WorldWideScience

Sample records for biological damage induced

  1. Early mechanisms in radiation-induced biological damage

    International Nuclear Information System (INIS)

    Powers, E.L.

    1983-01-01

    An introduction to the mechanisms of radiation action in biological systems is presented. Several questions about the nature of the radiation damage process are discussed, including recognition of the oxygen effects, dose-response relationships, and the importance of the hydroxyl radical

  2. The yield, processing, and biological consequences of clustered DNA damage induced by ionizing radiation

    International Nuclear Information System (INIS)

    Shikazono, Naoya; Noguchi, Miho; Fujii, Kentaro; Urushibara, Ayumi; Yokoya, Akinari

    2009-01-01

    After living cells are exposed to ionizing radiation, a variety of chemical modifications of DNA are induced either directly by ionization of DNA or indirectly through interactions with water-derived radicals. The DNA lesions include single strand breaks (SSB), base lesions, sugar damage, and apurinic/apyrimidinic sites (AP sites). Clustered DNA damage, which is defined as two or more of such lesions within one to two helical turns of DNA induced by a single radiation track, is considered to be a unique feature of ionizing radiation. A double strand break (DSB) is a type of clustered DNA damage, in which single strand breaks are formed on opposite strands in close proximity. Formation and repair of DSBs have been studied in great detail over the years as they have been linked to important biological endpoints, such as cell death, loss of genetic material, chromosome aberration. Although non-DSB clustered DNA damage has received less attention, there is growing evidence of its biological significance. This review focuses on the current understanding of (1) the yield of non-DSB clustered damage induced by ionizing radiation (2) the processing, and (3) biological consequences of non-DSB clustered DNA damage. (author)

  3. Cellular characterization of compression induced-damage in live biological samples

    Science.gov (United States)

    Bo, Chiara; Balzer, Jens; Hahnel, Mark; Rankin, Sara M.; Brown, Katherine A.; Proud, William G.

    2011-06-01

    Understanding the dysfunctions that high-intensity compression waves induce in human tissues is critical to impact on acute-phase treatments and requires the development of experimental models of traumatic damage in biological samples. In this study we have developed an experimental system to directly assess the impact of dynamic loading conditions on cellular function at the molecular level. Here we present a confinement chamber designed to subject live cell cultures in liquid environment to compression waves in the range of tens of MPa using a split Hopkinson pressure bars system. Recording the loading history and collecting the samples post-impact without external contamination allow the definition of parameters such as pressure and duration of the stimulus that can be related to the cellular damage. The compression experiments are conducted on Mesenchymal Stem Cells from BALB/c mice and the damage analysis are compared to two control groups. Changes in Stem cell viability, phenotype and function are assessed flow cytometry and with in vitro bioassays at two different time points. Identifying the cellular and molecular mechanisms underlying the damage caused by dynamic loading in live biological samples could enable the development of new treatments for traumatic injuries.

  4. Effects of carotenoids on damage of biological lipids induced by gamma irradiation

    International Nuclear Information System (INIS)

    Saito, Takeshi; Fujii, Noriko

    2014-01-01

    Carotenoids are considered to be involved in the radioresistant mechanisms of radioresistant bacteria. In these bacterial cells, carotenoids are present in biological lipids, and therefore may be related to the radiation-induced damage of lipids. However, only limited data are available for the role of carotenoids in such damage. In this study, we irradiated an α-linolenic acid–benzene solution with gamma rays and analyzed the resulting oxidative degradation and peroxidation damage in the presence or absence of two typical carotenoids: β-carotene and astaxanthin. The analyses revealed that oxidative degradation and peroxidation of α-linolenic acid, as evaluated by the amount of malondialdehyde and conjugated diene formed, respectively, increased in a dose-dependent manner. Moreover, 8.5×10 −3 M β-carotene inhibited gamma radiation-induced oxidative degradation of α-linolenic acid, whereas 5.0×10 −5 and 5.0×10 −6 M β-carotene, and 5.0×10 −7 and 5.0×10 −8 M astaxanthin promoted degradation. In contrast, neither β-carotene nor astaxanthin affected peroxidation of α-linolenic acid. These results suggest that an optimum concentration of carotenoids in radioresistant bacteria protects biological lipid structures from radiation-induced damage. - Highlights: • Gamma radiation dose-dependently increases degradation levels of α-linolenic acid. • Gamma radiation dose-dependently increases peroxidation levels of α-linolenic acid. • An optimum concentration of carotenoids inhibits degradation of α-linolenic acid. • Relatively low concentrations of carotenoids promote degradation of α-linolenic acid. • Carotenoids do not affect the peroxidation level of α-linolenic acid

  5. Repair of endogenous and ionizing radiation-induced DNA damages: mechanisms and biological functions

    International Nuclear Information System (INIS)

    Boiteux, S.

    2002-01-01

    The cellular DNA is continuously exposed to endogenous and exogenous stress. Oxidative stress due to cellular metabolism is the major cause of endogenous DNA damage. On the other hand, ionizing radiation (IR) is an important exogenous stress. Both induce similar DNA damages: damaged bases, abasic sites and strand breakage. Most of these lesions are lethal and/or mutagenic. The survival of the cell is managed by efficient and accurate DNA repair mechanisms that remove lesions before their replication or transcription. DNA repair pathways involved in the removal of IR-induced lesions are briefly described. Base excision repair (BER) is mostly involved in the removal of base damage, abasic sites and single strand breaks. In contrast, DNA double strand breaks are mostly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). How DNA repair pathways prevent cancer process is also discussed. (author)

  6. Wavelength dependence of biological damage induced by UV radiation on bacteria.

    Science.gov (United States)

    Santos, Ana L; Oliveira, Vanessa; Baptista, Inês; Henriques, Isabel; Gomes, Newton C M; Almeida, Adelaide; Correia, António; Cunha, Ângela

    2013-01-01

    The biological effects of UV radiation of different wavelengths (UVA, UVB and UVC) were assessed in nine bacterial isolates displaying different UV sensitivities. Biological effects (survival and activity) and molecular markers of oxidative stress [DNA strand breakage (DSB), generation of reactive oxygen species (ROS), oxidative damage to proteins and lipids, and the activity of antioxidant enzymes catalase and superoxide dismutase] were quantified and statistically analyzed in order to identify the major determinants of cell inactivation under the different spectral regions. Survival and activity followed a clear wavelength dependence, being highest under UVA and lowest under UVC. The generation of ROS, as well as protein and lipid oxidation, followed the same pattern. DNA damage (DSB) showed the inverse trend. Multiple stepwise regression analysis revealed that survival under UVA, UVB and UVC wavelengths was best explained by DSB, oxidative damage to lipids, and intracellular ROS levels, respectively.

  7. Development of radiation biological dosimetry and treatment of radiation-induced damaged tissue

    International Nuclear Information System (INIS)

    Cho, Chul Koo; Kim, Tae Hwan; Lee, Yun Sil

    2000-04-01

    Util now, only a few methods have been developed for radiation biological dosimetry such as conventional chromosome aberration and micronucleus in peripheral blood cell. However, because these methods not only can be estimated by the expert, but also have a little limitation due to need high technique and many times in the case of radiation accident, it is very difficult to evaluate the absorbed dose of victims. Therefore, we should develop effective, easy, simple and rapid biodosimetry and its guideline(triage) to be able to be treated the victims as fast as possible. We established the apoptotic fragment assay, PCC, comet assay, and micronucleus assay which was the significant relationship between dose and cell damages to evaluate the irradiated dose as correct and rapid as possible using lymphocytes and crypt cells, and compared with chromosome dosimetry and micronucleus assay

  8. Development of radiation biological dosimetry and treatment of radiation-induced damaged tissue

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Chul Koo; Kim, Tae Hwan; Lee, Yun Sil [and others

    2000-04-01

    Util now, only a few methods have been developed for radiation biological dosimetry such as conventional chromosome aberration and micronucleus in peripheral blood cell. However, because these methods not only can be estimated by the expert, but also have a little limitation due to need high technique and many times in the case of radiation accident, it is very difficult to evaluate the absorbed dose of victims. Therefore, we should develop effective, easy, simple and rapid biodosimetry and its guideline(triage) to be able to be treated the victims as fast as possible. We established the apoptotic fragment assay, PCC, comet assay, and micronucleus assay which was the significant relationship between dose and cell damages to evaluate the irradiated dose as correct and rapid as possible using lymphocytes and crypt cells, and compared with chromosome dosimetry and micronucleus assay.

  9. Protective Effect of Selected Medicinal Plants against Hydrogen Peroxide Induced Oxidative Damage on Biological Substrates

    Directory of Open Access Journals (Sweden)

    Namratha Pai Kotebagilu

    2014-01-01

    Full Text Available Oxidative stress is developed due to susceptibility of biological substrates to oxidation by generation of free radicals. In degenerative diseases, oxidative stress level can be reduced by antioxidants which neutralize free radicals. Primary objective of this work was to screen four medicinal plants, namely, Andrographis paniculata, Costus speciosus, Canthium parviflorum, and Abrus precatorius, for their antioxidant property using two biological substrates—RBC and microsomes. The antioxidative ability of three solvent extracts, methanol (100% and 80% and aqueous leaf extracts, was studied at different concentrations by thiobarbituric acid reactive substances method using Fenton’s reagent to induce oxidation in the substrates. The polyphenol and flavonoid content were analyzed to relate with the observed antioxidant effect of the extracts. The phytochemical screening indicated the presence of flavonoids, polyphenols, tannins, and β-carotene in the samples. In microsomes, 80% methanol extract of Canthium and Costus and, in RBC, 80% methanol extract of Costus showed highest inhibition of oxidation and correlated well with the polyphenol and flavonoid content. From the results it can be concluded that antioxidants from medicinal plants are capable of inhibiting oxidation in biological systems, suggesting scope for their use as nutraceuticals.

  10. Enzymatic recognition of DNA damage induced by UVB-photosensitized titanium dioxide and biological consequences in Saccharomyces cerevisiae: evidence for oxidatively DNA damage generation.

    Science.gov (United States)

    Pinto, A Viviana; Deodato, Elder L; Cardoso, Janine S; Oliveira, Eliza F; Machado, Sérgio L; Toma, Helena K; Leitão, Alvaro C; de Pádula, Marcelo

    2010-06-01

    Although titanium dioxide (TiO(2)) has been considered to be biologically inert, finding use in cosmetics, paints and food colorants, recent reports have demonstrated that when TiO(2) is attained by UVA radiation oxidative genotoxic and cytotoxic effects are observed in living cells. However, data concerning TiO(2)-UVB association is poor, even if UVB radiation represents a major environmental carcinogen. Herein, we investigated DNA damage, repair and mutagenesis induced by TiO(2) associated with UVB irradiation in vitro and in vivo using Saccharomyces cerevisiae model. It was found that TiO(2) plus UVB treatment in plasmid pUC18 generated, in addition to cyclobutane pyrimidine dimers (CPDs), specific damage to guanine residues, such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), which are characteristic oxidatively generated lesions. In vivo experiments showed that, although the presence of TiO(2) protects yeast cells from UVB cytotoxicity, high mutation frequencies are observed in the wild-type (WT) and in an ogg1 strain (deficient in 8-oxoG and FapyG repair). Indeed, after TiO(2) plus UVB treatment, induced mutagenesis was drastically enhanced in ogg1 cells, indicating that mutagenic DNA lesions are repaired by the Ogg1 protein. This effect could be attenuated by the presence of metallic ion chelators: neocuproine or dipyridyl, which partially block oxidatively generated damage occurring via Fenton reactions. Altogether, the results indicate that TiO(2) plus UVB potentates UVB oxidatively generated damage to DNA, possibly via Fenton reactions involving the production of DNA base damage, such as 8-oxo-7,8-dihydroguanine. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Enzymatic recognition of DNA damage induced by UVB-photosensitized titanium dioxide and biological consequences in Saccharomyces cerevisiae: Evidence for oxidatively DNA damage generation

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, A. Viviana, E-mail: alicia.pinto@incqs.fiocruz.br [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil); Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Deodato, Elder L. [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil); Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Cardoso, Janine S. [Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Oliveira, Eliza F.; Machado, Sergio L.; Toma, Helena K. [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil); Leitao, Alvaro C. [Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Padula, Marcelo de [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil)

    2010-06-01

    Although titanium dioxide (TiO{sub 2}) has been considered to be biologically inert, finding use in cosmetics, paints and food colorants, recent reports have demonstrated that when TiO{sub 2} is attained by UVA radiation oxidative genotoxic and cytotoxic effects are observed in living cells. However, data concerning TiO{sub 2}-UVB association is poor, even if UVB radiation represents a major environmental carcinogen. Herein, we investigated DNA damage, repair and mutagenesis induced by TiO{sub 2} associated with UVB irradiation in vitro and in vivo using Saccharomyces cerevisiae model. It was found that TiO{sub 2} plus UVB treatment in plasmid pUC18 generated, in addition to cyclobutane pyrimidine dimers (CPDs), specific damage to guanine residues, such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), which are characteristic oxidatively generated lesions. In vivo experiments showed that, although the presence of TiO{sub 2} protects yeast cells from UVB cytotoxicity, high mutation frequencies are observed in the wild-type (WT) and in an ogg1 strain (deficient in 8-oxoG and FapyG repair). Indeed, after TiO{sub 2} plus UVB treatment, induced mutagenesis was drastically enhanced in ogg1 cells, indicating that mutagenic DNA lesions are repaired by the Ogg1 protein. This effect could be attenuated by the presence of metallic ion chelators: neocuproine or dipyridyl, which partially block oxidatively generated damage occurring via Fenton reactions. Altogether, the results indicate that TiO{sub 2} plus UVB potentates UVB oxidatively generated damage to DNA, possibly via Fenton reactions involving the production of DNA base damage, such as 8-oxo-7,8-dihydroguanine.

  12. Enzymatic recognition of DNA damage induced by UVB-photosensitized titanium dioxide and biological consequences in Saccharomyces cerevisiae: Evidence for oxidatively DNA damage generation

    International Nuclear Information System (INIS)

    Pinto, A. Viviana; Deodato, Elder L.; Cardoso, Janine S.; Oliveira, Eliza F.; Machado, Sergio L.; Toma, Helena K.; Leitao, Alvaro C.; Padula, Marcelo de

    2010-01-01

    Although titanium dioxide (TiO 2 ) has been considered to be biologically inert, finding use in cosmetics, paints and food colorants, recent reports have demonstrated that when TiO 2 is attained by UVA radiation oxidative genotoxic and cytotoxic effects are observed in living cells. However, data concerning TiO 2 -UVB association is poor, even if UVB radiation represents a major environmental carcinogen. Herein, we investigated DNA damage, repair and mutagenesis induced by TiO 2 associated with UVB irradiation in vitro and in vivo using Saccharomyces cerevisiae model. It was found that TiO 2 plus UVB treatment in plasmid pUC18 generated, in addition to cyclobutane pyrimidine dimers (CPDs), specific damage to guanine residues, such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), which are characteristic oxidatively generated lesions. In vivo experiments showed that, although the presence of TiO 2 protects yeast cells from UVB cytotoxicity, high mutation frequencies are observed in the wild-type (WT) and in an ogg1 strain (deficient in 8-oxoG and FapyG repair). Indeed, after TiO 2 plus UVB treatment, induced mutagenesis was drastically enhanced in ogg1 cells, indicating that mutagenic DNA lesions are repaired by the Ogg1 protein. This effect could be attenuated by the presence of metallic ion chelators: neocuproine or dipyridyl, which partially block oxidatively generated damage occurring via Fenton reactions. Altogether, the results indicate that TiO 2 plus UVB potentates UVB oxidatively generated damage to DNA, possibly via Fenton reactions involving the production of DNA base damage, such as 8-oxo-7,8-dihydroguanine.

