrodes with tip diameters of 1-5 mu and a perfusion system whereby environmental conditions such as flow, temperature, and chemical makeup of the milieu could be measured and controlled. Plateau pO/sup 2/ values of less than 10 mm Hg were consistently obtained from spheroids under various conditions. We were able to modify these distributions by use of indirect radiation sensitizer drugs such as mechlorethamine HCl (mustargen) at nontoxic doses. We have also made determinations of the inhibitory capacities of several other drugs on the respiration rate of constituent cells of multicellular spheroids in single-cell suspensions. We have concluded that there are indeed hypoxic cells in spheroids whose radioresistance may be modified by essentially nontoxic levels of indirect radiosensitizer drugs and that the system described shows great promise for screening agents which may modify radiation response

  1. A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids

    Energy Technology Data Exchange (ETDEWEB)

    Kaufman, N.; Bicher, H.I.; Hetzel, F.W.; Brown, M.

    1981-01-01

    We have characterized some of the physiology of multicellular spheroids of different sizes grown from Chinese hamster lung fibroblast (V79) cells. Among the parameters studied were oxygen tension distributions within the spheroid. This was achieved using ultramicroelectrodes with tip diameters of 1-5 mu and a perfusion system whereby environmental conditions such as flow, temperature, and chemical makeup of the milieu could be measured and controlled. Plateau pO/sup 2/ values of less than 10 mm Hg were consistently obtained from spheroids under various conditions. We were able to modify these distributions by use of indirect radiation sensitizer drugs such as mechlorethamine HCl (mustargen) at nontoxic doses. We have also made determinations of the inhibitory capacities of several other drugs on the respiration rate of constituent cells of multicellular spheroids in single-cell suspensions. We have concluded that there are indeed hypoxic cells in spheroids whose radioresistance may be modified by essentially nontoxic levels of indirect radiosensitizer drugs and that the system described shows great promise for screening agents which may modify radiation response.

  2. Sensitivity Analysis on Fu-Liou-Gu Radiative Transfer Model for different lidar aerosol and cloud profiles

    Science.gov (United States)

    Lolli, Simone; Madonna, Fabio; Rosoldi, Marco; Pappalardo, Gelsomina; Welton, Ellsworth J.

    2016-04-01

    The aerosol and cloud impact on climate change is evaluated in terms of enhancement or reduction of the radiative energy, or heat, available in the atmosphere and at the Earth's surface, from the surface (SFC) to the Top Of the Atmosphere (TOA) covering a spectral range from the UV (extraterrestrial shortwave solar radiation) to the far-IR (outgoing terrestrial longwave radiation). Systematic Lidar network measurements from permanent observational sites across the globe are available from the beginning of this current millennium. From the retrieved lidar atmospheric extinction profiles, inputted in the Fu-Liou-Gu (FLG) Radiative Transfer code, it is possible to evaluate the net radiative effect and heating rate of the different aerosol species and clouds. Nevertheless, the lidar instruments may use different techniques (elastic lidar, Raman lidar, multi-wavelength lidar, etc) that translate into uncertainty of the lidar extinction retrieval. The goal of this study is to assess, applying a MonteCarlo technique and the FLG Radiative Transfer model, the sensitivity in calculating the net radiative effect and heating rate of aerosols and clouds for the different lidar techniques, using both synthetic and real lidar data. This sensitivity study is the first step to implement an automatic algorithm to retrieve the net radiative forcing effect of aerosols and clouds from the long records of aerosol measurements available in the frame of EARLINET and MPLNET lidar networks.

  3. A ΔdinB mutation that sensitizes Escherichia coli to the lethal effects of UV- and X-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mei-Chong W.; Franco, Magdalena; Vargas, Doris M. [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Hudman, Deborah A. [Department of Microbiology and Immunology, A.T. Still University, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501 (United States); White, Steven J. [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Fowler, Robert G., E-mail: rfowler@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192 (United States); Sargentini, Neil J. [Department of Microbiology and Immunology, A.T. Still University, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501 (United States)

    2014-05-15

    Highlights: • We describe Δ(dinB-yafN)883(::kan), a novel dinB allele, referred to as ΔdinB883, a deletion that sensitizes E. coli cells to UV irradiation. • This UV radiation sensitivity is most acute in the early logarithmic phase of culture growth. • This UV radiation sensitivity is completely dependent upon a functional umuDC operon. • Sequencing reveals ΔdinB883 retains the proximal 161 nucleotides, i.e., 54 amino acids, of the wild-type sequence. • The ΔdinB883 mutant is hypothesized to produce a peptide of 83 amino acids, DinB883, that compromises UmuDC function. - Abstract: The DinB (PolIV) protein of Escherichia coli participates in several cellular functions. We investigated a dinB mutation, Δ(dinB-yafN)883(::kan) [referred to as ΔdinB883], which strongly sensitized E. coli cells to both UV- and X-radiation killing. Earlier reports indicated dinB mutations had no obvious effect on UV radiation sensitivity which we confirmed by showing that normal UV radiation sensitivity is conferred by the ΔdinB749 allele. Compared to a wild-type strain, the ΔdinB883 mutant was most sensitive (160-fold) in early to mid-logarithmic growth phase and much less sensitive (twofold) in late log or stationary phases, thus showing a growth phase-dependence for UV radiation sensitivity. This sensitizing effect of ΔdinB883 is assumed to be completely dependent upon the presence of UmuDC protein; since the ΔdinB883 mutation did not sensitize the ΔumuDC strain to UV radiation killing throughout log phase and early stationary phase growth. The DNA damage checkpoint activity of UmuDC was clearly affected by ΔdinB883 as shown by testing a umuC104 ΔdinB883 double-mutant. The sensitivities of the ΔumuDC strain and the ΔdinB883 ΔumuDC double-mutant strain were significantly greater than for the ΔdinB883 strain, suggesting that the ΔdinB883 allele only partially suppresses UmuDC activity. The ΔdinB883 mutation partially sensitized (fivefold) uvrA and uvr

  4. Relationship Between Chromatin Structure and Sensitivity to Molecularly Targeted Auger Electron Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Terry, Samantha Y.A. [CR-UK/MRC Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Oxford (United Kingdom); Vallis, Katherine A., E-mail: katherine.vallis@oncology.ox.ac.uk [CR-UK/MRC Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Oxford (United Kingdom)

    2012-07-15

    Purpose: The open structure of euchromatin renders it susceptible to DNA damage by ionizing radiation (IR) compared with compact heterochromatin. The effect of chromatin configuration on the efficacy of Auger electron radiotherapy was investigated. Methods and Materials: Chromatin structure was altered in MDA-MB-468 and 231-H2N human breast cancer cells by suberoylanilide hydroxamic acid (SAHA), 5-aza-2-deoxycytidine, or hypertonic treatment. The extent and duration of chromatin structural changes were evaluated using the micrococcal nuclease assay. DNA damage ({gamma}H2AX assay) and clonogenic survival were evaluated after exposure to {sup 111}In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, or IR. The intracellular distribution of {sup 111}In-DTPA-hEGF after chromatin modification was investigated in cell fractionation experiments. Results: Chromatin remained condensed for up to 20 minutes after NaCl and in a relaxed state 24 hours after SAHA treatment. The number of {gamma}H2AX foci per cell was greater in MDA-MB-468 and 231-H2N cells after IR (0.5 Gy) plus SAHA (1 {mu}M) compared with IR alone (16 {+-} 0.6 and 14 {+-} 0.3 vs. 12 {+-} 0.4 and 11 {+-} 0.2, respectively). More {gamma}H2AX foci were observed in MDA-MB-468 and 231-H2N cells exposed to {sup 111}In-DTPA-hEGF (6 MBq/{mu}g) plus SAHA vs. {sup 111}In-DTPA-hEGF alone (11 {+-} 0.3 and 12 {+-} 0.7 vs. 9 {+-} 0.4 and 7 {+-} 0.3, respectively). 5-aza-2-deoxycytidine enhanced the DNA damage caused by IR and {sup 111}In-DTPA-hEGF. Clonogenic survival was reduced in MDA-MB-468 and 231-H2N cells after IR (6 Gy) plus SAHA (1 {mu}M) vs. IR alone (0.6% {+-} 0.01 and 0.3% {+-} 0.2 vs. 5.8% {+-} 0.2 and 2% {+-} 0.1, respectively) and after {sup 111}In-DTPA-hEGF plus SAHA compared to {sup 111}In-DTPA-hEGF alone (21% {+-} 0.4% and 19% {+-} 4.6 vs. 33% {+-} 2.3 and 32% {+-} 3.7). SAHA did not affect {sup 111}In-DTPA-hEGF nuclear localization. Hypertonic treatment resulted in fewer {gamma}H2AX foci per cell

  5. Short-duration exposure to radiofrequency electromagnetic radiation alters the chlorophyll fluorescence of duckweeds (Lemna minor).

    Science.gov (United States)

    Senavirathna, Mudalige Don Hiranya Jayasanka; Takashi, Asaeda; Kimura, Yuichi

    2014-12-01

    Plants growing in natural environments are exposed to radiofrequency electromagnetic radiation (EMR) emitted by various communication network base stations. The environmental concentration of this radiation is increasing rapidly with the congested deployment of base stations. Although numerous scientific studies have been conducted to investigate the effects of EMR on the physiology of humans and animals, there have been few attempts to investigate the effects of EMR on plants. In this study, we attempted to evaluate the effects of EMR on photosynthesis by investigating the chlorophyll fluorescence (ChF) parameters of duckweed fronds. During the experiment, the fronds were tested with 2, 2.5, 3.5, 5.5 and 8 GHz EMR frequencies, which are not widely studied even though there is a potentially large concentration of these frequencies in the environment. The duckweed fronds were exposed to EMR for 30 min, 1 h and 24 h durations with electric field strength of 45-50 V/m for each frequency. The results indicated that exposure to EMR causes a change in the non-photochemical quenching of the duckweeds. The changes varied with the frequency of the EMR and were time-varying within a particular frequency. The temperature remained unchanged in the duckweed fronds upon exposure to EMR, which confirms that the effect is non-thermal.

  6. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, Ann-Sofie, E-mail: ann-sofie.gustafsson@bms.uu.se; Abramenkovs, Andris; Stenerlöw, Bo

    2014-11-15

    Highlights: • We reduced the level of DNA-PKcs with siRNA and examined cells after γ-irradiation. • Low DNA-PKcs levels lead to radiosensitivity but did not affect repair of DSB. • Low DNA-PKcs levels may block progression of mitosis. • DNA-PKcs role in mitotic progression is independent of its role in DSB repair. • We suggest different mechanisms by which loss of DNA-PKcs function sensitize cells. - Abstract: Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80–95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure

  7. Prenatal stress alters progestogens to mediate susceptibility to sex-typical, stress-sensitive disorders, such as drug abuse: a review

    Directory of Open Access Journals (Sweden)

    Cheryl A Frye

    2011-10-01

    Full Text Available Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to prenatal stress and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, prenatal stress, with consequences for neurodevelopmental-, neuropsychiatric- and/or neurodegenerative- relevant processes, such as addiction.

  8. ALTERED SENSITIVITY OF THE MOUSE FETUS TO IMPAIRED PROSTATIC BUD FORMATION BY DIOXIN: INFLUENCE OF GENETIC BACKGROUND AND NULL EXPRESSION OF TGF-ALFA AND EGF

    Science.gov (United States)

    Altered sensitivity of the mouse fetus to impaired prostatic bud formation by dioxin: Influence of genetic background and null expression of TGF and EGF. Rasmussen, N.T., Lin T-M., Fenton, S.E., Abbott, B.D. and R.E. Peterson. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)...

  9. Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy

    Science.gov (United States)

    Tamarov, Konstantin P.; Osminkina, Liubov A.; Zinovyev, Sergey V.; Maximova, Ksenia A.; Kargina, Julia V.; Gongalsky, Maxim B.; Ryabchikov, Yury; Al-Kattan, Ahmed; Sviridov, Andrey P.; Sentis, Marc; Ivanov, Andrey V.; Nikiforov, Vladimir N.; Kabashin, Andrei V.; Timoshenko, Victor Yu

    2014-11-01

    Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50°C under relatively low nanoparticle concentrations (nanoparticles the heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy.

  10. A robust hypothesis test for the sensitive detection of constant speed radiation moving sources

    International Nuclear Information System (INIS)

    Radiation Portal Monitors are deployed in linear networks to detect radiological material in motion. As a complement to single and multichannel detection algorithms, inefficient under too low signal-to-noise ratios, temporal correlation algorithms have been introduced. Test hypothesis methods based on empirically estimated mean and variance of the signals delivered by the different channels have shown significant gain in terms of a tradeoff between detection sensitivity and false alarm probability. This paper discloses the concept of a new hypothesis test for temporal correlation detection methods, taking advantage of the Poisson nature of the registered counting signals, and establishes a benchmark between this test and its empirical counterpart. The simulation study validates that in the four relevant configurations of a pedestrian source carrier under respectively high and low count rate radioactive backgrounds, and a vehicle source carrier under the same respectively high and low count rate radioactive backgrounds, the newly introduced hypothesis test ensures a significantly improved compromise between sensitivity and false alarm. It also guarantees that the optimal coverage factor for this compromise remains stable regardless of signal-to-noise ratio variations between 2 and 0.8, therefore allowing the final user to parametrize the test with the sole prior knowledge of background amplitude

  11. A robust hypothesis test for the sensitive detection of constant speed radiation moving sources

    Science.gov (United States)

    Dumazert, Jonathan; Coulon, Romain; Kondrasovs, Vladimir; Boudergui, Karim; Moline, Yoann; Sannié, Guillaume; Gameiro, Jordan; Normand, Stéphane; Méchin, Laurence

    2015-09-01

    Radiation Portal Monitors are deployed in linear networks to detect radiological material in motion. As a complement to single and multichannel detection algorithms, inefficient under too low signal-to-noise ratios, temporal correlation algorithms have been introduced. Test hypothesis methods based on empirically estimated mean and variance of the signals delivered by the different channels have shown significant gain in terms of a tradeoff between detection sensitivity and false alarm probability. This paper discloses the concept of a new hypothesis test for temporal correlation detection methods, taking advantage of the Poisson nature of the registered counting signals, and establishes a benchmark between this test and its empirical counterpart. The simulation study validates that in the four relevant configurations of a pedestrian source carrier under respectively high and low count rate radioactive backgrounds, and a vehicle source carrier under the same respectively high and low count rate radioactive backgrounds, the newly introduced hypothesis test ensures a significantly improved compromise between sensitivity and false alarm. It also guarantees that the optimal coverage factor for this compromise remains stable regardless of signal-to-noise ratio variations between 2 and 0.8, therefore allowing the final user to parametrize the test with the sole prior knowledge of background amplitude.

  12. Radiation sensitivity of bacteria and virus in porcine xenoskin for dressing agent

    Science.gov (United States)

    Jo, Eu-Ri; Jung, Pil-Mun; Choi, Jong-il; Lee, Ju-Woon

    2012-08-01

    In this study, gamma irradiation sensitivities of bacteria and viruses in porcine skin were evaluated to establish the optimum sterilization condition for the dressing material and a xenoskin graft. Escherichia coli and Bacillus subtilis were used as model pathogens and inoculated at 106-107 log CFU/g. As model viruses, porcine parvovirus (PPV), bovine viral diarrhea virus (BVDV), and poliovirus were used and inoculated at 105-106 TCID50/g into porcine skin. The D10 value of E. coli was found to be 0.25±0.1 kGy. B. subtilis endospores produced under stressful environmental conditions showed lower radiation sensitivity as D10 was 3.88±0.3 kGy in porcine skin. The D10 values of PPV, BVDV, and poliovirus were found to be 1.73±0.2, 3.81±0.2, and 6.88±0.3 kGy, respectively. These results can offer the basic information required for inactivating pathogens by gamma irradiation and achieving dressing material and porcine skin grafts.

  13. A robust hypothesis test for the sensitive detection of constant speed radiation moving sources

    Energy Technology Data Exchange (ETDEWEB)

    Dumazert, Jonathan, E-mail: jonathan.dumazert@cea.fr [CEA, LIST, Laboratoire Capteurs Architectures Electroniques, 91191 Gif-sur-Yvette (France); Coulon, Romain; Kondrasovs, Vladimir; Boudergui, Karim; Moline, Yoann; Sannié, Guillaume; Gameiro, Jordan; Normand, Stéphane [CEA, LIST, Laboratoire Capteurs Architectures Electroniques, 91191 Gif-sur-Yvette (France); Méchin, Laurence [CNRS, UCBN, Groupe de Recherche en Informatique, Image, Automatique et Instrumentation de Caen, 14050 Caen (France)

    2015-09-21

    Radiation Portal Monitors are deployed in linear networks to detect radiological material in motion. As a complement to single and multichannel detection algorithms, inefficient under too low signal-to-noise ratios, temporal correlation algorithms have been introduced. Test hypothesis methods based on empirically estimated mean and variance of the signals delivered by the different channels have shown significant gain in terms of a tradeoff between detection sensitivity and false alarm probability. This paper discloses the concept of a new hypothesis test for temporal correlation detection methods, taking advantage of the Poisson nature of the registered counting signals, and establishes a benchmark between this test and its empirical counterpart. The simulation study validates that in the four relevant configurations of a pedestrian source carrier under respectively high and low count rate radioactive backgrounds, and a vehicle source carrier under the same respectively high and low count rate radioactive backgrounds, the newly introduced hypothesis test ensures a significantly improved compromise between sensitivity and false alarm. It also guarantees that the optimal coverage factor for this compromise remains stable regardless of signal-to-noise ratio variations between 2 and 0.8, therefore allowing the final user to parametrize the test with the sole prior knowledge of background amplitude.

  14. Actinic reticuloid idiopathic photodermatosis with cellular sensitivity to near ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Botcherby, P.K.; Marimo, B.; Giannelli, F. (Guy' s Hospital Medical School, London (UK)); Magnus, I.A. (Institute of Dermatology, London (UK))

    1984-05-01

    Long wavelength UV radiations (320-400 nm) cause persistent inhibition of RNA synthesis and marked cytopathic changes in fibroblasts from patients with actinic reticuloid (AR) but not in those from patients with Bloom syndrome or xeroderma pigmentosum. Furthermore, the AR cells show abnormal DNA fragmentation when they are irradiated at temperatures compatible with enzyme activity. Germicidal UVR (ca. 95% 254 nm) stimulates DNA repair synthesis and inhibits DNA replication to a normal extent in the AR cells. Thus, actinic reticuloid, a severe photodermatosis, characterised by skin sensitivity to UV-B, UV-A and part of the visible spectrum and infiltrates reminiscent of mycosis fungoides, is a human disease with in vitro cellular sensitivity to UV-A and is also the first to be reported. A hypothesis is advanced that inefficient cellular neutralisation of free radicals may explain the cellular phenotype of actinic reticuloid and contribute to the establishment of a vicious circle that would favour the chronic clinical course and persistent lympho-histiocytic skin infiltrates characteristic of the disease.

  15. Radiation sensitivity of bacteria and virus in porcine xenoskin for dressing agent

    International Nuclear Information System (INIS)

    In this study, gamma irradiation sensitivities of bacteria and viruses in porcine skin were evaluated to establish the optimum sterilization condition for the dressing material and a xenoskin graft. Escherichia coli and Bacillus subtilis were used as model pathogens and inoculated at 106–107 log CFU/g. As model viruses, porcine parvovirus (PPV), bovine viral diarrhea virus (BVDV), and poliovirus were used and inoculated at 105–106 TCID50/g into porcine skin. The D10 value of E. coli was found to be 0.25±0.1 kGy. B. subtilis endospores produced under stressful environmental conditions showed lower radiation sensitivity as D10 was 3.88±0.3 kGy in porcine skin. The D10 values of PPV, BVDV, and poliovirus were found to be 1.73±0.2, 3.81±0.2, and 6.88±0.3 kGy, respectively. These results can offer the basic information required for inactivating pathogens by gamma irradiation and achieving dressing material and porcine skin grafts.

  16. Calibration of non-discriminating scintillating instruments for sensitivities to naturally occuring gamma radiation emitting radionuclides at environmental concentrations

    International Nuclear Information System (INIS)

    A method of calibrating non-discriminating gamma radiation detectors for environmental level measurements is described. It is based on a method used to calibrate field gamma spectrometers, and has several advantages over the more traditional point-source approach. Radiological measurements are taken on pads with known concentrations of potassium, uranium and thorium, and the sensitivities to these naturally occurring terrestrial sources of gamma radiation are determined. Measurements can then be converted into radionuclide concentration or exposure rates. (author)

  17. S-phase cells are more sensitive to high-linear energy transfer radiation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H.; Naidu, M.; Liu, S.; Zhang, P.; Zhang, S.; Wang, H.; Wang, Y.

    2009-07-15

    S-phase cells are more resistant to low-linear energy transfer (LET) ionizing radiation (IR) than nonsynchronized and G{sub 1}-phase cells, because both nonhomologous end-joining (NHEJ) and homologous recombination repair can repair DNA double-strand breaks (DSBs) in the S phase. Although it was reported 3 decades ago that S-phase cells did not show more resistance to high-LET IR than cells in other phases, the mechanism remains unclear. We therefore attempted to study the phenotypes and elucidate the mechanism involved. Wild-type and NHEJ-deficient cell lines were synchronized using the double-thymidine approach. A clonogenic assay was used to detect the sensitivity of nonsynchronized, synchronized S-phase, and G{sub 2}-phase cells to high- and low-LET IR. The amounts of Ku bound to DSBs in the high- and low-LET-irradiated cells were also examined. S-phase wild-type cells (but not NHEJ-deficient cells) were more sensitive to high-LET IR than nonsynchronized and G{sub 2}-phase cells. In addition, S-phase wild-type cells showed less efficient Ku protein binding to DSBs than nonsynchronized and G{sub 2}-phase cells in response to high-LET IR, although all cells at all phases showed similarly efficient levels of Ku protein binding to DSBs in response to low-LET IR. S-phase cells are more sensitive to high-LET IR than nonsynchronized and G{sub 2}-phase cells, because of the following mechanism: it is more difficult for Ku protein to bind to high-LET IR-induced DNA DSBs in S-phase cells than in cells at other phases, which results in less efficient NHEJ.

  18. Investigation of some parameters influencing the sensitivity of human tooth enamel to gamma radiation using electron paramagnetic resonance

    International Nuclear Information System (INIS)

    Electron paramagnetic resonance (EPR) has been successfully used as a physical technique for gamma radiation dose reconstruction using calcified tissues. To minimize potential discrepancies between EPR readings in future studies, the effects of cavity response factor, tooth position and donor gender on the estimated gamma radiation dose were studied. It was found that the EPR response per sample mass used for assessment of doses in teeth outside of the 70-100 mg range should be corrected by a factor which is a function of the sample mass. In the EPR measurements, the difference in sensitivity of different tooth positions to γ-radiation was taken into consideration. It was determined that among all the premolars and molars tooth positions, the relative standard deviation of sensitivity was 6.5%, with the wisdom teeth and the first molars having the highest and lowest sensitivity to γ-radiation, respectively. The current results reveal no effect of the donor gender on the sensitivity to γ-radiation. (author)

  19. [Fluorescence used to investigate the sensitivity of spinach chloroplast membrane to low intensity electromagnetic radiation].

    Science.gov (United States)

    Xi, Gang; Yang, Yun-Jing; Lu, Hong

    2009-07-01

    A system for studying biological effect of radio frequency electromagnetic field was developed. The system can form an area where electromagnetic wave with large frequency range is well distributed. The strength of electromagnetic wave was measured easily. Electromagnetic wave in the system did not have effect on environment. The sensitivity of spinach chloroplast membrane to low intensity electromagnetic radiation of 300 MHz under power density of 5 mW x cm(-2) was studied by the spectral analysis method of fluorescence of 8-anilino-1-naphthalene-sulfonic acid (ANS) and the changes in chlorophyll a (Chla) fluorescence parameters of spinach chloroplast membrane. The result showed that the position of spectrum of ANS fluorescence of spinach chloroplast membrane did not change, but the intensity of ANS fluorescence was obviously increased under the action of electromagnetic radiation with power density of 1-5 mW x cm(-2). There was an increase in the intensity of ANS fluorescence with the increase in electromagnetic radiation. The increase of ANS fluorescence of spinach chloroplast membrane showed that low level electromagnetic field induced the decrease in fluidity of chloroplast membrane compared with control experiment. The cause of the change in the fluidity could be related to the polarization of chloroplast membrane under the electromagnetic field. The analysis of Chla fluorescence parameters of spinach chloroplast membrane indicated that low level electromagnetic field of 300 MHz made the fluorescence parameters F0 and F(VI/)F(V) decrease, and F(V)/Fo, Fv/F(m) and deltaF(V)/T increase. It was showed that low level electromagnetic field caused the change of non-active center of photosystem II of spinach chloroplast membrane to active center and the increase in potential active and photochemical efficiency of PSII, and promoted the transmit process of electron in photosynthesis of chloroplast membrane of photosynthesis cell in spinach leaf. The study confirmed

  20. Assessment of the radiation sensitivity of patients after conditioning irradiation as preparation for bone marrow or stem cell transplantation

    International Nuclear Information System (INIS)

    The knowledge on the radiation sensitivity of individual patients would allow a better planning of conditioning irradiation including the possibility of dose increase that might enhance the chance of a successful bone marrow or stem cell transplantation. The study was focused on the search of reliable and fast laboratory test procedures to predict the individual radiation sensitivity. Several blood tests were evaluated with respect to their appropriateness: mostly flow-cytometric test on lymphocytes: micronuclei, cell proliferation, apoptosis activation of cytokines and the total number of leucocytes, blood stem cells CD4+ and CD8+ lymphocytes, and a spectro-photometric test of blood plasma for the determination of the antioxidative capacity

  1. Female Flinders Sensitive Line rats show estrous cycle-independent depression-like behavior and altered tryptophan metabolism.

    Science.gov (United States)

    Eskelund, Amanda; Budac, David P; Sanchez, Connie; Elfving, Betina; Wegener, Gregers

    2016-08-01

    Clinical studies suggest a link between depression and dysfunctional tryptophan (TRP) metabolism. Even though depression is twice as prevalent in women as men, the impact of the estrous cycle on TRP metabolism is not well-understood. Here we investigated 13 kynurenine and serotonin metabolites in female Flinders Sensitive Line (FSL) rats, a genetic rat model of depression. FSL rats and controls (Flinders Resistant Line rats), 12-20weeks old, were subject to the forced swim test (FST), a commonly used measure of depression-like behavior. Open field was used to evaluate locomotor ability and agoraphobia. Subsequently, plasma and hemispheres were collected and analyzed for their content of TRP metabolites using liquid chromatography-tandem mass spectrometry. Vaginal saline lavages were obtained daily for ⩾2 cycles. To estimate the effects of sex and FST we included plasma from unhandled, naïve male FSL and FRL rats. Female FSL rats showed a depression-like phenotype with increased immobility in the FST, not confounded by anxiety. In the brain, 3-hydroxykynurenine was increased whereas anthranilate and 5-hydroxytryptophan were decreased. In plasma, anthranilate and quinolinate levels were lower in FSL rats compared to the control line, independent of sex and FST. The estrous cycle neither impacted behavior nor TRP metabolite levels in the FSL rat. In conclusion, the female FSL rat is an interesting preclinical model of depression with altered TRP metabolism, independent of the estrous cycle. The status of the pathway in brain was not reflected in the plasma, which may indicate that an inherent local, cerebral regulation of TRP metabolism occurs. PMID:27210075

  2. A position-sensitive scintillation detector for two-dimensional angular correlation of annihilation radiation using metal-package position-sensitive photomultiplier tubes

    CERN Document Server

    Inoue, K; Saito, H; Nagashima, Y; Hyodo, T; Muramatsu, S; Nagai, S

    1999-01-01

    We have constructed and tested a prototype of a new position sensitive gamma-ray detector which consists of an array of 2.6x2.6x18 mm sup 3 BGO scintillator blocks, a light guide, and four metal-package position-sensitive photomultiplier tubes (R5900-00-C8) recently developed by Hamamatsu Photonics Co. Ltd. Scalability of the detector of this type makes it possible to construct a larger detector using many PS-PMTs, which will be useful for the two-dimensional angular correlation of annihilation radiation apparatus.