  13. Laser-induced damage in biological tissue: Role of complex and dynamic optical properties of the medium

    Science.gov (United States)

    Ahmed, Elharith M.

    Since its invention in the early 1960's, the laser has been used as a tool for surgical, therapeutic, and diagnostic purposes. To achieve maximum effectiveness with the greatest margin of safety it is important to understand the mechanisms of light propagation through tissue and how that light affects living cells. Lasers with novel output characteristics for medical and military applications are too often implemented prior to proper evaluation with respect to tissue optical properties and human safety. Therefore, advances in computational models that describe light propagation and the cellular responses to laser exposure, without the use of animal models, are of considerable interest. Here, a physics-based laser-tissue interaction model was developed to predict the spatial and temporal temperature and pressure rise during laser exposure to biological tissues. Our new model also takes into account the dynamic nature of tissue optical properties and their impact on the induced temperature and pressure profiles. The laser-induced retinal damage is attributed to the formation of microbubbles formed around melanosomes in the retinal pigment epithelium (RPE) and the damage mechanism is assumed to be photo-thermal. Selective absorption by melanin creates these bubbles that expand and collapse around melanosomes, destroying cell membranes and killing cells. The Finite Element (FE) approach taken provides suitable ground for modeling localized pigment absorption which leads to a non-uniform temperature distribution within pigmented cells following laser pulse exposure. These hot-spots are sources for localized thermo-elastic stresses which lead to rapid localized expansions that manifest themselves as microbubbles and lead to microcavitations. Model predictions for the interaction of lasers at wavelengths of 193, 694, 532, 590, 1314, 1540, 2000, and 2940 nm with biological tissues were generated and comparisons were made with available experimental data for the retina

  14. Differential biologic effects of CPD and 6-4PP UV-induced DNA damage on the induction of apoptosis and cell-cycle arrest

    International Nuclear Information System (INIS)

    Lo, Hsin-Lung; Nakajima, Satoshi; Ma, Lisa; Walter, Barbara; Yasui, Akira; Ethell, Douglas W; Owen, Laurie B

    2005-01-01

    UV-induced damage can induce apoptosis or trigger DNA repair mechanisms. Minor DNA damage is thought to halt the cell cycle to allow effective repair, while more severe damage can induce an apoptotic program. Of the two major types of UV-induced DNA lesions, it has been reported that repair of CPD, but not 6-4PP, abrogates mutation. To address whether the two major forms of UV-induced DNA damage, can induce differential biological effects, NER-deficient cells containing either CPD photolyase or 6-4 PP photolyase were exposed to UV and examined for alterations in cell cycle and apoptosis. In addition, pTpT, a molecular mimic of CPD was tested in vitro and in vivo for the ability to induce cell death and cell cycle alterations. NER-deficient XPA cells were stably transfected with CPD-photolyase or 6-4PP photolyase to specifically repair only CPD or only 6-4PP. After 300 J/m 2 UVB exposure photoreactivation light (PR, UVA 60 kJ/m 2 ) was provided for photolyase activation and DNA repair. Apoptosis was monitored 24 hours later by flow cytometric analysis of DNA content, using sub-G1 staining to indicate apoptotic cells. To confirm the effects observed with CPD lesions, the molecular mimic of CPD, pTpT, was also tested in vitro and in vivo for its effect on cell cycle and apoptosis. The specific repair of 6-4PP lesions after UVB exposure resulted in a dramatic reduction in apoptosis. These findings suggested that 6-4PP lesions may be the primary inducer of UVB-induced apoptosis. Repair of CPD lesions (despite their relative abundance in the UV-damaged cell) had little effect on the induction of apoptosis. Supporting these findings, the molecular mimic of CPD, (dinucleotide pTpT) could mimic the effects of UVB on cell cycle arrest, but were ineffective to induce apoptosis. The primary response of the cell to UV-induced 6-4PP lesions is to trigger an apoptotic program whereas the response of the cell to CPD lesions appears to principally involve cell cycle arrest. These

  15. Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

    Science.gov (United States)

    Said, T; Dutot, M; Martin, C; Beaudeux, J-L; Boucher, C; Enee, E; Baudouin, C; Warnet, J-M; Rat, P

    2007-03-01

    The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

  16. Neutron induced radiation damage

    International Nuclear Information System (INIS)

    Williams, M.M.R.

    1977-01-01

    We derive a general expression for the number of displaced atoms of type j caused by a primary knock-on of type i. The Kinchin-Pease model is used, but considerably generalised to allow for realistic atomic potentials. Two cases are considered in detail: the single particle problem causing a cascade and the neutron initiated problem which leads to multiple subcascades. Numerical results have been obtained for a variety of scattering laws. An important conclusion is that neutron initiated damage is much more severe than atom-initiated damage and leads to the number of displaced atoms being a factor of (A+1) 2 /4A larger than the single primary knock-on theory predicts. A is the ratio of the atomic mass to the neutron mass. The importance of this result to the theory of neutron sputtering is explained. (orig.) [de

  17. Bowthruster-induced damage

    NARCIS (Netherlands)

    Schokking, L.A.; Janssen, P.C.; Verhagen, H.J.

    2003-01-01

    The stability of stones in propeller-induced jet wash is still difficult to predict. Especially the trend of bowthrusters increasing in size and power in sea going ships (especially ferries) over the last years may be a reason for concern when dealing with the protection of slopes and beds. But also

  18. CEREBRAL CORTEX DAMAGE INDUCED BY ACUTE ORAL ...

    African Journals Online (AJOL)

    2018-02-28

    Feb 28, 2018 ... This study examines alcohol-induced cerebral cortex damage and the association with oxidative ... alcohol has profound effects on the function ... Chronic use of ..... Alcohol induced brain damage and liver damage in young.

  19. A new analysis of radiation-induced cytogenetic damage in human lymphocytes using the PCC technique, and its implications for biological dosimetry and the understanding of cell-cycle-dependent radiosensitivity fluctuations

    International Nuclear Information System (INIS)

    Zannos, A.; Pantelias, G.E.

    1993-01-01

    The objectives of the project are: to develop a sensitive biological dosemeter, based on the analysis of C-banded peripheral blood lymphocyte prematurely condensed chromosomes (PCCs), for the early assessment of radiation injury and the establishment of absorbed dose estimates in accidental overexposures; and to elucidate the mechanisms of radiation action at the molecular, chromosomal and cellular levels by the study of the effects of DNA repair inhibitors on the repair of radiation damage, effects of BrdUrd incorporation on radiation damage, effects of hyperthermia on the induction and repair of radiation-induced damage, and induction and repair of radiation damage in an X-ray sensitive CHO mutant cell line. (authors) 16 refs., 1 fig

  20. UV-induced skin damage

    International Nuclear Information System (INIS)

    Ichihashi, M.; Ueda, M.; Budiyanto, A.; Bito, T.; Oka, M.; Fukunaga, M.; Tsuru, K.; Horikawa, T.

    2003-01-01

    Solar radiation induces acute and chronic reactions in human and animal skin. Chronic repeated exposures are the primary cause of benign and malignant skin tumors, including malignant melanoma. Among types of solar radiation, ultraviolet B (290-320 nm) radiation is highly mutagenic and carcinogenic in animal experiments compared to ultraviolet A (320-400 nm) radiation. Epidemiological studies suggest that solar UV radiation is responsible for skin tumor development via gene mutations and immunosuppression, and possibly for photoaging. In this review, recent understanding of DNA damage caused by direct UV radiation and by indirect stress via reactive oxygen species (ROS) and DNA repair mechanisms, particularly nucleotide excision repair of human cells, are discussed. In addition, mutations induced by solar UV radiation in p53, ras and patched genes of non-melanoma skin cancer cells, and the role of ROS as both a promoter in UV-carcinogenesis and an inducer of UV-apoptosis, are described based primarily on the findings reported during the last decade. Furthermore, the effect of UV on immunological reaction in the skin is discussed. Finally, possible prevention of UV-induced skin cancer by feeding or topical use of antioxidants, such as polyphenols, vitamin C, and vitamin E, is discussed

  1. Radiation-induced damage of membranes

    International Nuclear Information System (INIS)

    Yonei, Shuji

    1977-01-01

    An outline of membranous structure was stated, and radiation-induced damage of membranes were surveyed. By irradiation, permeability of membranes, especially passive transportation mechanism, was damaged, and glycoprotein in the surface layers of cells and the surface layer structures were changed. The intramembranous damage was induced by decrease of electrophoresis of nuclear mambranes and a quantitative change of cytochrome P450 of microsomal membranes of the liver, and peroxidation of membranous lipid and SH substitute damage of membranous protein were mentioned as the mechanism of membranous damage. Recovery of membranous damage depends on radiation dose and temperature, and membranous damage participates largely in proliferation death. (tsunoda, M.)

  2. Laser-induced damage in optical materials

    CERN Document Server

    Ristau, Detlev

    2014-01-01

    Dedicated to users and developers of high-powered systems, Laser-Induced Damage in Optical Materials focuses on the research field of laser-induced damage and explores the significant and steady growth of applications for high-power lasers in the academic, industrial, and military arenas. Written by renowned experts in the field, this book concentrates on the major topics of laser-induced damage in optical materials and most specifically addresses research in laser damage that occurs in the bulk and on the surface or the coating of optical components. It considers key issues in the field of hi

  3. Biologically important radiation damage in DNA

    International Nuclear Information System (INIS)

    Ward, J.F.

    1994-01-01

    Most DNA damage by the hydroxyl radical is confined to the bases, and this base damage represents an important component of locally multiply demanded sites (LMOS). The yields of the major damaged bases have been determined by gas chromatography mass spectrometry. For our propose, it was necessary to convert a known fraction of these damaged bases to strand breaks and then assay these labile sites as the increase in strand break yield over the normally observed level. Three potential agents by which this strategy of conversion of base damage to strand break could be implemented were identified in the original application: 1, Sl nuclease; 2, piperidine; and 3, base damage specific enzymes

  4. Radiation-induced liver damage

    International Nuclear Information System (INIS)

    Marcial, V.A.; Santiago-Delpin, E.A.; Lanaro, A.E.; Castro-Vita, H.; Arroyo, G.; Moscol, J.A.; Gomez, C.; Velazquez, J.; Prado, K.

    1977-01-01

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

  5. Pion-induced damage in silicon detectors

    CERN Document Server

    Bates, S; Glaser, M; Lemeilleur, F; León-Florián, E; Gössling, C; Kaiser, B; Rolf, A; Wunstorf, R; Feick, H; Fretwurst, E; Lindström, G; Moll, Michael; Taylor, G; Chilingarov, A G

    1995-01-01

    The damage induced by pions in silicon detectors is studied for positive and negative pions for fluence up to 10(14)cm-2 and 10(13) cm-2 respectively. Results on the energy dependence of the damage in the region of 65-330 MeV near to the  resonance are presented. The change in detector characteristics such as leakage current, charge collection efficiency and effective impurity concentration including long-term annealing effects have been studied. Comparisons to neutron and proton-induced damage are presented and discussed.

  6. Damage-induced tensile instability

    International Nuclear Information System (INIS)

    Hult, J.

    1975-01-01

    The paper presents a unified description of ductile and brittle rupture phenomena in structural components under tensile loading with particular emphasis on creep rupture. Two structural elements are analyzed in detail: 1) the uniform tensile bar subject to a Heaviside history of tensile force and superimposed such loadings, i.e. staircase histories, and 2) the thinwalled spherical pressure vessel subject to a Heaviside history of internal pressure. For both these structures the conditions for instantaneous as well as delayed rupture are analysed. It is shown that a state of mechanical instability will be reached at a certain load or after a certain time. The cases of purely ductile rupture and purely brittle fracture are identified as two limiting cases of this general instability phenomenon. The Kachanov-Rabotnov damage law implies that a structural component will fail in tension only when it has reached a state of complete damage, i.e. zero load carrying capacity. The extended law predicts failure at an earlier stage of the deterioration process and is therefore more compatible with experimental observation. Further experimental support is offered by predictions for staircase loading histories, both step-up and step-down type. The presented damage theory here predicts strain histories which are in closer agreement with test data than predictions based on other phenomenological theories

  7. Bean grain hysteresis with induced mechanical damage

    Directory of Open Access Journals (Sweden)

    Renata C. Campos

    Full Text Available ABSTRACT This study aimed to evaluate the effect of mechanical damage on the hysteresis of beans with induced mechanical damage under different conditions of temperature and relative humidity. Beans (Phaseolus vulgaris L. harvested manually with 35% water content (w.b. were used. Part of this product was subjected to induced mechanical damage by Stein Breakage Tester and controlled drying (damaged and control sample, for sorption processes. The sorption isotherms of water were analyzed for different temperature conditions: 20, 30, 40 and 50 oC; and relative humidity: 0.3; 0.4; 0.5; 0.7 and 0.9 (decimal. Equilibrium moisture content data were correlated with six mathematical models, and the Modified Oswin model was the one that best fitted to the experimental data. According to the above mentioned isotherms, it was possible to observe the phenomenon of hysteresis of damaged and control samples, and this phenomenon was more pronounced in control ones.

  8. Chemical determination of free radical-induced damage to DNA.

    Science.gov (United States)

    Dizdaroglu, M

    1991-01-01

    Free radical-induced damage to DNA in vivo can result in deleterious biological consequences such as the initiation and promotion of cancer. Chemical characterization and quantitation of such DNA damage is essential for an understanding of its biological consequences and cellular repair. Methodologies incorporating the technique of gas chromatography/mass spectrometry (GC/MS) have been developed in recent years for measurement of free radical-induced DNA damage. The use of GC/MS with selected-ion monitoring (SIM) facilitates unequivocal identification and quantitation of a large number of products of all four DNA bases produced in DNA by reactions with hydroxyl radical, hydrated electron, and H atom. Hydroxyl radical-induced DNA-protein cross-links in mammalian chromatin, and products of the sugar moiety in DNA are also unequivocally identified and quantitated. The sensitivity and selectivity of the GC/MS-SIM technique enables the measurement of DNA base products even in isolated mammalian chromatin without the necessity of first isolating DNA, and despite the presence of histones. Recent results reviewed in this article demonstrate the usefulness of the GC/MS technique for chemical determination of free radical-induced DNA damage in DNA as well as in mammalian chromatin under a vast variety of conditions of free radical production.

  9. Clustered DNA damage induced by proton and heavy ion irradiation

    International Nuclear Information System (INIS)

    Davidkova, M.; Pachnerova Brabcova, K; Stepan, V.; Vysin, L.; Sihver, L.; Incerti, S.

    2014-01-01

    Ionizing radiation induces in DNA strand breaks, damaged bases and modified sugars, which accumulate with increasing density of ionizations in charged particle tracks. Compared to isolated DNA damage sites, the biological toxicity of damage clusters can be for living cells more severe. We investigated the clustered DNA damage induced by protons (30 MeV) and high LET radiation (C 290 MeV/u and Fe 500 MeV/u) in pBR322 plasmid DNA. To distinguish between direct and indirect pathways of radiation damage, the plasmid was irradiated in pure water or in aqueous solution of one of the three scavengers (coumarin-3-carboxylic acid, dimethylsulfoxide, and glycylglycine). The goal of the contribution is the analysis of determined types of DNA damage in dependence on radiation quality and related contribution of direct and indirect radiation effects. The yield of double strand breaks (DSB) induced in the DNA plasmid-scavenger system by heavy ion radiation was found to decrease with increasing scavenging capacity due to reaction with hydroxyl radical, linearly with high correlation coefficients. The yield of non-DSB clusters was found to occur twice as much as the DSB. Their decrease with increasing scavenging capacity had lower linear correlation coefficients. This indicates that the yield of non-DSB clusters depends on more factors, which are likely connected to the chemical properties of individual scavengers. (authors)

  10. From ozone depletion to biological UV damage

    Energy Technology Data Exchange (ETDEWEB)

    Tamm, E; Thomalla, E; Koepke, P [Munich Univ. (Germany). Meteorological Inst.

    1996-12-31

    Based on the ozone data from the Meteorological Observatory Hohenpeissenberg (MOHP: 47.8 deg N, 11.01 deg E) and corresponding mean atmospheric conditions, high resolution UV spectra are calculated with a complex radiation transfer model STAR. Biologically weighted UV spectra are investigated as integrated irradiances (dose rates) for maximum zenith angles and as daily integrals for selected days of the year. Ozone variation and uncertainty of action spectra are investigated

  11. From ozone depletion to biological UV damage

    Energy Technology Data Exchange (ETDEWEB)

    Tamm, E.; Thomalla, E.; Koepke, P. [Munich Univ. (Germany). Meteorological Inst.

    1995-12-31

    Based on the ozone data from the Meteorological Observatory Hohenpeissenberg (MOHP: 47.8 deg N, 11.01 deg E) and corresponding mean atmospheric conditions, high resolution UV spectra are calculated with a complex radiation transfer model STAR. Biologically weighted UV spectra are investigated as integrated irradiances (dose rates) for maximum zenith angles and as daily integrals for selected days of the year. Ozone variation and uncertainty of action spectra are investigated

  12. Modelling of settlement induced building damage

    NARCIS (Netherlands)

    Giardina, G.

    2013-01-01

    This thesis focuses on the modelling of settlement induced damage to masonry buildings. In densely populated areas, the need for new space is nowadays producing a rapid increment of underground excavations. Due to the construction of new metro lines, tunnelling activity in urban areas is growing.

  13. The complexity of DNA damage: relevance to biological consequences

    International Nuclear Information System (INIS)

    Ward, J.F.

    1994-01-01

    Ionizing radiation causes both singly and multiply damaged sites in DNA when the range of radical migration is limited by the presence of hydroxyl radical scavengers (e.g. within cells). Multiply damaged sites are considered to be more biologically relevant because of the challenges they present to cellular repair mechanisms. These sites occur in the form of DNA double-strand breaks (dsb) but also as other multiple damages that can be converted to dsb during attempted repair. The presence of a dsb can lead to loss of base sequence information and/or can permit the two ends of a break to separate and rejoin with the wrong partner. (Multiply damaged sites may also be the biologically relevant type of damage caused by other agents, such as UVA, B and/or C light, and some antitumour antibiotics). The quantitative data available from radiation studies of DNA are shown to support the proposed mechanisms for the production of complex damage in cellular DNA, i.e. via scavengable and non-scavengable mechanisms. The yields of complex damages can in turn be used to support the conclusion that cellular mutations are a consequence of the presence of these damages within a gene. (Author)

  14. Laser-Induced Damage with Femtosecond Pulses

    Science.gov (United States)

    Kafka, Kyle R. P.

    The strong electric fields of focused femtosecond laser pulses lead to non-equilibrium dynamics in materials, which, beyond a threshold intensity, causes laser-induced damage (LID). Such a strongly non-linear and non-perturbative process renders important LID observables like fluence and intensity thresholds and damage morphology (crater) extremely difficult to predict quantitatively. However, femtosecond LID carries a high degree of precision, which has been exploited in various micro/nano-machining and surface engineering applications, such as human eye surgery and super-hydrophobic surfaces. This dissertation presents an array of experimental studies which have measured the damage behavior of various materials under femtosecond irradiation. Precision experiments were performed to produce extreme spatio-temporal confinement of the femtosecond laser-solid damage interaction on monocrystalline Cu, which made possible the first successful direct-benchmarking of LID simulation with realistic damage craters. A technique was developed to produce laser-induced periodic surface structures (LIPSS) in a single pulse (typically a multi-pulse phenomenon), and was used to perform a pump-probe study which revealed asynchronous LIPSS formation on copper. Combined with 1-D calculations, this new experimental result suggests more drastic electron heating than expected. Few-cycle pulses were used to study the LID performance and morphology of commercial ultra-broadband optics, which had not been systematically studied before. With extensive surface analysis, various morphologies were observed, including LIPSS, swelling (blisters), simple craters, and even ring-shaped structures, which varied depending on the coating design, number of pulses, and air/vacuum test environment. Mechanisms leading to these morphologies are discussed, many of which are ultrafast in nature. The applied damage behavior of multi-layer dielectric mirrors was measured and compared between long pulse (150 ps

  15. Parvovirus infection-induced DNA damage response

    Science.gov (United States)

    Luo, Yong; Qiu, Jianming

    2014-01-01

    Parvoviruses are a group of small DNA viruses with ssDNA genomes flanked by two inverted terminal structures. Due to a limited genetic resource they require host cellular factors and sometimes a helper virus for efficient viral replication. Recent studies have shown that parvoviruses interact with the DNA damage machinery, which has a significant impact on the life cycle of the virus as well as the fate of infected cells. In addition, due to special DNA structures of the viral genomes, parvoviruses are useful tools for the study of the molecular mechanisms underlying viral infection-induced DNA damage response (DDR). This review aims to summarize recent advances in parvovirus-induced DDR, with a focus on the diverse DDR pathways triggered by different parvoviruses and the consequences of DDR on the viral life cycle as well as the fate of infected cells. PMID:25429305

  16. Neutron induced permanent damage in Josephson junctions

    International Nuclear Information System (INIS)

    Mueller, G.P.; Rosen, M.

    1982-01-01

    14 MeV neutron induced permanent changes in the critical current density of Josephson junctions due to displacement damage in the junction barrier are estimated using a worst case model and the binary collision simulation code MARLOWE. No likelihood of single event hard upsets is found in this model. It is estimated that a fluence of 10 18 -10 19 neutrons/cm 2 are required to change the critical current density by 5%

  17. Mechanisms of free radical-induced damage to DNA.

    Science.gov (United States)

    Dizdaroglu, Miral; Jaruga, Pawel

    2012-04-01

    Endogenous and exogenous sources cause free radical-induced DNA damage in living organisms by a variety of mechanisms. The highly reactive hydroxyl radical reacts with the heterocyclic DNA bases and the sugar moiety near or at diffusion-controlled rates. Hydrated electron and H atom also add to the heterocyclic bases. These reactions lead to adduct radicals, further reactions of which yield numerous products. These include DNA base and sugar products, single- and double-strand breaks, 8,5'-cyclopurine-2'-deoxynucleosides, tandem lesions, clustered sites and DNA-protein cross-links. Reaction conditions and the presence or absence of oxygen profoundly affect the types and yields of the products. There is mounting evidence for an important role of free radical-induced DNA damage in the etiology of numerous diseases including cancer. Further understanding of mechanisms of free radical-induced DNA damage, and cellular repair and biological consequences of DNA damage products will be of outmost importance for disease prevention and treatment.

  18. The DNA-damage response in human biology and disease

    DEFF Research Database (Denmark)

    Jackson, Stephen P; Bartek, Jiri

    2009-01-01

    , signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management....

  19. Radiation induced genetic damage in Aspergillus nidulans

    International Nuclear Information System (INIS)

    Georgiou, J.T.

    1984-01-01

    The mechanism by which ionizing radiation induces genetic damage in haploid and diploid conidia of Aspergillus nidulans was investigated. Although the linear dose-response curves obtained following low LET irradiation implied a 'single-hit' action of radiation, high LET radiations were much more efficient than low LET radiations, which suggests the involvement of a multiple target system. It was found that the RBE values for non-disjunction and mitotic crossing-over were very different. Unlike mitotic crossing-over, the RBE values for non-disjunction were much greater than for cell killing. This suggests that non-disjunction is a particularly sensitive genetical endpoint that is brought about by damage to a small, probably non-DNA target. Radiosensitisers were used to study whether radiation acts at the level of the DNA or some other cellular component. The sensitisation to electrons and/or X-rays by oxygen, and two nitroimidazoles (metronidazole and misonidazole) was examined for radiation induced non-disjunction, mitotic crossing-over, gene conversion, point mutation and cell killing. It was found that these compounds sensitised the cells considerably more to genetic damage than to cell killing. (author)

  20. Smoke damages of forest from the biologic standpoint

    Energy Technology Data Exchange (ETDEWEB)

    Kisser, J

    1966-01-01

    Biological aspects of smoke damages are reviewed with special regard to forests. Due to the long exposures, smoke is more harmful to forests than to farm plants. Invisible physiological damages due to protoplasm lesions are counteracted by the regenerative effect of certain enzyme systems. Insoluble solid emissions reduce both light and assimilation, while soluble particles may penetrate into the plant or the soil, causing changes in the vegetation. Damage caused by soot and photochemical smog are detailed. Sulfur dioxide and hydrofluoric acid are two basic gaseous pollutants damaging forests. The importance of the damage is primarily determined by concentration and duration of exposure, with emphasis on concentration. In high concentrations, the substances are dissolved in the mesophyll cell wall fluid, causing point-like necroses. Low concentrations lead to necroses on the ends and edges of leaves and needles. The damages are also influenced by climatic factors. The transpiration and consequently the sensitivity for SO/sub 2/ are dependent of the relative humidity. Sharp increase in sensitivity can be observed from 60% to 90% relative humidity. There is no direct connection between transpiration rate and assimilation performance. High transpiration coefficients are characteristic of dry climates. There is no relation between transpiration and sensitivity, while any factor affecting the cuticular openings influences the extent of the damage. The resistance to smoke cannot be improved in forests by means of fertilizers. Different resistances of various species as well as problems of breeding smoke-resistant species are discussed.

  1. Genetic Damage Induced by Accidental Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Beatriz Pérez-Cadahía

    2006-01-01

    Full Text Available Petroleum is one of the main energy sources worldwide. Its transport is performed by big tankers following some established marine routes. In the last 50 years a total amount of 37 oil tankers have given rise to great spills in different parts of the world, Prestige being the last one. After the accident, a big human mobilisation took place in order to clean beaches, rocks and fauna, trying to reduce the environmental consequences of this serious catastrophe. These people were exposed to the complex mixture of compounds contained in the oil. This study aimed at determine the level of environmental exposure to volatile organic compounds (VOC, and the possible damage induced on the population involved in the different cleaning tasks by applying the genotoxicity tests sister chromatid exchanges (SCE, micronucleus (MN test, and comet assay. Four groups of individuals were included: volunteers (V, hired manual workers (MW, hired high-pressure cleaner workers (HPW and controls. The higher VOC levels were associated with V environment, followed by MW and lastly by HPW, probably due to the use of high-pressure cleaners. Oil exposure during the cleaning tasks has caused an increase in the genotoxic damage in individuals, the comet assay being the most sensitive biomarker to detect it. Sex, age and tobacco consumption have shown to influence the level of genetic damage, while the effect of using protective devices was less noticeable than expected, perhaps because the kind used was not the most adequate.

  2. Pathology of radiation induced lung damage

    International Nuclear Information System (INIS)

    Kawabata, Yoshinori; Murata, Yoshihiko; Ogata, Hideo; Katagiri, Shiro; Sugita, Hironobu; Iwai, Kazuo; Sakurai, Isamu.

    1985-01-01

    We examined pathological findings of radiation induced lung damage. Twenty-three cases are chosen from our hospital autopsy cases for 9 years, which fulfil strict criteria of radiation lung damage. Lung damage could be classified into 3 groups : 1) interstitial pneumonia type (9 cases), 2) intermediate pneumonia type (8 cases), and 3) alveolar pneumonia type (6 cases), according to the degree of intra-luminal exudation. These classification is well correlated with clinical findings. Pathological alveolar pneumonia type corresponds to symptomatic, radiologic ground glass pneumonic shadow. And pathologic interstitial type corresponds to clinical asymptomatic, radiologic reticulo-nodular shadow. From the clinico-pathological view point these classification is reasonable one. Radiation affects many lung structures and showed characteristic feature of repair. Elastofibrosis of the alveolar wall is observed in every cases, obstructive bronchiolitis are observed in 5 cases, and obstructive bronchiolitis in 9 cases. They are remarkable additional findings. Thickening of the interlobular septum, broncho-vascular connective tissue, and pleural layer are observed in every cases together with vascular lesions. (author)

  3. Modeling of Corrosion-induced Concrete Damage

    DEFF Research Database (Denmark)

    Thybo, Anna Emilie A.; Michel, Alexander; Stang, Henrik

    2013-01-01

    In the present paper a finite element model is introduced to simulate corrosion-induced damage in concrete. The model takes into account the penetration of corrosion products into the concrete as well as non-uniform formation of corrosion products around the reinforcement. To ac-count for the non...... of corrosion products affects both the time-to cover cracking and the crack width at the concrete surface.......In the present paper a finite element model is introduced to simulate corrosion-induced damage in concrete. The model takes into account the penetration of corrosion products into the concrete as well as non-uniform formation of corrosion products around the reinforcement. To ac-count for the non......-uniform formation of corrosion products at the concrete/reinforcement interface, a deterministic approach is used. The model gives good estimates of both deformations in the con-crete/reinforcement interface and crack width when compared to experimental data. Further, it is shown that non-uniform deposition...

  4. DNA damages induced by Ar F laser

    Energy Technology Data Exchange (ETDEWEB)

    Chapel, C.; Rose, S.; Chevrier, L.; Cordier, E.; Courant, D. [CEA Fontenay-aux-Roses, 92 (France). Dept. de Radiobiologie et de Radiopathologie

    2006-07-01

    The photo ablation process used in corneal refractive surgery by the Argon Fluoride (Ar F) laser emitting in ultraviolet C at 193 nm, exposes viable cells round the irradiated zone to sub ablative doses (< 400 joules.m -2). Despite that DNA absorption is higher at 193 nm than 254 nm, cytotoxicity of 193 nm laser radiation is lower than radiation emitted by 254 nm UV-C lamps. In situ, DNA could be protected of laser radiation by cellular components. Consequently, some authors consider that this radiation does not induce genotoxic effect whereas others suspect it to be mutagenic. These lasers are used for fifteen years but many questions remain concerning the long term effects on adjacent cells to irradiated area. The purpose of this study is to describe the effect of 193 nm laser radiation on DNA of stromal keratocytes which are responsible of the corneal structure. The 193 nm laser irradiation induces directly DNA breakage in keratocytes as it has been shown by the comet assay under alkaline conditions. Two hours post irradiation, damages caused by the highest exposure (150 J.m-2) are not repaired as it has been measured with the Olive Tail Moment (product of tail length and tail DNA content). They give partly evidence of induction of an apoptotic process in cells where DNA could be too damaged. In order to characterize specifically double strand breaks, a comparative analysis by immunofluorescence of the H2 Ax histone phosphorylation (H2 Ax) has been performed on irradiated keratocytes and unirradiated keratocytes. Results show a dose dependent increase of the number of H2 Ax positive cells. Consequences of unrepaired DNA lesions could be observed by the generation of micronuclei in cells. Results show again an increase of micronuclei in laser irradiated cells. Chromosomal aberrations have been pointed out by cytogenetic methods 30 mn after irradiation. These aberrations are dose dependent (from 10 to 150 J.m-2). The number of breakage decreases in the long run

  5. Carcinogen-induced damage to DNA

    International Nuclear Information System (INIS)

    Strauss, B.; Altamirano, M.; Bose, K.; Sklar, R.; Tatsumi, K.