  3. Sensitivity analysis of performance of crop growth simulation models to daily solar radiation estimation methods in Iran

    Energy Technology Data Exchange (ETDEWEB)

    Farhadi Bansouleh, B. [International Institute for Geo-Information Science and Earth Observation (ITC), P.O. Box 6, 7500 AA Enschede (Netherlands); Water Engineering Department, Faculty of Agriculture, Razi University, Kermanshah (Iran); Sharifi, M.A. [International Institute for Geo-Information Science and Earth Observation (ITC), P.O. Box 6, 7500 AA Enschede (Netherlands); Van Keulen, H. [Plant Production Systems Group, Wageningen University, P.O. Box 430, 6700 AK Wageningen (Netherlands); Plant Research International, Wageningen University and Research Centre, P.O. Box 16, 6700 AA Wageningen (Netherlands)

    2009-11-15

    Solar radiation is the single most important environmental factor driving canopy photosynthesis and transpiration. This weather characteristic is measured only in a limited number of weather stations. Hence, in many situations it has to be estimated from other weather characteristics such as sunshine duration and temperature using empirical relations. In this study, the Aangstrom and Hargreaves formulas have been used for solar radiation estimation, based on monthly and annual weather data for three weather stations in Esfahan province, Iran. Deviations of estimated solar radiation from measured values (both absolute and relative) varied with month of the year and with estimation method. Estimated and measured radiation values were used in a crop growth simulation model to explore sensitivity of simulated production with respect to radiation estimation method. Maximum deviation for winter barley and silage maize was around 9%. (author)

  4. Progressive alterations of central nervous system structure and function are caused by charged particle radiation

    Science.gov (United States)

    Nelson, G. A.; Cns Nscor Team

    A new NASA-sponsored program project (NSCOR) has been organized to conduct the first comprehensive investigation of the response of a mammalian brain structure (mouse hippocampus) to charged-particle radiation. The NSCOR collaboration has three main goals. The first goal is to quantify the time- and dose-dependent changes in cellular composition and architecture. By using stereology on preserved brains, subsets of cells (neurons, glia, endothelia and stem cells) will be quantified out to 2 years after irradiation with accelerated protons and iron ions. To further characterize changes in vasculature architecture a polymer infusion technique will be used to produce a three-dimensional vasculature cast that then will be mapped by x-ray tomography to determine topological changes, and microscopic infarcts associated with amyloid protein deposits. The 2nd goal is to quantify hippocampal function(s). The primary measurement of function will be extracellular electrical recordings from hippocampal ``brain slices'' that reflect underlying functions such as connectivity, action potential generation & conduction, and neurotransmitter formation, secretion, and uptake. Individual nerve membrane properties will be assessed by ``patch clamp'' recordings. Two non-invasive methods will evaluate brain function and the evolution of changes with time. Electroencephalograms will map macroscopic spontaneous electrical activity while two state-of-the-art MRI magnetization sequences will visualize and quantify local oxygen utilization and white matter fiber tracts structural integrity. To quantify the brains' overall performance under stress, animals will receive a systemic shock mediated by the immune system in the form of a reaction to lipopolysaccharide. A second strategy will employ the APP23 transgenic mouse that develops the pathological changes associated with Alzheimer's disease. Measurements of irradiated mice will determine whether radiation exposure affects the latency and

  5. Sensitivities to monochromatic 254-nm and 365-nm radiation of closely related strains of Saccharomyces cerevisiae with differing repair capabilities

    International Nuclear Information System (INIS)

    Sensitivity to monochromatic 254- and 365-nm radiation was compared in closely related yeast strains with defects in one or more of the excision-repair (rad1), error-prone repair (rad18), or recombinational-repair (rad51) pathways. At 254 nm, mutants defective in a single repair pathway exhibited slight to moderate UV sensitivity;,those defective in two separate pathways were somewhat more UV sensitive, while triple mutants defective in all three pathways exhibited extreme UV sensitivity with a lethal event corresponding to 0.05 J m-2. Repair defects also rendered mutants sensitive to 365-nm radiation: strains with single defects exhibited slight sensitivity, mutants with two defective pathways were more sensitive, and triple mutants exhibited maximal sensitivity with a lethal event corresponding to 2.4 x 104 J m-2. Evidence for dimer involvement in the yeast mutant was obtained by demonstrating that lethality at both 254 and 365 nm was photoreactivated by light at 405 nm. (author)

  6. Nimotuzumab enhances radiation sensitivity of NSCLC H292 cells in vitro by blocking epidermal growth factor receptor nuclear translocation and inhibiting radiation-induced DNA damage repair

    Directory of Open Access Journals (Sweden)

    Teng K

    2015-04-01

    Full Text Available Kai Teng,1,2,* Yong Zhang,1,* Xiaoyan Hu,1 Yihui Ding,1 Rui Gong,1 Li Liu1,* 1Department of Thoracic Oncology, Cancer Center of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Radiation Oncology, Hainan Cancer Hospital, Haikou, Hainan, People’s Republic of China *These authors contributed equally to this work Background: The epidermal growth factor receptor (EGFR signaling pathway plays a significant role in radiation resistance. There is evidence that EGFR nuclear translocation is associated with DNA double-strand breaks (DSB repair. Nimotuzumab has shown the effect of radiosensitization in various cancer cells, but little is known about the relationship between nimotuzumab and EGFR nuclear translocation in non-small cell lung cancer (NSCLC cell lines. In this study, we selected two NSCLC cell lines, namely, H292 (with high EGFR expression and H1975 (with low EGFR expression and explored the mechanisms underlying radiation sensitivity.Methods: MTT assay, clonogenic survival assay, and flow cytometry were performed separately to test cell viability, radiation sensitivity, cell cycle distribution, and apoptosis. Protein γ-H2AX, DNA-PK/p-DNA-PK, and EGFR/p-EGFR expression were further compared both in the cytoplasm and the nucleus with the western blot.Results: Nimotuzumab reduced the viability of H292 cells and sensitized H292 cells to ionizing radiation. The radiation sensitivity enhancement ratio (SER was 1.304 and 1.092 for H292 and H1975 cells, respectively. H292 cells after nimotuzumab administration were arrested at the G0/G1 phase in response to radiation. Apoptosis was without statistical significance in both cell lines. γ-H2AX formation in the combination group (nimotuzumab and radiation increased both in the cytoplasm and the nucleus along with the decreased expression of nuclear EGFR/p-EGFR and p-DNA-PK in H292 cells (P<0.05 that

  7. Sensitivity simulations with direct radiative forcing by aeolian dust during glacial cycles

    Science.gov (United States)

    Bauer, E.; Ganopolski, A.

    2014-01-01

    Possible feedback effects between aeolian dust, climate and ice sheets are studied for the first time with an Earth system model of intermediate complexity over the late Pleistocene period. Correlations between climate variables and dust deposits suggest that aeolian dust potentially plays an important role for the evolution of glacial cycles. Here climatic effects from the dust direct radiative forcing (DRF) caused by absorption and scattering of solar radiation are investigated. Key factors controlling the dust DRF are the atmospheric dust distribution and the absorption-scattering efficiency of dust aerosols. Effective physical parameters in the description of these factors are varied within uncertainty ranges known from available data and detailed model studies. Although the parameters are reasonably constrained by use of these studies, the simulated dust DRF spans a wide uncertainty range related to nonlinear dependencies. In our simulations, the dust DRF is highly localized. Medium-range parameters result in negative DRF of several W m-2 in regions close to major dust sources and negligible values elsewhere. In case of high absorption efficiency, the local dust DRF can reach positive values and the global mean DRF can be insignificantly small. In case of low absorption efficiency, the dust DRF can produce a significant global cooling in glacial periods which leads to a doubling of the maximum glacial ice volume relative to the case with small dust DRF. DRF-induced temperature and precipitation changes can either be attenuated or amplified through a feedback loop involving the dust cycle. The sensitivity experiments suggest that depending on dust optical parameters the DRF has the potential to either damp or reinforce glacial-interglacial climate changes.

  8. Sensitivity simulations with direct shortwave radiative forcing by aeolian dust during glacial cycles

    Science.gov (United States)

    Bauer, E.; Ganopolski, A.

    2014-07-01

    Possible feedback effects between aeolian dust, climate and ice sheets are studied for the first time with an Earth system model of intermediate complexity over the late Pleistocene period. Correlations between climate and dust deposition records suggest that aeolian dust potentially plays an important role for the evolution of glacial cycles. Here climatic effects from the dust direct radiative forcing (DRF) caused by absorption and scattering of solar radiation are investigated. Key elements controlling the dust DRF are the atmospheric dust distribution and the absorption-scattering efficiency of dust aerosols. Effective physical parameters in the description of these elements are varied within uncertainty ranges known from available data and detailed model studies. Although the parameters can be reasonably constrained, the simulated dust DRF spans a~wide uncertainty range related to the strong nonlinearity of the Earth system. In our simulations, the dust DRF is highly localized. Medium-range parameters result in negative DRF of several watts per square metre in regions close to major dust sources and negligible values elsewhere. In the case of high absorption efficiency, the local dust DRF can reach positive values and the global mean DRF can be insignificantly small. In the case of low absorption efficiency, the dust DRF can produce a significant global cooling in glacial periods, which leads to a doubling of the maximum glacial ice volume relative to the case with small dust DRF. DRF-induced temperature and precipitation changes can either be attenuated or amplified through a feedback loop involving the dust cycle. The sensitivity experiments suggest that depending on dust optical parameters, dust DRF has the potential to either damp or reinforce glacial-interglacial climate changes.

  9. Rearrangement of RAG-1 recombinase gene in radiation-sensitive ''wasted'' mice

    International Nuclear Information System (INIS)

    Mice recessive for the autosomal gene ''wasted'' (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/· mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/· mice, a two-fold increase in RAG-1 MRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/· and not from wst/wst or parental control BCF1 mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage

  10. Rearrangement of RAG-1 recombinase gene in radiation-sensitive ``wasted`` mice

    Energy Technology Data Exchange (ETDEWEB)

    Woloschak, G.E. [Argonne National Lab., IL (United States)]|[Loyola Univ., Maywood, IL (United States); Libertin, C.R.; Weaver, P. [Loyola Univ., Maywood, IL (United States); Churchill, M.; Chang-Liu, C.M. [Argonne National Lab., IL (United States)

    1993-09-01

    Mice recessive for the autosomal gene ``wasted`` (wst) display a disease pattern which includes increased sensitivity to the killing effects of ionizing radiation, immunodeficiency, and neurologic dysfunction. The recent cloning and characterization of recombinase genes (RAG-1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice. Our results revealed expression of RAG-1 mRNA in spinal cord (but not brain) of control mice; no expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/{center_dot} mice). In thymus tissue, a small RAG-1 transcript (1.0 kb) was detected in wst/wst mice that was not evident in thymus from control mice. In wst/{center_dot} mice, a two-fold increase in RAG-1 MRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/{center_dot} and not from wst/wst or parental control BCF{sub 1} mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage.

  11. Solar Load Inputs for USARIEM Thermal Strain Models and the Solar Radiation-Sensitive Components of the WBGT Index

    Science.gov (United States)

    Matthew, William T.; Santee, William R.; Berglund, Larry G.

    2001-06-01

    This report describes processes we have implemented to use global pyranometer-based estimates of mean radiant temperature as the common solar load input for the Scenario model, the USARIEM heat strain model, and for the computation of the solar radiation sensitive components of the Wet Bulb Globe Temperature (WBGT) index.

  12. Medullary Endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression.

    Science.gov (United States)

    Schaich, Chris L; Grabenauer, Megan; Thomas, Brian F; Shaltout, Hossam A; Gallagher, Patricia E; Howlett, Allyn C; Diz, Debra I

    2016-01-01

    CB1 cannabinoid receptors are expressed on vagal afferent fibers and neurons within the solitary tract nucleus (NTS), providing anatomical evidence for their role in arterial baroreflex modulation. To better understand the relationship between the brain renin-angiotensin system (RAS) and endocannabinoid expression within the NTS, we measured dorsal medullary endocannabinoid tissue content and the effects of CB1 receptor blockade at this brain site on cardiac baroreflex sensitivity (BRS) in ASrAOGEN rats with low glial angiotensinogen, normal Sprague-Dawley rats and (mRen2)27 rats with upregulated brain RAS expression. Mass spectrometry revealed higher levels of the endocannabinoid 2-arachidonoylglycerol in (mRen2)27 compared to ASrAOGEN rats (2.70 ± 0.28 vs. 1.17 ± 0.09 ng/mg tissue; P NTS did not change cardiac BRS in anesthetized Sprague-Dawley rats (1.04 ± 0.05 ms/mmHg baseline vs. 1.17 ± 0.11 ms/mmHg after 10 min). However, SR141716A in (mRen2)27 rats dose-dependently improved BRS in this strain: 0.36 pmol of SR141716A increased BRS from 0.43 ± 0.03 to 0.71 ± 0.04 ms/mmHg (P < 0.001), and 36 pmol of SR141716A increased BRS from 0.47 ± 0.02 to 0.94 ± 0.10 ms/mmHg (P < 0.01). In contrast, 0.36 pmol (1.50 ± 0.12 vs. 0.86 ± 0.08 ms/mmHg; P < 0.05) and 36 pmol (1.38 ± 0.16 vs. 0.46 ± 0.003 ms/mmHg; P < 0.01) of SR141716A significantly reduced BRS in ASrAOGEN rats. These observations reveal differential dose-related effects of the brain endocannabinoid system that influence cardiovagal BRS in animals with genetic alterations in the brain RAS. PMID:27375489

  13. Overfeeding reduces insulin sensitivity and increases oxidative stress, without altering markers of mitochondrial content and function in humans.

    Directory of Open Access Journals (Sweden)

    Dorit Samocha-Bonet

    Full Text Available BACKGROUND: Mitochondrial dysfunction and increased oxidative stress are associated with obesity and type 2 diabetes. High fat feeding induces insulin resistance and increases skeletal muscle oxidative stress in rodents, but there is controversy as to whether skeletal muscle mitochondrial biogenesis and function is altered. METHODOLOGY AND PRINCIPAL FINDINGS: Forty (37 ± 2 y non-obese (25.6 ± 0.6 kg/m(2 sedentary men (n = 20 and women (n = 20 were overfed (+1040 ± 100 kcal/day, 46 ± 1% of energy from fat for 28 days. Hyperinsulinemic-euglycemic clamps were performed at baseline and day 28 of overfeeding and skeletal muscle biopsies taken at baseline, day 3 and day 28 of overfeeding in a sub cohort of 26 individuals (13 men and 13 women that consented to having all 3 biopsies performed. Weight increased on average in the whole cohort by 0.6 ± 0.1 and 2.7 ± 0.3 kg at days 3 and 28, respectively (P<0.0001, without a significant difference in the response between men and women (P = 0.4. Glucose infusion rate during the hyperinsulinemic-euglycemic clamp decreased from 54.8 ± 2.8 at baseline to 50.3 ± 2.5 µmol/min/kg FFM at day 28 of overfeeding (P = 0.03 without a significant difference between men and women (P = 0.4. Skeletal muscle protein carbonyls and urinary F2-isoprostanes increased with overfeeding (P<0.05. Protein levels of muscle peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α and subunits from complex I, II and V of the electron transport chain were increased at day 3 (all P<0.05 and returned to basal levels at day 28. No changes were detected in muscle citrate synthase activity or ex vivo CO(2 production at either time point. CONCLUSIONS: Peripheral insulin resistance was induced by overfeeding, without reducing any of the markers of mitochondrial content that were examined. Oxidative stress was however increased, and may have contributed to the reduction in insulin sensitivity observed.

  14. Medullary Endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression

    Science.gov (United States)

    Schaich, Chris L.; Grabenauer, Megan; Thomas, Brian F.; Shaltout, Hossam A.; Gallagher, Patricia E.; Howlett, Allyn C.; Diz, Debra I.

    2016-01-01

    CB1 cannabinoid receptors are expressed on vagal afferent fibers and neurons within the solitary tract nucleus (NTS), providing anatomical evidence for their role in arterial baroreflex modulation. To better understand the relationship between the brain renin-angiotensin system (RAS) and endocannabinoid expression within the NTS, we measured dorsal medullary endocannabinoid tissue content and the effects of CB1 receptor blockade at this brain site on cardiac baroreflex sensitivity (BRS) in ASrAOGEN rats with low glial angiotensinogen, normal Sprague-Dawley rats and (mRen2)27 rats with upregulated brain RAS expression. Mass spectrometry revealed higher levels of the endocannabinoid 2-arachidonoylglycerol in (mRen2)27 compared to ASrAOGEN rats (2.70 ± 0.28 vs. 1.17 ± 0.09 ng/mg tissue; P NTS did not change cardiac BRS in anesthetized Sprague-Dawley rats (1.04 ± 0.05 ms/mmHg baseline vs. 1.17 ± 0.11 ms/mmHg after 10 min). However, SR141716A in (mRen2)27 rats dose-dependently improved BRS in this strain: 0.36 pmol of SR141716A increased BRS from 0.43 ± 0.03 to 0.71 ± 0.04 ms/mmHg (P < 0.001), and 36 pmol of SR141716A increased BRS from 0.47 ± 0.02 to 0.94 ± 0.10 ms/mmHg (P < 0.01). In contrast, 0.36 pmol (1.50 ± 0.12 vs. 0.86 ± 0.08 ms/mmHg; P < 0.05) and 36 pmol (1.38 ± 0.16 vs. 0.46 ± 0.003 ms/mmHg; P < 0.01) of SR141716A significantly reduced BRS in ASrAOGEN rats. These observations reveal differential dose-related effects of the brain endocannabinoid system that influence cardiovagal BRS in animals with genetic alterations in the brain RAS. PMID:27375489

  15. microRNA Alterations Driving Acute and Late Stages of Radiation-Induced Fibrosis in a Murine Skin Model

    Energy Technology Data Exchange (ETDEWEB)

    Simone, Brittany A. [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Ly, David; Savage, Jason E. [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Hewitt, Stephen M. [Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Dan, Tu D. [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Ylaya, Kris [Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Shankavaram, Uma [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Lim, Meng; Jin, Lianjin [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Camphausen, Kevin [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Mitchell, James B. [Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Simone, Nicole L., E-mail: nicole.simone@jeffersonhospital.org [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States)

    2014-09-01

    Purpose: Although ionizing radiation is critical in treating cancer, radiation-induced fibrosis (RIF) can have a devastating impact on patients' quality of life. The molecular changes leading to radiation-induced fibrosis must be elucidated so that novel treatments can be designed. Methods and Materials: To determine whether microRNAs (miRs) could be responsible for RIF, the fibrotic process was induced in the right hind legs of 9-week old CH3 mice by a single-fraction dose of irradiation to 35 Gy, and the left leg served as an unirradiated control. Fibrosis was quantified by measurements of leg length compared with control leg length. By 120 days after irradiation, the irradiated legs were 20% (P=.013) shorter on average than were the control legs. Results: Tissue analysis was done on muscle, skin, and subcutaneous tissue from irradiated and control legs. Fibrosis was noted on both gross and histologic examination by use of a pentachrome stain. Microarrays were performed at various times after irradiation, including 7 days, 14 days, 50 days, 90 days, and 120 days after irradiation. miR-15a, miR-21, miR-30a, and miR-34a were the miRs with the most significant alteration by array with miR-34a, proving most significant on confirmation by reverse transcriptase polymerase chain reaction, c-Met, a known effector of fibrosis and downstream molecule of miR-34a, was evaluated by use of 2 cell lines: HCT116 and 1522. The cell lines were exposed to various stressors to induce miR changes, specifically ionizing radiation. Additionally, in vitro transfections with pre-miRs and anti-miRs confirmed the relationship of miR-34a and c-Met. Conclusions: Our data demonstrate an inverse relationship with miR-34a and c-Met; the upregulation of miR-34a in RIF causes inhibition of c-Met production. miRs may play a role in RIF; in particular, miR-34a should be investigated as a potential target to prevent or treat this devastating side effect of irradiation.

  16. Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Nakadate, Yusuke [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kodera, Yasuo; Kitamura, Yuka [Shien-Lab, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Tachibana, Taro [Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Tamura, Tomohide [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Koizumi, Fumiaki, E-mail: fkoizumi@ncc.go.jp [Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2013-11-29

    Highlights: •Radiosensitization by PARG silencing was observed in multiple lung cancer cells. •PAR accumulation was enhanced by PARG silencing after DNA damage. •Radiation-induced G2/M arrest and checkpoint activation were impaired by PARG siRNA. -- Abstract: Poly(ADP-ribose) glycohydrolase (PARG) is a major enzyme that plays a role in the degradation of poly(ADP-ribose) (PAR). PARG deficiency reportedly sensitizes cells to the effects of radiation. In lung cancer, however, it has not been fully elucidated. Here, we investigated whether PARG siRNA contributes to an increased radiosensitivity using 8 lung cancer cell lines. Among them, the silencing of PARG induced a radiosensitizing effect in 5 cell lines. Radiation-induced G2/M arrest was largely suppressed by PARG siRNA in PC-14 and A427 cells, which exhibited significantly enhanced radiosensitivity in response to PARG knockdown. On the other hand, a similar effect was not observed in H520 cells, which did not exhibit a radiosensitizing effect. Consistent with a cell cycle analysis, radiation-induced checkpoint signals were not well activated in the PC-14 and A427 cells when treated with PARG siRNA. These results suggest that the increased sensitivity to radiation induced by PARG knockdown occurs through the abrogation of radiation-induced G2/M arrest and checkpoint activation in lung cancer cells. Our findings indicate that PARG could be a potential target for lung cancer treatments when used in combination with radiotherapy.

  17. Effects of thermal sensitization on radiation-induced segregation in type 304 stainless steel irradiated with He-ions

    International Nuclear Information System (INIS)

    Type 304 stainless steels, solution-annealed and thermally sensitized at 923 K for 0.5 to 24 h, were He-ion-irradiated up to about 4 dpa at 723 K and radiation-induced segregation (RIS) at grain boundaries was measured by EDS analysis using a FEG-TEM. Ni, Si and P were enriched, and Cr was depleted at the grain boundaries by irradiation. However, although the irradiation dose was the same for the specimens, the RIS of the elements linearly increased with the logarithm of the thermally sensitizing time, except for Cr in the specimen thermally sensitized for 24 h. The enhancement of RIS was attributed to the radiation-induced point defects having large mobility in thermally sensitized stainless steels, because of an expected decrease in C near the grain boundaries and in the matrix after the sensitization heat treatments. It was clarified by the electrochemical potentiokinetic reactivation test (EPR) that the degree of sensitization increased with the progress of Cr depletion at grain boundaries. The Cr concentration at grain boundaries in the heavily sensitized specimen was not changed, and the width of the depleted area was slightly narrowed by the irradiation. This result could be explained that the diffusion of Cr due to initial Cr concentration gradient near grain boundaries exceeded the inverse Kirkendall effect. (orig.)

  18. Sensitivity of aerosol optical thickness and aerosol direct radiative effect to relative humidity

    Directory of Open Access Journals (Sweden)

    H. Bian

    2008-07-01

    Full Text Available We present a sensitivity study on the effects of spatial and temporal resolution of atmospheric relative humidity (RH on calculated aerosol optical thickness (AOT and the aerosol direct radiative effects (DRE in a global model. Using the same aerosol fields simulated in the Global Modeling Initiative (GMI model, we find that, on a global average, the calculated AOT from RH in 1° latitude by 1.25° longitude spatial resolution is 11% higher than that in 2° by 2.5° resolution, and the corresponding DRE at the top of the atmosphere is 8–9% higher for total aerosols and 15% higher for only anthropogenic aerosols in the finer spatial resolution case. The difference is largest over surface escarpment regions (e.g. >200% over the Andes Mountains where RH varies substantially with surface terrain. The largest zonal mean AOT difference occurs at 50–60°N (16–21%, where AOT is also relatively larger. A similar increase is also found when the time resolution of RH is increased. This increase of AOT and DRE with the increase of model resolution is due to the highly non-linear relationship between RH and the aerosol mass extinction efficiency (MEE at high RH (>80%. Our study suggests that caution should be taken in a multi-model comparison (e.g. AeroCom since the comparison usually deals with results coming from different spatial/temporal resolutions.

  19. Individual sensitivity to radiations and DNA repair proficiency: the comet assay contribution

    International Nuclear Information System (INIS)

    Some are hereditary syndromes demonstrate high cancer risk and hypersensitivity in response to exposures to agents such as ultraviolet or ionising radiation, and are characterized by a defective processing of DNA damage. They highlight the importance of the individual risk associated to exposures. The comet assay, a simple technique that detects DNA strand breaks, requires few cells and allows examination of DNA repair capacities in established cell lines, in blood samples or biopsies. The assay has been validated on cellular systems with known repair defects such as xeroderma pigmentosum defective in nucleotide excision repair, on mutant rodent cell lines defective in DNA single strand breaks rejoining (XRCC5/Ku80 and XRCC7/DNAPKcs) (neutral conditions). This assay does not allow to distinguish a defective phenotype in ataxia telangiectasia cells. It shows in homozygous mouse embryo fibroblasts Brca2-/- an impaired DNA double strand break rejoining. Simplicity, rapidity and sensitivity of the alkaline comet assay allow to examine the response of lymphocytes. It has been applied to the analysis of the role of DNA repair in the pathogenesis of collagen diseases, and the involvement of individual DNA repair proficiency in the thyroid tumorigenesis induced in some patients after therapeutic irradiation at childhood has been questioned. Preliminary results of these studies suggest that this type of approach could help for adapting treatment modalities and surveillance in subgroups of patients defective in DNA repair process. It could also have some incidence in the radioprotection field. (author)

  20. Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Chiu

    Full Text Available Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells and PC-3 cells (androgen-independent human prostate cancer cells were used to investigate the anti-cancer effects of ionizing radiation (IR combined with arsenic trioxide (ATO and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer.

  1. Control of radiation sensitivity of mammalian cells. Regulation of expression of DNA repair genes

    International Nuclear Information System (INIS)

    This review describes authors' investigations concerning regulation of expression of DNA repair genes for the purpose of control of radiosensitivity of mammalian cells for cancer radiotherapy. One of their experiments concerns the enhancement of sensitivity to radiation and anti-tumor agents by suppressing the expression of mammalian Rad51 gene which playing a central role in recombination repair against DNA double-strand break, by RNA interference (RNAi). Described are the mode of action of RNAi, mechanism of suppression of Rad51 gene expression by it, enhancing effect in radiosensitivity, stable suppression and enhancement by hairpin RNA and its possible usefulness in cancer therapy. The other concerns the histone H2AX gene, which delivering the repair signal post phosphorylation in chromatin against the double-strand break. Experimental results of suppression of the histone H2AX gene by tet-off system, enhancement of radiosensitivity by the suppression and functional recovery by the gene transfer are described, and the radiosensitivity can be thus artificially controlled by tetracycline in authors' F9 2AX (tet/tet) cells. (N.I.)

  2. Analysis of the common deletions in the mitochondrial DNA is a sensitive biomarker detecting direct and non-targeted cellular effects of low dose ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Schilling-Toth, Boglarka; Sandor, Nikolett; Kis, Eniko [Department of Molecular and Tumor Radiobiology, Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Anna u 5, H-1221 Budapest (Hungary); Kadhim, Munira [Genomic Instability Research Group, School of Life Sciences, Oxford Brookes University, Oxford OX3 0BP (United Kingdom); Safrany, Geza, E-mail: safrany.geza@osski.hu [Department of Molecular and Tumor Radiobiology, Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Anna u 5, H-1221 Budapest (Hungary); Hegyesi, Hargita [Department of Molecular and Tumor Radiobiology, Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Anna u 5, H-1221 Budapest (Hungary)

    2011-11-01

    One of the key issues of current radiation research is the biological effect of low doses. Unfortunately, low dose science is hampered by the unavailability of easily performable, reliable and sensitive quantitative biomarkers suitable detecting low frequency alterations in irradiated cells. We applied a quantitative real time polymerase chain reaction (qRT-PCR) based protocol detecting common deletions (CD) in the mitochondrial genome to assess direct and non-targeted effects of radiation in human fibroblasts. In directly irradiated (IR) cells CD increased with dose and was higher in radiosensitive cells. Investigating conditioned medium-mediated bystander effects we demonstrated that low and high (0.1 and 2 Gy) doses induced similar levels of bystander responses and found individual differences in human fibroblasts. The bystander response was not related to the radiosensitivity of the cells. The importance of signal sending donor and signal receiving target cells was investigated by placing conditioned medium from a bystander response positive cell line (F11-hTERT) to bystander negative cells (S1-hTERT) and vice versa. The data indicated that signal sending cells are more important in the medium-mediated bystander effect than recipients. Finally, we followed long term effects in immortalized radiation sensitive (S1-hTERT) and normal (F11-hTERT) fibroblasts up to 63 days after IR. In F11-hTERT cells CD level was increased until 35 days after IR then reduced back to control level by day 49. In S1-hTERT cells the increased CD level was also normalized by day 42, however a second wave of increased CD incidence appeared by day 49 which was maintained up to day 63 after IR. This second CD wave might be the indication of radiation-induced instability in the mitochondrial genome of S1-hTERT cells. The data demonstrated that measuring CD in mtDNA by qRT-PCR is a reliable and sensitive biomarker to estimate radiation-induced direct and non-targeted effects.

  3. Analysis of the common deletions in the mitochondrial DNA is a sensitive biomarker detecting direct and non-targeted cellular effects of low dose ionizing radiation.

    Science.gov (United States)

    Schilling-Tóth, Boglárka; Sándor, Nikolett; Kis, Eniko; Kadhim, Munira; Sáfrány, Géza; Hegyesi, Hargita

    2011-11-01

    One of the key issues of current radiation research is the biological effect of low doses. Unfortunately, low dose science is hampered by the unavailability of easily performable, reliable and sensitive quantitative biomarkers suitable detecting low frequency alterations in irradiated cells. We applied a quantitative real time polymerase chain reaction (qRT-PCR) based protocol detecting common deletions (CD) in the mitochondrial genome to assess direct and non-targeted effects of radiation in human fibroblasts. In directly irradiated (IR) cells CD increased with dose and was higher in radiosensitive cells. Investigating conditioned medium-mediated bystander effects we demonstrated that low and high (0.1 and 2Gy) doses induced similar levels of bystander responses and found individual differences in human fibroblasts. The bystander response was not related to the radiosensitivity of the cells. The importance of signal sending donor and signal receiving target cells was investigated by placing conditioned medium from a bystander response positive cell line (F11-hTERT) to bystander negative cells (S1-hTERT) and vice versa. The data indicated that signal sending cells are more important in the medium-mediated bystander effect than recipients. Finally, we followed long term effects in immortalized radiation sensitive (S1-hTERT) and normal (F11-hTERT) fibroblasts up to 63 days after IR. In F11-hTERT cells CD level was increased until 35 days after IR then reduced back to control level by day 49. In S1-hTERT cells the increased CD level was also normalized by day 42, however a second wave of increased CD incidence appeared by day 49 which was maintained up to day 63 after IR. This second CD wave might be the indication of radiation-induced instability in the mitochondrial genome of S1-hTERT cells. The data demonstrated that measuring CD in mtDNA by qRT-PCR is a reliable and sensitive biomarker to estimate radiation-induced direct and non-targeted effects. PMID:21843534

  4. Modification of radiation sensitivity by salts of the metals beryllium and indium and the rare earths cerium, lanthanum and scandium.