    1979-01-01

    Human cells respond to carcinogen-induced damage in their DNA in at least two ways. The first response, excision repair, proceeds by at least three variations, depending on the nature of the damage. Nucleotide excision results in relatively large repair patches but few free DNA breaks, since the endonuclease step is limiting. Apurinic repair is characterized by the appearance of numerous breaks in the DNA and by short repair patches. The pathways behave as though they function independently. Lymphoic cells derived from a xeroderma pigmentosum complementation group C patient are deficient in their ability to perform nucleotide excision and also to excise 6 methoxyguanine adducts, but they are apurinic repair competent. Organisms may bypass damage in their DNA. Lymphoblastoid cells, including those derived from xeroderma pigmentosum treated with 3 H-anti-BPDE, can replicate their DNA at low doses of carcinogen. Unexcised 3 H is found in the light or parental strand of the resulting hybrid DNA when replication occurs in medium with BrdUrd. This observation indicates a bypass reaction occurring by a mechanism involving branch migration at DNA growing points. Branch migration in DNA preparations have been observed, but the evidence is that most occurs in BrdUrd-containing DNA during cell lysis. The measurement of the bifilarly substituted DNA resulting from branch migration is a convenient method of estimating the proportion of new synthesis remaining in the vicinity of the DNA growing point. Treatment with carcinogens or caffeine results in accumulation of DNA growing points accompanied by the synthesis of shortened pieces of daughter DNA

  6. The AID-induced DNA damage response in chromatin

    DEFF Research Database (Denmark)

    Daniel, Jeremy A; Nussenzweig, André

    2013-01-01

    Chemical modifications to the DNA and histone protein components of chromatin can modulate gene expression and genome stability. Understanding the physiological impact of changes in chromatin structure remains an important question in biology. As one example, in order to generate antibody diversity...... with somatic hypermutation and class switch recombination, chromatin must be made accessible for activation-induced cytidine deaminase (AID)-mediated deamination of cytosines in DNA. These lesions are recognized and removed by various DNA repair pathways but, if not handled properly, can lead to formation...... of oncogenic chromosomal translocations. In this review, we focus the discussion on how chromatin-modifying activities and -binding proteins contribute to the native chromatin environment in which AID-induced DNA damage is targeted and repaired. Outstanding questions remain regarding the direct roles...

  7. Biological rhythms for rehabilitation of radiation damage of population

    International Nuclear Information System (INIS)

    Goncharova, T.G.; Vasil'eva, G.S.; Efimov, M.L.

    1999-01-01

    Considerable disturbances in biological eurhythmycal structure of redoracu were discovered for people living in Borodulikha area of the Semipalatinsk test site. The deep desynchronise may result in a development of the cardiovascular, bronco-pulmonary, endocrine, oncologic, neuro psychic diseases. A method to correct the biological eurhythmycal structure was developed. Homeopathic doses of melatonin ('rhythm driver' managing the most regenerating and immune systems) and uthynol (promoting production of dehydroepiandrosterone of maternal prehormone of 27 hormones) were used to provide the general correction. The endocrine diseases are not practically subjected to the homeopathic correction. The sub correction was sometimes carried out after 5 months. The developed methods of rehabilitation of the radiation damages are unique, since they allow performing the homeopathic correction using the acupuncture monitoring

  8. Current study on ionizing radiation-induced mitochondial DNA damage and mutations

    International Nuclear Information System (INIS)

    Zhou Xin; Wang Zhenhua; Zhang Hong

    2012-01-01

    Current advance in ionizing radiation-induced mitochondrial DNA damage and mutations is reviewed, in addition with the essential differences between mtDNA and nDNA damage and mutations. To extent the knowledge about radiation induced mitochondrial alterations, the researchers in Institute of Modern Physics, Chinese Academy of Sciences developed some technics such as real-time PCR, long-PCR for accurate quantification of radiation induced damage and mutations, and in-depth investigation about the functional changes of mitochondria based on mtDNA damage and mutations were also carried out. In conclusion, the important role of mitochondrial study in radiation biology is underlined, and further study on mitochondrial study associated with late effect and metabolism changes in radiation biology is pointed out. (authors)

  9. Potential biological indicators of multi-organ damage: Application to radiation accident victims

    International Nuclear Information System (INIS)

    Bertho, J.M.; Souidi, M.; Gourmelon, P.

    2009-01-01

    Accidental irradiations induce a complex pathological situation, difficult to assess and to treat. However, recent results describing new biological indicators of radiation-induced damages such as Flt3-ligand, citrulline and oxy-sterol concentration in the plasma, together with results obtained in large animal models of high dose irradiation, allowed a better understanding of pathophysiological mechanisms induced by uncontrolled irradiations. This conducted to leave the classical paradigm of the acute radiation syndrome, described as the association of three individual syndromes, the hematopoietic syndrome, the gastro-intestinal syndrome and the cerebrovascular syndrome, in favour of a multiple organ dysfunction syndrome, with the implication of other organs and systems. Follow-up of victims from two recent radiation accidents brings a confirmation of the usefulness of the newly described biological indicators, and also a partial confirmation of this new concept of a multiple organ dysfunction syndrome. (authors)

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

    International Nuclear Information System (INIS)

    Feinendegen, L.E.

    2005-01-01

    Absorption of ionizing radiation in biological tissue stochastically interacts with constituent atoms and molecules and always generates energy deposition (track) events accompanied by bursts of reactive oxygen species (ROS). These ROS are quite similar to those ROS that arise abundantly and constantly by normal oxidative metabolism. ROS effects from either source need attention when assessing radiation-induced alterations in biological structure and function. Endogenous ROS alone induce about 10 6 DNA oxyadducts per cell per day compared to about 5x10 -3 total DNA damage per average cell per day from background radiation exposure (1 mGy per year). At this background level, the corresponding ratio of probabilities of endogenous versus radiogenic DNA double strand breaks (DSBs) per cell per day is about 103 with some 25-40 % of low-LET caused radiogenic DNA-DSBs being of the multi-damage-site type. Radiogenic DNA damage increases in proportion to absorbed dose over a certain dose range. By evolution, tissues possess physiological mechanisms of protection against an array of potentially toxic agents, externally from the environment and endogenously from metabolism, mainly against the abundantly and constantly produced ROS. Ad hoc protection operates at a level that is genetically determined. Following small to moderate perturbation of cell-tissue homeostasis by a toxic impact, adaptive responses develop with a delay and may last from hours to weeks, even months, and aim at protecting the system against renewed insults. Protective responses encompass defense by scavenging mechanisms, DNA repair, damage removal largely by apoptosis and immune responses, as well as changes in cell proliferation. Acute low-dose irradiation below about 0.2 Gy can not only disturb cell-tissue homeostasis but also initiate adaptived protection that appears with a delay of hours and may last from less than a day to months. The balance between damage production and adaptive protection favors

  11. Renal tissue damage induced by focused shock waves

    Science.gov (United States)

    Ioritani, N.; Kuwahara, M.; Kambe, K.; Taguchi, K.; Saitoh, T.; Shirai, S.; Orikasa, S.; Takayama, K.; Lush, P. A.

    1990-07-01

    Biological evidence of renal arterial wall damage induced by the microjet due to shock wave-cavitation bubble interaction was demonstrated in living dog kidneys. We also intended to clarify the mechanism of renal tissue damage and the effects of different conditions of shock wave exposure (peak pressure of focused area, number of shots, exposure rate) on the renal tissue damage in comparison to stone disintegration. Disruption of arterial wall was the most remarkable histological change in the focused area of the kidneys. This lesion appeared as if the wall had been punctured by a needle. Large hematoma formation in the renal parenchym, and interstitial hemorrhage seemed to be the results of the arterial lesion. This arterial disorder also led to ischemic necrosis of the tubules surrounding the hematoma. Micro-angiographic examination of extracted kidneys also proved such arterial puncture lesions and ischemic lesions. The number of shots required for model stone disintegration was not inversely proportional to peak pressure. It decreased markedly when peak pressure was above 700 bar. Similarly thenumber of shots for hematoma formation was not inversely proportional to peak pressure, however, this decreased markedly above 500 bar. These results suggested that a hematoma could be formed under a lower peak pressure than that required for stone disintegration.

  12. Damage detection in high-rise buildings using damage-induced rotations

    International Nuclear Information System (INIS)

    Sung, Seung Hun; Jung, Ho Youn; Lee, Jung Hoon; Jung, Hyung Jo

    2016-01-01

    In this paper, a new damage-detection method based on structural vibration is proposed. The essence of the proposed method is the detection of abrupt changes in rotation. Damage-induced rotation (DIR), which is determined from the modal flexibility of the structure, initially occurs only at a specific damaged location. Therefore, damage can be localized by evaluating abrupt changes in rotation. We conducted numerical simulations of two damage scenarios using a 10-story cantilever-type building model. Measurement noise was also considered in the simulation. We compared the sensitivity of the proposed method to localize damage to that of two conventional modal-flexibility-based damage-detection methods, i.e., uniform load surface (ULS) and ULS curvature. The proposed method was able to localize damage in both damage scenarios for cantilever structures, but the conventional methods could not

  13. Damage detection in high-rise buildings using damage-induced rotations

    International Nuclear Information System (INIS)

    Sung, Seung Hoon; Jung, Ho Youn; Lee, Jung Hoon; Jung, Hyung Jo

    2014-01-01

    In this paper, a new damage-detection method based on structural vibration is proposed. The essence of the proposed method is the detection of abrupt changes in rotation. Damage-induced rotation (DIR), which is determined from the modal flexibility of the structure, initially occurs only at a specific damaged location. Therefore, damage can be localized by evaluating abrupt changes in rotation. We conducted numerical simulations of two damage scenarios using a 10-story cantilever-type building model. Measurement noise was also considered in the simulation. We compared the sensitivity of the proposed method to localize damage to that of two conventional modal-flexibility-based damage-detection methods, i.e., uniform load surface (ULS) and ULS curvature. The proposed method was able to localize damage in both damage scenarios for cantilever structures, but the conventional methods could not.

  14. Visualization of DNA clustered damage induced by heavy ion exposure

    International Nuclear Information System (INIS)

    Tomita, M.; Yatagai, F.

    2003-01-01

    Full text: DNA double-strand breaks (DSBs) are the most lethal damage induced by ionizing radiations. Accelerated heavy-ions have been shown to induce DNA clustered damage, which is two or more DNA lesions induced within a few helical turns. Higher biological effectiveness of heavy-ions could be provided predominantly by induction of complex DNA clustered damage, which leads to non-repairable DSBs. DNA-dependent protein kinase (DNA-PK) is composed of catalytic subunit (DNA-PKcs) and DNA-binding heterodimer (Ku70 and Ku86). DNA-PK acts as a sensor of DSB during non-homologous end-joining (NHEJ), since DNA-PK is activated to bind to the ends of double-stranded DNA. On the other hand, NBS1 and histone H2AX are essential for DSB repair by homologous recombination (HR) in higher vertebrate cells. Here we report that phosphorylated H2AX at Ser139 (named γ-H2AX) and NBS1 form large undissolvable foci after exposure to accelerated Fe ions, while DNA-PKcs does not recognize DNA clustered damage. NBS1 and γ-H2AX colocalized with forming discrete foci after exposure to X-rays. At 0.5 h after Fe ion irradiation, NBS1 and γ-H2AX also formed discrete foci. However, at 3-8 h after Fe ion irradiation, highly localized large foci turned up, while small discrete foci disappeared. Large NBS1 and γ-H2AX foci were remained even 16 h after irradiation. DNA-PKcs recognized Ku-binding DSB and formed foci shortly after exposure to X-rays. DNA-PKcs foci were observed 0.5 h after 5 Gy of Fe ion irradiation and were almost completely disappeared up to 8 h. These results suggest that NBS1 and γ-H2AX can be utilized as molecular marker of DNA clustered damage, while DNA-PK selectively recognizes repairable DSBs by NHEJ

  15. WE-DE-202-03: Modeling of Biological Processes - What Happens After Early Molecular Damage?

    International Nuclear Information System (INIS)

    McMahon, S.

    2016-01-01

    Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological

  16. WE-DE-202-03: Modeling of Biological Processes - What Happens After Early Molecular Damage?

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, S. [Massachusetts General Hospital and Harvard Medical School (United States)

    2016-06-15

    Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological

  17. Blood-induced joint damage: novel targets for therapy

    NARCIS (Netherlands)

    van Meegeren, M.E.R.

    2012-01-01

    -induced joint damage can occur due to a trauma but also during surgery when blood leaks into the joint cavity. Besides that, it is one of the major causes of morbidity amongst haemophilia patients. The aims of this thesis were to further unravel the pathogenesis of blood-induced joint damage and to

  18. Cellular Responses to Cisplatin-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Alakananda Basu

    2010-01-01

    Full Text Available Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It is generally considered as a cytotoxic drug which kills cancer cells by damaging DNA and inhibiting DNA synthesis. How cells respond to cisplatin-induced DNA damage plays a critical role in deciding cisplatin sensitivity. Cisplatin-induced DNA damage activates various signaling pathways to prevent or promote cell death. This paper summarizes our current understandings regarding the mechanisms by which cisplatin induces cell death and the bases of cisplatin resistance. We have discussed various steps, including the entry of cisplatin inside cells, DNA repair, drug detoxification, DNA damage response, and regulation of cisplatin-induced apoptosis by protein kinases. An understanding of how various signaling pathways regulate cisplatin-induced cell death should aid in the development of more effective therapeutic strategies for the treatment of cancer.

  19. UVBR-induced DNA damage in natural marine picoplankton assemblages in the tropical Atlantic Ocean

    NARCIS (Netherlands)

    Boelen, P; de Boer, MK; Kraay, GW; Veldhuis, MJW; Buma, AGJ

    2000-01-01

    UVBR (ultraviolet-B radiation: 280 to 315 nm)-induced DNA damage, measured as cyclobutane pyrimidine dimers (CPDs), was determined in size fractions of natural populations of bacterio- and phytoplankton collected in marine tropical waters. Mean biologically effective UVBR doses in the wind-mixed

  20. Damage-induced nonassociated inelastic flow in rock salt

    International Nuclear Information System (INIS)

    Chan, K.S.; Bodner, S.R.; Brodsky, N.S.; Fossum, A.F.; Munson, D.E.

    1993-01-01

    The multi-mechanism deformation coupled fracture model recently developed by CHAN, et al. (1992), for describing time-dependent, pressure-sensitive inelastic flow and damage evolution in crystalline solids was evaluated against triaxial creep experiments on rock salt. Guided by experimental observations, the kinetic equation and the flow law for damage-induced inelastic flow in the model were modified to account for the development of damage and inelastic dilatation in the transient creep regime. The revised model was then utilized to obtain the creep response and damage evolution in rock salt as a function of confining pressure and stress difference. Comparison between model calculation and experiment revealed that damage-induced inelastic flow is nonassociated, dilatational, and contributes significantly to the macroscopic strain rate observed in rock salt deformed at low confining pressures. The inelastic strain rate and volumetric strain due to damage decrease with increasing confining pressures, and all are suppressed at sufficiently high confining pressures

  1. Delayed chromosomal instability induced by DNA damage

    International Nuclear Information System (INIS)

    Morgan, W.F.; Marder, B.A.; Day, J.P.