    Science.gov (United States)

    Floersheim, G L

    1995-03-01

    The LD50 of 46 salts of metals and rare earths (lanthanoids) was determined in mice. Half the LD50 of the compounds was then combined with lethal radiation (10.5 Gy) and the modification of survival time was scored. Only the metals beryllium and indium and the rare earths cerium, lanthanum and scandium displayed activity in our assay. They were then tested at a wider range of lower doses and reduced survival time in a dose-dependent fashion. This appears to be compatible with enhancement of radiation sensitivity. The interaction of these metals and rare earths with radiation adds a new facet to their toxicological spectrum and, by enhancing radiation effects, may influence estimates of risk. On the other hand, the radiosensitizing properties of the metals may be useful for further development of compounds to be used as adjuncts in specific situations of cancer radiotherapy.

  5. Evaluation of the radiation-sensitizer/protector and/or antioxidant efficiencies using Fricke and PAG dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Meesat, Ridthee; Jay-Gerin, Jean-Paul; Khalil, Abdelouahed; Lepage, Martin [Departement de medecine nucleaire et de radiobiologie, Faculte de medecine et des sciences de la sante, Universite de Sherbrooke, Sherbrooke (Quebec) J1H 5N4 (Canada)], E-mail: Martin.Lepage@USherbrooke.ca

    2009-05-01

    In this study, our aim is to assess the potential of Fricke and polyacrylamide gel (PAG) dosimeters to quantitatively evaluate the efficiency of potential radiation sensitizers/protectors and antioxidants. These compounds are of importance in radiotherapy as well as in disease prevention and promotion of health. The basic principle of the Fricke dosimeter is the radiation-induced oxidation of Fe{sup 2+} to Fe{sup 3+} in an aerated aqueous 0.4 M H{sub 2}SO{sub 4}. The production of ferric ions is most sensitive to the radical species produced in the radiolysis of water. Using this method, we observed that cystamine (one of the best of the known radioprotectors) can prevent oxydation of Fe{sup 2+} from reactive radiolysis species. However, one obvious disadvantage of the Fricke dosimeter is that it operates under highly acidic conditions (pH 0.46), which may degrade biological compounds. In contrast, the pH of the polyacrylamide gel (PAG) dosimeter is almost neutral, such that degradation of compounds is less probable. A change in R{sub 2}-dose sensitivity was observed in the presence of radiosensitizers/radioprotectors and antioxidants. The protective effect of Trolox (a well-known antioxidant) and thiourea (a radioprotector) was readily observed using the PAG dosimeter. Incorporation of iodinated radiation sensitizers such as NaI and an iodine contrast agent led to a quantifiable sensitizer enhancement ratio. These studies suggest that the Fricke and the PAG dosimeters have the potential to evaluate the efficiency of radiation sensitizers/protectors and antioxidants.

  6. Proinflammatory and Th1 cytokine alterations following ultraviolet radiation enhancement of disease due to influenza infection in mice.

    Science.gov (United States)

    Ryan, Lisa K; Copeland, Lisa R; Daniels, Mary J; Costa, Elisabeth R; Selgrade, Mary Jane K

    2002-05-01

    Exposure of rodents to immunosuppressive agents such as ozone, dioxin, or ultraviolet radiation (UVR) leads to increased morbidity and mortality following influenza virus infection. However, these adverse effects are not related to the suppression of virus-specific immune responses. Our laboratory showed that UVR increased the morbidity, mortality, and pathogenesis of influenza virus without affecting protective immunity to the virus, as measured by resistance to reinfection, suggesting that UVR and other immunosuppressive pollutants such as dioxin and ozone may exacerbate early responses that contribute to the pathogenesis of a primary viral infection. In the present study, we examined the mechanism of UVR-enhanced mortality in the absence of effects on virus-specific immunity and tested the hypothesis that modulation of cytokine levels was associated with increased deaths and body weight loss. BALB/c mice were exposed to 8.2 kJ/m(2) UVR and were infected 3 days later with a sublethal influenza virus infection (LD(40) of mouse-adapted Hong Kong influenza A/68, H(3)N(2)). Influx of inflammatory cells, proinflammatory cytokines, and cytokines produced by T-helper lymphocytes (Th1 and Th2) were measured in lung homogenates (LH) as well as in bronchoalveolar lavage fluid (BAL). UVR preexposure decreased the influenza-induced lymphocytic influx 5 days after infection, but did not alter macrophage and neutrophil influx into the lung, or increase virus titers significantly. Although interferon (IFN)-gamma, total interleukin (IL)-12, IL-6, and TNF-alpha were altered in mice that received UVR exposure prior to infection, no clear association was made that correlated with the UVR-induced increase in body weight loss and mortality due to influenza infection. PMID:11961220

  7. Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation

    Institute of Scientific and Technical Information of China (English)

    Mai-cang GAO; Xiao-di JIA; Qi-fei WU; Yan CHENG; Fen-rong CHEN; Jun ZHANG

    2011-01-01

    Aim:To investigate whether down-regulation of peroxiredoxin 1(Prx1)and/or peroxiredoxin 5(Prx5)sensitizes human esophageal cancer cells to ionizing radiation(IR).Methods:Human esophageal carcinoma celllines Eca-109 and TE-1 were used.Prx mRNA expression profiles in Eca-109 and TE-1cells were determined using RT-PCR.Two highly expressed isoforms of Prxs,Prx1 and Prx5,were silenced by RNA interference(RNAi).Following IR,intracellular reactive oxygen species(ROS)and apoptosis were measured using flow cytometry,the activities of catalase,superoxide dismutase and glutathione peroxidase were measured,and the radiosensjtjzjng effect of RNAi was observed.Tumor xenograft model was also used to examine the radiOsensitizing effect of RNAi in vivo.Results:Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase,but made human tumor cells more sensitive to IR-induced apoptosis both fn vitro and in vivO.When the two isoforms were decreased simultaneously,intracellular ROS and apoptosis significantly increased after IR.Conclusion:Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.

  8. Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Praveen Kumar, M.K., E-mail: here.praveen@gmail.com [Department of Zoology, Goa University, Goa 403206 (India); Shyama, S.K., E-mail: skshyama@gmail.com [Department of Zoology, Goa University, Goa 403206 (India); Sonaye, B.S. [Department of Radiation Oncology, Goa Medical College, Goa (India); Naik, U Roshini; Kadam, S.B.; Bipin, P.D.; D’costa, A. [Department of Zoology, Goa University, Goa 403206 (India); Chaubey, R.C. [Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai (India)

    2014-05-01

    Highlights: • Possible genotoxic effect of accidental exposure of aquatic fauna to γ radiation. • Relative sensitivity of bivalves to γ radiation is also analyzed using comet assay. • γ radiation induced significant genetic damage in both the species of bivalves. • P. malabarica and M. casta exhibited a similar level of sensitivity to γ radiation. • Comet assay may be used as a biomarker for the environmental biomonitoring. - Abstract: Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of ‘Comet assay’ for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in

  9. Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay

    International Nuclear Information System (INIS)

    Highlights: • Possible genotoxic effect of accidental exposure of aquatic fauna to γ radiation. • Relative sensitivity of bivalves to γ radiation is also analyzed using comet assay. • γ radiation induced significant genetic damage in both the species of bivalves. • P. malabarica and M. casta exhibited a similar level of sensitivity to γ radiation. • Comet assay may be used as a biomarker for the environmental biomonitoring. - Abstract: Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of ‘Comet assay’ for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in

  10. Melatonin sensitizes human breast cancer cells to ionizing radiation by downregulating proteins involved in double-strand DNA break repair.

    Science.gov (United States)

    Alonso-González, Carolina; González, Alicia; Martínez-Campa, Carlos; Gómez-Arozamena, José; Cos, Samuel

    2015-03-01

    Radiation and adjuvant endocrine therapy are nowadays considered a standard treatment option after surgery in breast cancer. Melatonin exerts oncostatic actions on human breast cancer cells. In the current study, we investigated the effects of a combination of radiotherapy and melatonin on human breast cancer cells. Melatonin (1 mm, 10 μm and 1 nm) significantly inhibited the proliferation of MCF-7 cells. Radiation alone inhibited the MCF-7 cell proliferation in a dose-dependent manner. Pretreatment of breast cancer cells with melatonin 1 wk before radiation led to a significantly greater decrease of MCF-7 cell proliferation compared with radiation alone. Melatonin pretreatment before radiation also decreased G2 -M phase arrest compared with irradiation alone, with a higher percentage of cells in the G0 -G1 phase and a lower percentage of cells in S phase. Radiation alone diminished RAD51 and DNA-protein kinase (PKcs) mRNA expression, two main proteins involved in double-strand DNA break repair. Treatment with melatonin for 7 days before radiation led to a significantly greater decrease in RAD51 and DNA-PKcs mRNA expression compared with radiation alone. Our findings suggest that melatonin pretreatment before radiation sensitizes breast cancer cells to the ionizing effects of radiation by decreasing cell proliferation, inducing cell cycle arrest and downregulating proteins involved in double-strand DNA break repair. These findings may have implications for designing clinical trials using melatonin and radiotherapy. PMID:25623566

  11. Prenatal Stress Alters Progestogens to Mediate Susceptibility to Sex-Typical, Stress-Sensitive Disorders, such as Drug Abuse: A Review

    OpenAIRE

    Frye, Cheryl A.; Paris, Jason J.; Osborne, Danielle M.; Campbell, Joannalee C.; Kippin, Tod E.

    2011-01-01

    Maternal–offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well underst...

  12. Prenatal stress alters progestogens to mediate susceptibility to sex-typical, stress-sensitive disorders, such as drug abuse: a review

    OpenAIRE

    Frye, Cheryl A.; Paris, Jason J.; Danielle eOsborne; Joanna eCampbell; Tod eKippin

    2011-01-01

    Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well unders...

  13. Locally Targeted Delivery of a Micron-Size Radiation Therapy Source Using Temperature-Sensitive Hydrogel

    International Nuclear Information System (INIS)

    Purpose: To propose a novel radiation therapy (RT) delivery modality: locally targeted delivery of micron-size RT sources by using temperature-sensitive hydrogel (RT-GEL) as an injectable vehicle. Methods and Materials: Hydrogel is a water-like liquid at room temperature but gels at body temperature. Two US Food and Drug Administration-approved polymers were synthesized. Indium-111 (In-111) was used as the radioactive RT-GEL source. The release characteristics of In-111 from polymerized RT-GEL were evaluated. The injectability and efficacy of RT-GEL delivery to human breast tumor were tested using animal models with control datasets of RT-saline injection. As proof-of-concept studies, a total of 6 nude mice were tested by injecting 4 million tumor cells into their upper backs after a week of acclimatization. Three mice were injected with RT-GEL and 3 with RT-saline. Single-photon emission computed tomography (SPECT) and CT scans were performed on each mouse at 0, 24, and 48 h after injection. The efficacy of RT-GEL was determined by comparison with that of the control datasets by measuring kidney In-111 accumulation (mean nCi/cc), representing the distant diffusion of In-111. Results: RT-GEL was successfully injected into the tumor by using a 30-gauge needle. No difficulties due to polymerization of hydrogel during injection and intratumoral pressure were observed during RT-GEL injection. No back flow occurred for either RT-GEL or RT-saline. The residual tumor activities of In-111 were 49% at 24 h (44% at 48 h, respectively) for RT-GEL and 29% (22%, respectively) for RT-saline. Fused SPECT-CT images of RT-saline showed considerable kidney accumulation of In-111 (2886%, 261%, and 262% of RT-GEL at 0, 24, and 48 h, respectively). Conclusions: RT-GEL was successfully injected and showed much higher residual tumor activity: 170% (200%, respectively), than that of RT-saline at 24 h (48 h, respectively) after injection with a minimal accumulation of In-111 to the

  14. A Polymorphism Within the Promoter of the TGFβ1 Gene Is Associated With Radiation Sensitivity Using an Objective Radiologic Endpoint

    International Nuclear Information System (INIS)

    Purpose: To evaluate whether single nucleotide polymorphisms (SNPs) in the transforming growth factor-β1 (TGFβ1) gene are associated with radiation sensitivity using an objective radiologic endpoint. Methods and Materials: Preradiation therapy and serial postradiation therapy single photon emission computed tomography (SPECT) lung perfusion scans were obtained in patients undergoing treatment for lung cancer. Serial blood samples were obtained to measure circulating levels of TGFβ1. Changes in regional perfusion were related to regional radiation dose yielding a patient-specific dose–response curve, reflecting the patient’s inherent sensitivity to radiation therapy. Six TGFβ1 SNPs (-988, -800, -509, 869, 941, and 1655) were assessed using high-resolution melting assays and DNA sequencing. The association between genotype and slope of the dose–response curve, and genotype and TGFβ1 ratio (4-week/preradiation therapy), was analyzed using the Kruskal-Wallis test. Results: 39 white patients with preradiation therapy and ≥6-month postradiation therapy SPECT scans and blood samples were identified. Increasing slope of the dose–response curve was associated with the C(-509)T SNP (p = 0.035), but not the other analyzed SNPs. This SNP was also associated with higher TGFβ1 ratios. Conclusions: This study suggests that a polymorphism within the promoter of the TGFβ1 gene is associated with increased radiation sensitivity (defined objectively by dose-dependent changes in SPECT lung perfusion).

  15. Higher sensitivity in induction of apoptosis in fibroblast cell lines derived from LEC strain rats to ultraviolet B radiation.

    Science.gov (United States)

    Hayashi, M; Hamasu, T; Turukame, M; Endoh, D; Okui, T

    2001-07-01

    When lung fibroblast cell lines from LEC and WKAH rats were irradiated with ultraviolet B (UVB) and assayed for colony formation, LEC rat cells showed a higher sensitivity than did WKAH rat cells. The LEC rat cells were approximately 1.5-fold more sensitive to UVB radiation than were the WKAH rat cells in terms of D37 values, which are the doses of UVB required to reduce cell survival to 37%. When the rat cells were irradiated with UVB in the presence of 0.5 M dimethyl sulfoxide (DMSO), which efficiently scavenges free radicals such as hydroxyl radicals, no significant difference was observed between the survival curves of either LEC or WKAH rat cells irradiated with UVB in the presence of 0.5 M DMSO and those irradiated with UVB in the absence of DMSO. Therefore, formation of free radicals may not be involved in cell death induced by UVB radiation. Flow cytometry showed that the percentage of apoptotic cells in the LEC rat cell population increased with post-incubation time after UVB radiation. The proportion of apoptotic cells in the UVB-irradiated LEC rat cell population increased as the dose of UVB was increased. In contrast, no significant proportion of apoptotic cells was observed in the UVB-irradiated WKAH rat cell population. These results showed a higher sensitivity in induction of apoptosis by UVB radiation in LEC rat cells than in WKAH rat cells.

  16. Near-ultraviolet radiation-induced damage using an actinic reticuloid strain as a possible sensitive model

    Energy Technology Data Exchange (ETDEWEB)

    Kralli, A.

    1987-01-01

    The introduction to this thesis consists of a review of current concepts regarding the effects of ultraviolet radiation on living cells. Actinic reticuloid, a disease condition for which a near-ultraviolet radiation cellular sensitivity has been proposed as an underlying cause, is described. The experimental work, the broad aim of which is to expand existing knowledge of the effects of near-ultraviolet radiation that may lead to cell lethality, has centred upon the irradiation of a normal human skin fibroblast strain, GM730, and a strain derived from an actinic reticuloid patient, AR6LO. Parts 1 and 2 examine the effects of the irradiation on both normal and actinic fibroblast sensitivities to a range of ultraviolet wavelengths. The next two sections include observations on the protective effect of Trolox-C, a vitamin E analogue and the sensitization resulting from the replacement of the irradiation medium by a deuterated one, using both normal and actinic reticuloid fibroblasts. The final part examines broad-band near- and far-ultraviolet radiation induced membrane damage by the use of radioactively labelled rubidium as a potassium analogue.

  17. In vivo sensitivity of the embryonic and adult neural stem cell compartments to low-dose radiation.

    Science.gov (United States)

    Barazzuol, Lara; Jeggo, Penny A

    2016-08-01

    The embryonic brain is radiation-sensitive, with cognitive deficits being observed after exposure to low radiation doses. Exposure of neonates to radiation can cause intracranial carcinogenesis. To gain insight into the basis underlying these outcomes, we examined the response of the embryonic, neonatal and adult brain to low-dose radiation, focusing on the neural stem cell compartments. This review summarizes our recent findings. At E13.5-14.5 the embryonic neocortex encompasses rapidly proliferating stem and progenitor cells. Exploiting mice with a hypomorphic mutation in DNA ligase IV (Lig4(Y288C) ), we found a high level of DNA double-strand breaks (DSBs) at E14.5, which we attribute to the rapid proliferation. We observed endogenous apoptosis in Lig4(Y288C) embryos and in WT embryos following exposure to low radiation doses. An examination of DSB levels and apoptosis in adult neural stem cell compartments, the subventricular zone (SVZ) and the subgranular zone (SGZ) revealed low DSB levels in Lig4(Y288C) mice, comparable with the levels in differentiated neuronal tissues. We conclude that the adult SVZ does not incur high levels of DNA breakage, but sensitively activates apoptosis; apoptosis was less sensitively activated in the SGZ, and differentiated neuronal tissues did not activate apoptosis. P5/P15 mice showed intermediate DSB levels, suggesting that DSBs generated in the embryo can be transmitted to neonates and undergo slow repair. Interestingly, this analysis revealed a stage of high endogenous apoptosis in the neonatal SVZ. Collectively, these studies reveal that the adult neural stem cell compartment, like the embryonic counterpart, can sensitively activate apoptosis. PMID:27125639

  18. Radiation induced chemotherapy sensitization in trimodality therapy of stage 3 non small cell lung cancer. A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Takita, H. [Millard Fillmore Hospital, Buffalo (United States); Shin, K. H. [CCS Oncology Center, Kenmore, NY, (United States)

    2000-12-01

    The overall cure rate of locally advanced non-small cell lung carcinoma (NSCLC) remains poor. Although there have been encouraging reports of preoperative use of chemotherapy, more recent trend is the trimodal approach of radiation, chemo, and surgical-therapies. With the trimodal therapy, increased tumor response and resectability are reported, however, there are increased treatment related side effects. It was observed that a relatively small dose of radiation given prior to induction chemotherapy greatly enhanced the tumor response to the chemotherapy without increased toxicity. A total of 18 patients (8 3. A and 10 3.B) were initially given 20 Gy of radiation therapy in 10 fractions and then received 2 courses of Taxol combination chemotherapy. The overall response rate was 83% (15/18) and 13 out of 18 patients underwent surgery. There was one postoperative death (not therapy related). It is speculated that the small dose of radiation therapy may have sensitized the tumor to subsequent chemotherapy, and it was suggested a new hypothesis of radiation therapy induced chemotherapy sensitization.

  19. Deficient Expression of Aldehyde Dehydrogenase 1A1 Is Consistent with Increased Sensitivity of Gorlin Syndrome Patients to Radiation Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Aaron T.; Magnaldo, Thierry; Sontag, Ryan L.; Anderson, Lindsey N.; Sadler, Natalie C.; Piehowski, Paul D.; Gache, Yannick; Weber, Thomas J.

    2015-06-01

    Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive phenotypes often display robust regulation of molecular features that modify biological response, which can facilitate identification of relevant pathways/networks. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who display a pronounced tumorigenic response to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our approach exploits newly developed thiol-reactive probes with a flexible click chemistry functional group to define changes in protein thiol profiles in live cell studies, which minimizes artifacts associated with cell lysis. We observe qualitative differences in protein thiol profiles by SDS-PAGE analysis when detection by iodoacetamide vs maleimide probe chemistries are compared, and pretreatment of cells with hydrogen peroxide eliminates detection of the majority of SDS-PAGE bands. Redox probes revealed deficient expression of an apparent 55 kDa protein thiol in GDFs from independent donors, compared with NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase 1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and this deficiency was confirmed by Western blot. Redox probes revealed additional protein thiol differences between GDFs and NHDFs, including radiation responsive annexin family members. Our results indicate a multifactorial basis for the unusual sensitivity of Gorlin syndrome to radiation carcinogenesis, and the pathways identified have plausible implications for radiation health effects.

  20. Role of membrane Hsp70 in radiation sensitivity of tumor cells

    International Nuclear Information System (INIS)

    The major stress-inducible heat shock protein 70 (Hsp70) is frequently overexpressed in the cytosol and integrated in the plasma membrane of tumor cells via lipid anchorage. Following stress such as non-lethal irradiation Hsp70 synthesis is up-regulated. Intracellular located Hsp70 is known to exert cytoprotective properties, however, less is known about membrane (m)Hsp70. Herein, we investigate the role of mHsp70 in the sensitivity towards irradiation in tumor sublines that differ in their cytosolic and/or mHsp70 levels. The isogenic human colon carcinoma sublines CX+ with stable high and CX− with stable low expression of mHsp70 were generated by fluorescence activated cell sorting, the mouse mammary carcinoma sublines 4 T1 (4 T1 ctrl) and Hsp70 knock-down (4 T1 Hsp70 KD) were produced using the CRISPR/Cas9 system, and the Hsp70 down-regulation in human lung carcinoma sublines H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/EPLC-272H HSF-1 KD was achieved by small interfering (si)RNA against Heat shock factor 1 (HSF-1). Cytosolic and mHsp70 was quantified by Western blot analysis/ELISA and flow cytometry; double strand breaks (DSBs) and apoptosis were measured by flow cytometry using antibodies against γH2AX and real-time PCR (RT-PCR) using primers and antibodies directed against apoptosis related genes; and radiation sensitivity was determined using clonogenic cell surviving assays. CX+/CX− tumor cells exhibited similar cytosolic but differed significantly in their mHsp70 levels, 4 T1 ctrl/4 T1 Hsp70 KD cells showed significant differences in their cytosolic and mHsp70 levels and H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/EPLC-272H HSF-1 KD lung carcinoma cell sublines had similar mHsp70 but significantly different cytosolic Hsp70 levels. γH2AX was significantly up-regulated in irradiated CX− and 4 T1 Hsp70 KD with low basal mHsp70 levels, but not in their mHsp70 high expressing counterparts, irrespectively of their cytosolic Hsp70 content. After

  1. Photosynthesis of two Arctic macroalgae under different ambient radiation levels and their sensitivity to enhanced UV radiation

    NARCIS (Netherlands)

    Brouwer, P.E.M.; Bischof, K.; Hanelt, D.; Kromkamp, J.C.

    2000-01-01

    The change in optimal quantum efficiency (F-v/F-m) of the Arctic species Laminaria saccharina and Palmaria palmata was investigated in a long-term experiment in situ under different radiation levels during the summer of 1997 in the Kongsfjord (Ny-Alesund, Spitsbergen, Norway, 78 degrees 55.5'N, 11 d

  2. Sensitivity of aerosol optical thickness and aerosol direct radiative effect to relative humidity

    Directory of Open Access Journals (Sweden)

    H. Bian

    2009-04-01

    Full Text Available We present a sensitivity study of the effects of spatial and temporal resolution of atmospheric relative humidity (RH on calculated aerosol optical thickness (AOT and the aerosol direct radiative effects (DRE in a global model. We carry out different modeling experiments using the same aerosol fields simulated in the Global Modeling Initiative (GMI model at a resolution of 2° latitude by 2.5° longitude, using time-averaged fields archived every three hours by the Goddard Earth Observation System Version 4 (GEOS-4, but we change the horizontal and temporal resolution of the relative humidity fields. We find that, on a global average, the AOT calculated using RH at a 1°×1.25° horizontal resolution is 11% higher than that using RH at a 2°×2.5° resolution, and the corresponding DRE at the top of the atmosphere is 8–9% and 15% more negative (i.e., more cooling for total aerosols and anthropogenic aerosol alone, respectively, in the finer spatial resolution case. The difference is largest over surface escarpment regions (e.g. >200% over the Andes Mountains where RH varies substantially with surface terrain. The largest zonal mean AOT difference occurs at 50–60° N (16–21%, where AOT is also relatively larger. A similar impact is also found when the time resolution of RH is increased. This increase of AOT and aerosol cooling with the increase of model resolution is due to the highly non-linear relationship between RH and the aerosol mass extinction efficiency (MEE at high RH (>80%. Our study is a specific example of the uncertainty in model results highlighted by multi-model comparisons such as AeroCom, and points out one of the many inter-model differences that can contribute to the overall spread among models.

  3. Positron emission tomography (PET) study of the alterations in brain pharmacokinetics of methamphetamine in methamphetamine sensitized animals

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hitoshi [Tohoku Univ., Sendai (Japan). Hospital

    2001-08-01

    I investigated the differences in brain pharmacokinetics of [{sup 11}C]methamphetamine ([{sup 11}C]MAP) in normal and MAP sensitized animals using positron emission tomography (PET). [{sup 11}C]MAP was synthesized by an automated on-line [{sup 11}C]methylation system. I newly produced MAP sensitized dog and monkey by repeated MAP treatment. The maximal level of accumulation of [{sup 11}C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. This result suggests the changes in the pharmacokinetic profile of MAP in the brain affect the development or expression of MAP-induced behavioral sensitization. However, the overaccumulation of [{sup 11}C]MAP in the sensitized monkey brain was not observed due to the influence of anesthesia. (author)

  4. The L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase alters stability in U87MG glioma cells but not temozolomide sensitivity

    OpenAIRE

    Remington, Maya; Chtchetinin, Jana; Ancheta, Karen; Nghiemphu, Phioanh Leia; Cloughesy, Timothy; Lai, Albert

    2009-01-01

    First-line therapy for patients with glioblastoma multiforme includes treatment with radiation and temozolomide (TMZ), an oral DNA alkylating chemotherapy. Sensitivity of glioma cells to TMZ is dependent on the level of cellular O6-methylguanine-DNA methyltransferase (MGMT) repair activity. Several common coding- region polymorphisms in the MGMT gene (L84F and the linked pair I143V/K178R) modify functional characteristics of MGMT and cancer risk. To determine whether these polymorphic changes...

  5. Sensitivity of APSIM/ORYZA model due to estimation errors in solar radiation

    OpenAIRE

    Alexandre Bryan Heinemann; Pepijn A.J. van Oort; Diogo Simões Fernandes; Aline de Holanda Nunes Maia

    2012-01-01

    Crop models are ideally suited to quantify existing climatic risks. However, they require historic climate data as input. While daily temperature and rainfall data are often available, the lack of observed solar radiation (Rs) data severely limits site-specific crop modelling. The objective of this study was to estimate Rs based on air temperature solar radiation models and to quantify the propagation of errors in simulated radiation on several APSIM/ORYZA crop model seasonal outputs, yield, ...

  6. Cell Cycle Control and Adhesion Molecule Expression in Cells of the Immune System are Sensitive to Altered Gravity

    Science.gov (United States)

    Ullrich, O.; Paulsen, K.; Thiel, C.; Herrmann, K.; Sang, C.; Han, G.; Hemmersbach, R.; von der Wiesche, M.; Kroll, H.; Zhuang, F.; Grote, K. H.; Cogoli, A.; Zipp, F.; Engelmann, F.

    2008-06-01

    Life on earth developed in the presence and under the constant influence of gravity. Thus, it is a fundamental biological question, whether gravity is required for cellular functions and signal transduction in mammalian cells. Since the first Spacelab-Mission 20 years ago, it is known that activation and function of T lymphocytes is severely suppressed in microgravity, but the underlying molecular mechanisms are not elucidated. Experiments have been performed using ground-based facilities such as fast-rotating clinostat and hyper-g-centrifuges, and real microgravity provided by parabolic flights. We found that 1.) cells of the immune system responded cell type specifically to altered gravity, 2.) microgravity induced a multitude of initial alterations in signal transduction, whereas 3.) hypergravity of 1.8g did not induce any changes of the pathways tested, and that 4.) most of the initially altered pathways in microgravity adapted to "normal" levels within 15min. However, some pathways remained altered and could explain cell cycle arrest of T lymphocytes as observed in several long-term space experiments.

  7. Genomic alterations in BCL2L1 and DLC1 contribute to drug sensitivity in gastric cancer.

    Science.gov (United States)

    Park, Hansoo; Cho, Sung-Yup; Kim, Hyerim; Na, Deukchae; Han, Jee Yun; Chae, Jeesoo; Park, Changho; Park, Ok-Kyoung; Min, Seoyeon; Kang, Jinjoo; Choi, Boram; Min, Jimin; Kwon, Jee Young; Suh, Yun-Suhk; Kong, Seong-Ho; Lee, Hyuk-Joon; Liu, Edison T; Kim, Jong-Il; Kim, Sunghoon; Yang, Han-Kwang; Lee, Charles

    2015-10-01

    Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Recent high-throughput analyses of genomic alterations revealed several driver genes and altered pathways in GC. However, therapeutic applications from genomic data are limited, largely as a result of the lack of druggable molecular targets and preclinical models for drug selection. To identify new therapeutic targets for GC, we performed array comparative genomic hybridization (aCGH) of DNA from 103 patients with GC for copy number alteration (CNA) analysis, and whole-exome sequencing from 55 GCs from the same patients for mutation profiling. Pathway analysis showed recurrent alterations in the Wnt signaling [APC, CTNNB1, and DLC1 (deleted in liver cancer 1)], ErbB signaling (ERBB2, PIK3CA, and KRAS), and p53 signaling/apoptosis [TP53 and BCL2L1 (BCL2-like 1)] pathways. In 18.4% of GC cases (19/103), amplification of the antiapoptotic gene BCL2L1 was observed, and subsequently a BCL2L1 inhibitor was shown to markedly decrease cell viability in BCL2L1-amplified cell lines and in similarly altered patient-derived GC xenografts, especially when combined with other chemotherapeutic agents. In 10.9% of cases (6/55), mutations in DLC1 were found and were also shown to confer a growth advantage for these cells via activation of Rho-ROCK signaling, rendering these cells more susceptible to a ROCK inhibitor. Taken together, our study implicates BCL2L1 and DLC1 as potential druggable targets for specific subsets of GC cases. PMID:26401016

  8. Alterations in whole-body insulin sensitivity resulting from repeated eccentric exercise of a single muscle group: a pilot investigation

    OpenAIRE

    Gonzalez, Javier; Barwood, Martin; Goodall, Stuart; Thomas, Kevin; Howatson, Glyn

    2015-01-01

    Unaccustomed eccentric exercise using large muscle groups elicits soreness, decrements in physical function and impairs markers of whole-body insulin sensitivity; although these effects are attenuated with a repeated exposure. Eccentric exercise of a small muscle group (elbow flexors) displays similar soreness and damage profiles in response to repeated exposure. However, it is unknown whether damage to small muscle groups impacts upon whole-body insulin sensitivity. This pilot investigation ...