    1994-01-01

    Cellular exposure to DNA damaging agents rapidly results in a dose dependent increase in chromosomal breakage and gross structural chromosomal rearrangements. Over recent years, evidence has been accumulating indicating genomic instability can manifest multiple generations after cellular exposure to physical and chemical DNA damaging agents. Genomic instability manifests in the progeny of surviving cells, and has been implicated in mutation, gene application, cellular transformation, and cell killing. To investigate chromosome instability following DNA damage, we have used fluorescence in situ hybridization to detect chromosomal rearrangements in a human/hamster somatic hybrid cell line following exposure to ionizing radiation. Delayed chromosomal instability was detected when multiple populations of uniquely arranged metaphases were observed in clonal isolates raised from single cells surviving X-irradiation many generations after exposure. At higher radiation doses, chromosomal instability was observed in a relatively high frequency of surviving clones and, in general, those clones showed delayed chromosome instability also showed reduced survival as measured by colony forming ability

  2. DNA damage induced by radionuclide internal irradiation

    International Nuclear Information System (INIS)

    Cui Fengmei; Zhao Jingyong; Hong Chengjiao; Lao Qinhua; Wang Liuyi; Yang Shuqin

    2004-01-01

    Objective: To study the DNA damage of peripheral blood mononuclear cell (PBMC) in rats exposed to radionuclide internal irradiation. Methods: The radionuclides were injected into the rats and single cell get electrophoresis (SCGE) was performed to detect the length of DNA migration in the rat PBMC. Results: DNA migration in the rat PBMC increased with accumulative dose or dose-rate. It showed good relationship of dose vs. response and of dose-rate vs. response, both relationship could be described as linear models. Conclusion: Radionuclide internal irradiation could cause DNA damage in rat PBMC. (authors)

  3. Preventing Ultraviolet Light-Induced Damage: The Benefits of Antioxidants

    Science.gov (United States)

    Yip, Cheng-Wai

    2007-01-01

    Extracts of fruit peels contain antioxidants that protect the bacterium "Escherichia coli" against damage induced by ultraviolet light. Antioxidants neutralise free radicals, thus preventing oxidative damage to cells and deoxyribonucleic acid. A high survival rate of UV-exposed cells was observed when grapefruit or grape peel extract was…

  4. Laser induced damage threshold on metallic surfaces during laser cleaning

    CSIR Research Space (South Africa)

    Labuschagne, K

    2005-07-01

    Full Text Available laser paint removal. Laser induced damage on 316L stainless steel was studied, with the target subjected to single and multiple pulse irradiations using a Q-switched Nd:YAG, with fluences between 0.15 and 11.8 J/cm2. Several different damage morphologies...

  5. Simulation study of radiation damage induced by energetic helium nuclei

    International Nuclear Information System (INIS)

    Hoang Dac Luc; Vo Tuong Hanh; Hoang Dac Dat

    2003-01-01

    High energy alpha particles produced by neutron-induced nuclear reactions can damage severely reactor materials. Simulation of this process is described using theoretical calculation and ion irradiation experiments at different displacement doses and Helium doses. (author)

  6. Density of oxidation-induced stacking faults in damaged silicon

    NARCIS (Netherlands)

    Kuper, F.G.; Hosson, J.Th.M. De; Verwey, J.F.

    1986-01-01

    A model for the relation between density and length of oxidation-induced stacking faults on damaged silicon surfaces is proposed, based on interactions of stacking faults with dislocations and neighboring stacking faults. The model agrees with experiments.

  7. Simulation study of radiation damage induced by energetic helium nuclei

    CERN Document Server

    Hoang Dac Luc; Hoang Dac Dat

    2003-01-01

    High energy alpha particles produced by neutron-induced nuclear reactions can damage severely reactor materials. Simulation of this process is described using theoretical calculation and ion irradiation experiments at different displacement doses and Helium doses.

  8. Quercitrin protects skin from UVB-induced oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Yuanqin [Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Yao, Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J. [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY (United States); Gao, Ning [Department of Pharmacognos, College of Pharmacy, 3rd Military Medical University, Chongqing (China); Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States)

    2013-06-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

  9. Quercitrin protects skin from UVB-induced oxidative damage

    International Nuclear Information System (INIS)

    Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J.; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

    2013-01-01

    Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries

  10. Elastoplastic simulation coupled to the induced anisotropic damage for argilites

    International Nuclear Information System (INIS)

    Chiarelli, A.S.; Shao, J.F.

    2002-01-01

    A constitutive model coupling plastic deformation and induced damage is proposed to describe the mechanical behaviour of a shale rock, the argilites of East. The plastic behaviour is produced by a typical cohesive-frictional model. The material damage is represented by a second rank symmetric tensor. The damage criterion and evolution rate is related to tensile strains. The damage effect on plastic flow is also considered by an anisotropic transformation. The model formulation and a simple procedure for the determination of model parameters from standards tests is proposed. The validity of the model is checked against experimental data in various loading conditions. (author)

  11. Photoexcited riboflavin induces oxidative damage to human serum albumin

    Science.gov (United States)

    Hirakawa, Kazutaka; Yoshioka, Takuto

    2015-08-01

    Photoexcited riboflavin induced damage of human serum albumin (HSA), a water soluble protein, resulting in the diminishment of fluorescence from the tryptophan residue. Because riboflavin hardly photosensitized singlet oxygen generation and sodium azide, a singlet oxygen quencher, did not inhibit protein damage, electron transfer-mediated oxidation of HSA was speculated. Fluorescence lifetime of riboflavin was not affected by HSA, suggesting that the excited triplet state of riboflavin is responsible for protein damage through electron transfer. In addition, the preventive effect of xanthone derivatives, triplet quenchers, on photosensitized protein damage could be evaluated using this photosensitized reaction system of riboflavin and HSA.

  12. Laser Induced Damage in Optical Materials: 1980.

    Science.gov (United States)

    1981-10-01

    conference organization. As many of you have experienced, the printed proceedings of these Laser Damage Symposia in our personal libraries are...responsible person or agency. I look forward to our continued relationship. Finally, let me thank the organizers of this Symposium. They have done a...the professional operation of the Symposium and Ms. Susie Rivera and Ms. Sheila Aaker for their part in the preparation and publication of the

  13. Modelling low velocity impact induced damage in composite laminates

    Science.gov (United States)

    Shi, Yu; Soutis, Constantinos

    2017-12-01

    The paper presents recent progress on modelling low velocity impact induced damage in fibre reinforced composite laminates. It is important to understand the mechanisms of barely visible impact damage (BVID) and how it affects structural performance. To reduce labour intensive testing, the development of finite element (FE) techniques for simulating impact damage becomes essential and recent effort by the composites research community is reviewed in this work. The FE predicted damage initiation and propagation can be validated by Non Destructive Techniques (NDT) that gives confidence to the developed numerical damage models. A reliable damage simulation can assist the design process to optimise laminate configurations, reduce weight and improve performance of components and structures used in aircraft construction.

  14. Effects of Ionizing Radiation on Biological Molecules—Mechanisms of Damage and Emerging Methods of Detection

    Science.gov (United States)

    Reisz, Julie A.; Bansal, Nidhi; Qian, Jiang; Zhao, Weiling

    2014-01-01

    Abstract Significance: The detrimental effects of ionizing radiation (IR) involve a highly orchestrated series of events that are amplified by endogenous signaling and culminating in oxidative damage to DNA, lipids, proteins, and many metabolites. Despite the global impact of IR, the molecular mechanisms underlying tissue damage reveal that many biomolecules are chemoselectively modified by IR. Recent Advances: The development of high-throughput “omics” technologies for mapping DNA and protein modifications have revolutionized the study of IR effects on biological systems. Studies in cells, tissues, and biological fluids are used to identify molecular features or biomarkers of IR exposure and response and the molecular mechanisms that regulate their expression or synthesis. Critical Issues: In this review, chemical mechanisms are described for IR-induced modifications of biomolecules along with methods for their detection. Included with the detection methods are crucial experimental considerations and caveats for their use. Additional factors critical to the cellular response to radiation, including alterations in protein expression, metabolomics, and epigenetic factors, are also discussed. Future Directions: Throughout the review, the synergy of combined “omics” technologies such as genomics and epigenomics, proteomics, and metabolomics is highlighted. These are anticipated to lead to new hypotheses to understand IR effects on biological systems and improve IR-based therapies. Antioxid. Redox Signal. 21: 260–292. PMID:24382094

  15. Hypochlorite-induced damage to nucleosides

    DEFF Research Database (Denmark)

    Hawkins, C L; Davies, Michael Jonathan

    2001-01-01

    HOCl damage to DNA bases. We show that reaction of HOCl with the exocyclic -NH(2) groups of cytidine, adenosine, and guanosine, and the ring NH groups of all bases, yields chloramines (RNHCl/RR'NCl). These are the major initial products. Chloramine decay can be accelerated by UV light and metal ions...... for radical formation is cytidine > adenosine = guanosine > uridine = thymidine. These data are inconsistent with the selectivity of HOCl attack and the stability of the resulting chloramines, but can be rationalized if chlorine transfer between bases is rapid and yields the most stable chloramine...

  16. Ion-induced damage and amorphization in Si

    International Nuclear Information System (INIS)

    Holland, O.W.; White, C.W.

    1990-01-01

    Ion-induced damage growth in high-energy, self-ion irradiated Si was studied using electron microscopy and Rutherford backscattering spectroscopy. The results show that there is a marked variation in the rate of damage growth, as well as the damage morphology, along the path of the ion. Near the ion end-of-range (eor), damage increases monotonically with ion fluence until a buried amorphous layer is formed, while damage growth saturates at a low level in the region ahead. The morphology of the damage in the saturated region is shown to consist predominantly of simple defect clusters such as the divacancy. Damage growth remains saturated ahead of the eor until expansion of the buried amorphous layer encroaches into the region. A homogeneous growth model is presented which accounts for damage saturation, and accurately predicts the dose-rate dependence of the saturation level. Modifications of the model are discussed which are needed to account for the rapid growth in the eor region and near the interface of the buried amorphous layer. Two important factors contributing to rapid damage growth are identified. Spatial separation of the Frenkel defect pairs (i.e. interstitials and vacancies) due to the momentum of the interstitials is shown to greatly impact damage growth near the eor, while uniaxial strain in the interfacial region of the amorphous layer is identified as an important factor contributing to growth at that location. 20 refs., 10 figs

  17. Laser-induced damage to thin film dielectric coatings

    International Nuclear Information System (INIS)

    Walker, T.W.

    1980-01-01

    The laser-induced damage thresholds of dielectric thin film coatings have been found to be more than an order of magnitude lower than the bulk material damage thresholds. Prior damage studies have been inconclusive in determining the damage mechanism which is operative in thin films. A program was conducted in which thin film damage thresholds were measured as a function of laser wavelength (1.06 μm, 0.53 μm, 0.35 μm and 0.26 μm), laser pulse length (5 and 15 nanoseconds), film materials and film thickness. The large matrix of data was compared to predictions given by avalanche ionization, multiphoton ionization and impurity theories of laser damage. When Mie absorption cross-sections and the exact thermal equations were included into the impurity theory excellent agreement with the data was found. The avalanche and multiphoton damage theories could not account for most parametric variations in the data. For example, the damage thresholds for most films increased as the film thickness decreased and only the impurity theory could account for this behavior. Other observed changes in damage threshold with changes in laser wavelength, pulse length and film material could only be adequately explained by the impurity theory. The conclusion which results from this study is that laser damage in thin film coatings results from absorbing impurities included during the deposition process

  18. WILD PIGS: BIOLOGY, DAMAGE, CONTROL TECHINQUES AND MANAGEMENT

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, John; Brisbin, I. Lehr

    2009-12-31

    about anything; and, they can live just about anywhere. On top of that, wild pigs are both very difficult to control and, with the possible exception of island ecosystems, almost impossible to eradicate (Dickson et al. 2001, Sweeney et al. 2003). The solution to the wild pig problem has not been readily apparent. The ultimate answer as to how to control these animals has not been found to date. In many ways, wild pigs are America's most successful large invasive species. All of which means that wild pigs are a veritable nightmare for land and resource managers trying to keep the numbers of these animals and the damage that they do under control. Since the more that one knows about an invasive species, the easier it is to deal with and hopefully control. For wild pigs then, it is better to 'know thy enemy' than to not, especially if one expects to be able to successfully control them. In an effort to better 'know thy enemy,' a two-day symposium was held in Augusta, Georgia, on April 21-22, 2004. This symposium was organized and sponsored by U.S.D.A. Forest Service-Savannah River (USFS-SR), U. S. Department of Energy-Savannah River Operations Office (DOE-SR), the Westinghouse Savannah River Company (WSRC), the South Carolina Chapter of the Soil & Water Conservation Society, and the Savannah River Ecology Laboratory (SREL). The goal of this symposium was to assemble researchers and land managers to first address various aspects of the biology and damage of wild pigs, and then review the control techniques and management of this invasive species. The result would then be a collected synopsis of what is known about wild pigs in the United States. Although the focus of the symposium was primarily directed toward federal agencies, presenters also included professionals from academic institutions, and private-sector control contractors and land managers. Most of the organizations associated with implementing this symposium were affiliated with the

  19. Radiation-induced Pulmonary Damage in Lung Cancer Patients

    International Nuclear Information System (INIS)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Mi Mun; Kim, In Ah; Shinn, Kyung Sub

    1993-01-01

    Purpose: A retrospective analysis was performed to evaluate the incidence of radiation induced lung damage after the radiation therapy for the patients with carcinoma of the lung. Method and Materials: Sixty-six patients with lung cancer (squamous cell carcinoma 27, adenocarcinoma 14, large cell carcinoma 2, small cell carcinoma 13, unknown 10) were treated with definitive, postoperative or palliative radiation therapy with or without chemotherapy between July 1987 and December 1991. There were 50 males and 16 females with median age of 63 years(range: 33-80 years). Total lung doses ranged from 500 to 6,660 cGy (median 3960 cGy) given in 2 to 38 fractions (median 20) over a range of 2 to 150 days (median 40 days) using 6 MV or 15 MV linear accelerator. To represent different fractionation schedules of equivalent biological effect, the estimated single dose(ED) model, ED=D·N-0.377·T-0.058 was used in which D was the lung dose in cGy, N was the number of fractions, and T was the overall treatment time in days. The range of ED was 370 to 1357. The endpoint was a visible increase in lung density within the irradiated volume on chest X-ray as observed independently by three diagnostic radiologists. Patients were grouped according to ED, treatment duration, treatment modality and age, and the percent incidence of pulmonary damage for each group was determined. Result: In 40 of 66 patients, radiation induced change was seen on chest radiographs between 11 days and 314 days after initiation of radiation therapy. The incidence of radiation pneumonitis was increased according to increased ED, which was statistically significant (p=0.001). Roentgenographic charges consistent with radiation pneumonitis were seen in 100% of patients receiving radiotherapy after lobectomy or pneumonectomy, which was not statistically significant. In 32 patients who also received chemotherapy, there was no difference in the incidence of radiation induced charge between the group with radiation

  20. Hypochlorite-induced damage to proteins

    DEFF Research Database (Denmark)

    Hawkins, C L; Davies, Michael Jonathan

    1998-01-01

    Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl damages proteins by reaction with amino acid side-chains or backbone cleavage. Little information is available about the mechanisms and intermediates involved...... in these reactions. EPR spin trapping has been employed to identify radicals on proteins, peptides and amino acids after treatment with HOCl. Reaction with HOCl gives both high- and low-molecular-mass nitrogen-centred, protein-derived radicals; the yield of the latter increases with both higher HOCl:protein ratios...... and enzymic digestion. These radicals, which arise from lysine side-chain amino groups, react with ascorbate, glutathione and Trolox. Reaction of HOCl-treated proteins with excess methionine eliminates radical formation, which is consistent with lysine-derived chloramines (via homolysis of N-Cl bonds) being...