  9. Effects of Simulated Microgravity on Sensitivity of Human Fibroblasts to Radiation

    Science.gov (United States)

    Whitehead, Nickolas

    2016-01-01

    Living organisms are exposed to radiation in space that consists of high energy protons and heavy charged particles. For humans, exposure to this environment is expected to cause cancer and other harmful effects. Current assessment of space radiation risk to astronauts is based on the information gained from human data and animal experiments under 1g gravity. If spaceflight factors, such as microgravity, affect the repair of space radiation-induced damage, then one would expect an additional impact on the mutation rate in living cells and consequently on the accuracy of current ground-based risk assessment methods. The project I worked on consisted of using clonogenic assays to analyze the survival of human fibroblast AG01522 cells exposed to radiation with and without simulated microgravity. A random positioning machine (RPM) was used to simulate microgravity because of the principle of gravity-vector-averaging. The effects of simulated microgravity were studied after exposing the cells to different doses of gamma radiation.

  10. Characterization and application of radiation-sensitizing genes by DNA methylation in lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Il Lae; Kim, In Gyu; Kim, Kug Chan

    2011-03-15

    The sensitivity or resistance of cancer cells and normal tissues to ionizing radiation plays an important role in the clinical setting of lung cancer treatment. However, to date the exact molecular mechanisms of intrinsic radiosensitivity have not been well explained. In this study, we compared the radiosensitivity or radioresistance in two non-small cell lung cancers (NSCLCs), H460 and A549, and investigated the signaling pathways that confer radioresistance. H460 cells showed a significant G2/M arrest after 12 h of irradiation (5 Gy), reaching 60% of G2/M phase arrest. A549 cells also showed a significant G2/M arrest after 12 h of exposure; however, this arrest completely disappeared after 24 h of exposure. A549 has higher methylated CpG sites in PTEN, which is correlated with tumor radioresistance in some cancer cells, than H460 cells, and the average of the extent of the methylation was {approx}4.3 times higher in A549 cells than in H460 cells. As a result, PTEN expression was lower in A549 than in H460. Conducting Western blot analysis, we found that PTEN acted as a negative regulator for pAkt, and the pAkt acted as a negative regulator for p53 expression. According to the above results, we concluded that the radiosensitivity shown in H460 cells may be due to the higher expression of PTEN through p53 signaling pathway. The expression of the Wnt-antagonist Dickkopf gene (DKK) is downregulated in several types of tumors as a consequence of epigenetic DNA modification; four DKK members, DKK1, DKK2, DKK3, and DKK4, have been identified. In this study, we investigated another function of DKK3 in non-small cell lung cancer H460 cells, in which DKK3 was hypermethylated (44%) but still expressed, by interfering with DKK3 expression using DKK3-silencing RNA (SiRNA). We found that knockdown of DKK3 expression by DKK3 SiRNA transfection led to the detachment of H460 cells from the bottom of the culture plate and caused apoptosis. The expression of cyclindependent kinases

  11. Comparison of heat and radiation sensitivity in normal C3H-10T1/2 cells and cells transformed by radiation or the H ras oncogene

    International Nuclear Information System (INIS)

    C/sub 3/H 10T1/2 cells were transformed from the normal to the malignant state using X-rays or by transfection with a plasmid containing the active H ras oncogene. Clones of cells with a transformed morphology were isolated and grown into large populations. These cells were tested and produced tumors in C/sub 3/H mice. Seven clones transformed by radiation showed a range of sensitivity to heat and X-rays that varied from greater to lesser than the heat and X-ray sensitivity in normal cells. Similar results were observed for the cells transformed by the H ras oncogene. Thus, the malignant transformation of C/sub 3/H 10T1/2 cells by X-rays or H ras oncogenes did not, in general result in increased thermal sensitivity, implying that the malignant phenotype is not intrinsically more heat sensitive than the normal cell. The thermal sensitivity in the various transformed cell lines was not correlated with membrane cholesterol or phospholipid content

  12. Vinpocetine and Vitamin E Modulates Some Biochemical Alterations Induced by Exposure to Ionizing Radiation and Chloropyrifos in Rats

    International Nuclear Information System (INIS)

    Acapi-Cav is a well balanced and well tolerated formula containing vinpocetine and vitamin E. The objective of this study was to investigate the effect of vinpocetine and vitamin E on the oxidative stress, electrolytes and monoamines level in rats exposed to ionizing radiation (gamma rays), chloropyrifos (CPF) as well as rats exposed to a combination of gamma rays and CPF. Irradiation was performed by whole body exposure of rats to 8 Gy delivered at 1 Gy every 4 days. CPF was administered to rats by oral gavages at a dose of 3.6 mg/kg body weight ( 1/10 LD50 ) daily for 30 days. Vinpocetine and vitamin E were administered to rats by oral gavages at a dose of 20 mg/kg body weight daily during 7 days before starting the experiment and continued during the period of exposure to gamma rays and/or CPF. The results revealed significant increase of malondialdehyde (MDA) level associated with a significant decrease of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in the blood of rats exposed to gamma rays and/or CPF indicating oxidative stress. The levels of serum electrolytes (sodium Na+, potassium K+, calcium Ca++ and magnesium Mg) showed significant decrease. Serum dopamine (DA) level was decreased and norepinephrine (NE) was increased while epinephrine (EPI) showed non-significant change. The level of serum monoamine oxidase (MAO) showed significant increase. The administration of vinpocetine and vitamin E to rats exposed to gamma rays and/or CPF significantly reduced the amount of MDA which associated with an increase in the level of antioxidants and significant improvement was recorded for electrolytes level. The results demonstrated that vinpocetine and vitamin E significantly attenuated the increase of MAO and induced significant amelioration in the level of monoamines. It could be concluded that vinpocetine and vitamin E might protect the body from oxidative damage and electrolytes and monoamines alterations in rats exposed to gamma rays and

  13. Strain-dependent susceptibility to radiation-induced mammary cancer is a result of differences in epithelial cell sensitivity to transformation.

    Science.gov (United States)

    Ullrich, R L; Bowles, N D; Satterfield, L C; Davis, C M

    1996-09-01

    Variations in sensitivity to radiation-induced mammary cancer among different strains of mice are well known. However, the reasons for these variations have not been determined. In the present study, the cell dissociation assay was used to determine the radiation-induced transformation frequencies in sensitive BALB/c mice and resistant C57BL mice as well as the resistant hybrid B6CF1 independent of host environment. The influence of host environment on the progression of transformed cells to the neoplastic phenotype was also examined. Results demonstrated that the variations in sensitivity among these sensitive and resistant mice are a result of inherent differences in the sensitivity of the mammary epithelial cells to radiation-induced transformation. Under the conditions used, host environment played no role in the initiation of transformed cells by radiation or in the progression of these cells to the neoplastic phenotype.

  14. Strain-dependent susceptibiltiy to radiation-induced mammary cancer is a result of differences in epithelial cell sensitivity to transformation

    Energy Technology Data Exchange (ETDEWEB)

    Ullrich, R.L.; Davis, C.M. [Univ. of Texas Medical Branch, Galveston, TX (United States); Bowles, N.D.; Satterfield, L.C. [Oak Ridge National Lab., Oak Ridge, TN (United States)

    1996-09-01

    Variations in sensitivity to radiation-induced mammary cancer among different strains of mice are well known. However, the reasons for these variations have not been determined. In the present study, the cell dissociation assay was used to determine the radiation-induced transformation frequencies in sensitive BALB/c mice and resistant C57BL mice as well as the resistant hybrid B6Cf{sub 1} independent of host environment. The influence of host environment on the progression of transformed cells to the neoplastic phenotype was also examined. Results demonstrated that the variations in sensitivity among these sensitive and resistant mice are a result of inherent differences in the sensitivity of the mammary epithelial cells to radiation-induced transformation. Under the conditions used, host environment played no role in the initiation of transformed cells by radiation or in the progression of these cells to the neoplastic phenotype. 19 refs., 1 tab.

  15. Can UV radiation affect benthic deposit-feeders through biochemical alteration of food resources? An experimental study with juveniles of the benthic polychaete Eupolymnia nebulosa.

    Science.gov (United States)

    Nahon, Sarah; Pruski, Audrey M; Duchêne, Jean-Claude; Méjanelle, Laurence; Vétion, Gilles; Desmalades, Martin; Charles, François

    2011-05-01

    The growth, tentacle development and feeding activity of the benthic polychaete Eupolymnia nebulosa were examined to determine whether UV might affect marine deposit-feeders indirectly through the modification of the nutritional quality of their resources. Since marine invertebrates have higher nutritional requirements during the period following settlement, we tested the effect of UV-altered phytodetritus on freshly settled juveniles of E. nebulosa. Phytodetritus was prepared from cultures of the diatom Skeletonema costatum either grown under or sheltered from UVB radiation. Sterol content of phytodetritus was unmodified by UV radiation. Conversely, phytodetritus was noticeably depleted in polyunsaturated fatty acids. Growth and tentacle development of juveniles fed on altered phytodetritus were reduced by 35% and 15% respectively, suggesting potential deficiencies in essential nutrients. In response to the lower quality of the phytodetritus, juveniles explored a wider area as they search for food, a strategy that could compensate for low food quality. PMID:21388674

  16. Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, enlarge the parasite's food vacuole and alter drug sensitivities.

    Science.gov (United States)

    Pulcini, Serena; Staines, Henry M; Lee, Andrew H; Shafik, Sarah H; Bouyer, Guillaume; Moore, Catherine M; Daley, Daniel A; Hoke, Matthew J; Altenhofen, Lindsey M; Painter, Heather J; Mu, Jianbing; Ferguson, David J P; Llinás, Manuel; Martin, Rowena E; Fidock, David A; Cooper, Roland A; Krishna, Sanjeev

    2015-01-01

    Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in sensitivity to artemisinins, when compared with parental strains. A transgenic parasite line expressing the L272F variant of PfCRT confirmed this increased chloroquine sensitivity and enlarged food vacuole phenotype. Furthermore, the introduction of the C101F or L272F mutation into a chloroquine-resistant variant of PfCRT reduced the ability of this protein to transport chloroquine by approximately 93 and 82%, respectively, when expressed in Xenopus oocytes. These data provide, at least in part, a mechanistic explanation for the increased sensitivity of the mutant parasite lines to chloroquine. Taken together, these findings provide new insights into PfCRT function and PfCRT-mediated drug resistance, as well as the food vacuole, which is an important target of many antimalarial drugs.

  17. Sensitivity of surface radiation budget to clouds over the Asian monsoon region

    Indian Academy of Sciences (India)

    S Balachandran; M Rajeevan

    2007-04-01

    Using the ISCCP–FD surface radiative flux data for the summer season (June to September) of the period 1992 to 1995, an analysis was done to understand the role of clouds on the surface radiation budget over the Asian monsoon region. At the top of atmosphere (TOA) of convective regions of the Asian monsoon region, the short wave radiative forcing (SWCRF) and long wave radiative forcing (LWCRF) do not cancel each other resulting in occurrence of the net cloud radiative forcing values exceeding −30W/m2. This type of imbalance between SWCRF and LWCRF at TOA is reflected down on the earth surface–atmosphere system also as an imbalance between surface netcloud radiative forcing (NETCRF) and atmospheric NETCRF. Based on the regression analysis of the cloud effects on the surface radiation budget quantities, it has been observed that generally, the variance explained by multiple type cloud data is 50% more than that of total cloud cover alone. In case of SWCRF, the total cloud cover can explain about 3% (7%) of the variance whereas the three cloud type descriptions of clouds can explain about 44% (42%) of the variance over oceanic (land) regions. This highlights the importance of cloud type information in explaining the variations of surface radiation budget. It has been observed that the clouds produce more cooling effect in short-wave band than the warming effect in long-wave band resulting in a net cooling at the surface. Over the oceanic region, variations in high cloud amount contribute more to variations in SWCRF while over land regions both middle and high cloud variations make substantial contributions to the variations in both SWCRF and NETCRF.

  18. Estimation of mineral dust longwave radiative forcing: sensitivity study to particle properties and application to real cases over Barcelona

    Directory of Open Access Journals (Sweden)

    M. Sicard

    2014-03-01

    Full Text Available The aerosol radiative effect in the longwave (LW spectral range is sometimes not taken into account in atmospheric aerosol forcing studies at local scale because the LW aerosol effect is assumed to be negligible. At regional and global scale this effect is partially taken into account: aerosol absorption is taken into account but scattering is still neglected. However, aerosols with strong absorbing and scattering properties in the LW region, like mineral dust, can have a non-negligible radiative effect in the LW spectral range (both at surface and top of the atmosphere which can counteract their cooling effect occurring in the shortwave spectral range. The first objective of this research is to perform a sensitivity study of mineral dust LW radiative forcing (RF as a function of dust microphysical and optical properties using an accurate radiative transfer model which can compute vertically-resolved shortwave and longwave aerosol RF. Radiative forcing simulations in the LW range have shown an important sensitivity to the following parameters: aerosol load, radius of the coarse mode, refractive index, aerosol vertical distribution, surface temperature and surface albedo. The scattering effect has been estimated to contribute to the LW RF up to 18% at the surface and up to 38% at the top of the atmosphere. The second objective is the estimation of the shortwave and longwave dust RF for 11 dust outbreaks observed in Barcelona. At the surface, the LW RF varies between +2.8 and +10.2 W m−2, which represents between 11 and 26% (with opposite sign of the SW component, while at the top of the atmosphere the LW RF varies between +0.6 and +5.8 W m−2, which represents between 6 and 26% (with opposite sign of the SW component.

  19. Ionising radiation induces persistent alterations in the cardiac mitochondrial function of C57BL/6 mice 40 weeks after local heart exposure

    International Nuclear Information System (INIS)

    Background and purpose: Radiotherapy of thoracic and chest-wall tumours increases the long-term risk of radiation-induced heart disease. The aim of this study was to investigate the long-term effect of local heart irradiation on cardiac mitochondria. Methods: C57BL/6 and atherosclerosis-prone ApoE−/− mice received local heart irradiation with a single X-ray dose of 2 Gy. To investigate the low-dose effect, C57BL/6 mice also received a single heart dose of 0.2 Gy. Functional and proteomic alterations of cardiac mitochondria were evaluated after 40 weeks, compared to age-matched controls. Results: The respiratory capacity of irradiated C57BL/6 cardiac mitochondria was significantly reduced at 40 weeks. In parallel, protein carbonylation was increased, suggesting enhanced oxidative stress. Considerable alterations were found in the levels of proteins of mitochondria-associated cytoskeleton, respiratory chain, ion transport and lipid metabolism. Radiation induced similar but less pronounced effects in the mitochondrial proteome of ApoE−/− mice. In ApoE−/−, no significant change was observed in mitochondrial respiration or protein carbonylation. The dose of 0.2 Gy had no significant effects on cardiac mitochondria. Conclusion: This study suggests that ionising radiation causes non-transient alterations in cardiac mitochondria, resulting in oxidative stress that may ultimately lead to malfunctioning of the heart muscle

  20. Studies of variation in inherent sensitivities to radiation, 5-fluorouracil and methotrexate in a series of human and murine tumor cell lines in vitro

    International Nuclear Information System (INIS)

    Clinical studies have reported reduced response rates to subsequent chemotherapy in certain tumors recurring after radiotherapy. These authors have investigated whether there are any correlations between radiation and drug responses in vitro using a range of murine and human tumor cell lines. They have compared sensitivities to X-irradiation and to 24 hr exposures to two widely used antitumor drugs, methotrexate and 5-fluorouracil. The 4 murine lines selected showed a range of radiation responses with Do values of 0.48-0.76 Gy. Methotrexate sensitivities also exhibited an 800-fold difference which appeared to correlate inversely with radiation response. Sensitivity to 5-FU was less variable in these cells and was unrelated to radiation response. In contrast, in the human lines tested, no correlations were observed between drug sensitivities and radiation response. The six lines tested showed a range of radiation responses with Do values of 0.66-1.59 Gy. Methotrexate sensitivities ranged only over a 150-fold concentration but, contrasting with data from the murine cells, no correlation with radiation response was apparent. Similarly, no correlations between response to 5-fluorouracil and radiation or 5-fluorouracil and methotrexate were noted, which is inconsistent with results using murine cells

  1. Mutants of Ralstonia (Pseudomonas) solanacearum sensitive to antimicrobial peptides are altered in their lipopolysaccharide structure and are avirulent in tobacco

    OpenAIRE

    Titarenko, Elena; Lopez Solanilla, Emilia; García Olmedo, Francisco; Rodriguez Palenzuela, Pablo

    1997-01-01

    Ralstonia solanacearum K60 was mutagenized with the transposon Tn5, and two mutants, M2 and M88, were isolated. Both mutants were selected based on their increased sensitivity to thionins, and they had the Tn5 insertion in the same gene, 34 bp apart. Sequence analysis of the interrupted gene showed clear homology with the rfaF gene from Escherichia coli and Salmonella typhimurium (66% similarity), which encodes a heptosyltransferase involved in the synthesis of the lipopolysaccharide (LPS) co...

  2. Action video game playing is associated with improved visual sensitivity, but not alterations in visual sensory memory.

    Science.gov (United States)

    Appelbaum, L Gregory; Cain, Matthew S; Darling, Elise F; Mitroff, Stephen R

    2013-08-01

    Action video game playing has been experimentally linked to a number of perceptual and cognitive improvements. These benefits are captured through a wide range of psychometric tasks and have led to the proposition that action video game experience may promote the ability to extract statistical evidence from sensory stimuli. Such an advantage could arise from a number of possible mechanisms: improvements in visual sensitivity, enhancements in the capacity or duration for which information is retained in visual memory, or higher-level strategic use of information for decision making. The present study measured the capacity and time course of visual sensory memory using a partial report performance task as a means to distinguish between these three possible mechanisms. Sensitivity measures and parameter estimates that describe sensory memory capacity and the rate of memory decay were compared between individuals who reported high evels and low levels of action video game experience. Our results revealed a uniform increase in partial report accuracy at all stimulus-to-cue delays for action video game players but no difference in the rate or time course of the memory decay. The present findings suggest that action video game playing may be related to enhancements in the initial sensitivity to visual stimuli, but not to a greater retention of information in iconic memory buffers. PMID:23709062

  3. NAC1 modulates sensitivity of ovarian cancer cells to cisplatin by altering the HMGB1-mediated autophagic response.

    Science.gov (United States)

    Zhang, Y; Cheng, Y; Ren, X; Zhang, L; Yap, K L; Wu, H; Patel, R; Liu, D; Qin, Z-H; Shih, I-M; Yang, J-M

    2012-02-23

    Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, is known to have important roles in proliferation and growth of tumor cells and in chemotherapy resistance. Yet, the mechanisms underlying how NAC1 contributes to drug resistance remain largely unclear. We report here that autophagy was involved in NAC1-mediated resistance to cisplatin, a commonly used chemotherapeutic drug in the treatment of ovarian cancer. We found that treatment with cisplatin caused an activation of autophagy in ovarian cancer cell lines, A2780, OVCAR3 and SKOV3. We further demonstrated that knockdown of NAC1 by RNA interference or inactivation of NAC1 by inducing the expression of a NAC1 deletion mutant that contains only the BTB/POZ domain significantly inhibited the cisplatin-induced autophagy, resulting in increased cisplatin cytotoxicity. Moreover, inhibition of autophagy and sensitization to cisplatin by NAC1 knockdown or inactivation were accompanied by induction of apoptosis. To confirm that the sensitizing effect of NAC1 inhibition on the cytotoxicity of cisplatin was attributed to suppression of autophagy, we assessed the effects of the autophagy inhibitors 3-methyladenosine and chloroquine, and small interfering RNAs (siRNAs) targeting beclin 1 or Atg5 on the cytotoxicity of cisplatin. Treatment with 3-methyladenosine, chloroquine or beclin 1 and Atg5-targeted siRNA also enhanced the sensitivity of SKOV3, A2780 and OVCAR3 cells to cisplatin, indicating that suppression of autophagy indeed renders tumor cells more sensitive to cisplatin. Regulation of autophagy by NAC1 was mediated by the high-mobility group box 1 (HMGB1), as the functional status of NAC1 was associated with the expression, translocation and release of HMGB1. The results of our study not only revealed a new mechanism determining cisplatin sensitivity but also identified NAC1 as a novel regulator of autophagy. Thus, the NAC1-mediated autophagy may be exploited as a new target for

  4. Grafting of thermo-sensitive N-vinylcaprolactam onto silicone rubber through the direct radiation method

    Science.gov (United States)

    Valencia-Mora, Ricardo A.; Zavala-Lagunes, Edgar; Bucio, Emilio

    2016-07-01

    The modification of silicone rubber films (SR) was performed by radiation-induced graft polymerization of thermosensitive poly(N-vinylcaprolactam) (PNVCL) using gamma rays from a Co-60 source. The graft polymerization was obtained by a direct radiation method with doses from 5 to 70 kGy, at monomer concentrations between 5% and 70% in toluene. Grafting was confirmed by infrared, differential scanning calorimetry, thermogravimetric analysis, and swelling studies. The lower critical solution temperature (LCST) of the grafted SR was measured by swelling and differential scanning calorimetry.

  5. Down-regulation of ATM Protein Sensitizes Human Prostate Cancer Cells to Radiation-induced Apoptosis*

    OpenAIRE

    Truman, Jean-Philip; Gueven, Nuri; Lavin, Martin; Leibel, Steven; Kolesnick, Richard; Fuks, Zvi; Haimovitz-Friedman, Adriana

    2005-01-01

    Treatment with the protein kinase C activator 12-O tetradecanoylphorbol 12-acetate (TPA) enables radiation-resistant LNCaP human prostate cancer cells to undergo radiation-induced apoptosis, mediated via activation of the enzyme ceramide synthase (CS) and de novo synthesis of the sphingolipid ceramide (Garzotto, M., Haimovitz-Friedman, A., Liao, W. C., White-Jones, M., Huryk, R., Heston, D. W. W., Cardon-Cardo, C., Kolesnick, R., and Fuks, Z. (1999) Cancer Res. 59, 5194-5201). Here, we show t...

  6. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Directory of Open Access Journals (Sweden)

    Amandine Girousse

    Full Text Available When energy is needed, white adipose tissue (WAT provides fatty acids (FAs for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  7. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Science.gov (United States)

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity. PMID:23431266

  8. Cinnamon improves insulin sensitivity and alters the body composition in an animal model of the metabolic syndrome.

    OpenAIRE

    Couturier, Karine; Batandier, Cécile; Awada, M.; Hininger-Favier, Isabelle; Canini, Frédéric; Anderson, Richard; Leverve, Xavier,; Roussel, Anne-Marie

    2010-01-01

    International audience Polyphenols from cinnamon (CN) have been described recently as insulin sensitizers and antioxidants but their effects on the glucose/insulin system in vivo have not been totally investigated. The aim of this study was to determine the effects of CN on insulin resistance and body composition, using an animal model of the metabolic syndrome, the high fat/high fructose (HF/HF) fed rat. Four groups of 22 male Wistar rats were fed for 12 weeks with: (i) (HF/HF) diet to in...

  9. Comparison of the sensitivity of surface downward longwave radiation to changes in water vapor at two high elevation sites

    International Nuclear Information System (INIS)

    Among the potential reasons for enhanced warming rates in many high elevation regions is the nonlinear relationship between surface downward longwave radiation (DLR) and specific humidity (q). In this study we use ground-based observations at two neighboring high elevation sites in Southwestern Colorado that have different local topography and are 1.3 km apart horizontally and 348 m vertically. We examine the spatial consistency of the sensitivities (partial derivatives) of DLR with respect to changes in q, and the sensitivities are obtained from the Jacobian matrix of a neural network analysis. Although the relationship between DLR and q is the same at both sites, the sensitivities are higher when q is smaller, which occurs more frequently at the higher elevation site. There is a distinct hourly distribution in the sensitivities at both sites especially for high sensitivity cases, although the range is greater at the lower elevation site. The hourly distribution of the sensitivities relates to that of q. Under clear skies during daytime, q is similar between the two sites, however under cloudy skies or at night, it is not. This means that the DLR–q sensitivities are similar at the two sites during daytime but not at night, and care must be exercised when using data from one site to infer the impact of water vapor feedbacks at another site, particularly at night. Our analysis suggests that care should be exercised when using the lapse rate adjustment to infill high frequency data in a complex topographical region, particularly when one of the stations is subject to cold air pooling as found here. (letter)

  10. Irradiation of ethylene/styrene copolymers: evidence of sensitization of the aromatic moiety as counterpart of the radiation protection effect.

    Science.gov (United States)

    Ferry, M; Bessy, E; Harris, H; Lutz, P J; Ramillon, J-M; Ngono-Ravache, Y; Balanzat, E

    2012-02-16

    Molecules containing aromatics systems are more stable in the presence of ionizing radiations than alkanes. In the same way, introducing aromatic rings into aliphatic compounds increases their stability. The protective effect is nonlocal and likely results from the transfer of energy and species from the aliphatic moiety to the aromatic one. For years, it was commonly assumed that the aromatic moiety, which is very radiation resistant, accommodates the extra energy remaining unaffected. The use of Fourier transform infrared spectroscopy, online with high energy ion beam irradiation of ethylene/styrene random copolymers, allows us to bring experimental evidence that the benzene rings are sensitized by transfer reactions and consequently that this effect is more important in polymers with low benzene ring molar content. PMID:22236059

  11. Quasi-analytical solutions of hybrid platform and the optimization of highly sensitive thin-film sensors for terahertz radiation

    CERN Document Server

    Tapsanit, Piyawath; Ishihara, Teruya; Otani, Chiko

    2016-01-01

    We present quasi-analytical solutions (QANS) of hybrid platform (HP) comprising metallic grating (MG) and stacked-dielectric layers for terahertz (THz) radiation. The QANS are validated by finite difference time domain simulation. It is found that the Wood anomalies induce the high-order spoof surface plasmon resonances in the HP. The QANS are applied to optimize new perfect absorber for THz sensing of large-area thin film with ultrahigh figure of merit reaching fifth order of magnitude for the film thickness 0.0001p (p: MG period). The first-order Wood's anomaly of the insulator layer and the Fabry-Perot in the slit's cavity account for the resonance of the perfect absorber. The QANS and the new perfect absorber may lead to highly sensitive and practical nano-film refractive index sensor for THz radiation.

  12. WE-E-BRE-03: Biological Validation of a Novel High-Throughput Irradiator for Predictive Radiation Sensitivity Bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, TL; Martin, JA; Shepard, AJ; Bailey, AM; Nickel, KP; Kimple, RJ; Bednarz, BP [University of Wisconsin, Madison, WI (United States)

    2014-06-15

    Purpose: The large dose-response variation in both tumor and normal cells between individual patients has led to the recent implementation of predictive bioassays of patient-specific radiation sensitivity in order to personalize radiation therapy. This exciting new clinical paradigm has led us to develop a novel high-throughput, variable dose-rate irradiator to accompany these efforts. Here we present the biological validation of this irradiator through the use of human cells as a relative dosimeter assessed by two metrics, DNA double-strand break repair pathway modulation and intercellular reactive oxygen species production. Methods: Immortalized human tonsilar epithelial cells were cultured in 96-well micro titer plates and irradiated in groups of eight wells to absorbed doses of 0, 0.5, 1, 2, 4, and 8 Gy. High-throughput immunofluorescent microscopy was used to detect γH2AX, a DNA double-strand break repair mechanism recruiter. The same analysis was performed with the cells stained with CM-H2DCFDA that produces a fluorescent adduct when exposed to reactive oxygen species during the irradiation cycle. Results: Irradiations of the immortalized human tonsilar epithelial cells at absorbed doses of 0, 0.5, 1, 2, 4, and 8 Gy produced excellent linearity in γH2AX and CM-H2DCFDA with R2 values of 0.9939 and 0.9595 respectively. Single cell gel electrophoresis experimentation for the detection of physical DNA double-strand breaks in ongoing. Conclusions: This work indicates significant potential for our high-throughput variable dose rate irradiator for patient-specific predictive radiation sensitivity bioassays. This irradiator provides a powerful tool by increasing the efficiency and number of assay techniques available to help personalize radiation therapy.

  13. Variation of Cholinesterase-Based Biosensor Sensitivity to Inhibition by Organophosphate Due To Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2009-07-01

    Full Text Available A cholinesterase based biosensor was constructed in order to assess the effects of ionizing radiation on exposed AChE. Although the primary objective of the experiment was to investigate the effect of ionizing radiation on the activity of the biosensor, no changes in cholinesterase activity were observed. Current provided by oxidation of thiocholine previously created from acetylthiocholine by enzyme catalyzed reaction was in a range 395–455 nA. No significant influence of radiation on AChE activity was found, despite the current variation. However, a surprising phenomenon was observed when a model organophosphate paraoxon was assayed. Irradiated biosensors seem to be more susceptible to the inhibitory effects of paraoxon. Control biosensors provided a 94 ± 5 nA current after exposure to 1 ppm paraoxon. The biosensors irradiated by a 5 kGy radiation dose and exposed to paraoxon provided a current of 49 ± 6 nA. Irradiation by doses ranging from 5 mGy to 100 kGy were investigated and the mentioned effect was confirmed at doses above 50 Gy. After the first promising experiments, biosensors irradiated by 5 kGy were used for calibration on paraoxon and compared with the control biosensors. Limits of detection 2.5 and 3.8 ppb were achieved for irradiated and non-irradiated biosensors respectively. The overall impact of this effect is discussed.

  14. Relationship between chromatin structure and sensitivity to molecularly targeted auger electron radiation therapy.

    NARCIS (Netherlands)

    Terry, S.Y.A.; Vallis, K.A.

    2012-01-01

    PURPOSE: The open structure of euchromatin renders it susceptible to DNA damage by ionizing radiation (IR) compared with compact heterochromatin. The effect of chromatin configuration on the efficacy of Auger electron radiotherapy was investigated. METHODS AND MATERIALS: Chromatin structure was alte

  15. Sensitivity of APSIM/ORYZA model due to estimation errors in solar radiation

    NARCIS (Netherlands)

    Heinemann, A.B.; Oort, van P.A.J.; Simoes Fernandes, D.; Maia, A.H.N.

    2012-01-01

    Crop models are ideally suited to quantify existing climatic risks. However, they require historic climate data as input. While daily temperature and rainfall data are often available, the lack of observed solar radiation (Rs) data severely limits site-specific crop modelling. The objective of this

  16. The role of autophagy in sensitizing malignant glioma cells to radiation therapy

    Institute of Scientific and Technical Information of China (English)

    Wenzhuo Zhuang; Zhenghong Qin; Zhongqin Liang

    2009-01-01

    Malignant gliomas representthe majority of primary brain tumors.The current standard treatments for malignant gliomas include surgical resection,radiation therapy,and chemotherapy.Radiotherapy,a standard adjuvant therapy,confers some survival advantages,but resistance of the glioma cells to the efficacy of radiation limits the success of the treatment.The mechanisms underlying glioma cell radioresistance have remained elusive.Autophagy is a protein degradation system characterized by a prominent formation of double-membrane vesicles in the cytoplasm.Recent studies suggest that autophagy may be important in the regulation of cancer development and progression and in determining the response of tumor cells to anticancer therapy.Also,autophagy is a novel response of glioma cells to ionizing radiation.Autophagic cell death is considered programmed cell death type Ⅱ,whereas apoptosis is programmed cell death type Ⅰ.These two types of cell death are predominantly distinctive,but many studies demonstrate a cross-talk between them.Whether autophagy in cancer cells causes death or protects cells is controversial.The regulatory pathways of autophagy share several molecules.P13K/Akt/Mtor,DNA-PK,tumor suppressor genes, mitochondrial damage,and lysosome may play important roles in radiation-induced autophagy in glioma cells.Recently,a highly tumorigenic glioma tumor subpopulation,termed cancer stem cell or tumor-initiating cell,has been shown to promote therapeutic resistance.This review summarizes the main mediators associated with radiation-induced autophagy in malignant glioma cells and discusses the implications of the cancer stem cell hypothesis for the development of future therapies for brain tumors.

  17. Preparation of PbSeO3 as a new material, sensitive to the electromagnetic radiation in UV range

    Science.gov (United States)

    Tomaev, V. V.; Smolyaninov, V. D.; Stoyanova, T. V.; Egorov, S. V.

    2016-08-01

    The new technology of the formation of photoresistive structures sensitive in ultraviolet range of electromagnetic spectrum based on lead selenide and lead selenite composite is discussed. Studies of photosensitivity were carried out using a set of LEDs in the visible and ultraviolet spectral range. Obtained structures show considerable sensitivity in ultraviolet and blue range of radiation, meanwhile that in red and yellow region of light turned to be small. The structures were formed by oxidation of PbSe crystals. Diffusion of the oxygen through the surface layer of PbSe was suggested to be a key mechanism of oxidation. Oxidation kinetics were studied by means of roentgen lines chemical shift and roentgen diffraction.

  18. Characterization of pH-sensitive Poly (acrylic acid-co-N-vinyl-2-pyrrolidone) Hydrogels Prepared by Gamma Radiation

    Institute of Scientific and Technical Information of China (English)

    YANG Ming-cheng; HE Su-qin; LIU Wen-tao; SONG Hong-yan; ZHU Cheng-shen

    2007-01-01

    The pH-sensitive copolymer hydrogels were prepared with the monomers of acrylic acid and N-vinyl-2-pyrrolidone based on gamma radiation technique. The morphology of the hydrogels was monitored by using scanning electron microscope. The influence of absorbed dose, monomer compasition and concentration on the swelling ratio (SR) of the hydrogels were investigated in detail. The effect of pH and temperature of the swelling medium on the swelling behavior of the hydrogels were also examined. The results show that the SR of the copolymer hydrogels decreases with the monomer concentration and absorbed dose increasing. The copolymer hydrogels show a better pH-sensitive behavior. In alkaline solution, the SR of the hydrogels is much higher than in acid solution.

  19. High-throughput identification of ionizing radiation-sensitive plant genes and development of radiation indicator plant and radiation sensing Genechip

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Sub; Kim, Jinbaek; Ha, Bokeun; Kim, Sang Hoon; Kim, Sunhee

    2013-05-15

    Physiological analysis of monocot model plant (rice) in response to ionizing radiation (cosmic-ray, gamma-ray, Ion beam). - Identification of antioxidant characters through cytochemical analysis. - Comparison of antioxidant activities in response to ionizing irradiation. - Evaluation of anthocyanin quantity in response to ionizing irradiation. Ionization energy response gene family analysis via bioinformatic validation. - Expression analysis of monocot and dicot gene families. - In silico and bioinformatic approach to elucidate gene function. Characterization and functional analysis of genes specifically expressed in response to ionizing irradiation (cosmic-ray, gamma-ray, Ion beam). - High throughput trancriptomic analysis of plants under ionizing radiation using microarray. - Promotor and cis-element analysis of genes specifically expressed in response to ionizing radiation. - Validation and function analysis of candidate genes. - Elucidation of plant mechanism of sensing and response to ionization energy. Development of bioindicator plants detecting ionization energy. - Cloning and identification of 'Radio marker genes (RMG)'. - Development of Over-expression (O/E) or Knock-out (K/O) plant using RMG. Development of Genechip as an ionization energy detector. - Expression profiling analysis of genes specifically expression in response to ionization energy. - Prepare high-conserved gene specific oligomer. - Development of ionization energy monitoring Genechip and application.

  20. Female Flinders Sensitive Line rats show estrous cycle-independent depression-like behavior and altered tryptophan metabolism

    DEFF Research Database (Denmark)

    Eskelund, Amanda; Budac, David P; Sanchez, Connie;

    2016-01-01

    female Flinders Sensitive Line (FSL) rats, a genetic rat model of depression. FSL rats and controls (Flinders Resistant Line rats), 12-20weeks old, were subject to the forced swim test (FST), a commonly used measure of depression-like behavior. Open field was used to evaluate locomotor ability and......Clinical studies suggest a link between depression and dysfunctional tryptophan (TRP) metabolism. Even though depression is twice as prevalent in women as men, the impact of the estrous cycle on TRP metabolism is not well-understood. Here we investigated 13 kynurenine and serotonin metabolites in...... male FSL and FRL rats. Female FSL rats showed a depression-like phenotype with increased immobility in the FST, not confounded by anxiety. In the brain, 3-hydroxykynurenine was increased whereas anthranilate and 5-hydroxytryptophan were decreased. In plasma, anthranilate and quinolinate levels were...

  1. Vegetation types alter soil respiration and its temperature sensitivity at the field scale in an estuary wetland.

    Directory of Open Access Journals (Sweden)

    Guangxuan Han

    Full Text Available Vegetation type plays an important role in regulating the temporal and spatial variation of soil respiration. Therefore, vegetation patchiness may cause high uncertainties in the estimates of soil respiration for scaling field measurements to ecosystem level. Few studies provide insights regarding the influence of vegetation types on soil respiration and its temperature sensitivity in an estuary wetland. In order to enhance the understanding of this issue, we focused on the growing season and investigated how the soil respiration and its temperature sensitivity are affected by the different vegetation (Phragmites australis, Suaeda salsa and bare soil in the Yellow River Estuary. During the growing season, there were significant linear relationships between soil respiration rates and shoot and root biomass, respectively. On the diurnal timescale, daytime soil respiration was more dependent on net photosynthesis. A positive correlation between soil respiration and net photosynthesis at the Phragmites australis site was found. There were exponential correlations between soil respiration and soil temperature, and the fitted Q10 values varied among different vegetation types (1.81, 2.15 and 3.43 for Phragmites australis, Suaeda salsa and bare soil sites, respectively. During the growing season, the mean soil respiration was consistently higher at the Phragmites australis site (1.11 µmol CO2 m(-2 s(-1, followed by the Suaeda salsa site (0.77 µmol CO2 m(-2 s(-1 and the bare soil site (0.41 µmol CO2 m(-2 s(-1. The mean monthly soil respiration was positively correlated with shoot and root biomass, total C, and total N among the three vegetation patches. Our results suggest that vegetation patchiness at a field scale might have a large impact on ecosystem-scale soil respiration. Therefore, it is necessary to consider the differences in vegetation types when using models to evaluate soil respiration in an estuary wetland.

  2. DNA alterations and effects on growth and reproduction in Daphnia magna during chronic exposure to gamma radiation over three successive generations

    International Nuclear Information System (INIS)

    Highlights: • We exposed three successive generations of Daphnia magna to chronic gamma radiation. • We examined DNA alterations and effects on survival, growth and reproduction. • DNA alterations were accumulated over a generation and transmitted to the progeny. • Effects on survival and reproduction, and delay in growth increased over generations. - Abstract: This study examined chronic effects of external Cs-137 gamma radiation on Daphnia magna exposed over three successive generations (F0, F1 and F2) to environmentally relevant dose rates (ranging from 0.007 to 35.4 mGy h−1). Investigated endpoints included survival, growth, reproduction and DNA alterations quantified using random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Results demonstrated that radiation effects on survival, growth and reproduction increased in severity from generation F0 to generation F2. Mortality after 21 days at 35.4 mGy h−1 increased from 20% in F0 to 30% in F2. Growth was affected by a slight reduction in maximum length at 35.4 mGy h−1 in F0 and by reductions of 5 and 13% in growth rate, respectively, at 4.70 and 35.4 mGy h−1 in F2. Reproduction was affected by a reduction of 19% in 21 day-fecundity at 35.4 mGy h−1 in F0 and by a delay of 1.9 days in brood release as low as 0.070 mGy h−1 in F2. In parallel, DNA alterations became significant at decreasing dose rates over the course of F0 (from 4.70 mGy h−1 at hatching to 0.007 mGy h−1 after ∼21 days) and from F0 to F2 (0.070 mGy h−1 at hatching to 0.007 mGy h−1 after ∼21 days), demonstrating their rapid accumulation in F0 daphnids and their transmission to offspring generations. Transiently more efficient DNA repair leading to some recovery at the organism level was suggested in F1, with no effect on survival, a slight reduction of 12% in 21 day-fecundity at 35.4 mGy h−1 and DNA alterations significant at highest dose rates only. The study improved our understanding of long term

  3. Sensitization to the behavioural effects of cocaine: alterations in tyrosine hydroxylase or endogenous opioid mRNAs are not necessarily involved.

    Science.gov (United States)

    Alvarez Fischer, D; Schäfer, M K; Ferger, B; Gross, S; Westermann, R; Weihe, E; Kuschinsky, K

    2001-03-01

    After repeated administration of cocaine at intervals, sensitization phenomena can be observed, so that its behavioural effects are enhanced. Since this phenomenon is long-lasting, it was of interest to study which persistent alterations in the activity of dopaminergic neurones or of endogenous opioid systems downstream of dopaminergic synapses in the basal ganglia are involved in the sensitization. Cocaine (10 mg/kg i.p.) was administered to rats on days 1, 3, 5 and 7 and saline on days 2, 4 and 6 ("repeated cocaine"), or saline was injected on days 1-6 and cocaine on day 7 ("acute cocaine"), or saline was injected on days 1-7 ("saline group"). The "repeated cocaine" schedule led to a significant sensitization to the locomotor activation produced by cocaine on day 7 or on day 17, 10 days after the end of sensitization protocol. Microdialysis in the nucleus accumbens which was performed after administration of cocaine (10 mg/kg i.p.) on day 7, or after an administration of the same dose 10 days after the last administration of cocaine, respectively, revealed significant acute increases of extracellular dopamine to about 200% of basal values. These increases were similar in "acute cocaine" and in "repeated cocaine" animals both after 7 days and after 17 days. For in situ hybridization studies, rats were sacrificed on day 7, 4.5 h after the last cocaine or saline administration. The mRNA for tyrosine hydroxylase (TH) in substantia nigra + ventral tegmental area was significantly elevated to about 140% of saline controls both in the "repeated cocaine" and the "acute cocaine" group as compared with the "saline group". In contrast, there were no differences between the three groups in the mRNAs of preprodynorphin or preproenkephalin levels measured in the nucleus accumbens (core and shell). These results suggest that sensitization phenomena to cocaine are not necessarily connected with alterations in the dopaminergic activity in the mesolimbic system or in the

  4. Thermal Enhancement with Optically Activated Gold Nanoshells Sensitizes Breast Cancer Stem Cells to Radiation Therapy

    OpenAIRE

    Atkinson, Rachel L; ZHANG, MEI; Diagaradjane, Parmeswaran; Peddibhotla, Sirisha; Contreras, Alejandro; Hilsenbeck, Susan G; Woodward, Wendy A.; Krishnan, Sunil; Chang, Jenny C.; Rosen, Jeffrey M

    2010-01-01

    Breast cancer metastasis and disease recurrence are hypothesized to result from residual cancer stem cells, also referred to as tumor-initiating cells, which evade initial treatment. Using both syngeneic mouse and human xenograft models of triple-negative breast cancer, we have demonstrated that a subpopulation enriched in cancer stem cells was more resistant to treatment with 6 gray of ionizing radiation than the bulk of the tumor cells, and accordingly their relative proportion increased 48...

  5. Sensitivity of radiative properties of persistent contrails to the ice water path

    Directory of Open Access Journals (Sweden)

    R. R. De León

    2012-09-01

    Full Text Available The dependence of the radiative properties of persistent linear contrails on the variability of their ice water path is assessed in a two-stream radiative transfer model. It is assumed that the ice water content and the effective size of ice crystals in aged contrails do not differ from those observed in natural cirrus; the parameterization of these two variables, based on a correlation with ambient temperature derived from in situ observations, allows a more realistic representation than the common assumption of fixed values for the contrail optical depth and ice crystal effective radius.

    The results show that the large variability in ice water content that aged contrails may share with natural cirrus, together with an assumed contrail vertical thickness between 220 and 1000 m, translate into a wider range of radiative forcings from linear contrails [1 to 66 m Wm−2] than that reported in previous studies, including IPCC's [3 to 30 m Wm−2]. Further field and modelling studies of the temporal evolution of contrail properties will thus be needed to reduce the uncertainties associated with the values assumed in large scale contrail studies.

  6. Improved Intratumoral Oxygenation Through Vascular Normalization Increases Glioma Sensitivity to Ionizing Radiation

    International Nuclear Information System (INIS)

    Purpose: Ionizing radiation, an important component of glioma therapy, is critically dependent on tumor oxygenation. However, gliomas are notable for areas of necrosis and hypoxia, which foster radioresistance. We hypothesized that pharmacologic manipulation of the typically dysfunctional tumor vasculature would improve intratumoral oxygenation and, thus, the antiglioma efficacy of ionizing radiation. Methods and Materials: Orthotopic U87 xenografts were treated with either continuous interferon-β (IFN-β) or bevacizumab, alone, or combined with cranial irradiation (RT). Tumor growth was assessed by quantitative bioluminescence imaging; the tumor vasculature using immunohistochemical staining, and tumor oxygenation using hypoxyprobe staining. Results: Both IFN-β and bevaziumab profoundly affected the tumor vasculature, albeit with different cellular phenotypes. IFN-β caused a doubling in the percentage of area of perivascular cell staining, and bevacizumab caused a rapid decrease in the percentage of area of endothelial cell staining. However, both agents increased intratumoral oxygenation, although with bevacizumab, the effect was transient, being lost by 5 days. Administration of IFN-β or bevacizumab before RT was significantly more effective than any of the three modalities as monotherapy or when RT was administered concomitantly with IFN-β or bevacizumab or 5 days after bevacizumab. Conclusion: Bevacizumab and continuous delivery of IFN-β each induced significant changes in glioma vascular physiology, improving intratumoral oxygenation and enhancing the antitumor activity of ionizing radiation. Additional investigation into the use and timing of these and other agents that modify the vascular phenotype, combined with RT, is warranted to optimize cytotoxic activity.

  7. Sensitization and protection in the radiation chemistry of biologically active DNA

    International Nuclear Information System (INIS)

    The results are reported of a study of the effects of the well-known sensitizers paranitroacetophenone (PNAP), triacetone-amine-N-oxyl (TAN) and oxygen, and of the protector cysteamine on the radiosensitivity of purified biologically active DNA of bacteriophages. Irradiation conditions are stated. The results are discussed. (U.K.)

  8. Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation.

    Science.gov (United States)

    Huang, Amin; Ju, Huai-Qiang; Liu, Kaiyan; Zhan, Guilian; Liu, Daolu; Wen, Shijun; Garcia-Manero, Guillermo; Huang, Peng; Hu, Yumin

    2016-07-28

    Internal tandem duplication (ITD) of the juxtamembrane region of FMS-like tyrosine kinase-3 (FLT3) receptor is a common type of mutation in adult acute myeloid leukemia (AML), and patient response to FLT3 inhibitors appears to be transient due to the emergence of drug resistance. We established two sorafenib-resistant cell lines carrying FLT3/ITD mutations, including the murine BaF3/ITD-R and human MV4-11-R cell lines. Gene expression profile analysis of the resistant and parental cells suggests that the highest ranked molecular and cellular functions of the differentially expressed genes are related to mitochondrial dysfunction. Both murine and human resistant cell lines display a longer doubling time, along with a significant inhibition of mitochondrial respiratory chain activity and substantial upregulation of glycolysis. The sorafenib-resistant cells exhibit increased expression of a majority of glycolytic enzymes, including hexokinase 2, which is also highly expressed in the mitochondrial fraction and is associated with resistance to apoptotic cell death. The sorafenib-resistant cells are collaterally sensitive to a number of glycolytic inhibitors including 2-deoxyglucose and 3-bromopyruvate propylester. Our study reveals a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation. PMID:27132990

  9. TERRA Expression Levels Do Not Correlate With Telomere Length and Radiation Sensitivity in Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Alexandra eSmirnova

    2013-05-01

    Full Text Available Mammalian telomeres are transcribed into long non-coding telomeric RNA molecules (TERRA that seem to play a role in the maintenance of telomere stability. In human cells, CpG island promoters drive TERRA transcription and are regulated by methylation. It was suggested that the amount of TERRA may be related to telomere length. To test this hypothesis we measured telomere length and TERRA levels in single clones isolated from five human cell lines: HeLa (cervical carcinoma, BRC-230 (breast cancer, AKG and GK2 (gastric cancers and GM847 (SV40 immortalized skin fibroblasts. We observed great clonal heterogeneity both in TRF (Terminal Restriction Fragment length and in TERRA levels. However, these two parameters did not correlate with each other. Moreover, cell survival to γ-rays did not show a significant variation among the clones, suggesting that, in this cellular system, the intra-population variability in telomere length and TERRA levels does not influence sensitivity to ionizing radiation. This conclusion was supported by the observation that in a cell line in which telomeres were greatly elongated by the ectopic expression of telomerase, TERRA expression levels and radiation sensitivity were similar to the parental HeLa cell line.

  10. AN ESCHERICHIA-COLI STRAIN DEFICIENT FOR BOTH EXONUCLEASE-V AND DEOXYCYTIDINE TRIPHOSPHATE DEAMINASE SHOWS ENHANCED SENSITIVITY TO IONIZING-RADIATION

    NARCIS (Netherlands)

    ESTEVENON, AM; KOOISTRA, J; SICARD, N

    1995-01-01

    An Escherichia coli mutant lacking deoxycytidine triphosphate deaminase (Dcd) activity and an unknown function encoded by a gene designated ior exhibits sensitivity to ionizing radiation whereas dcd mutants themselves are not sensitive. A DNA fragment from an E. coli genomic library that restores th

  11. The sensitivity of Mycoplasma mycoides var. capri cells to γ-radiation after growth in a medium containing the thymine analogue 5-vinyluracil

    International Nuclear Information System (INIS)

    Cells of the bacterium Mycoplasma mycoides var. capri grown in a medium containing the potential radiation-sensitive thymine analogue 5-vinyluracil show a 3-fold increase in sensitivity towards irradiation of a dose of 15 krads of γ-rays. (author)

  12. Sensitivity of modeled ocean heat content to errors in short wave radiation and its attenuation with depth

    Science.gov (United States)

    Shulman, Igor; Gould, Richard W.; Anderson, Stephanie; Sakalaukus, Peter

    2016-05-01

    Short wave radiation (SWR) and its attenuation with depth have a major impact on the vertical distribution of the oceanic water temperature, dynamical processes, and ocean-atmosphere interactions. In numerical modeling of oceanic processes, the SWR usually comes from the atmospheric model predictions, while the short wave attenuation schemes are internally prescribed (estimated) inside the oceanic dynamical model. It has been reported that atmospheric models show a tendency to overestimate the shortwave radiation due to underestimation of predicted low-level clouds. Most existing schemes to specify the attenuation of SWR with depth in numerical models are based on: the Jerlov (1976) water-types classification; climatological estimates of attenuation coefficients or from the biological model predictions of light-absorbing and scattering water constituents. All of the above attenuation schemes are prone to introducing errors in the attenuation of short wave radiation with depth. As a result, we have to deal with two types of errors in the oceanic modeling: those due to the incorrect specification of the magnitude of SWR at the surface (from the atmospheric model), and those due to inaccurate vertical attenuation of SWR (prescribed in the oceanic model). We have developed an approach for estimating errors in the oceanic model heat budget due to errors in surface values of SWR and in its attenuation with depth. Based on this approach, we present examples illustrating sensitivities of the heat budget of the water column to the changes in specification of surface SWR and its attenuation.

  13. Sex hormones alter sex ratios in the Indian skipper frog, Euphlyctis cyanophlyctis: Determining sensitive stages for gonadal sex reversal.

    Science.gov (United States)

    Phuge, S K; Gramapurohit, N P

    2015-09-01

    In amphibians, although genetic factors are involved in sex determination, gonadal sex differentiation can be modified by exogenous steroid hormones suggesting a possible role of sex steroids in regulating the process. We studied the effect of testosterone propionate (TP) and estradiol-17β (E2) on gonadal differentiation and sex ratio at metamorphosis in the Indian skipper frog, Euphlyctis cyanophlyctis with undifferentiated type of gonadal differentiation. A series of experiments were carried out to determine the optimum dose and sensitive stages for gonadal sex reversal. Our results clearly indicate the importance of sex hormones in controlling gonadal differentiation of E. cyanophlyctis. Treatment of tadpoles with 10, 20, 40, and 80μg/L TP throughout larval period resulted in the development of 100% males at metamorphosis at all concentrations. Similarly, treatment of tadpoles with 40μg/L TP during ovarian and testicular differentiation resulted in the development of 90% males, 10% intersexes and 100% males respectively. Treatment of tadpoles with 10, 20, 40, and 80μg/L E2 throughout larval period likewise produced 100% females at all concentrations. Furthermore, exposure to 40μg/L E2 during ovarian and testicular differentiation produced 95% females, 5% intersexes and 91% females, 9% intersexes respectively. Both TP and E2 were also effective in advancing the stages of gonadal development. Present study shows the effectiveness of both T and E2 in inducing complete sex reversal in E. cyanophlyctis. Generally, exposure to E2 increased the larval period resulting in significantly larger females than control group while the larval period of control and TP treated groups was comparable.

  14. Sensitivity of the Upper Ocean Temperature and Circulation in the Equatorial Pacific to Solar Radiation Penetration Due to Phytoplankton

    Institute of Scientific and Technical Information of China (English)

    LIN Pengfei; LIU Hailong; ZHANG Xuehong

    2007-01-01

    Solar radiation penetration in the upper ocean is strongly modulated by phytoplankton, which impacts the upper ocean temperature structure, especially in the regions abundant with phytoplankton. In the paper,a new solar radiation penetration scheme, based on the concentration of chlorophyll-a, was introduced into the LASG/IAP (State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics/Institute of Atmospheric Physics) Climate system Ocean Model (LICOM). By comparing the simulations using this new scheme with those using the old scheme that included the constant e-folding attenuation depths in LICOM, it was found that the sea surface temperature (SST) and circulation in the central and eastern equatorial Pacific were both sensitive to the amount of phytoplankton present. Distinct from other regions, the increase of chlorophyll-a concentration would lead to SST decrease in the central and eastern equatorial Pacific. The higher chlorophyll-a concentration at the equator in comparison to the off-equator regions can enlarge the subsurface temperature gradient, which in turn strengthens the upper current near the equator and induces an enhancing upwelling. The enhancing upwelling can then lead to a decrease in the SST in the central and eastern equatorial Pacific. The results of these two sensitive experiments testify to the fact that the meridional gradient in the chlorophyll-a concentration can result in an enhancement in the upper current and a decrease in the SST, along with the observation that a high chlorophyll-a concentration at the equator is one of the predominant reasons leading to a decrease in the SST. This study points out that these results can be qualitatively different simply because of the choice of the solar radiation penetration schemes for comparison. This can help explain previously reported contradictory conclusions.

  15. Sensitivity of radiative properties of persistent contrails to the ice water path

    Directory of Open Access Journals (Sweden)

    R. Rodríguez De León

    2011-07-01

    Full Text Available The dependence of the radiative properties of persistent linear contrails on the variability of their ice water path is assessed in a two-stream radiative transfer model. It is assumed that the ice water content and the effective size of ice crystals in aged contrails do not differ from those observed in natural cirrus; the parameterization of these two variables, based on in situ observations, allows a more realistic representation than the common assumption of fixed values for the contrail optical depth and ice crystal effective radius.

    The results show that the large variability in ice water content that aged contrails may share with natural cirrus, together with an assumed contrail vertical thickness between 220 and 1000 m, translate into a wider range of radiative forcings from linear contrails (0.3 to 51.6 mW m−2 than that reported in previous studies, including IPCC's (3 to 30 mW m−2. The derivation of a best estimate within this range is complicated by the fact that the ice water contents measured in situ imply mean optical depths between 0.08 and 0.32, coinciding with the range commonly assumed in contrail studies, while optical depths derived from satellite ice water content retrievals are significantly larger (0.51–2.02. Further field and modelling studies of the temporal evolution of contrail properties will thus be needed to reduce the uncertainties associated with the values assumed in large scale contrail studies.

  16. Studies on the radiation sensitivity of food microorganism by high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Han Joon; Lee, Eun Jung; Yu, Hyun Hee; Lee, Jae Ho [Korea University, Seoul (Korea, Republic of)

    2010-04-15

    We investigated the radio resistance of pathogenic microorganisms (Bacillus cereus, Staphylococcus aureus, Methicillin resistant Staphylococcus aureus(MRSA) and Escherichia coli O157) in irradiating environments. Their radiation conditions of pathogenic microorganisms varied with pH(3-10), salt concentration(1-15%), temperature(-20, 4 and 25 .deg. C) and atmospheric condition. In addition, the effect of {gamma}-irradiation on the inactivation of pathogenic microorganisms inoculated into food (saengsik, sliced ham, chopped beef) was investigated. The radiation dose ranged from 0 to 3 kGy. The {gamma}--irradiated B.cereus({gamma}--BC) St.aureus({gamma}--SA), MRSA({gamma}--MRSA) and E.coli O157({gamma}--EC) were then cultured and the viable cell count on plate count agar and D10-values(dose required to inactivate 90% of a microbial population) were calculated. The number of pathogenic microorganisms at pH(3-10) and salt concentration(1-15%), temperature(-20, 4 and 25 .deg. C) and atmospheric condition decreased by 1 log CFU/ml after irradiation. The D{sub 10}-value of {gamma}--SA in the optimum condition was 0.152 kGy, and these of {gamma}--MRSA and {gamma}--EC were 0.346 and 0.240 kGy, respectively. The initial cell counts of pathogenic microorganisms in culture broth were slightly decreased as the decrease of pH and the increase of salt concentration. However, radiation resistance of pathogenic microorganisms was increased at frozen state. Moreover, D{sub 10}-values of these is test strains in saengsik, sliced ham and chopped beef were 0.597, 0.226 , 0.398 and 0.416 kGy, respectively. These results provide the basic information for the in activation of pathogenic microorganisms in foods by irradiation

  17. Studies on the radiation sensitivity of food microorganism by high dose irradiation

    International Nuclear Information System (INIS)

    We investigated the radio resistance of pathogenic microorganisms (Bacillus cereus, Staphylococcus aureus, Methicillin resistant Staphylococcus aureus(MRSA) and Escherichia coli O157) in irradiating environments. Their radiation conditions of pathogenic microorganisms varied with pH(3-10), salt concentration(1-15%), temperature(-20, 4 and 25 .deg. C) and atmospheric condition. In addition, the effect of γ-irradiation on the inactivation of pathogenic microorganisms inoculated into food (saengsik, sliced ham, chopped beef) was investigated. The radiation dose ranged from 0 to 3 kGy. The γ--irradiated B.cereus(γ--BC) St.aureus(γ--SA), MRSA(γ--MRSA) and E.coli O157(γ--EC) were then cultured and the viable cell count on plate count agar and D10-values(dose required to inactivate 90% of a microbial population) were calculated. The number of pathogenic microorganisms at pH(3-10) and salt concentration(1-15%), temperature(-20, 4 and 25 .deg. C) and atmospheric condition decreased by 1 log CFU/ml after irradiation. The D10-value of γ--SA in the optimum condition was 0.152 kGy, and these of γ--MRSA and γ--EC were 0.346 and 0.240 kGy, respectively. The initial cell counts of pathogenic microorganisms in culture broth were slightly decreased as the decrease of pH and the increase of salt concentration. However, radiation resistance of pathogenic microorganisms was increased at frozen state. Moreover, D10-values of these is test strains in saengsik, sliced ham and chopped beef were 0.597, 0.226 , 0.398 and 0.416 kGy, respectively. These results provide the basic information for the in activation of pathogenic microorganisms in foods by irradiation

  18. Calculus of radiolytic products generation in water due to alpha radiation. Determination of the spent nuclear fuels matrix alteration rate Determination of velocity of spent fuel matrix

    International Nuclear Information System (INIS)

    The generation of radiolytic products as a result of alpha radiation in the surface of the spent fuel is a key process in order to understand how the it becomes degraded in repository conditions. The present work has established a radiolytic model based on a set of reactions involving fuel oxidation-dissolution and radiolytic products recombination. It also includes the decrease of the dose rates as the main alpha emitters decay away. Four cases, with varying parameters of the system, have been assessed. The results show a decrease in both the concentration of the radiolytic products in the gap water and the degradation of the fuel matrix. It has been estimated that in the period of the evaluation (10''6 years) up to 52% of the pellet is altered in the conservative cases, whereas only 11% is altered in the realistic cases. No significant differences were observed when the carbonates reactions were included in the system. (Author)

  19. Mitotic chromosome loss in a radiation-sensitive strain of the yeast Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Mortimer, R.K.; Contopoulou, R.; Schild, D.