  1. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Halliday, Gary M. [Dermatology Research Laboratories, Division of Medicine, Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital at the University of Sydney, Sydney, NSW (Australia)]. E-mail: garyh@med.usyd.edu.au

    2005-04-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.

  2. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

    International Nuclear Information System (INIS)

    Halliday, Gary M.

    2005-01-01

    Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans

  3. Processing of radiation-induced clustered DNA damage generates DSB in mammalian cells

    International Nuclear Information System (INIS)

    Gulston, M.K.; De Lara, C.M.; Davis, E.L.; Jenner, T.J.; O'Neill, P.

    2003-01-01

    Full text: Clustered DNA damage sites, in which two or more lesions are formed within a few helical turns of the DNA after passage of a single radiation track, are signatures of DNA modifications induced by ionizing radiation in mammalian cell. With 60 Co-radiation, the abundance of clustered DNA damage induced in CHO cells is ∼4x that of prompt double strand breaks (DSB) determined by PFGE. Less is known about the processing of non-DSB clustered DNA damage induced in cells. To optimize observation of any additional DSB formed during processing of DNA damage at 37 deg C, xrs-5 cells deficient in non-homologous end joining were used. Surprisingly, ∼30% of the DSB induced by irradiation at 37 deg C are rejoined within 4 minutes in both mutant and wild type cells. No significant mis-repair of these apparent DSB was observed. It is suggested that a class of non-DSB clustered DNA damage is formed which repair correctly within 4 min but, if 'trapped' prior to repair, are converted into DSB during the lysis procedure of PFGE. However at longer times, a proportion of non-DSB clustered DNA damage sites induced by γ-radiation are converted into DSB within ∼30 min following post-irradiation incubation at 37 deg C. The corresponding formation of additional DSB was not apparent in wild type CHO cells. From these observations, it is estimated that only ∼10% of the total yield of non DSB clustered DNA damage sites are converted into DSB through cellular processing. The biological consequences that the majority of non-DSB clustered DNA damage sites are not converted into DSBs may be significant even at low doses, since a finite chance exists of these clusters being formed in a cell by a single radiation track

  4. DNA damage-inducible transcripts in mammalian cells

    International Nuclear Information System (INIS)

    Fornace, A.J. Jr.; Alamo, I. Jr.; Hollander, M.C.

    1988-01-01

    Hybridization subtraction at low ratios of RNA to cDNA was used to enrich for the cDNA of transcripts increased in Chinese hamster cells after UV irradiation. Forty-nine different cDNA clones were isolated. Most coded for nonabundant transcripts rapidly induced 2- to 10-fold after UV irradiation. Only 2 of the 20 cDNA clones sequenced matched known sequences (metallothionein I and II). The predicted amino acid sequence of one cDNA had two localized areas of homology with the rat helix-destabilizing protein. These areas of homology were at the two DNA-binding sites of this nucleic acid single-strand-binding protein. The induced transcripts were separated into two general classes. Class I transcripts were induced by UV radiation and not by the alkylating agent methyl methanesulfonate. Class II transcripts were induced by UV radiation and by methyl methanesulfonate. Many class II transcripts were induced also by H2O2 and various alkylating agents but not by heat shock, phorbol 12-tetradecanoate 13-acetate, or DNA-damaging agents which do not produce high levels of base damage. Since many of the cDNA clones coded for transcripts which were induced rapidly and only by certain types of DNA-damaging agents, their induction is likely a specific response to such damage rather than a general response to cell injury

  5. DNA damage-induced inflammation and nuclear architecture.

    Science.gov (United States)

    Stratigi, Kalliopi; Chatzidoukaki, Ourania; Garinis, George A

    2017-07-01

    Nuclear architecture and the chromatin state affect most-if not all- DNA-dependent transactions, including the ability of cells to sense DNA lesions and restore damaged DNA back to its native form. Recent evidence points to functional links between DNA damage sensors, DNA repair mechanisms and the innate immune responses. The latter raises the question of how such seemingly disparate processes operate within the intrinsically complex nuclear landscape and the chromatin environment. Here, we discuss how DNA damage-induced immune responses operate within chromatin and the distinct sub-nuclear compartments highlighting their relevance to chronic inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Radiation-induced brain damage in children

    International Nuclear Information System (INIS)

    Oi, Shizuo; Kokunai, Takashi; Ijichi, Akihiro; Matsumoto, Satoshi; Raimondi, A.J.

    1990-01-01

    The nature and sequence of the radiation-induced changes in the brain were studied postmortem in 34 children with glioma, 22 of whom underwent central nervous system radiation therapy. Twenty received whole-brain or whole-neuroaxis radiation at a total mean dosage of 4063 cGy. Brain tissue alternations were analyzed histologically by means of various staining methods, including immunohistochemical techniques. The histological features of irradiated brains were compared with those of non-irradiated brains. Microscopic findings included demyelination (seven cases), focal necrosis (six cases), cortical atrophy (four cases), endothelial proliferation (four cases), and telangiectatic vascular proliferation with vascular thickening and oozing of a thick fluid (one case). Such findings were rare in non-irradiated patients. Demyelination was observed earliest in a patient who died 5 months after radiation therapy and was more common after 9 months. Focal necrosis was first observed 9 months post-irradiation but was more advanced and extensive after 1 year. Calcified foci were found only after 60 months. Various vascular changes such as vascular thickening and thrombosis suggested ischemic insult to the brain as a late effect of radiation injury. The results of this study suggest that the immature brain may be more sensitive to radiation than is the adult brain, and that the manifestations of radiation-induced injury depend on the time elapsed after irradiation. (author)

  7. Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status

    DEFF Research Database (Denmark)

    Lyckesvärd, Madeleine Nordén; Delle, Ulla; Kahu, Helena

    2014-01-01

    Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same...... mechanism as (131)I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation...... and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ((60)Co) and alpha particles from (211)At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity...

  8. Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ifigeneia V. Mavragani

    2017-07-01

    Full Text Available Cellular effects of ionizing radiation (IR are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs, single strand breaks (SSBs and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1 repair resistant, increasing genomic instability (GI and malignant transformation and (2 can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity. Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair.

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

    Science.gov (United States)

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

    2000-01-01

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

  10. Smeared crack modelling approach for corrosion-induced concrete damage

    DEFF Research Database (Denmark)

    Thybo, Anna Emilie Anusha; Michel, Alexander; Stang, Henrik

    2017-01-01

    In this paper a smeared crack modelling approach is used to simulate corrosion-induced damage in reinforced concrete. The presented modelling approach utilizes a thermal analogy to mimic the expansive nature of solid corrosion products, while taking into account the penetration of corrosion...... products into the surrounding concrete, non-uniform precipitation of corrosion products, and creep. To demonstrate the applicability of the presented modelling approach, numerical predictions in terms of corrosion-induced deformations as well as formation and propagation of micro- and macrocracks were......-induced damage phenomena in reinforced concrete. Moreover, good agreements were also found between experimental and numerical data for corrosion-induced deformations along the circumference of the reinforcement....

  11. UV and ionizing radiations induced DNA damage, differences and similarities

    Science.gov (United States)

    Ravanat, Jean-Luc; Douki, Thierry

    2016-11-01

    Both UV and ionizing radiations damage DNA. Two main mechanisms, so-called direct and indirect pathways, are involved in the degradation of DNA induced by ionizing radiations. The direct effect of radiation corresponds to direct ionization of DNA (one electron ejection) whereas indirect effects are produced by reactive oxygen species generated through water radiolysis, including the highly reactive hydroxyl radicals, which damage DNA. UV (and visible) light damages DNA by again two distinct mechanisms. UVC and to a lesser extend UVB photons are directly absorbed by DNA bases, generating their excited states that are at the origin of the formation of pyrimidine dimers. UVA (and visible) light by interaction with endogenous or exogenous photosensitizers induce the formation of DNA damage through photosensitization reactions. The excited photosensitizer is able to induce either a one-electron oxidation of DNA (type I) or to produce singlet oxygen (type II) that reacts with DNA. In addition, through an energy transfer from the excited photosensitizer to DNA bases (sometime called type III mechanism) formation of pyrimidine dimers could be produced. Interestingly it has been shown recently that pyrimidine dimers are also produced by direct absorption of UVA light by DNA, even if absorption of DNA bases at these wavelengths is very low. It should be stressed that some excited photosensitizers (such as psoralens) could add directly to DNA bases to generate adducts. The review will described the differences and similarities in terms of damage formation (structure and mechanisms) between these two physical genotoxic agents.

  12. An extended sequence specificity for UV-induced DNA damage.

    Science.gov (United States)

    Chung, Long H; Murray, Vincent

    2018-01-01

    The sequence specificity of UV-induced DNA damage was determined with a higher precision and accuracy than previously reported. UV light induces two major damage adducts: cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). Employing capillary electrophoresis with laser-induced fluorescence and taking advantages of the distinct properties of the CPDs and 6-4PPs, we studied the sequence specificity of UV-induced DNA damage in a purified DNA sequence using two approaches: end-labelling and a polymerase stop/linear amplification assay. A mitochondrial DNA sequence that contained a random nucleotide composition was employed as the target DNA sequence. With previous methodology, the UV sequence specificity was determined at a dinucleotide or trinucleotide level; however, in this paper, we have extended the UV sequence specificity to a hexanucleotide level. With the end-labelling technique (for 6-4PPs), the consensus sequence was found to be 5'-GCTC*AC (where C* is the breakage site); while with the linear amplification procedure, it was 5'-TCTT*AC. With end-labelling, the dinucleotide frequency of occurrence was highest for 5'-TC*, 5'-TT* and 5'-CC*; whereas it was 5'-TT* for linear amplification. The influence of neighbouring nucleotides on the degree of UV-induced DNA damage was also examined. The core sequences consisted of pyrimidine nucleotides 5'-CTC* and 5'-CTT* while an A at position "1" and C at position "2" enhanced UV-induced DNA damage. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  13. Mechanisms of subsidence for induced damage and techniques for analysis

    International Nuclear Information System (INIS)

    Drumm, E.C.; Bennett, R.M.; Kane, W.F.

    1988-01-01

    Structural damage due to mining induced subsidence is a function of the nature of the structure and its position on the subsidence profile. A point on the profile may be in the tensile zone, the compressive zone, or the no-deformation zone at the bottom of the profile. Damage to structures in the tension zone is primarily due to a reduction of support during vertical displacement of the ground surface, and to shear stresses between the soil and structure resulting from horizontal displacements. The damage mechanisms due to tension can be investigated effectively using a two-dimensional plane stress analysis. Structures in the compression zone are subjected to positive moments in the footing and large compressive horizontal stresses in the foundation walls. A plane strain analysis of the foundation wall is utilized to examine compression zone damage mechanisms. The structural aspects affecting each mechanism are identified and potential mitigation techniques are summarized

  14. Laser-induced damage study of polymer PMMA

    International Nuclear Information System (INIS)

    Mansour, N.

    2001-01-01

    This article presents the results of bulk laser-induced damage measurements in polymer PMMA at 532 nm and 1064 nm for nanosecond laser pulses. The damage thresholds were measured for focused spot sizes ranging over two orders of magnitude. In this work, self-focusing effects were verified to be absent by measurements of breakdown thresholds using both linearly and circularly polarized light. At both 1064 nm and 532 nm, the dependence of the breakdown field, E B , on the spot size, ω, was empirically determined to be E B = C/√ω, where C depends on the wavelength. The extracted value for C(λ) at 1064 nm is larger by a factor of 5 than at 532 nm. Possible reasons for this strong dispersion and mechanism for laser-induced damage in polymer materials will be discussed

  15. Myostatin as a Marker for Doxorubicin Induced Cardiac Damage.

    Science.gov (United States)

    Kesik, Vural; Honca, Tevfik; Gulgun, Mustafa; Uysal, Bulent; Kurt, Yasemin Gulcan; Cayci, Tuncer; Babacan, Oguzhan; Gocgeldi, Ercan; Korkmazer, Nadir

    2016-01-01

    Doxorubicin (DXR) is an effective chemotherapeutic agent but causes severe cardiac failure over known doses. Thus, early detection and prevention of cardiac damage is important. Various markers have been tested for early detection of cardiac damage. Myostatin is a protein produced in skeletal muscle cells inhibits muscle differentiation and growth during myogenesis. We evaluated the role of myostatin as a marker for showing DXR induced cardiac damage and compared with well known cardiac markers like NT-proBNP, hs-TnT and CK in a rat model of chronic DXR cardiotoxicity. Myostatin, NT-proBNP, and hs-TnT but not CK rose significantly during DXR treatment. Myostatin can be used as an early marker of DXR induced cardiotoxicity. © 2016 by the Association of Clinical Scientists, Inc.

  16. Plasmid DNA damage induced by helium atmospheric pressure plasma jet

    Science.gov (United States)

    Han, Xu; Cantrell, William A.; Escobar, Erika E.; Ptasinska, Sylwia

    2014-03-01

    A helium atmospheric pressure plasma jet (APPJ) is applied to induce damage to aqueous plasmid DNA. The resulting fractions of the DNA conformers, which indicate intact molecules or DNA with single- or double-strand breaks, are determined using agarose gel electrophoresis. The DNA strand breaks increase with a decrease in the distance between the APPJ and DNA samples under two working conditions of the plasma source with different parameters of applied electric pulses. The damage level induced in the plasmid DNA is also enhanced with increased plasma irradiation time. The reactive species generated in the APPJ are characterized by optical emission spectra, and their roles in possible DNA damage processes occurring in an aqueous environment are also discussed.

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

    International Nuclear Information System (INIS)

    Di Giorgio, M.; Nasazzi, N.B.; Taja, M.R.

    1998-01-01

    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 60 Co 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 60 Co 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

  18. Protective effects of vitamin C against gamma-ray induced wholly damage and genetic damage

    International Nuclear Information System (INIS)

    Fu Chunling; Jiang Weiwei; Zhang Ping; Chen Xiang; Zhu Shengtao

    2000-01-01

    Objective: Protective effects of supplemental vitamin C against 60 Co-gamma-ray induced wholly damage and genetic damage was investigated in mice. Method: Mice were divided into normal control group, irradiation control group and vitamin C experimental group 1,2,3 (which were orally given vitamin C 15, 30, 45 mg/kg.bw for 10 successive days respectively prior to gamma-ray irradiation). Micronuclei in the bone marrow polychromatophilic erythrocytes in each group of mice were examined and the 30 day survival rate of mice following whole-body 5.0 Gy γ irradiation were also determined. Results: Supplemental vitamin C prior to gamma-rays irradiation can significantly decrease bone marrow PECMN rate of mice and increase 30 day survival rate and prolong average survival time. The protection factor is 2.09. Conclusion: Vitamin C has potent protective effects against gamma irradiation induced damage in mice. In certain dose range, vitamin C can absolutely suppress the gamma-rays induced genetic damage in vivo

  19. The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signalling and their interplay

    Directory of Open Access Journals (Sweden)

    James Nathan Cobley

    2015-06-01

    Full Text Available Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1 redox signalling and (2 macromolecule damage. Mechanistic knowledge of how exercise-induced redox signalling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signalling and DNA damage, using hydroxyl radical (·OH and hydrogen peroxide (H2O2 as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signalling and damage. Indeed, H2O2 can participate in two electron signalling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and ·OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signalling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signalling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation.