    1981-09-01

    Cells of Saccharomyces cerevisiae with mutations in the RAD52 gene have previously been shown to be defective in meiotic and mitotic recombination, in sporulation, and in repair of radiation-induced damage to DNA. In this study we show that diploid cells homozygous for rad52 lose chromosomes at high frequencies and that these frequencies of loss can be increased dramatically by exposure of these cells to x-rays. Genetic analyses of survivors of x-ray treatment demonstrate that chromosome loss events result in the conversion of diploid cells to cells with near haploid chromosome numbers.

  20. Dynamics of chromosomal aberrations, induction of apoptosis, BRCA2 degradation and sensitization to radiation by hyperthermia.

    Science.gov (United States)

    Bergs, Judith W J; Oei, Arlene L; Ten Cate, Rosemarie; Rodermond, Hans M; Stalpers, Lukas J; Barendsen, Gerrit W; Franken, Nicolaas A P

    2016-07-01

    Hyperthermia can transiently degrade BRCA2 and thereby inhibit the homologous recombination pathway. Induced DNA-double strand breaks (DSB) then have to be repaired via the error prone non-homologous end-joining pathway. In the present study, to investigate the role of hyperthermia in genotoxicity and radiosensitization, the induction of chromosomal aberrations was examined by premature chromosome condensation and fluorescence in situ hybridisation (PCC-FISH), and cell survival was determined by clonogenic assay shortly (0-1 h) and 24 h following exposure to hyperthermia in combination with ionizing radiation. Prior to exposure to 4 Gy γ-irradiation, confluent cultures of SW‑1573 (human lung carcinoma) and RKO (human colorectal carcinoma) cells were exposed to mild hyperthermia (1 h, 41˚C). At 1 h, the frequency of chromosomal translocations was higher following combined exposure than following exposure to irradiation alone. At 24 h, the number of translocations following combined exposure was lower than following exposure to irradiation only, and was also lower than at 1 h following combined exposure. These dynamics in translocation frequency can be explained by the hyperthermia-induced transient reduction of BRCA2 observed in both cell lines. In both cell lines exposed to radiation only, potentially lethal damage repair (PLDR) correlated with a decreased number of chromosomal fragments at 24 h compared to 1 h. With combined exposure, PLDR did not correlate with a decrease in fragments, as in the RKO cells at 24 h following combined exposure, the frequency of fragments remained at the level found after 1 h of exposure and was also significantly higher than that found following exposure to radiation alone. This was not observed in the SW‑1573 cells. Cell survival experiments demonstrated that exposure to hyperthermia radiosensitized the RKO cells, but not the SW‑1573 cells. This radiosensitization was at least partly due to the induction

  1. Surface solar radiation patterns over the climatically sensitive region of Eastern Mediterranean

    Science.gov (United States)

    Alexandri, Georgia; Georgoulias, Aristeidis K.; Meleti, Charikleia; Balis, Dimitris; Kourtidis, Konstantinos; Sanchez-Lorenzo, Arturo; Trentmann, Jörg; Zanis, Prodromos

    2016-04-01

    In this work, the spatiotemporal variability of surface solar radiation (SSR) is examined over the region of Eastern Mediterranean for the 31-year period 1983-2013. For the scopes of this research, high resolution (0.05 x 0.05 degrees) satellite data from the CM SAF SARAH (Satellite Application Facility on Climate Monitoring Solar surfAce RAdiation Heliosat) product were used. The CM SAF SARAH dataset was validated against quality-assured observations from five ground stations located in the region showing that the satellite data are in good agreement with the ground-based data. Also, the dataset was found to be homogeneous and hence appropriate for climatological studies. The high spatial resolution of the product allows for studying various local features which are mostly connected to the topography. The comparison of the CM SAF SARAH product against three satellite-based (CERES, GEWEX, ISCCP) and one reanalysis (ERA-Interim) products showed that the satellite-based datasets underestimate SSR while the reanalysis dataset overestimates SSR. A novel method that incorporates radiative transfer simulations was applied on satellite data from CM SAF and CERES and a set of other data in order to figure out which are the parameters that drive the observed SSR differences between the two products. According to the CM SAF SARAH dataset, the SSR trend is positive and statistically significant at the 95 % confidence level (0.2 W/m2/year or 0.1 %/year) over Eastern Mediterranean for the period 1983-2013. Compared to the other satellite-based and reanalysis products, the CM SAF SARAH SSR trends are closer to the ground-based ones possibly due to the high spatial resolution and the better representation of cloud radiative effects in the dataset. It is suggested here that the inclusion of the interannual variability of aerosol load and composition within CM SAF SARAH would allow for a more accurate reproduction of the SSR trends over regions with high aerosol variability.

  2. Photomultiplier circuit including means for rapidly reducing the sensitivity thereof. [and protection from radiation damage

    Science.gov (United States)

    Mcclenahan, J. O. (Inventor)

    1974-01-01

    A simple, reliable and inexpensive control circuit is described for rapidly reducing the bias voltage across one or more of the dynode stages of a photomultiplier, to substantially decrease its sensitivity to incoming light at those times where excess light intensity might damage the tube. The control circuit comprises a switching device, such as a silicon controlled rectifier (SCR), coupled between a pair of the electrodes in the tube, preferably the cathode and first dynode, or the first and second dynodes, the switching device operating in response to a trigger pulse applied to its gate to short circuit the two electrodes. To insure the desired reduction in sensitivity, two switching stages, the devices be employed between two of the electrode stages, the devices being operated simultaneously to short circuit both stages.

  3. X-ray survival characteristics and genetic analysis for nineSaccharomyces deletion mutants that affect radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2006-07-21

    We examine ionizing radiation (IR) sensitivity and epistasisrelationships of several Saccharomyces mutants affectingpost-translational modifications of histones H2B and H3. Mutantsbre1delta, lge1delta, and rtf1delta, defective in histone H2B lysine 123ubiquitination, show IR sensitivity equivalent to that of the dot1deltamutant that we reported on earlier, consistent with published findingsthat Dot1p requires H2B K123 ubiquitination to fully methylate histone H3K79. This implicates progressive K79 methylation rather thanmono-methylation in IR resistance. The set2delta mutant, defective in H3K36 methylation, shows mild IR sensitivity whereas mutants that abolishH3 K4 methylation resemble wild type. The dot1delta, bre1delta, andlge1delta mutants show epistasis for IR sensitivity. The paf1deltamutant, also reportedly defective in H2B K123 ubiquitination, confers nosensitivity. The rad6delta, rad51null, rad50delta, and rad9deltamutations are epistatic to bre1? and dot1delta, but rad18delta andrad5delta show additivity with bre1delta, dot1delta, and each other. Thebre1delta rad18delta double mutant resembles rad6delta in sensitivity;thus the role of Rad6p in ubiquitinating H2B accounts for its extrasensitivity compared to rad18delta. We conclude that IR resistanceconferred by BRE1 and DOT1 is mediated through homologous recombinationalrepair, not postreplication repair, and confirm findings of a G1checkpoint role for the RAD6/BRE1/DOT1 pathway.

  4. Sensitivity of climate simulations to radiative effects of tropical anvil structure

    OpenAIRE

    Zender, Charles S.; Kiehl, J. T.

    1997-01-01

    Climate sensitivity to the representation of tropical anvil is investigated in a version of the National Center for Atmospheric Research Community Climate Model. Common features of tropical anvil generation and structure, consistent with observations and cloud resolving models, are incorporated into a simple prognostic anvil parameterization. These features include anvil convective origin, vertical profile, phase, areal extent, and life span. Two numerical climate integrations are forced by 1...

  5. Shortwave radiative heating rate profiles in hazy and clear atmosphere: a sensitivity study

    Science.gov (United States)

    Doppler, Lionel; Fischer, Jürgen; Ravetta, François; Pelon, Jacques; Preusker, René

    2010-05-01

    Aerosols have an impact on shortwave heating rate profiles (additional heating or cooling). In this survey, we quantify the impact of several key-parameters on the heating rate profiles of the atmosphere with and without aerosols. These key-parameters are: (1) the atmospheric model (tropical, midlatitude summer or winter, US Standard), (2) the integrated water vapor amount (IWV ), (3) the ground surface (flat and rough ocean, isotropic surface albedo for land), (4) the aerosol composition (dusts, soots or maritimes mixtures with respect to the OPAC-database classification), (5) the aerosol optical depth and (6) vertical postion, and (7) the single-scattering albedo (?o) of the aerosol mixture. This study enables us to evaluate which parameters are most important to take into account in a radiative energy budget of the atmosphere and will be useful for a future study: the retrieval of heating rates profiles from satellite data (CALIPSO, MODIS, MERIS) over the Mediterranean Sea. All the heating rates are computed by using the vector irradiances computed at each pressure level in the spectral interval 0.2 - 3.6μm (shortwave) by the 1D radiative transfer model for atmosphere and ocean: MOMO (Matrix-Operator MOdel) of the Institute for Space Science, FU Berlin 1

  6. Application of a One-Dimensional Position Sensitive Chamber on Synchrotron Radiation

    Science.gov (United States)

    Qi, Huirong; Liu, Mei

    2014-02-01

    In the last few years, wire chambers have been frequently used for X-ray detection because of their low cost, large area and reliability. X-ray diffraction is an irreplaceable method for powder crystal lattice measurements. A one-dimensional single-wire chamber has been developed in our lab to provide high position resolution for powder diffraction experiments using synchrotron radiation. There are 200 readout strips of 0.5 mm width with a pitch of 1.0 mm in the X direction, and the working gas is a mixture of Ar and CO2 (90/10). The one-dimensional position of the original ionization point is determined by the adjacent strip's distribution information using the center of gravity method. Recently, a study of the detector's performance and diffraction image was completed at the 1W1B laboratory of the Beijing Synchrotron Radiation Facility (BSRF) using a sample of SiO2. Most of the relative errors between the measured values of diffraction angles and existing data were less than 1%. The best position resolution achieved for the detector in the test was 71 μm (σ value) with a 20 μm slit collimator. Finally, by changing the detector height in incremental distances from the center of the sample, the one-dimensional detector achieved a two-dimensional diffraction imaging function, and the results are in good agreement with standard data.

  7. Beam test of a one-dimensional position sensitive chamber on synchrotron radiation

    CERN Document Server

    Mei, Liu; Hui-Rong, Qi; Bao-An, Zhuang; Jian, Zhang; Rong-Guang, Liu; Qi-Ming, Zhu; Qun, Ouyang; Yuan-Bo, Chen; Xiao-Shan, Jiang; Ya-Jie, Wang; Peng, Liu; Guang-Cai, Chang

    2013-01-01

    One-dimensional single-wire chamber was developed to provide high position resolution for powder diffraction experiments with synchrotron radiation. A diffraction test using the sample of SiO2 has been accomplished at 1W2B laboratory of Beijing Synchrotron Radiation Source. The data of beam test were analyzed and some diffraction angles were obtained. The experimental results were in good agreement with standard data from ICDD powder diffraction file. The precision of diffraction angles was 1% to 4.7%. Most of relative errors between measured values of diffraction angles and existing data were less than 1%. As for the detector, the best position resolution in the test was 138 um (sigma value) with an X-ray tube. Finally, discussions of the results were given. The major factor that affected the precision of measurement was deviation from the flat structure of detector. The effect was analyzed and it came to a conclusion that it would be the optimal measurement scheme when the distance between the powder sample...

  8. BIIB021, a novel Hsp90 inhibitor, sensitizes esophageal squamous cell carcinoma to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin-Tong; Bao, Ci-Hang; Jia, Yi-Bin; Wang, Nana [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Ma, Wei [Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University, Yinchuan 750000 (China); Liu, Fang [Medical Imaging, Shandong Medical College, Jinan 250002 (China); Wang, Cong; Wang, Jian-Bo; Song, Qing-Xu [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China); Cheng, Yu-Feng, E-mail: qlcyf1965@126.com [Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012 (China)

    2014-10-03

    Highlights: • BIIB021 downregulated radioresistant proteins in ESCC cell lines. • BIIB021 increased radiation-induced apoptotic cells. • BIIB021 enhanced G{sub 2} arrest in ESCC cell lines. • BIIB021 is a good candidate for radiosensitizer in radiotherapy of ESCC patients. - Abstract: BIIB021 is a novel, orally available inhibitor of heat shock protein 90 (Hsp90) that is currently in phase I/II clinical trials. BIIB021 induces the apoptosis of various types of tumor cells in vitro and in vivo. The aim of this study is to investigate the effect of BIIB021 on the radiosensitivity of esophageal squamous cell carcinoma (ESCC). The results indicated that BIIB021 exhibited strong antitumor activity in ESCC cell lines, either as a single agent or in combination with radiation. BIIB021 significantly downregulated radioresistant proteins including EGFR, Akt, Raf-1 of ESCC cell lines, increased apoptotic cells and enhanced G{sub 2} arrest that is more radiosensitive cell cycle phase. These results suggest that this synthetic Hsp90 inhibitor simultaneously affects multiple pathways involved in tumor development and progression in the ESCC setting and may represent a better strategy for the treatment of ESCC patients, either as a monotherapy or a radiosensitizer.

  9. Sensitivity of clear-sky direct radiative effect of the aerosol to micro-physical properties by using 6SV radiative transfer model: preliminary results

    Science.gov (United States)

    Bassani, Cristiana; Tirelli, Cecilia; Manzo, Ciro; Pietrodangelo, Adriana; Curci, Gabriele

    2015-04-01

    The aerosol micro-physical properties are crucial to analyze their radiative impact on the Earth's radiation budget [IPCC, 2007]. The 6SV model, last generation of the Second Simulation of a Satellite Signal in the Solar Spectrum (6S) radiative transfer code [Kotchenova et al., 2007; Vermote et al., 1997] has been used to perform physically-based atmospheric correction of hyperspectral airborne and aircraft remote sensing data [Vermote et al., 2009; Bassani et al. 2010; Tirelli et al., 2014]. The atmospheric correction of hyperspectral data has been shown to be sensitive to the aerosol micro-physical properties, as reported in Bassani et al., 2012. The role of the aerosol micro-physical properties on the accuracy of the atmospheric correction of hyperspectral data acquired over water and land targets is investigated within the framework of CLAM-PHYM (Coasts and Lake Assessment and Monitoring by PRISMA HYperspectral Mission) and PRIMES (Synergistic use of PRISMA products with high resolution meteo-chemical simulations and their validation on ground and from satellite) projects, both funded by Italian Space Agency (ASI). In this work, the results of the radiative field of the Earth/Atmosphere coupled system simulated by using 6SV during the atmospheric correction of hyperspectral data are presented. The analysis of the clear-sky direct radiative effect is performed considering the aerosol micro-physical properties used to define the aerosol model during the atmospheric correction process. In particular, the AERONET [Holben et al., 1998] and FLEXAOD [Curci et al., 2014] micro-physical properties are used for each image to evaluate the contribution of the size distribution and refractive index of the aerosol type on the surface reflectance and on the direct radiative forcing. The results highlight the potential of the hyperspectral remote sensing data for atmospheric studies as well as for environmental studies. Currently, the future hyperspectral missions, such as the

  10. Angular dependence of dose sensitivity of nanoDot optically stimulated luminescent dosimeters in different radiation geometries

    Energy Technology Data Exchange (ETDEWEB)

    Jursinic, Paul A., E-mail: pjursinic@wmcc.org [West Michigan Cancer Center, 200 North Park Street, Kalamazoo, Michigan 49007 (United States)

    2015-10-15

    Purpose: A type of in vivo dosimeter, an optically stimulated luminescent dosimeter, OSLD, may have dose sensitivity that depends on the angle of incidence of radiation. This work measures how angular dependence of a nanoDot changes with the geometry of the phantom in which irradiation occurs and with the intrinsic structure of the nanoDot. Methods: The OSLDs used in this work were nanoDot dosimeters (Landauer, Inc., Glenwood, IL), which were read with a MicroStar reader (Landauer, Inc., Glenwood, IL). Dose to the OSLDs was delivered by 6 MV x-rays. NanoDots with various intrinsic sensitivities were irradiated in numerous phantoms that had geometric shapes of cylinders, rectangles, and a cube. Results: No angular dependence was seen in cylindrical phantoms, cubic phantoms, or rectangular phantoms with a thickness to width ratio of 0.3 or 1.5. An angular dependence of 1% was observed in rectangular phantoms with a thickness to width of 0.433–0.633. A group of nanoDots had sensitive layers with mass density of 2.42–2.58 g/cm{sup 3} and relative sensitivity of 0.92–1.09 and no difference in their angular dependence. Within experimental uncertainty, nanoDot measurements agree with a parallel-plate ion chamber at a depth of maximum dose. Conclusions: When irradiated in cylindrical, rectangular, and cubic phantoms, nanoDots show a maximum angular dependence of 1% or less at an incidence angle of 90°. For a sample of 78 new nanoDots, the range of their relative intrinsic sensitivity is 0.92–1.09. For a sample of ten nanoDots, on average, the mass in the sensitive layer is 73.1% Al{sub 2}O{sub 3}:C and 26.9% polyester. The mass density of the sensitive layer of a nanoDot disc is between 2.42 and 2.58 g/cm{sup 3}. The angular dependence is not related to Al{sub 2}O{sub 3}:C loading of the nanoDot disc. The nanoDot at the depth of maximum dose has no more angular dependence than a parallel-plate ion chamber.

  11. Identification and Expression Profiling of Radiation-sensitive Genes Using Plant Model System, Arabidopsis thaliana

    International Nuclear Information System (INIS)

    The purpose of this study is to characterize genes specifically expressed in response to ionizing energy (gamma-rays) of acute irradiation and elucidate signalling mechanisms via functional analysis of isolated genes in Arabidopsis thaliana. Recent improvements in DNA microarray technologies and bioinformatics have made it possible to look for common features of ionizing radiation-responsive genes and their regulatory regions. It has produced massive quantities of gene expression and other functional genomics data, and its application will increase in plant genomics. In this study, we used oligonucleotide microarrays to detect the Arabidopsis genes expressed differentially by a gamma-irradiation during the vegetative (VT, 21 DAG) and reproductive (RT, 28 DAG) stages. Wild-type (Ler) Arabidopsis was irradiated with gamma-rays with 100 and 800 Gy doses. Among the 21,500 genes represented in the Agilent chip, approximately 13,500 (∼61.4 %) responsive genes to ν -irradiation were expressed with signal intensity greater than 192 when compared to the combined control (non-irradiated vegetative and reproductive pool). Expression patterns of several radiation inducible genes were confirmed by RT-PCR and Northern blotting. Our microarray results may contribute to an overall understanding of the type and quantities of genes that are expressed by an acute gamma-irradiation. In addition, to investigate the oxidative damage caused by irradiation, RT-PCR analysis for the expression of antioxidant isoenzyme genes, and a Transmission Electron Microscope (TEM) observation for visualizing the H2O2 scavenging activity in leaves were applied

  12. Radiative forcing and feedback by forests in warm climates - a sensitivity study

    Science.gov (United States)

    Port, Ulrike; Claussen, Martin; Brovkin, Victor

    2016-07-01

    We evaluate the radiative forcing of forests and the feedbacks triggered by forests in a warm, basically ice-free climate and in a cool climate with permanent high-latitude ice cover using the Max Planck Institute for Meteorology Earth System Model. As a paradigm for a warm climate, we choose the early Eocene, some 54 to 52 million years ago, and for the cool climate, the pre-industrial climate, respectively. To isolate first-order effects, we compare idealised simulations in which all continents are covered either by dense forests or by deserts with either bright or dark soil. In comparison with desert continents covered by bright soil, forested continents warm the planet for the early Eocene climate and for pre-industrial conditions. The warming can be attributed to different feedback processes, though. The lapse-rate and water-vapour feedback is stronger for the early Eocene climate than for the pre-industrial climate, but strong and negative cloud-related feedbacks nearly outweigh the positive lapse-rate and water-vapour feedback for the early Eocene climate. Subsequently, global mean warming by forests is weaker for the early Eocene climate than for pre-industrial conditions. Sea-ice related feedbacks are weak for the almost ice-free climate of the early Eocene, thereby leading to a weaker high-latitude warming by forests than for pre-industrial conditions. When the land is covered with dark soils, and hence, albedo differences between forests and soil are small, forests cool the early Eocene climate more than the pre-industrial climate because the lapse-rate and water-vapour feedbacks are stronger for the early Eocene climate. Cloud-related feedbacks are equally strong in both climates. We conclude that radiative forcing by forests varies little with the climate state, while most subsequent feedbacks depend on the climate state.

  13. Identification and Expression Profiling of Radiation-sensitive Genes Using Plant Model System, Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong-Sub; Kang, Si-Yong; Lee, Geung-Joo; Kim, Jin-Baek

    2008-06-15

    The purpose of this study is to characterize genes specifically expressed in response to ionizing energy (gamma-rays) of acute irradiation and elucidate signalling mechanisms via functional analysis of isolated genes in Arabidopsis thaliana. Recent improvements in DNA microarray technologies and bioinformatics have made it possible to look for common features of ionizing radiation-responsive genes and their regulatory regions. It has produced massive quantities of gene expression and other functional genomics data, and its application will increase in plant genomics. In this study, we used oligonucleotide microarrays to detect the Arabidopsis genes expressed differentially by a gamma-irradiation during the vegetative (VT, 21 DAG) and reproductive (RT, 28 DAG) stages. Wild-type (Ler) Arabidopsis was irradiated with gamma-rays with 100 and 800 Gy doses. Among the 21,500 genes represented in the Agilent chip, approximately 13,500 ({sup {approx}}61.4 %) responsive genes to {nu} -irradiation were expressed with signal intensity greater than 192 when compared to the combined control (non-irradiated vegetative and reproductive pool). Expression patterns of several radiation inducible genes were confirmed by RT-PCR and Northern blotting. Our microarray results may contribute to an overall understanding of the type and quantities of genes that are expressed by an acute gamma-irradiation. In addition, to investigate the oxidative damage caused by irradiation, RT-PCR analysis for the expression of antioxidant isoenzyme genes, and a Transmission Electron Microscope (TEM) observation for visualizing the H{sub 2}O{sub 2} scavenging activity in leaves were applied.

  14. Altered expression of renal bumetanide-sensitive sodium-pota-ssium-2 chloride cotransporter and Cl- channel -K2 gene in angiotensin Ⅱ-infused hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    YE Tao; LIU Zhi-quan; SUN Chao-feng; ZHENG Yong; MA Ai-qun; FANG Yuan

    2005-01-01

    Background Little information is available regarding the effect of angiotensin Ⅱ (Ang Ⅱ) on the bumetanide-sensitive sodium-potassium-2 chloride cotransporter (NKCC2), the thiazide-sensitive sodium-chloride cotransporter (NCC), and the Cl- channel (CLC)-K2 at both mRNA and protein expression level in Ang Ⅱ-induced hypertensive rats. This study was conducted to investigate the influence of Ang Ⅱ with chronic subpressor infusion on nephron-specific gene expression of NKCC2, NCC and CLC-K2. Results Ang Ⅱ significantly increased blood pressure and up-regulated NKCC2 mRNA and protein expression in the kidney. Expression of CLC-K2 mRNA in the kidney increased 1.6 fold (P<0.05).There were no changes in NCC mRNA or protein expression in AngII-treated rats versus control. Conclusions Chronic subpressor Ang Ⅱ infusion can significantly alter NKCC2 and CLC-K2 mRNA expression in the kidney, and protein abundance of NKCC2 in kidney is positively regulated by Ang Ⅱ. These effects may contribute to enhanced renal Na+ and Cl- reabsorption in response to Ang Ⅱ.

  15. Extracellular Cl(-) regulates human SO4 (2-)/anion exchanger SLC26A1 by altering pH sensitivity of anion transport.

    Science.gov (United States)

    Wu, Meng; Heneghan, John F; Vandorpe, David H; Escobar, Laura I; Wu, Bai-Lin; Alper, Seth L

    2016-08-01

    Genetic deficiency of the SLC26A1 anion exchanger in mice is known to be associated with hyposulfatemia and hyperoxaluria with nephrolithiasis, but many aspects of human SLC26A1 function remain to be explored. We report here the functional characterization of human SLC26A1, a 4,4'-diisothiocyanato-2,2'-stilbenedisulfonic acid (DIDS)-sensitive, electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, bicarbonate, thiosulfate, and (with divergent properties) chloride. Human SLC26A1-mediated anion exchange differs from that of its rodent orthologs in its stimulation by alkaline pHo and inhibition by acidic pHo but not pHi and in its failure to transport glyoxylate. SLC26A1-mediated transport of sulfate and oxalate is highly dependent on allosteric activation by extracellular chloride or non-substrate anions. Extracellular chloride stimulates apparent V max of human SLC26A1-mediated sulfate uptake by conferring a 2-log decrease in sensitivity to inhibition by extracellular protons, without changing transporter affinity for extracellular sulfate. In contrast to SLC26A1-mediated sulfate transport, SLC26A1-associated chloride transport is activated by acid pHo, shows reduced sensitivity to DIDS, and exhibits cation dependence of its DIDS-insensitive component. Human SLC26A1 resembles SLC26 paralogs in its inhibition by phorbol ester activation of protein kinase C (PKC), which differs in its undiminished polypeptide abundance at or near the oocyte surface. Mutation of SLC26A1 residues corresponding to candidate anion binding site-associated residues in avian SLC26A5/prestin altered anion transport in patterns resembling those of prestin. However, rare SLC26A1 polymorphic variants from a patient with renal Fanconi Syndrome and from a patient with nephrolithiasis/calcinosis exhibited no loss-of-function phenotypes consistent with disease pathogenesis. PMID:27125215

  16. Naltrexone-sensitive analgesia following exposure of mice to 2450-MHz radiofrequency radiation (RFR)

    Energy Technology Data Exchange (ETDEWEB)

    Maillefer, R.H.; Quock, R.M. (Univ. of Illinois, Rockford (United States))

    1991-03-11

    This study was conducted to determine whether exposure to RFR might induce sufficient thermal stress to activate endogenous opioid mechanisms and induce analgesia. Male Swiss Webster mice, 20-25 g, were exposed to 10, 15 or 20 mV/cm{sup 2} RFR in a 2,450-MHz waveguide system for 10 min, then tested in the abdominal constriction paradigm. Specific absorption rates (SAR) were 23.7 W/kg at 10 mW/cm{sup 2}, 34.6 W/kg at 15 mW/cm{sup 2} and 45.5 W/kg at 20 mW/cm{sup 2}. Confinement in the exposure chamber alone did not appreciably alter body temperature but did appear to induce a stress-associated analgesia that was insensitive to the opioid receptor blocker naltrexone. Exposure of confined mice to RFR elevated body temperature and further increased analgesia in SAR-dependent manner. The high-SAR RFR-induced analgesia, but not the hyperthermia, was reduced by naltrexone. These findings suggest that (1) RFR produces SAR-dependent hyperthermia and analgesia and (2) RFR-induced analgesia is mediated by opioid mechanisms while confinement-induced analgesia involves non-opioid mechanisms.

  17. Immunoregulatory adherent cells in human tuberculosis: radiation-sensitive antigen-specific suppression by monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kleinhenz, M.E.; Ellner, J.J.

    1985-07-01

    In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKM1-reactive monocytes. Adherent cell suppression was studied in the (/sup 3/H)thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fc portion of IgG (T gamma cells) as antigen-responsive cells. PPD-induced (/sup 3/H)thymidine incorporation by these non gamma T cells was uniformly reduced (mean, 42% +/- 10% (SD)) when autologous AMC were added to non gamma T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-rosetting T cells or treatment with indomethacin. However, AMC treated with OKM1 and complement or gamma irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKM1-reactive, non-erythrocyte-rosetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition.

  18. Fe-Radiation-Induced Alterations in Circulating Leukocyte Populations in the ApoE Mouse Atherosclerosis Model are Temporary

    Science.gov (United States)

    Yu, Tao; Yu, Shaohua; Parks, Brian W.; Gupta, Kiran; Wu, Xing; Khaled, Saman; Chang, Polly Y.; Srivastava, Roshni; Kabarowski, Janusz H. S.; Kucik, Dennis F.

    2008-06-01

    Radiation is associated with an increased risk of heart disease and stroke, likely due in part to vascular inflammation. One model used to understand this is the apoE mouse, where gamma irradiation accelerates development of atherosclerosis. Less is known, though, about the effects of high linear energy transfer (LET) radiation, such as 56Fe, likely to be encountered by astronauts in deep space. Radiation, however, also affects leukocyte numbers. For example, whole-body 56Fe irradiation has been shown to decrease circulating B-cells and T-cells, but whether this was due to radiation of the thymus, of the bone marrow, or both was not determined. We irradiated ApoE mice with 56Fe focused to the aorta and carotids to determine how irradiation of the thymus with 56Fe affects circulating lymphocyte number, and ultimately to determine the effect of iron ion irradiation on development of atherosclerosis. We found that only T-cells were affected at 13 weeks post-irradiation, but even these recovered at 40 weeks, suggesting that effects on the immune system are limited and temporary. Analysis of atherosclerosis development is pending sacrifice and histological analysis of irradiated mice.