  20. MDM2 Antagonists Counteract Drug-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Anna E. Vilgelm

    2017-10-01

    Full Text Available Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA re-replication, and polyploidy. Here we show that re-replication of the polyploid genome generates replicative stress which leads to DNA damage. MDM2-p53 antagonists relieve replicative stress via the p53-dependent activation of p21 which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in melanoma cells and enhanced anti-tumor activity of therapy combining MDM2 antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists may reduce DNA damaging effects of anti-cancer drugs if they are administered together, while targeting p21 can improve the efficacy of such combinations.

  1. Multiple pulse nanosecond laser induced damage threshold on hybrid mirrors

    Science.gov (United States)

    Vanda, Jan; Muresan, Mihai-George; Bilek, Vojtech; Sebek, Matej; Hanus, Martin; Lucianetti, Antonio; Rostohar, Danijela; Mocek, Tomas; Škoda, Václav

    2017-11-01

    So-called hybrid mirrors, consisting of broadband metallic surface coated with dielectric reflector designed for specific wavelength, becoming more important with progressing development of broadband mid-IR sources realized using parametric down conversion system. Multiple pulse nanosecond laser induced damage on such mirrors was tested by method s-on-1, where s stands for various numbers of pulses. We show difference in damage threshold between common protected silver mirrors and hybrid silver mirrors prepared by PVD technique and their variants prepared by IAD. Keywords: LIDT,

  2. Curcumin Attenuates Methotrexate-Induced Hepatic Oxidative Damage in Rats

    International Nuclear Information System (INIS)

    HEMEIDA, R.A.M.; MOHAFEZ, O.M.

    2008-01-01

    In the present study, we have addressed the ability of curcumin to suppress MTX-induced liver damage. Hepatotoxicity was induced by injection of a single dose of MTX (20 mg/kg I.P.). MTX challenge induced liver damage that was well characterized histopathologically and biochemically. MTX increased relative liver/body weight ratio. Histologically, MTX produced fatty changes in hepatocytes and sinusoidal lining cells, mild necrosis and inflammation. Biochemically, the test battery entailed elevated activities of serum ALT and AST. Liver activities of superoxide dismutase (SOD), catalase (CAT) and level of reduced glutathione (GSH), were notably reduced, while lipid peroxidation, expressed as malondialdhyde (MDA) level was significantly increased. Administration of curcumin (100mg/kg, I.P.) once daily for 5 consecutive days after MTX challenge mitigated the injurious effects of MTX and ameliorated all the altered biochemical parameters. These results showed that administration of curcumin decreases MTX-induced liver damage probably via regulation of oxidant/anti-oxidant balance. In conclusion, the present study indicates that curcumin may be of therapeutic benefit against MTX-cytotoxicity.

  3. Damage-induced DNA repair processes in Escherichia coli cells

    International Nuclear Information System (INIS)

    Slezarikova, V.

    1986-01-01

    The existing knowledge is summed up of the response of Escherichia coli cells to DNA damage due to various factors including ultraviolet radiation. So far, three inducible mechanisms caused by DNA damage are known, viz., SOS induction, adaptation and thermal shock induction. Greatest attention is devoted to SOS induction. Its mechanism is described and the importance of the lexA recA proteins is shown. In addition, direct or indirect role is played by other proteins, such as the ssb protein binding the single-strand DNA sections. The results are reported of a study of induced repair processes in Escherichia coli cells repeatedly irradiated with UV radiation. A model of induction by repeated cell irradiation discovered a new role of induced proteins, i.e., the elimination of alkali-labile points in the daughter DNA synthetized on a damaged model. The nature of the alkali-labile points has so far been unclear. In the adaptation process, regulation proteins are synthetized whose production is induced by the presence of alkylation agents. In the thermal shock induction, new proteins synthetize in cells, whose function has not yet been clarified. (E.S.)

  4. Role of endothelium in radiation-induced normal tissue damages

    International Nuclear Information System (INIS)

    Milliat, F.

    2007-05-01

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  5. Radiation induced crystallinity damage in poly(L-lactic acid)

    CERN Document Server

    Kantoglu, O

    2002-01-01

    The radiation-induced crystallinity damage in poly(L-lactic acid) (PLLA) in the presence of air and in vacuum, is studied. From the heat of fusion enthalpy values of gamma irradiated samples, some changes on the thermal properties were determined. To identify these changes, first the glass transition temperature (T sub g) of L-lactic acid polymers irradiated to various doses in air and vacuum have been investigated and it is found that it is independent of irradiation atmosphere and dose. The fraction of damaged units of PLLA per unit of absorbed energy has been measured. For this purpose, SAXS and differential scanning calorimetry methods were used, and the radiation yield of number of damaged units (G(-u)) is found to be 0.74 and 0.58 for PLLA samples irradiated in vacuum and air, respectively.

  6. Contribution of endogenous and exogenous damage to the total radiation-induced damage in the bacterial spore

    International Nuclear Information System (INIS)

    Jacobs, G.P.; Samuni, A.; Czapski, G.

    1980-01-01

    Radical scavengers such as polyethylene glycol 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous damage to the total radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous

  7. Study on DNA damages induced by UV radiation

    International Nuclear Information System (INIS)

    Doan Hong Van; Dinh Ba Tuan; Tran Tuan Anh; Nguyen Thuy Ngan; Ta Bich Thuan; Vo Thi Thuong Lan; Tran Minh Quynh; Nguyen Thi Thom

    2015-01-01

    DNA damages in Escherichia coli (E. coli) exposed to UV radiation have been investigated. After 30 min of exposure to UV radiation of 5 mJ/cm"2, the growth of E. coli in LB broth medium was about only 10% in compared with non-irradiated one. This results suggested that the UV radiation caused the damages for E. coli genome resulted in reduction in its growth and survival, and those lesions can be somewhat recovered. For both solutions of plasmid DNAs and E. coli cells containing plasmid DNA, this dose also caused the breakage on single and double strands of DNA, shifted the morphology of DNA plasmid from supercoiled to circular and linear forms. The formation of pyrimidine dimers upon UV radiation significantly reduced when the DNA was irradiated in the presence of Ganoderma lucidum extract. Thus, studies on UV-induced DNA damage at molecular level are very essential to determine the UV radiation doses corresponding to the DNA damages, especially for creation and selection of useful radiation-induced mutants, as well as elucidation the protective effects of the specific compounds against UV light. (author)

  8. Radiation induced DNA damage and repair in mutagenesis

    International Nuclear Information System (INIS)

    Strniste, G.F.; Chen, D.J.; Okinaka, R.T.

    1987-01-01

    The central theme in cellular radiobiological research has been the mechanisms of radiation action and the physiological response of cells to this action. Considerable effort has been directed toward the characterization of radiation-induced DNA damage and the correlation of this damage to cellular genetic change that is expressed as mutation or initiating events leading to cellular transformation and ultimately carcinogenesis. In addition, there has been a significant advancement in their understanding of the role of DNA repair in the process of mutation leading to genetic change in cells. There is extensive literature concerning studies that address radiation action in both procaryotic and eucaryotic systems. This brief report will make no attempt to summarize this voluminous data but will focus on recent results from their laboratory of experiments in which they have examined, at both the cellular and molecular levels, the process of ionizing radiation-induced mutagenesis in cultured human cells

  9. Impact of mechanical stress induced in silica vacuum windows on laser-induced damage.

    Science.gov (United States)

    Gingreau, Clémence; Lanternier, Thomas; Lamaignère, Laurent; Donval, Thierry; Courchinoux, Roger; Leymarie, Christophe; Néauport, Jérôme

    2018-04-15

    At the interface between vacuum and air, optical windows must keep their optical properties, despite being subjected to mechanical stress. In this Letter, we investigate the impact of such stress on the laser-induced damage of fused silica windows at the wavelength of 351 nm in the nanosecond regime. Different stress values, from 1 to 30 MPa, both tensile and compressive, were applied. No effect of the stress on the laser-induced damage was evidenced.

  10. Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

    International Nuclear Information System (INIS)

    Milatovic, Dejan; Zaja-Milatovic, Snjezana; Gupta, Ramesh C.; Yu, Yingchun; Aschner, Michael

    2009-01-01

    Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterations in biomarkers of oxidative damage, F 2 -isoprostanes (F 2 -IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 μM Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E 2 (PGE 2 ). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F 2 -IsoPs and PGE 2 in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.

  11. Electro-induced reactions of biologically important molecules

    International Nuclear Information System (INIS)

    Kocisek, J.

    2010-01-01

    The thesis presents the results of research activities in the field of electron interactions with biologically relevant molecules which was carried out during my PhD studies at the Department of Experimental Physics, Comenius University in Bratislava. Electron induced interactions with biologically relevant molecules were experimentally studied using crossed electron-molecule beams experiment. The obtained results, were presented in four publications in international scientific journals. First study of deals with electron impact ionisation of furanose alcohols [see 1. in list of author publications on page 22]. It has been motivated by most important works in the field of electron induced damages of DNA bases [4]. Studied 3-hydroxytetrahydrofuran and tetrahydrofurfuryl alcohol, are important model molecules for more complex biological systems (e.g. deoxyribose).The influence of hydroxyl group on stabilisation of the positive ions of the molecules, together with the stability of furan ring in ionized form are main themes of the study. The studies of small amides and aminoacids are connected to scientific studies in the field of formation of the aminoacids and other biologically relevant molecules in space and works trying to explain electron induced processes in more complex molecules[12, 13, 24]. The most important results were obtained for aminoacid Serine [see 2. in list of author publications on page 22]. We have showed that additional OH group of Serine considerably lower the reaction enthalpy limit of reactions resulting to formation of neutral water molecules, in comparison to other amino acids. Also the study of (M-H)- reaction channel using the electron beam with FWHM under 100 meV is of high importance in the field. The last part of the thesis is focused on the electron interactions with organosilane compounds. Materials prepared from organosilane molecules in plasmas have wide range of applications in both biology and medicine. We have studied electron

  12. The small molecule calactin induces DNA damage and apoptosis in human leukemia cells.

    Science.gov (United States)

    Lee, Chien-Chih; Lin, Yi-Hsiung; Chang, Wen-Hsin; Wu, Yang-Chang; Chang, Jan-Gowth

    2012-09-01

    We purified calactin from the roots of the Chinese herb Asclepias curassavica L. and analyzed its biologic effects in human leukemia cells. Our results showed that calactin treatment caused DNA damage and resulted in apoptosis. Increased phosphorylation levels of Chk2 and H2AX were observed and were reversed by the DNA damage inhibitor caffeine in calactin-treated cells. In addition, calactin treatment showed that a decrease in the expression of cell cycle regulatory proteins Cyclin B1, Cdk1, and Cdc25C was consistent with a G2/M phase arrest. Furthermore, calactin induced extracellular signal-regulated kinase (ERK) phosphorylation, activation of caspase-3, caspase-8, and caspase-9, and PARP cleavage. Pretreatment with the ERK inhibitor PD98059 significantly blocked the loss of viability in calactin-treated cells. It is indicated that calactin-induced apoptosis may occur through an ERK signaling pathway. Our data suggest that calactin is a potential anticancer compound.

  13. Radiation damage relative to transmission electron microscopy of biological specimens at low temperature: a review

    International Nuclear Information System (INIS)

    Glaeser, R.M.; Taylor, K.A.

    1978-01-01

    When biological specimens are irradiated by the electron beam in the electron microscope, the specimen structure is damaged as a result of molecular excitation, ionization, and subsequent chemical reactions. The radiation damage that occurs in the normal process of electron microscopy is known to present severe limitations for imaging high resolution detail in biological specimens. The question of radiation damage at low temperatures has therefore been investigated with the view in mind of reducing somewhat the rate at which damage occurs. The radiation damage protection found for small molecule (anhydrous) organic compounds is generally rather limited or even non-existent. However, large molecule, hydrated materials show as much as a 10-fold reduction at low temperature in the rate at which radiation damage occurs, relative to the damage rate at room temperature. In the case of hydrated specimens, therefore, low temperature electron microscopy offers an important advantage as part of the overall effort required in obtaining high resolution images of complex biological structures. (author)

  14. Investigation of cutting-induced damage in CMC bend bars

    Directory of Open Access Journals (Sweden)

    Neubrand A.

    2015-01-01

    Full Text Available Ceramic matrix composites (“CMC” with a strong fibre-matrix interface can be made damage-tolerant by introducing a highly porous matrix. Such composites typically have only a low interlaminar shear strength, which can potentially promote damage when preparing specimens or components by cutting. In order to investigate the damage induced by different cutting methods, waterjet cutting with and without abrasives, laser-cutting, wire eroding and cutoff grinding were used to cut plates of two different CMCs with a matrix porosity up to 35 vol.-%. For each combination of cutting method and composite, the flexural and interlaminar shear strength of the resulting specimens was determined. Additionally, the integrity of the regions near the cut surfaces was investigated by high-resolution x-ray computer tomography. It could be shown that the geometrical quality of the cut is strongly affected by the cutting method employed. Laser cut and waterjet cut specimens showed damage and delaminations near the cut surface leading to a reduced interlaminar shear strength of short bend bars in extreme cases.

  15. Damage-induced ectopic recombination in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Kupiec, M; Steinlauf, R

    1997-06-09

    Mitotic recombination in the yeast Saccharomyces cerevisiae is induced when cells are irradiated with UV or X-rays, reflecting the efficient repair of damage by recombinational repair mechanisms. We have used multiply marked haploid strains that allow the simultaneous detection of several types of ectopic recombination events. We show that inter-chromosomal ectopic conversion of lys2 heteroalleles and, to a lesser extent, direct repeat recombination (DRR) between non-tandem repeats, are increased by DNA-damaging agents; in contrast, ectopic recombination of the naturally occurring Ty element is not induced. We have tested several hypotheses that could explain the preferential lack of induction of Ty recombination by DNA-damaging agents. We have found that the lack of induction cannot be explained by a cell cycle control or by an effect of the mating-type genes. We also found no role for the flanking long terminal repeats (LTRs) of the Ty in preventing the induction. Ectopic conversion, DRR, and forward mutation of artificial repeats show different kinetics of induction at various positions of the cell cycle, reflecting different mechanisms of recombination. We discuss the mechanistic and evolutionary aspects of these results.