  19. Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level.

    Science.gov (United States)

    Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

    2015-12-01

    The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h(-1) up to 1.5 Gy h(-1). Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h(-1). A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR10) was estimated at 95 ± 7 mGy h(-1), followed by 153 ± 13 mGy h(-1) and 169 ± 12 mGy h(-1) on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h(-1), antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h(-1) which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic stress conditions

  20. HIV-1 Tat depresses DNA-PKCS expression and DNA repair, and sensitizes cells to ionizing radiation

    International Nuclear Information System (INIS)

    Purpose There is accumulating evidence that cancer patients with human immmunodeficiency virus-1/acquired immunodeficency syndrome (HIV-1/AIDS) have more severe tissue reactions and often develop cutaneous toxic effects when subjected to radiotherapy. Here we explored the effects of the HIV-1 Tat protein on cellular responses to ionizing radiation. Methods and Materials Two Tat-expressing cell lines, TT2 and TE671-Tat, were derived from human rhabdomyosarcoma cells by transfecting with the HIV-1 tat gene. Radiosensitivity was determined using colony-forming ability. Gene expression was assessed by cDNA microarray and immunohybridization. The Comet assay and γ-H2AX foci were use to detect DNA double-strand breaks (DSBs) and repair. Radiation-induced cell cycle changes were detected by flow cytometry. Results The radiosensitivity of TT2 and TE671-Tat cells was significantly increased as compared with parental TE671 cells or the control TE671-pCI cells. Tat also increased proliferation activity. The comet assay and γH2AX foci detection revealed a decreased capacity to repair radiation-induced DNA DSBs in Tat-expressing cells. Microarray assay demonstrated that the DNA repair gene DNA-PKcs, and cell cycle-related genes Cdc20, Cdc25C, KIF2C and CTS1 were downregulated in Tat-expressing cells. Depression of DNA-PKcs in Tat-expressing cells was further confirmed by RT-PCR and immuno-hybridization analysis. Tat-expressing cells exhibited a prolonged S phase arrest after 4 Gy γ-irradiation, and a noticeable delay in the initiation and elimination of radiation-induced G2/M arrest as compared with parental cells. In addition, the G2/M arrest was incomplete in TT2 cells. Moreover, HIV-1 Tat resulted in a constitutive overexpression of cyclin B1 protein. Conclusion HIV-1 Tat protein sensitizes cells to ionizing radiation via depressing DNA repair and dysregulating cell cycle checkpoints. These observations provide new insight into the increased tissue reactions of AIDS

  1. Rearrangement of RAG-1 recombinase gene in radiation-sensitive ''wasted'' mice

    International Nuclear Information System (INIS)

    The recent cloning and characterization of recombinase genes (RAG- 1/RAG-2) expressed in lymphoid and possibly central nervous system tissues prompted us to examine expression of these genes in DNA repair-deficient/immunodeficient wasted mice (wst). Our results revealed expression of RAG-1 mRNA was detected in spinal cord or brain from wst/wst mice or their normal littermates (wst/sm-bullet mice). In thymus tissue, a small RAG-1 transcript was detected in wst/wst mice that was not evident in thymus from control mice. In wst/lg-bullet mice, a two-fold increase in RAG-1 mRNA was evident in thymus tissue. RAG-2 mRNA could only be detected in thymus tissue from wst/sm-bullet and not from wst;/wst or parental control BCF1 mice. Southern blots revealed a rearrangement/deletion within the RAG-1 gene of affected wasted mice, not evident in known strain-specific parental or littermate controls. These results support the idea that the RAG-1 gene may map at or near the locus for the wasted mutation. In addition, they suggest the importance of recombinase function in normal immune and central nervous system development as well as the potential contribution of this gene family to the normal repair of radiation-induced DNA damage

  2. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    International Nuclear Information System (INIS)

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-κB activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or γ-glutamyl transpeptidase activity. Radiation activated NF-κB was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-κB activity, without toxicity to bone marrow, liver, and kidney

  3. HIV Protease Inhibitors Sensitize Human Head and Neck Squamous Carcinoma Cells to Radiation by Activating Endoplasmic Reticulum Stress.

    Directory of Open Access Journals (Sweden)

    Runping Liu

    Full Text Available Human head and neck squamous cell carcinoma (HNSCC is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that HIV PIs induce cell apoptosis via activation of endoplasmic reticulum (ER stress. The aim of this study was to examine the role of ER stress in HIV PI-induced radiosensitivity in human HNSCC.HNSCC cell lines, SQ20B and FaDu, and the most commonly used HIV PIs, lopinavir and ritonavir (L/R, were used in this study. Clonogenic assay was used to assess the radiosensitivity. Cell viability, apoptosis and cell cycle were analyzed using Cellometer Vision CBA. The mRNA and protein levels of ER stress-related genes (eIF2α, CHOP, ATF-4, and XBP-1, as well as cell cycle related protein, cyclin D1, were detected by real time RT-PCR and Western blot analysis, respectively. The results demonstrated that L/R dose-dependently sensitized HNSCC cells to irradiation and inhibited cell growth. L/R-induced activation of ER stress was correlated to down-regulation of cyclin D1 expression and cell cycle arrest under G0/G1 phase.HIV PIs sensitize HNSCC cells to radiotherapy by activation of ER stress and induction of cell cycle arrest. Our results provided evidence that HIV PIs can be potentially used in combination with radiation in the treatment of HNSCC.

  4. Amelioration of radiation induced DNA damage and biochemical alterations by Punica Granatum (L) extracts and synthetic ellagic acid in Swiss albino mice

    International Nuclear Information System (INIS)

    Radiation therapy has been used in cancer treatment for many decades; Although effective in killing tumor cells, ROS produced in radiotherapy threaten the integrity and survival of surrounding normal cells. ROS are scavenged by radioprotectors before they can interact with biochemical molecules, thus reducing harmful effects of radiation. The pomegranate, Punica granatum L., an ancient, mystical, and highly distinctive fruit, is the predominant member of the Punicaceae family. It is used in several systems of medicine for a variety of ailments. The objective of the present study was to investigate the protective effects of ethanolic extracts of pomegranate whole fruit (EPWF) and seeds (EPS) and Synthetic Ellagic acid (EA) against Electron Beam Radiation (EBR) induced DNA damage and biochemical alterations in Swiss Albino mice. The extracts and synthetic compound were assessed for its radical scavenging property by DPPH radical scavenging and Ferric Reducing Antioxidant Power assays. The animals were treated with 200 mg/kg body wt. of pomegranate extracts and Ellagic acid for 15 days before exposure to 6 Gy of EBR. Radiation induced DNA damage was assessed by comet assay in the peripheral blood lymphocytes of mice. The biochemical estimations were carried out in the serum and RBC lysate of the animals. The plant extracts and synthetic compound exhibited good radical scavenging and reducing properties.The pretreated animals before irradiation caused a reduction in the comet length, olive tail moment, % DNA in tail when compared to irradiated group. The biochemical parameters such as lipid peroxidation was significantly depleted in the treated groups when compared to irradiated group followed by significant elevation in reduced glutathione. Our findings indicate the ameliorating effects of pomegranate extracts and synthetic ellagic acid on radiation induced DNA damage and biochemical changes in mice may be due to its free radical scavenging and increased antioxidant

  5. Trefoil factor 3 (TFF3) enhances the oncogenic characteristics of prostate carcinoma cells and reduces sensitivity to ionising radiation.

    Science.gov (United States)

    Perera, Omesha; Evans, Angharad; Pertziger, Mikhail; MacDonald, Christa; Chen, Helen; Liu, Dong-Xu; Lobie, Peter E; Perry, Jo K

    2015-05-28

    Trefoil factor 3 (TFF3) is a secreted protein which functions in mucosal repair of the gastrointestinal tract. This is achieved through the combined stimulation of cell migration and prevention of apoptosis and anoikis, thus facilitating repair. Deregulated TFF3 expression at the gene and protein level is implicated in numerous cancers. In prostate cancer TFF3 has previously been reported as a potential biomarker, overexpressed in a subset of primary and metastatic cases. Here we investigated the effect of increased TFF3 expression on prostate cancer cell behaviour. Oncomine analysis demonstrated that TFF3 mRNA expression was upregulated in prostate cancer compared to normal tissue. Forced-expression models were established in the prostate cancer cell lines, DU145 and PC3, by stable transfection of an expression vector containing the TFF3 cDNA. Forced expression of TFF3 significantly increased total cell number and cell viability, cell proliferation and cell survival. In addition, TFF3 enhanced anchorage independent growth, 3-dimensional colony formation, wound healing and cell migration compared to control transfected cell lines. We also observed reduced sensitivity to ionising radiation in stably transfected cell lines. In dose response experiments, forced expression of TFF3 significantly enhanced the regrowth of PC3 cells following ionising radiation compared with control transfected cells. In addition, TFF3 enhanced clonogenic survival of DU145 and PC3 cells. These studies indicate that targeting TFF3 for the treatment of prostate cancer warrants further investigation.

  6. Alteration of sensitivity of intratumor quiescent and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound

    International Nuclear Information System (INIS)

    Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total cells to γ-rays following thermal neutron irradiation with or without 10B-compound were examined. Methods and Materials: 5-Bromo-2'-deoxyuridine (BrdU) was injected to SCC VII tumor-bearing mice intraperitoneally 10 times to label all the proliferating (P) tumor cells. As priming irradiation, thermal neutrons alone or thermal neutrons with 10B-labeled sodium borocaptate (BSH) or dl-p-boronophenylalanine (BPA) were administered. The tumor-bearing mice then received a series of γ-ray radiation doses, 0 through 24 h after the priming irradiation. During this period, no BrdU was administered. Immediately after the second irradiation, the tumors were excised, minced, and trypsinized. Following incubation of tumor cells with cytokinesis blocker, the micronucleus (MN) frequency in cells without BrdU labeling (= Q cells at the time of priming irradiation) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU before the priming irradiation. To determine the BrdU-labeled cell ratios in the tumors at the time of the second irradiation, each group also included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the priming irradiation. Results: In total cells, during the interval between the two irradiations, the tumor sensitivity to γ-rays relative to that immediately after priming irradiation decreased with the priming irradiation ranking in the following order: thermal neutrons only > thermal neutrons with BSH > thermal neutrons with BPA. In contrast, in Q cells, during that time the sensitivity increased in the following order: thermal neutrons only 10B-compound, especially BPA, in thermal neutron irradiation causes the recruitment from the Q to P population

  7. Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation.

    Science.gov (United States)

    Matsuu-Matsuyama, Mutsumi; Shichijo, Kazuko; Okaichi, Kumio; Kurashige, Tomomi; Kondo, Hisayoshi; Miura, Shiro; Nakashima, Masahiro

    2015-05-01

    Exposure to ionizing radiation during childhood is a well-known risk factor for thyroid cancer. Our study evaluated the effect of age on the radiosensitivity of rat thyroid glands. Four-week-old (4W), 7 -week-old (7W), and 8-month-old (8M) male Wistar rats were exposed to 8 Gy of whole-body X-ray irradiation. Thyroids were removed 3-72 h after irradiation, and non-irradiated thyroids served as controls. Ki67-positivity and p53 binding protein 1 (53BP1) focus formation (a DNA damage response) were evaluated via immunohistochemistry. Amounts of proteins involved in DNA damage response (p53, p53 phosphorylated at serine 15, p21), apoptosis (cleaved caspase-3), and autophagy (LC3, p62) were determined via western blotting. mRNA levels of 84 key autophagy-related genes were quantified using polymerase chain reaction arrays. Ki67-positive cells in 4W (with high proliferative activity) and 7W thyroids significantly decreased in number post-irradiation. The number of 53BP1 foci and amount of p53 phosphorylated at serine 15 increased 3 h after irradiation, regardless of age. No increase in apoptosis or in the levels of p53, p21 or cleaved caspase-3 was detected for any ages. Levels of LC3-II and p62 increased in irradiated 4W but not 8M thyroids, whereas expression of several autophagy-related genes was higher in 4W than 8M irradiated thyroids. Irradiation increased the expression of genes encoding pro-apoptotic proteins in both 4W and 8M thyroids. In summary, no apoptosis or p53 accumulation was noted, despite the expression of some pro-apoptotic genes in immature and adult thyroids. Irradiation induced autophagy in immature, but not in adult, rat thyroids.

  8. Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation

    International Nuclear Information System (INIS)

    Exposure to ionizing radiation during childhood is a well-known risk factor for thyroid cancer. Our study evaluated the effect of age on the radiosensitivity of rat thyroid glands. Four-week-old (4W), 7-week-old (7W), and 8-month-old (8M) male Wistar rats were exposed to 8 Gy of whole-body X-ray irradiation. Thyroids were removed 3–72 h after irradiation, and non-irradiated thyroids served as controls. Ki67-positivity and p53 binding protein 1 (53BP1) focus formation (a DNA damage response) were evaluated via immunohistochemistry. Amounts of proteins involved in DNA damage response (p53, p53 phosphorylated at serine 15, p21), apoptosis (cleaved caspase-3), and autophagy (LC3, p62) were determined via western blotting. mRNA levels of 84 key autophagy-related genes were quantified using polymerase chain reaction arrays. Ki67-positive cells in 4W (with high proliferative activity) and 7W thyroids significantly decreased in number post-irradiation. The number of 53BP1 foci and amount of p53 phosphorylated at serine 15 increased 3 h after irradiation, regardless of age. No increase in apoptosis or in the levels of p53, p21 or cleaved caspase-3 was detected for any ages. Levels of LC3-II and p62 increased in irradiated 4W but not 8M thyroids, whereas expression of several autophagy-related genes was higher in 4W than 8M irradiated thyroids. Irradiation increased the expression of genes encoding pro-apoptotic proteins in both 4W and 8M thyroids. In summary, no apoptosis or p53 accumulation was noted, despite the expression of some pro-apoptotic genes in immature and adult thyroids. Irradiation induced autophagy in immature, but not in adult, rat thyroids. (author)

  9. Structure alterations of human lymphocyte nuclei affected by ionizing radiation within the range of doses that cause the adaptive response

    International Nuclear Information System (INIS)

    Low-level radiation either from external or from incorporated sources is shown to cause a nonmonotonous change in some intranuclear parameters of human peripheral blood lymphocytes. For instance, radiation induces changes in the parameters that characterize the location of perecentromeric regions within the interphase nucleus and a nonmonotonous increase in nuclear sizes. The exposure to doses exceeding 5 cGy impairs the realtionship between the nuclear sizes and location therein of the perecentromeric regions of interphase chromosomes which exist in the control and after exposure to 2.5 cGy. Differences between the dose ranges of 1.5-3.5 and 17-25 cGy are manifested by the kinetics of restoration of the pattern of distribution of lymphocyte nuclear sizes

  10. Reduction of radioactive backgrounds in electroformed copper for ultra-sensitive radiation detectors

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, E.W., E-mail: eric.hoppe@pnnl.gov [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Aalseth, C.E.; Farmer, O.T.; Hossbach, T.W.; Liezers, M.; Miley, H.S.; Overman, N.R. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Reeves, J.H. [Reeves and Son LLC, 10 Albert Ave., Richland, WA 99352 (United States)

    2014-11-11

    Ultra-pure construction materials are required for the next generation of neutrino physics, dark matter and environmental science applications. These materials are also important for use in high-purity germanium spectrometers used in screening materials for radiopurity. The next-generation science applications require materials with radiopurity levels at or below 1 μBq/kg {sup 232}Th and {sup 238}U. Yet radiometric analysis lacks sensitivity below ∼10 μBq/kg for the U and Th decay chains. This limits both the selection of clean materials and the validation of purification processes. Copper is an important high-purity material for low-background experiments due to the ease with which it can be purified by electrochemical methods. Electroplating for purification into near-final shapes, known as electroforming, is one such method. Continued refinement of the copper electroforming process is underway, for the first time guided by an ICP-MS based assay method that can measure {sup 232}Th and {sup 238}U near the desired purity levels. An assay of electroformed copper at a μBq/kg level has been achieved and is described. The implications of electroformed copper at or better than this purity on next-generation low-background experiments are discussed.

  11. Radiation sensitivities of Listeria monocytogenes isolated from chicken meat and their growth at refrigeration temperatures

    International Nuclear Information System (INIS)

    Listeria monocytogenes were isolated in 5 lots, more than one cell in each 25-g sample of 10 lots of chicken meat, which was obtained from several different areas in Japan. From taxonomic study, the psychrotrophic type of 3 isolates grew well at 4°C on Trypticase soy agar slant, whereas 2 isolates grew poorly. Cells of all isolates were sensitive to γ-irradiation in phosphate buffer, and the D10 values obtained were 0.16 to 0.18 kGy under aerobic irradiation conditions similar to the values of salmonellae. In the chicken meat sample, the D10 value obtained was 0.42 kGy the same value as in phosphate buffer under anaerobic irradiation conditions, and the necessary dose for inactivation of L. monocytogenes was estimated to be 2 kGy in raw chicken meat below 10-4 CFU (colony forming unit) per gram. In the storage study of chicken meat which was inoculated with about 3×103 CFU per gram of L. monocytogenes, the psychrotrophic type of the isolates grew quickly at 7 to 10°C storage. However, a dose of 1 kGy was also effective to suppress the growth of L. monocytogenes at refrigeration temperatures below 10°C

  12. Adenovirus-mediated expression of Tob1 sensitizes breast cancer cells to ionizing radiation

    Institute of Scientific and Technical Information of China (English)

    Yang JIAO; Chun-min GE; Qing-hui MENG; Jian-ping CAO; Jian TONG; Sai-jun FAN

    2007-01-01

    Aim: To investigate the effect of the Tobl gene, a member of the Transducing Molecule of ErbB2/B-cell Translocation Ggene (TOB/BTG) family, by using the adenovirus-mediated expression of Tob 1 on radiosensitivity in a human breast cancer cell line MDA-MB-231. Methods: Cell survival was determined by clonogenic assay. Apoptosis was evaluated by DNA fragmentation gel electro-phoresis and terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Protein expression was analyzed by Western blot assay and DNA repair was measured by a host cell reactivation assay. Results: We demonstrated that pre-irradiation treatment with Ad5-Tob 1 significantly increased radiosensitivity,accompanying the increased induction of apoptosis and the repression of DNA damage repair. Furthermore, Ad5-Tob 1-mediated radiosensitivity correlates with the upregulation of the pro-apoptotic protein Bax and the downregulation of several DNA double strand break repair proteins, including DNA-dependent protein kinases, Ku70 and Ku80, and X-ray-sensitive complementation group 4.Conclusion: Tobl, as a new radiosensitizer, is a new target in the radiotherapy of breast cancer via increasing apoptosis and suppressing DNA repair.

  13. Reduction of Radioactive Backgrounds in Electroformed Copper for Ultra-Sensitive Radiation Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, Eric W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Aalseth, Craig E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Farmer, Orville T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hossbach, Todd W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Liezers, Martin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Miley, Harry S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Overman, Nicole R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Reeves, James H. [Reeves and Son LLC., Richland, WA (United States)

    2014-07-07

    Abstract Ultra-pure construction materials are required for the next generation of neutrino physics, dark matter and environmental science applications. These new efforts require materials with purity levels at or below 1 uBq/kg 232Th and 238U. Yet radiometric analysis lacks sensitivity below ~10 uBq/kg for the U and Th decay chains. This limits both the selection of clean materials and the validation of purification processes. Copper is an important high-purity material for low-background experiments due to the ease with which it can be purified by electrochemical methods. Electroplating for purification into near-final shapes, known as electroforming, is one such method. Continued refinement of the copper electroforming process is underway, for the first time guided by an ICP-MS based assay method that can measure 232Th and 238U near the desired purity levels. An assay of electroformed copper at 10 uBq/kg for 232Th has been achieved and is described. The implications of electroformed copper at or better than this purity on next-generation low-background experiments are discussed.

  14. Role of wheat germ oil in radiation-induced oxidative stress and alteration in energy metabolism in rats

    International Nuclear Information System (INIS)

    The liver is essential in keeping the body functioning properly while muscular strength is important in sport as well as in daily activities. Exposure to ionizing radiation is thought to increase oxidative stress and damage liver and muscle tissues. Wheat germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be beneficial in neutralizing the free oxygen radicals. This study was designed to investigate the efficacy of wheat germ oil, on radiation induced oxidative damage in rat's liver and skeletal muscle. Wheat germ oil was supplemented orally via gavage to rats at a dose of 54 mg/ kg body weight for 14 successive days pre- and 7 days post-exposure to 5 Gy (single dose) of whole body gamma irradiation. Animals were sacrificed 7, 14 and 21 days post radiation exposure. The results revealed that whole body gamma irradiation of rats induces oxidative stress in liver and skeletal muscles obvious by significant elevation in the levels of xanthine oxidase and thiobarbituric acid reactive substances (TBARS) associated with significant decreases in the content of reduced glutathione, as well as decreases in xanthine dehydrogenase, superoxide dismutase, catalase and glutathione peroxidase activities. Irradiated rats showed also significant decreases in creatine phosphokinase, glutamate dehydrogenase and glucose-6- phosphate dehydrogenase activities while lactate dehydrogenase were significantly increased. Total iron, total copper and total calcium levels significantly increased in the liver and skeletal muscles of irradiated rats group compared to control group. Wheat germ oil treated-irradiated rats showed significantly less severe damage and remarkable improvement in all the measured parameters, compared to irradiated rats. It could be concluded that wheat germ oil by attenuating radiation-induced oxidative stress might play a role in maintaining liver and skeletal muscle

  15. Characterization of genomic alterations in radiation-associated breast cancer among childhood cancer survivors, using comparative genomic hybridization (CGH arrays.

    Directory of Open Access Journals (Sweden)

    Xiaohong R Yang

    Full Text Available Ionizing radiation is an established risk factor for breast cancer. Epidemiologic studies of radiation-exposed cohorts have been primarily descriptive; molecular events responsible for the development of radiation-associated breast cancer have not been elucidated. In this study, we used array comparative genomic hybridization (array-CGH to characterize genome-wide copy number changes in breast tumors collected in the Childhood Cancer Survivor Study (CCSS. Array-CGH data were obtained from 32 cases who developed a second primary breast cancer following chest irradiation at early ages for the treatment of their first cancers, mostly Hodgkin lymphoma. The majority of these cases developed breast cancer before age 45 (91%, n = 29, had invasive ductal tumors (81%, n = 26, estrogen receptor (ER-positive staining (68%, n = 19 out of 28, and high proliferation as indicated by high Ki-67 staining (77%, n = 17 out of 22. Genomic regions with low-copy number gains and losses and high-level amplifications were similar to what has been reported in sporadic breast tumors, however, the frequency of amplifications of the 17q12 region containing human epidermal growth factor receptor 2 (HER2 was much higher among CCSS cases (38%, n = 12. Our findings suggest that second primary breast cancers in CCSS were enriched for an "amplifier" genomic subgroup with highly proliferative breast tumors. Future investigation in a larger irradiated cohort will be needed to confirm our findings.

  16. The sensitivity of tropical convective precipitation to the direct radiative forcings of black carbon aerosols emitted from major regions

    Directory of Open Access Journals (Sweden)

    C. Wang

    2009-10-01

    Full Text Available Previous works have suggested that the direct radiative forcing (DRF of black carbon (BC aerosols are able to force a significant change in tropical convective precipitation ranging from the Pacific and Indian Ocean to the Atlantic Ocean. In this in-depth analysis, the sensitivity of this modeled effect of BC on tropical convective precipitation to the emissions of BC from 5 major regions of the world has been examined. In a zonal mean base, the effect of BC on tropical convective precipitation is a result of a displacement of ITCZ toward the forcing (warming hemisphere. However, a substantial difference exists in this effect associated with BC over different continents. The BC effect on convective precipitation over the tropical Pacific Ocean is found to be most sensitive to the emissions from Central and North America due to a persistent presence of BC aerosols from these two regions in the lowermost troposphere over the Eastern Pacific. The BC effect over the tropical Indian and Atlantic Ocean is most sensitive to the emissions from South as well as East Asia and Africa, respectively. Interestingly, the summation of these individual effects associated with emissions from various regions mostly exceeds their actual combined effect as shown in the model run driven by the global BC emissions, so that they must offset each other in certain locations and a nonlinearity of this type of effect is thus defined. It is known that anthropogenic aerosols contain many scattering-dominant constituents that might exert an effect opposite to that of absorbing BC. The combined aerosol forcing is thus likely differing from the BC-only one. Nevertheless, this study along with others of its kind that isolates the DRF of BC from other forcings provides an insight of the potentially important climate response to anthropogenic forcings particularly related to the unique particulate solar absorption.

  17. DNA alterations and effects on growth and reproduction in Daphnia magna during chronic exposure to gamma radiation over three successive generations

    Energy Technology Data Exchange (ETDEWEB)

    Parisot, Florian [Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, St Paul-lez-Durance 13115 (France); Bourdineaud, Jean-Paul [UMR 5805 EPOC – OASU, Station marine d’Arcachon, Université Bordeaux 1, Arcachon 33120 (France); Plaire, Delphine; Adam-Guillermin, Christelle [Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, St Paul-lez-Durance 13115 (France); Alonzo, Frédéric, E-mail: frederic.alonzo@irsn.fr [Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, St Paul-lez-Durance 13115 (France)

    2015-06-15

    Highlights: • We exposed three successive generations of Daphnia magna to chronic gamma radiation. • We examined DNA alterations and effects on survival, growth and reproduction. • DNA alterations were accumulated over a generation and transmitted to the progeny. • Effects on survival and reproduction, and delay in growth increased over generations. - Abstract: This study examined chronic effects of external Cs-137 gamma radiation on Daphnia magna exposed over three successive generations (F0, F1 and F2) to environmentally relevant dose rates (ranging from 0.007 to 35.4 mGy h{sup −1}). Investigated endpoints included survival, growth, reproduction and DNA alterations quantified using random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Results demonstrated that radiation effects on survival, growth and reproduction increased in severity from generation F0 to generation F2. Mortality after 21 days at 35.4 mGy h{sup −1} increased from 20% in F0 to 30% in F2. Growth was affected by a slight reduction in maximum length at 35.4 mGy h{sup −1} in F0 and by reductions of 5 and 13% in growth rate, respectively, at 4.70 and 35.4 mGy h{sup −1} in F2. Reproduction was affected by a reduction of 19% in 21 day-fecundity at 35.4 mGy h{sup −1} in F0 and by a delay of 1.9 days in brood release as low as 0.070 mGy h{sup −1} in F2. In parallel, DNA alterations became significant at decreasing dose rates over the course of F0 (from 4.70 mGy h{sup −1} at hatching to 0.007 mGy h{sup −1} after ∼21 days) and from F0 to F2 (0.070 mGy h{sup −1} at hatching to 0.007 mGy h{sup −1} after ∼21 days), demonstrating their rapid accumulation in F0 daphnids and their transmission to offspring generations. Transiently more efficient DNA repair leading to some recovery at the organism level was suggested in F1, with no effect on survival, a slight reduction of 12% in 21 day-fecundity at 35.4 mGy h{sup −1} and DNA alterations significant at highest

  18. Identification of the common radiation-sensitive and glucose metabolism-related expressed genes in the thymus of ICR and AKR/J mice

    Energy Technology Data Exchange (ETDEWEB)

    Bong, Jin Jong; Kang, Yumi; Choi, Suk Cjul; Choi, Moo Hyun; Choi, Seung Jin; Kim, Hee Sun [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd, Seoul (Korea, Republic of)

    2011-11-15

    Our goal was to identify the common radiation-sensitive expressed genes in the thymus of ICR and AKR/J mice on 100 days after irradiation. Thus, we performed microarray analysis for thymus of ICR and AKR/J mice, respectively. We categorized differential expressed genes by the analysis of DAVID Bioinformatics Resources v 6.7 and GeneSpring GX 11.5.1 and validated gene expression patterns by QPCR analysis. Our result demonstrated that radiation-sensitive expressed genes and signaling pathways in the thymus of irradiated ICR and AKR/J mice.

  19. Individual sensitivity to radiations and DNA repair proficiency: the comet assay contribution; Sensibilite individuelle aux radiations et reparation de l`ADN: apport du test des cometes

    Energy Technology Data Exchange (ETDEWEB)

    Alapetite, C. [Institut Curie, 75 - Paris (France)

    1998-09-01

    Some are hereditary syndromes demonstrate high cancer risk and hypersensitivity in response to exposures to agents such as ultraviolet or ionising radiation, and are characterized by a defective processing of DNA damage. They highlight the importance of the individual risk associated to exposures. The comet assay, a simple technique that detects DNA strand breaks, requires few cells and allows examination of DNA repair capacities in established cell lines, in blood samples or biopsies. The assay has been validated on cellular systems with known repair defects such as xeroderma pigmentosum defective in nucleotide excision repair, on mutant rodent cell lines defective in DNA single strand breaks rejoining (XRCC5/Ku80 and XRCC7/DNAPKcs) (neutral conditions). This assay does not allow to distinguish a defective phenotype in ataxia telangiectasia cells. It shows in homozygous mouse embryo fibroblasts Brca2-/- an impaired DNA double strand break rejoining. Simplicity, rapidity and sensitivity of the alkaline comet assay allow to examine the response of lymphocytes. It has been applied to the analysis of the role of DNA repair in the pathogenesis of collagen diseases, and the involvement of individual DNA repair proficiency in the thyroid tumorigenesis induced in some patients after therapeutic irradiation at childhood has been questioned. Preliminary results of these studies suggest that this type of approach could help for adapting treatment modalities and surveillance in subgroups of patients defective in DNA repair process. It could also have some incidence in the radioprotection field. (author)

  20. DNA alterations and effects on growth and reproduction in Daphnia magna during chronic exposure to gamma radiation over three successive generations.

    Science.gov (United States)

    Parisot, Florian; Bourdineaud, Jean-Paul; Plaire, Delphine; Adam-Guillermin, Christelle; Alonzo, Frédéric

    2015-06-01

    This study examined chronic effects of external Cs-137 gamma radiation on Daphnia magna exposed over three successive generations (F0, F1 and F2) to environmentally relevant dose rates (ranging from 0.007 to 35.4 mGy h(-1)). Investigated endpoints included survival, growth, reproduction and DNA alterations quantified using random-amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Results demonstrated that radiation effects on survival, growth and reproduction increased in severity from generation F0 to generation F2. Mortality after 21 days at 35.4 mGy h(-1) increased from 20% in F0 to 30% in F2. Growth was affected by a slight reduction in maximum length at 35.4 mGy h(-1) in F0 and by reductions of 5 and 13% in growth rate, respectively, at 4.70 and 35.4 mGy h(-1) in F2. Reproduction was affected by a reduction of 19% in 21 day-fecundity at 35.4 mGy h(-1) in F0 and by a delay of 1.9 days in brood release as low as 0.070 mGy h(-1) in F2. In parallel, DNA alterations became significant at decreasing dose rates over the course of F0 (from 4.70 mGy h(-1) at hatching to 0.007 mGy h(-1) after ∼21 days) and from F0 to F2 (0.070 mGy h(-1) at hatching to 0.007 mGy h(-1) after ∼21 days), demonstrating their rapid accumulation in F0 daphnids and their transmission to offspring generations. Transiently more efficient DNA repair leading to some recovery at the organism level was suggested in F1, with no effect on survival, a slight reduction of 12% in 21 day-fecundity at 35.4 mGy h(-1) and DNA alterations significant at highest dose rates only. The study improved our understanding of long term responses to low doses of radiation at the molecular and organismic levels in a non-human species for a better radioprotection of aquatic ecosystems. PMID:25840277

  1. Sensitivity and applications of a new method for the simultaneous measurement of convective and radiative heat flux in underhood applications—toward multiple versions

    Science.gov (United States)

    Khaled, M.; Shaer, A. Al; Ramadan, M.; Elmarakbi, A.; Harambat, F.; Peerhossaini, H.

    2014-03-01

    Convective and radiative heat fluxes enter simultaneously into most thermal engineering applications, especially in the vehicle underhood. However, separate measurements of these fluxes are needed for understanding and analyzing underhood aerothermal phenomena. In this context, a new experimental technique has been proposed (Khaled et al 2010 Meas. Sci. Technol. 21 025903) that allows the simultaneous measurement of convective and radiative heat fluxes. The technique uses a pair of fluxmeters with different radiative properties: the two fluxmeters measure the same convective flux but different radiative fluxes proportional to the fluxmeters’ emissivities. This permits the separate calculation of the convective and radiative fluxes. This paper presents a sensitivity and applicability analysis of the new technique, taking into account the effects of a number of parameters such as emissivities, the precision of emissivity estimation and the difference in convective heat fluxes due to fluxmeter position. Also, new applications of this novel technique are proposed as an alternative when the initial version becomes inaccurate.

  2. Dose-dependent and gender-related radiation-induced transcription alterations of Gadd45a and Ier5 in human lymphocytes exposed to gamma ray emitted by 60Co

    International Nuclear Information System (INIS)

    Growth arrest DNA damage-inducible 45a gene (Gadd45a) and immediate early response gene 5 (Ier5) have been emphasised as ideal radiation bio-markers in several reports. However, some aspects of radiation-induced transcriptional alterations of these genes are unknown. In this study, gender-dependency and dose-dependency as two factors that may affect radiation induced transcription of Gadd45a and Ier5 genes were investigated. Human lymphocyte cells from six healthy voluntary blood donors (three women and three men) were irradiated in vitro with doses of 0.5-4.0 Gy from a 60Co source and RNA isolated 4 h later using the High Pure RNA Isolation Kit. Dose and gender dependency of radiation-induced transcriptional alterations of Gadd45a and Ier5 genes were studied by quantitative real-time polymerase chain reaction. The results showed that as a whole, Gadd45a and Ier5 gave responses to gamma rays, while the responses were independent of radiation doses. Therefore, regardless of radiation dose, Gadd45a and Ier5 can be considered potential radiation bio-markers. Besides, although radiation-induced transcriptional alterations of Gadd45a in female and male lymphocyte samples were insignificant at 0.5 Gy, at other doses, their quantities in female samples were at a significantly higher level than in male samples. Radiation induced transcription of Ier5 of females samples had a reduction in comparison with male samples at 1 and 2 Gy, but at doses of 0.5 and 4 Gy, females were significantly more susceptible to radiation-induced transcriptional alteration of Ier5. (authors)

  3. Beef Fat Enriched with Polyunsaturated Fatty Acid Biohydrogenation Products Improves Insulin Sensitivity Without Altering Dyslipidemia in Insulin Resistant JCR:LA-cp Rats.

    Science.gov (United States)

    Diane, Abdoulaye; Borthwick, Faye; Mapiye, Cletos; Vahmani, Payam; David, Rolland C; Vine, Donna F; Dugan, Michael E R; Proctor, Spencer D

    2016-07-01

    The main dietary sources of trans fatty acids are partially hydrogenated vegetable oils (PHVO), and products derived from polyunsaturated fatty acid biohydrogenation (PUFA-BHP) in ruminants. Trans fatty acid intake has historically been associated with negative effects on health, generating an anti-trans fat campaign to reduce their consumption. The profiles and effects on health of PHVO and PUFA-BHP can, however, be quite different. Dairy products naturally enriched with vaccenic and rumenic acids have many purported health benefits, but the putative benefits of beef fat naturally enriched with PUFA-BHP have not been investigated. The objective of the present experiment was to determine the effects of beef peri-renal fat (PRF) with differing enrichments of PUFA-BHP on lipid and insulin metabolism in a rodent model of dyslipidemia and insulin resistance (JCR:LA-cp rat). The results showed that 6 weeks of diet supplementation with beef PRF naturally enriched due to flaxseed (FS-PRF) or sunflower-seed (SS-PRF) feeding to cattle significantly improved plasma fasting insulin levels and insulin sensitivity, postprandial insulin levels (only in the FS-PRF) without altering dyslipidemia. Moreover, FS-PRF but not SS-PRF attenuated adipose tissue accumulation. Therefore, enhancing levels of PUFA-BHP in beef PRF with FS feeding may be a useful approach to maximize the health-conferring value of beef-derived fats.

  4. Beef Fat Enriched with Polyunsaturated Fatty Acid Biohydrogenation Products Improves Insulin Sensitivity Without Altering Dyslipidemia in Insulin Resistant JCR:LA-cp Rats.

    Science.gov (United States)

    Diane, Abdoulaye; Borthwick, Faye; Mapiye, Cletos; Vahmani, Payam; David, Rolland C; Vine, Donna F; Dugan, Michael E R; Proctor, Spencer D

    2016-07-01

    The main dietary sources of trans fatty acids are partially hydrogenated vegetable oils (PHVO), and products derived from polyunsaturated fatty acid biohydrogenation (PUFA-BHP) in ruminants. Trans fatty acid intake has historically been associated with negative effects on health, generating an anti-trans fat campaign to reduce their consumption. The profiles and effects on health of PHVO and PUFA-BHP can, however, be quite different. Dairy products naturally enriched with vaccenic and rumenic acids have many purported health benefits, but the putative benefits of beef fat naturally enriched with PUFA-BHP have not been investigated. The objective of the present experiment was to determine the effects of beef peri-renal fat (PRF) with differing enrichments of PUFA-BHP on lipid and insulin metabolism in a rodent model of dyslipidemia and insulin resistance (JCR:LA-cp rat). The results showed that 6 weeks of diet supplementation with beef PRF naturally enriched due to flaxseed (FS-PRF) or sunflower-seed (SS-PRF) feeding to cattle significantly improved plasma fasting insulin levels and insulin sensitivity, postprandial insulin levels (only in the FS-PRF) without altering dyslipidemia. Moreover, FS-PRF but not SS-PRF attenuated adipose tissue accumulation. Therefore, enhancing levels of PUFA-BHP in beef PRF with FS feeding may be a useful approach to maximize the health-conferring value of beef-derived fats. PMID:27072368

  5. Alterations in architecture and metabolism induced by ultraviolet radiation-B in the carragenophyte Chondracanthus teedei (Rhodophyta, Gigartinales).

    Science.gov (United States)

    Schmidt, Eder C; Pereira, Beatriz; Pontes, Carime L Mansur; dos Santos, Rodrigo; Scherner, Fernando; Horta, Paulo A; de Paula Martins, Roberta; Latini, Alexandra; Maraschin, Marcelo; Bouzon, Zenilda L

    2012-04-01

    The in vivo effect of ultraviolet radiation-B (UVBR) in apical segments of Chondracanthus teedei was examined. Over a period of 7 days, the segments were cultivated and exposed to photosynthetically active radiation (PAR) at 80 μmol photons m(-2) s(-1) and PAR + UVBR at 1.6 W m(-2) for 3 h per day. The samples were processed for electron microscopy and histochemistry; also was analyzed growth rates, mitochondrial activity, protein levels, content of photosynthetic pigments and photosynthetic performance. UVBR elicited increased cell wall thickness and accumulation of plastoglobuli, changes in mitochondrial organization and destruction of chloroplast internal organization. Compared to controls, algae exposed to PAR + UVBR showed a growth rate reduction of 55%. The content of photosynthetic pigments, including chlorophyll a and phycobiliproteins, decreased after exposure to PAR + UVBR. This result agrees with the decreased photosynthetic performance observed after exposing algae to PAR + UVBR. Irradiation also elicited increased activity of the antioxidant enzyme glutathione peroxidase and decreased mitochondrial NADH dehydrogenase activity, which correlated with the decreased protein content in plants exposed to PAR + UVBR. Taken together, these findings strongly indicate that UVBR negatively affects the architecture and metabolism of the carragenophyte C. teedei.

  6. Radiation

    International Nuclear Information System (INIS)

    The basic facts about radiation are explained, along with some simple and natural ways of combating its ill-effects, based on ancient healing wisdom as well as the latest biochemical and technological research. Details are also given of the diet that saved thousands of lives in Nagasaki after the Atomic bomb attack. Special comment is made on the use of radiation for food processing. (U.K.)

  7. Increased genomic alteration complexity and telomere shortening in B-CLL cells resistant to radiation-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Salin, H.; Ricoul, M.; Morat, L.; Sabatier, L. [CEA, DSV, iRCM, LRO, F-92265 Fontenay Aux Roses (France); Salin, H. [Museum Natl Hist Nat, F-75231 Paris (France)

    2008-07-01

    B-cell chronic lymphocytic leukemia (B-CLL) results in an accumulation of mature CD5{sup +}/CD23{sup +} B cells due to an uncharacterised defect in apoptotic cell death. B-CLL is not characterized by a unique recurrent genomic alteration but rather by genomic instability giving rise frequently to several chromosomal aberrations. Besides we reported that similar to 15% of B-CLL patients present malignant B-cells resistant to irradiation-induced apoptosis, contrary to similar to 85% of patients and normal human lymphocytes. Telomere length shortening is observed in radioresistant B-CLL cells. Using fluorescence in situ hybridization (FISH) and multicolour FISH, we tested whether specific chromosomal aberrations might be associated with the radioresistance of a subset of B-CLL cells and whether they are correlated with telomere shortening. In a cohort of 30 B-CLL patients, all of the radioresistant B-CLL cell samples exhibited homozygous or heterozygous deletion of 13q14.3 in contrast to 52% of the radiosensitive samples. In addition to the 13q14.3 deletion, ten out of the 11 radioresistant B-cell samples had another clonal genomic alteration such as trisomy 12, deletion 17p13.1, mutation of the p53 gene or translocations in contrast to only three out of 19 radiosensitive samples. Telomere fusions and non-reciprocal translocations, hallmarks of telomere dysfunction, are not increased in radioresistant B-CLL cells. These findings suggest (i) that the 13q14.3 deletion accompanied by another chromosomal aberration is associated with radioresistance of B-CLL cells and (ii) that telomere shortening is not causative of increased clonal chromosomal aberrations in radioresistant B-CLL cells. (authors)

  8. Alteration of radiation induced hematotoxicity by Amifostine (Ethyol {sup trademark}); Veraenderte bestrahlungsinduzierte Haematotoxizitaet durch Amifostin (Ethyol {sup trademark})

    Energy Technology Data Exchange (ETDEWEB)

    Momm, F.; Bechtold, C.; Fischer, K.; Tsekos, A.; Henke, M. [Freiburg Univ. (Germany). Abt. Roentgen- und Strahlentherapie

    1999-11-01

    Background: Radiotherapy - even of small volumes - can decrease leukocyte counts. We examined whether the radioprotector amifostine can reduce this hematotoxicity. Patients and methods: Twenty-six patients undergoing radiotherapy for squamous cell carcinoma of the head and neck were evaluated. All were given 60 (to 70) Gy 5x2 Gy per week in standard radiation techniques. Thirteen patients are randomized to receive 200 mg/m{sup 2} amifostine i.v., 30 minutes before radiation. Blood counts and differentials were determined before, during and following radiotherapy. Differences of these parameters are calculated and compared by t-test. Results: The blood hemoglobin and the thrombocyte levels did not change during the radiotherapy course, neither for the amifostine treated, nor the control patients. Similarly the leukocyte counts of amifostine treated patients did not change during irradiation. The control patients, however, had a decrease of leukocytes from 8.4 to 6.0x10{sup 3}/{mu}l, p=0.03, and the reduction of the neutrophilic granulocyte count was more impressive for these patients. Conclusion: In this explorative study amifostine diminished radiation induced leukocyte toxicity. (orig.) [German] Hintergrund: Eine Strahlentherapie - selbst kleiner Volumina - kann die Blutbildung beeintraechtigen. Wir untersuchten die Wirkung des Radioprotektors Amifostin auf diese Haematotoxizitaet. Patienten und Methoden: 26 Patienten mit Kopf-Hals-Tumoren wurden evaluiert. Sie wurden mit 60 (bis 70) Gy und einer Fraktionierung von 5mal 2 Gy/Woche in Standardtechnik bestrahlt, 13 von ihnen wurden zusaetzlich - nach Randomisierung - mit Amifostin (200 mg/m{sup 3} intravenoes, 30 Minuten vor jeder Fraktion) behandelt. Vor, waehrend und nach der Radiotherapie wurden Haemoglobinwert, Thrombozytenzahl, Leukozytenzahl und Differentialblutbild bestimmt. Die Veraenderungen dieser Werte waehrend der Bestrahlung wurden als Differenz bestimmt und mit einem t-Test verglichen. Ergebnisse: Die

  9. Troxerutin induces protective effects against ultraviolet B radiation through the alteration of microRNA expression in human HaCaT keratinocyte cells.

    Science.gov (United States)

    Lee, Kwang Sik; Cha, Hwa Jun; Lee, Ghang Tai; Lee, Kun Kook; Hong, Jin Tae; Ahn, Kyu Joong; An, In-Sook; An, Sungkwan; Bae, Seunghee

    2014-04-01

    Ultraviolet light B (UVB), contained in sunlight, induces damaging effects on skin by impairing cells in the epidermis and dermis. In particular, keratinocytes in the epidermis are those cells which are mainly affected by UVB light. UVB radiation induces cell death, growth arrest, DNA damage and restricts cell migration. Various phytochemicals have been shown to alleviate UVB-induced cellular damage. Troxerutin is a natural flavonoid rutin mainly found in extracts of Sophora japonica, and is a well-known antioxidant and anti-inflammatory compound used in experimental mouse models. In this study, we examined the effects of troxerutin on UVB-induced damage in HaCaT cells. HaCaT cells were pre-treated with troxerutin (0-10 µM) and then exposed to UVB radiation (50 mJ/cm2). Cell viability, cell cycle and migration assays were performed to determine the protective effects of troxerutin on the cells. DNA repair activity was also measured. Troxerutin protected the cells against UVB-induced damage, such as cell death, growth arrest, restriction of cell migration and decreased DNA repair activity in HaCaT cells. Analyses of microRNA (miRNA) expression demonstrated that the protective effects of troxerutin correlated with alterations in miRNA expression, as indicated by Gene Ontology analyses of putative target genes. Overall, our data demonstrate that troxerutin exerts protective effects against UVB-induced damage by regulating miRNA expression.

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

    Directory of Open Access Journals (Sweden)

    Françoise Bernerd

    2012-01-01

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

  11. Evaluation of the morphological alteration of the root surface radiated with a diode laser; Avaliacao da alteracao morfologica da superficie cimentaria irradiada com laser de diodo

    Energy Technology Data Exchange (ETDEWEB)

    Gulin, Mauricio

    2003-07-01

    The diode laser has been studied for periodontal therapy, as much for removal of calculus as for microbial reduction of periodontal pockets, as well as the visible analgesic effects and biomodulation capacity. For this reason the purpose of this study was to evaluate the morphological alteration of the root surface after radiation with the diode laser, 808 nm through analysis by scanning electron microscopy (SEM). Besides this, to verify the temperature variations caused during the radiation, a thermometer put into the dentinal wall of the root canal was used. In all, 18 teeth were used, 15 of which for the SEM study, and the other 3 were used to temperature variation analysis. The 25 samples were scraped on the root surface and planed with manual instruments. The other 5 were not subjected to any type of treatment. This, 6 groups of 5 samples each were formed. Control Group C whose samples had not received any treatment; Control Group C 1 was only scraped and polished conventionally with Hu-Friedy Gracey curettes 5 and 6; the other samples groups L1, L2, L3, L4 were radiated by diode laser using parameters of power 1,0 W; 1,2 W; 1,4 W; and 1,6 W respectively, 2 times for 10 seconds with 20 seconds intervals between each radiation in continuous mode. The results with relation to the increase of temperature in the interior of the root canal demonstrated that there was an increase of more than 5 degree Celsius. The results of the scanning electron microscope analysis of Control Group C demonstrated great irregularity and ridges on the root surface, with the presence of a dentine layer. Control Group C1 presented a similar aspect to Group L 1's, smoother and more homogeneous surface. Groups L2, L3, and L4 presented scratches alternating with smoother areas showing that fiber contacted the surface of the sample. The results reconfirmed the necessity of further studies using diode laser, with a beam of light emitted in an interrupted mode to improve the control of

  12. A sensitivity function-based conjugate gradient method for optical tomography with the frequency-domain equation of radiative transfer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Keol [Departement des Sciences Appliquees, Universite du Quebec a Chicoutimi, Chicoutimi, Que., G7H 2B1 (Canada); Charette, Andre [Departement des Sciences Appliquees, Universite du Quebec a Chicoutimi, Chicoutimi, Que., G7H 2B1 (Canada)]. E-mail: andre_charette@uqac.ca

    2007-03-15

    The Sensitivity Function-based Conjugate Gradient Method (SFCGM) is described. This method is used to solve the inverse problems of function estimation, such as the local maps of absorption and scattering coefficients, as applied to optical tomography for biomedical imaging. A highly scattering, absorbing, non-reflecting, non-emitting medium is considered here and simultaneous reconstructions of absorption and scattering coefficients inside the test medium are achieved with the proposed optimization technique, by using the exit intensity measured at boundary surfaces. The forward problem is solved with a discrete-ordinates finite-difference method on the framework of the frequency-domain full equation of radiative transfer. The modulation frequency is set to 600 MHz and the frequency data, obtained with the source modulation, is used as the input data. The inversion results demonstrate that the SFCGM can retrieve simultaneously the spatial distributions of optical properties inside the medium within a reasonable accuracy, by significantly reducing a cross-talk between inter-parameters. It is also observed that the closer-to-detector objects are better retrieved.

  13. Radiation-induced alterations in murine lymphocyte homing patterns. II. Recovery and function of memory cells in LBN rats

    International Nuclear Information System (INIS)

    Suspensions of lymph node cells from dinitrophenylated bovine gamma globulin (DNP-BGG)-immune LBN F1 hybrid rats (Lewis X Brown Norway) were prepared, irradiated, and injected intravenously into unirradiated syngeneic intermediate hosts and irradiated syngeneic adoptive controls. After allowance of 24 hr for homing to occur, the intermediate hosts were killed and cell preparations from the lymph nodes and spleen were injected intravenously into separate irradiated LBN final host groups. All control and experimental groups were challenged (DNP-BGG saline iv) 24 hr after the injection of the lymphoid cells. Rats were bled on Days 7, 11, and 14 after challenge and the antigen-binding capacity (ABC) of the serum was determined. After correction for the fraction of the total cell population transferred from the intermediate host, the peak ABC of the final hosts was related to the number of memory cells present. It was thus possible to determine the relative distribution of the memory cell population to the spleen and lymph nodes of the intermediate hosts. In the intermediate control animals, irradiated memory cells provided a secondary antibody response which was delayed but not suppressed when compared to unirradiated cells. In intermediate hosts, the homing of lymph node memory cells to the spleen and lymph nodes was significantly reduced by an exposure to 200 R of x radiation

  14. Epidermal transmittance and phenolic composition in leaves of atrazine-tolerant and atrazine-sensitive cultivars of Brassica napus grown under enhanced UV-B radiation

    International Nuclear Information System (INIS)

    Experiments were conducted on the atrazine-tolerant mutant Stallion and the atrazine-sensitive cv. Paroll of Brassica napus L., which were grown under either visible light or with the addition of UV-B radiation (280–320 nm) for 15 days. The mutant has been shown to be sensitive to high levels of visible light as compared to the atrazine-sensitive cultivar and therefore we wished to determine plant response to UV-B radiation with respect to potential pigment changes, certain anatomical features, radiation penetration and partial photosynthesis. With regard to pigment changes, we were particularly interested in whether the compositional shift in flavonol pigments under enhanced UV-B radiation, previously suggested to favour increased antioxidant activity, is confined to the adaxial epidermis, which generally receives most UV-B radiation or whether the pigment shift is also inducible in the abaxial epidermis.As was to be expected, the penetration of UV-B radiation (310 nm) was lower in the UV-B-exposed plants, which was correlated with an increased amount of UV-screening pigments in the adaxial and abaxial epidermal layers. The main flavonoid glycosides showed the largest shift from kaempferol to quercetin as aglycone moiety in the adaxial epidermal layer. However, in the abaxial epidermal layer the hydroxycinnamic acid (HCA) derivatives and kaempferol glycosides were predominant. Penetration of 430 nm light was higher after UV-B exposure, and probably contributed to the fact that photosynthetic efficiency of photosystem II was unchanged or higher after UV-B exposure. UV-B radiation decreased leaf area in the atrazine-tolerant mutant only. Both cultivars showed an increased leaf thickness after UV-B exposure due to cell elongation mainly of the palisade tissue. This was especially evident in the mutant

  15. The fibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor {alpha}-mediated superoxide dismutase induction in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xianguang; An, Zhengzhe; Song, Hye Jin; Kim, Won Dong; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of); Jang, Seong Soon [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Yu, Jae Ran [Konkuk University College of Medicine, Chungju (Korea, Republic of)

    2012-06-15

    The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) {alpha} and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofi brate (FF). Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. In HeLa cells total SOD activity was increased with increasing FF doses up to 30 {mu}M. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPAR{alpha} and PPAR{gamma} were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPAR{alpha} were not increased with FF. However, the mRNA of PPAR{gamma} was increased with FF. FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPAR{alpha}.

  16. Analysis of miRNA and mRNA expression profiles highlights alterations in ionizing radiation response of human lymphocytes under modeled microgravity.

    Directory of Open Access Journals (Sweden)

    Cristina Girardi

    Full Text Available BACKGROUND: Ionizing radiation (IR can be extremely harmful for human cells since an improper DNA-damage response (DDR to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL incubated for 4 and 24 h in normal gravity (1 g and in modeled microgravity (MMG during the repair time after irradiation with 0.2 and 2Gy of γ-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of "Response to DNA damage" is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses. CONCLUSIONS/SIGNIFICANCE: On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL.

  17. Post-factum detection of radiation treatment of meat and fish by means of DNA alterations identified by gas chromatography-mass spectrometry or pulsed-field gel electrophoresis

    International Nuclear Information System (INIS)

    The doctoral thesis explains methods and experiments for post-factum detection of radiation-induced alterations of DNA. There are various manifestations of such alterations. Ionizing radiation can directly alter the bases and/or sugar component, or can indirectly induce DNA damage by way of forming water radicals. Both mechanisms result in base derivatives, released for some part from the DNA strand, or formed by alterations of the 2-deoxyribose, inducing strand breaks ( single and double strand breaks). The first part of the thesis explains the approach applying GC-MS for detection of radiation-induced base derivatives, using herring sperm DNA as a model DNA. Some typical types of base derivatives were identified (thymine glycol, 5-hydroxycytosine).Some base derivatives were also found in DNA samples derived from poultry meat. These base derivatives are known to be indicators of food processing with ionizing radiation, but surprisingly were also found in non-irradiated controls, although in minor amounts. The second part discusses the identification of strand breaks applying the pused-field gel electrophoresis. This method is capable of producing evidence that irradiation markedly enhances the short-chain DNA molecules as compared to non-irradiated controls. DNA molecules of a size of approx. 2.2 million base pairs are almost completely broken into short-chain fragments. The method reliably detects radiation treatments down to 1500 Gy, even if applied long ago. (orig./MG)

  18. Effects of age and liquid holding on the UV-radiation sensitivities of wild-type and mutant Caenorhabditis elegans dauer larvae

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, P.S.

    1984-01-01

    The dauer larva is a facultative developmental stage in the life cycle of the nematode Caenorhabditis elegans. Dauer larvae, which can survive under starvation for over 60 days, resume normal development when feeding is resumed. Wild-type (N2) and 4 radiation-sensitive (rad) mutant dauer larvae were tested for their abilities to develop into adults after UV-irradiation. The rad-3 mutant was over 30 times as sensitive as N2; rad-1, rad-2 and rad-7 mutants were not hypersensitive. Irradiation also delayed development in survivors. Wild-type dauer larvae did not differ in radiation sensitivity from 0 through 50 days of age. There was no liquid holding recovery (LHR); that is, survival did not increase when wild-type dauer larvae were held in buffer after irradiation. (orig.). 28 refs.; 4 figs.

  19. Interactive Soil Dust Aerosol Model in the GISS GCM. Part 1; Sensitivity of the Soil Dust Cycle to Radiative Properties of Soil Dust Aerosols

    Science.gov (United States)

    Perlwitz, Jan; Tegen, Ina; Miller, Ron L.

    2000-01-01

    The sensitivity of the soil dust aerosol cycle to the radiative forcing by soil dust aerosols is studied. Four experiments with the NASA/GISS atmospheric general circulation model, which includes a soil dust aerosol model, are compared, all using a prescribed climatological sea surface temperature as lower boundary condition. In one experiment, dust is included as dynamic tracer only (without interacting with radiation), whereas dust interacts with radiation in the other simulations. Although the single scattering albedo of dust particles is prescribed to be globally uniform in the experiments with radiatively active dust, a different single scattering albedo is used in those experiments to estimate whether regional variations in dust optical properties, corresponding to variations in mineralogical composition among different source regions, are important for the soil dust cycle and the climate state. On a global scale, the radiative forcing by dust generally causes a reduction in the atmospheric dust load corresponding to a decreased dust source flux. That is, there is a negative feedback in the climate system due to the radiative effect of dust. The dust source flux and its changes were analyzed in more detail for the main dust source regions. This analysis shows that the reduction varies both with the season and with the single scattering albedo of the dust particles. By examining the correlation with the surface wind, it was found that the dust emission from the Saharan/Sahelian source region and from the Arabian peninsula, along with the sensitivity of the emission to the single scattering albedo of dust particles, are related to large scale circulation patterns, in particular to the trade winds during Northern Hemisphere winter and to the Indian monsoon circulation during summer. In the other regions, such relations to the large scale circulation were not found. There, the dependence of dust deflation to radiative forcing by dust particles is probably

  20. Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization

    Directory of Open Access Journals (Sweden)

    Wang Min

    2010-09-01

    Full Text Available Abstract Background All antipsychotics work via dopamine D2 receptors (D2Rs, suggesting a critical role for D2Rs in psychosis; however, there is little evidence for a change in receptor number or pharmacological nature of D2Rs. Recent data suggest that D2Rs form dimers in-vitro and in-vivo, and we hypothesized that schizophrenia, as well as preclinical models of schizophrenia, would demonstrate altered dimerization of D2Rs, even though the overall number of D2Rs was unaltered. Methods We measured the expression of D2Rs dimers and monomers in patients with schizophrenia using Western blots, and then in striatal tissue from rats exhibiting the amphetamine-induced sensitized state (AISS. We further examined the interaction between D2Rs and the dopamine transporter (DAT by co-immunoprecipitation, and measured the expression of dopamine D2High receptors with ligand binding assays in rat striatum slices with or without acute amphetamine pre-treatment. Results We observed significantly enhanced expression of D2Rs dimers (277.7 ± 33.6% and decreased expression of D2Rs monomers in post-mortem striatal tissue of schizophrenia patients. We found that amphetamine facilitated D2Rs dimerization in both the striatum of AISS rats and in rat striatal neurons. Furthermore, amphetamine-induced D2Rs dimerization may be associated with the D2R-DAT protein-protein interaction as an interfering peptide that disrupts the D2R-DAT coupling, blocked amphetamine-induced up-regulation of D2Rs dimerization. Conclusions Given the fact that amphetamine induces psychosis and that the AISS rat is a widely accepted animal model of psychosis, our data suggest that D2R dimerization may be important in the pathophysiology of schizophrenia and may be a promising new target for novel antipsychotic drugs.

  1. Altered dark- and photoconversion of phytochrome B mediate extreme light sensitivity and loss of photoreversibility of the phyB-401 mutant.

    Directory of Open Access Journals (Sweden)

    Éva Ádám

    Full Text Available The phyB-401 mutant is 10(3 fold more sensitive to red light than its wild-type analogue and shows loss of photoreversibility of hypocotyl growth inhibition. The phyB-401 photoreceptor displays normal spectral properties and shows almost no da