  16. Protective Effect of HSP25 on Radiation Induced Tissue Damage

    International Nuclear Information System (INIS)

    Lee, Hae-June; Lee, Yoon-Jin; Kwon, Hee-Choong; Bae, Sang-Woo; Lee, Yun-Sil; Kim, Sung Ho

    2007-01-01

    Control of cancer by irradiation therapy alone or in conjunction with combination chemotherapy is often limited by organ specific toxicity. Ionizing irradiation toxicity is initiated by damage to normal tissue near the tumor target and within the transit volume of radiotherapy beams. Irradiation-induced cellular, tissue, and organ damage is mediated by acute effects, which can be dose limiting. A latent period follows recovery from the acute reaction, then chronic irradiation fibrosis (late effects) pose a second cause of organ failure. HSP25/27 has been suggested to protect cells against apoptotic cell death triggered by hyperthermia, ionizing radiation, oxidative stress, Fas ligand, and cytotoxic drugs. And several mechanisms have been proposed to account for HSP27-mediated apoptotic protection. However radioprotective effect of HSP25/27 in vivo system has not yet been evaluated. The aim of this study was to evaluate the potential of exogenous HSP25 expression, as delivered by adenoviral vectors, to protect animal from radiation induced tissue damage

  17. Relative Biological Effectiveness and Peripheral Damage of Antiproton Annihilation

    CERN Multimedia

    Kavanagh, J N; Kaiser, F; Tegami, S; Schettino, G; Kovacevic, S; Hajdukovic, D; Knudsen, H; Currell, F J; Toelli, H T; Doser, M; Holzscheiter, M; Herrmann, R; Timson, D J; Alsner, J; Landua, R; Comor, J; Moller, S P; Beyer, G

    2002-01-01

    The use of ions to deliver radiation to a body for therapeutic purposes has the potential to be significant improvement over the use of low linear energy transfer (LET) radiation because of the improved energy deposition profile and the enhanced biological effects of ions relative to photons. Proton therapy centers exist and are being used to treat patients. In addition, the initial use of heavy ions such as carbon is promising to the point that new treatment facilities are planned. Just as with protons or heavy ions, antiprotons can be used to deliver radiation to the body in a controlled way; however antiprotons will exhibit additional energy deposition due to annihilation of the antiprotons within the body. The slowing down of antiprotons in matter is similar to that of protons except at the very end of the range beyond the Bragg peak. Gray and Kalogeropoulos estimated the additional energy deposited by heavy nuclear fragments within a few millimeters of the annihilation vertex to be approximately 30 MeV (...

  18. Electrolytic reduction of nitroheterocyclic drugs leads to biologically important damage in DNA

    International Nuclear Information System (INIS)

    Lafleur, M.V.M.; Pluijmackers-Westmijze, E.J.; Loman, H.

    1985-01-01

    The effects of electrolytic reduction of nitroimidazole drugs on biologically active DNA was studied. The results show that reduction of the drugs in the presence of DNA affects inactivation for both double-stranded (RF) and single-stranded phiX174 DNA. However, stable reduction products did not make a significant contribution to the lethal damage in DNA. This suggests that probably a short-lived intermediate of reduction of nitro-compounds is responsible for damage to DNA. (author)

  19. Modulation of mutagen-induced biological effects by inhibitors of DNA repair

    International Nuclear Information System (INIS)

    Natarajan, A.T.; Mullenders, L.F.H.; Zwanenburg, T.S.B.

    1986-01-01

    When lesions are induced in the DNA by mutagenic agents, they are subjected to cellular repair. Unrepaired and misrepaired lesions lead to biological effects, such as cell killing, point mutations and chromosomal alterations (aberrations and sister chromatid exchanges - SCEs). It is very difficult to directly correlate any particular type of lesion to a specific biological effect. However, in specific cases, this has been done. For example, short wave UV induced biological effects (cell killing, chromosomal alterations) result predominantly from induced cyclobutane dimers and by photoreactivation experiments, one can demonstrate that with the removal of dimers all types biological effects are diminished. In cases where many types of lesions are considered responsible for the observed biological effects other strategies have been employed to identify the possible lesion. The frequencies of induced chromosomal alterations and point mutations increase with the dose of the mutagen employed and an inhibition of DNA repair following treatment with the mutagen. Prevention of the cells from dividing following mutagen treatment allows them to repair premutational damage, thus reducing the biological effects induced. By comprehensive studies involving quantification of primary DNA lesions, their repair and biological effects will enable us to understand to some extent the complex processes involved in the manifestation of specific biological effects that follow the treatment of cells with mutagenic carcinogens

  20. Influence of anoxic sensitizers on the radiation damage in biologically active DNA in aqueous solution

    International Nuclear Information System (INIS)

    Lafleur, M.V.M.; Loman, H.

    1982-01-01

    The competition between biologically active single-stranded phiX174 DNA and the anoxic radiosensitizers metronidazole, misonidazole, paranitroacetophenone or nifuroxime for OH radicals is studied. The results are compared with experiments in which the protection of the DNA by t-butanol is determined. Also the effects of the sensitizers on the chemical nature of the damage (immediate and potential break, immediate and potential base damage) is studied. It is found that in diluted aqueous solutions of DNA these radiosensitizers do not sensitize with respect to the biological inactivation. The only effect observed is a shift from potential to immediate breaks with misonidazole and also nifuroxime. (author)

  1. Gender differences in alcohol-induced neurotoxicity and brain damage.

    Science.gov (United States)

    Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

    2013-09-06

    Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. DNA damage and mutagenesis of lambda phage induced by gamma-rays

    International Nuclear Information System (INIS)

    Bertram, Heidi

    1988-01-01

    Lambda phage DNA was gamma irradiated in aqueous solution and strand breakage determined. Twice as much minor structural damage per lethal hit was found in this DNA compared with DNA from irradiated phage suspensions. The in vitro irradiated DNA was repackaged into infectious particles. Induction of mutations in the cI or cII cistron was scored using SOS-induced host cells. In vitro prepared particles were found to have second-order kinetics for mutagenesis induced by gamma rays indicating two pre-mutational events were necessary to produce a mutation, but bacteria-free phage suspensions ('lys-phage') showed single hit kinetics for mutagenesis after irradiation. Increase in the mutation rate in the phage particles was mainly due to minor lesions, i.e. ssb, als and unidentified base damage. In lys-phage, mutagenesis might be enhanced by clustered DNA damage - configuration not existing in pack-phage. Loss of infectivity was analysed in comparison with structural damage. All lesions contributed to biological inactivation. Minor lesions were tolerated by lambda phage to a limited extent. Major lesions (e.g. dsb) contributed most to infectivity loss and were considered lethal events. (U.K.)

  3. Trophic complexity and the adaptive value of damage-induced plant volatiles.

    Directory of Open Access Journals (Sweden)

    Ian Kaplan

    Full Text Available Indirect plant defenses are those facilitating the action of carnivores in ridding plants of their herbivorous consumers, as opposed to directly poisoning or repelling them. Of the numerous and diverse indirect defensive strategies employed by plants, inducible volatile production has garnered the most fascination among plant-insect ecologists. These volatile chemicals are emitted in response to feeding by herbivorous arthropods and serve to guide predators and parasitic wasps to their prey. Implicit in virtually all discussions of plant volatile-carnivore interactions is the premise that plants "call for help" to bodyguards that serve to boost plant fitness by limiting herbivore damage. This, by necessity, assumes a three-trophic level food chain where carnivores benefit plants, a theoretical framework that is conceptually tractable and convenient, but poorly depicts the complexity of food-web dynamics occurring in real communities. Recent work suggests that hyperparasitoids, top consumers acting from the fourth trophic level, exploit the same plant volatile cues used by third trophic level carnivores. Further, hyperparasitoids shift their foraging preferences, specifically cueing in to the odor profile of a plant being damaged by a parasitized herbivore that contains their host compared with damage from an unparasitized herbivore. If this outcome is broadly representative of plant-insect food webs at large, it suggests that damage-induced volatiles may not always be beneficial to plants with major implications for the evolution of anti-herbivore defense and manipulating plant traits to improve biological control in agricultural crops.

  4. Radiation-induced neuropathies: collateral damage of improved cancer prognosis

    International Nuclear Information System (INIS)

    Pradat, Pierre-Francois; Maisonobe, Thierry; Psimaras, Dimitri; Lenglet, Timothee; Porcher, Raphael; Lefaix, J.L.; Delenian, S.

    2012-01-01

    Because of the improvement of cancer prognosis, long-term damages of treatments become a medical and public health problem. Among the iatrogenic complications, neurological impairment is crucial to consider since motor disability and pain have a considerable impact on quality of life of long cancer survivors. However, radiation-induced neuropathies have not been the focus of great attention. The objective of this paper is to provide an updated review about the radiation-induced lesions of the peripheral nerve system. Radiation-induced neuropathies are characterized by their heterogeneity in both symptoms and disease course. Signs and symptoms depend on the affected structures of the peripheral nerve system (nerve roots, nerve plexus or nerve trunks). Early-onset complications are often transient and late complications are usually progressive and associated with a poor prognosis. The most frequent and well known is delayed radiation-induced brachial plexopathy, which may follow breast cancer irradiation. Radiation-induced lumbosacral radiculoplexopathy is characterized by pure or predominant lower motor neuron signs. They can be misdiagnosed, confused with amyotrophic lateral sclerosis (ALS) or with leptomeningeal metastases since nodular MRI enhancement of the nerve roots of the cauda equina and increased cerebrospinal fluid protein content can be observed. In the absence of specific markers of the link with radiotherapy, the diagnosis of post-radiation neuropathy may be difficult. Recently, a posteriori conformal radiotherapy with 3D dosimetric reconstitution has been developed to link a precise anatomical site to unexpected excess irradiation. The importance of early diagnosis of radiation-induced neuropathies is underscored by the emergence of new disease-modifying treatments. Although the pathophysiology is not fully understood, it is already possible to target radiation-induced fibrosis but also associated factors such as ischemia, oxidative stress and

  5. Dihydropyridines decrease X-ray-induced DNA base damage in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Wojewodzka, M., E-mail: marylaw@ichtj.waw.pl [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland); Gradzka, I.; Buraczewska, I.; Brzoska, K.; Sochanowicz, B. [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland); Goncharova, R.; Kuzhir, T. [Institute of Genetics and Cytology, Belarussian National Academy of Sciences, Minsk (Belarus); Szumiel, I. [Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa (Poland)

    2009-12-01

    Compounds with the structural motif of 1,4-dihydropyridine display a broad spectrum of biological activities, often defined as bioprotective. Among them are L-type calcium channel blockers, however, also derivatives which do not block calcium channels exert various effects at the cellular and organismal levels. We examined the effect of sodium 3,5-bis-ethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine-4-carboxylate (denoted here as DHP and previously also as AV-153) on X-ray-induced DNA damage and mutation frequency at the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) locus in Chinese hamster ovary CHO-K1 cells. Using formamido-pyrimidine glycosylase (FPG) comet assay, we found that 1-h DHP (10 nM) treatment before X-irradiation considerably reduced the initial level of FPG-recognized DNA base damage, which was consistent with decreased 8-oxo-7,8-dihydro-2'-deoxyguanosine content and mutation frequency lowered by about 40%. No effect on single strand break rejoining or on cell survival was observed. Similar base damage-protective effect was observed for two calcium channel blockers: nifedipine (structurally similar to DHP) or verapamil (structurally unrelated). So far, the specificity of the DHP-caused reduction in DNA damage - practically limited to base damage - has no satisfactory explanation.

  6. Role of paramagnetic chromium in chromium(VI)-induced damage in cultured mammalian cells.

    OpenAIRE

    Sugiyama, M

    1994-01-01

    Chromium(VI) compounds are known to be potent toxic and carcinogenic agents. Because chromium(VI) is easily taken up by cells and is subsequently reduced to chromium(III), the formation of paramagnetic chromium such as chromium(V) and chromium(III) is believed to play a role in the adverse biological effects of chromium(VI) compounds. The present report, uses electron spin resonance (ESR) spectroscopy; the importance of the role of paramagnetic chromium in chromium(VI)-induced damage in intac...

  7. Skin protection against UVA-induced iron damage by multiantioxidants and iron chelating drugs/prodrugs.

    Science.gov (United States)

    Reelfs, Olivier; Eggleston, Ian M; Pourzand, Charareh

    2010-03-01

    In humans, prolonged sunlight exposure is associated with various pathological states. The continuing drive to develop improved skin protection involves not only approaches to reduce DNA damage by solar ultraviolet B (UVB) but also the development of methodologies to provide protection against ultraviolet A (UVA), the oxidising component of sunlight. Furthermore identification of specific cellular events following ultraviolet (UV) irradiation is likely to provide clues as to the mechanism of the development of resulting pathologies and therefore strategies for protection. Our discovery that UVA radiation, leads to an immediate measurable increase in 'labile' iron in human skin fibroblasts and keratinocytes provides a new insight into UVA-induced skin damage, since iron is a catalyst of biological oxidations. The main purpose of this overview is to bring together some of the new findings related to mechanisms underlying UVA-induced iron release and to discuss novel approaches based on the use of multiantioxidants and light-activated caged-iron chelators for efficient protection of skin cells against UVA-induced iron damage.

  8. Bee products prevent agrichemical-induced oxidative damage in fish.

    Directory of Open Access Journals (Sweden)

    Daiane Ferreira

    Full Text Available In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™ and a group that was exposed to 0.88 mg L(-1 of TEB alone (corresponding to 16.6% of the 96-h LC50. We show that waterborne bee products, including royal jelly (RJ, honey (H, bee pollen (BP and propolis (P, reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD, catalase (CAT and glutathione-S-transferase (GST are increased.

  9. Bee products prevent agrichemical-induced oxidative damage in fish.

    Science.gov (United States)

    Ferreira, Daiane; Rocha, Helio Carlos; Kreutz, Luiz Carlos; Loro, Vania Lucia; Marqueze, Alessandra; Koakoski, Gessi; da Rosa, João Gabriel Santos; Gusso, Darlan; Oliveira, Thiago Acosta; de Abreu, Murilo Sander; Barcellos, Leonardo José Gil

    2013-01-01

    In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g) were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™) and a group that was exposed to 0.88 mg L(-1) of TEB alone (corresponding to 16.6% of the 96-h LC50). We show that waterborne bee products, including royal jelly (RJ), honey (H), bee pollen (BP) and propolis (P), reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) are increased.

  10. Photodynamic therapy induced vascular damage: an overview of experimental PDT

    International Nuclear Information System (INIS)

    Wang, W; Moriyama, L T; Bagnato, V S

    2013-01-01

    Photodynamic therapy (PDT) has been developed as one of the most important therapeutic options in the treatment of cancer and other diseases. By resorting to the photosensitizer and light, which convert oxygen into cytotoxic reactive oxygen species (ROS), PDT will induce vascular damage and direct tumor cell killing. Another consequence of PDT is the microvascular stasis, which results in hypoxia and further produces tumor regression. To improve the treatment with PDT, three promising strategies are currently attracting much interest: (1) the combination of PDT and anti-angiogenesis agents, which more effectively prevent the proliferation of endothelial cells and the formation of new blood vessels; (2) the nanoparticle-assisted delivery of photosensitizer, which makes the photosensitizer more localized in tumor sites and thus renders minimal damage to the normal tissues; (3) the application of intravascular PDT, which can avoid the loss of energy during the transmission and expose the target area directly. Here we aim to review the important findings on vascular damage by PDT on mice. The combination of PDT with other approaches as well as its effect on cancer photomedicine are also reviewed. (review)

  11. Ion beam induced fluorescence imaging in biological systems

    International Nuclear Information System (INIS)

    Bettiol, Andrew A.; Mi, Zhaohong; Vanga, Sudheer Kumar; Chen, Ce-belle; Tao, Ye; Watt, Frank

    2015-01-01

    Imaging fluorescence generated by MeV ions in biological systems such as cells and tissue sections requires a high resolution beam (<100 nm), a sensitive detection system and a fluorescent probe that has a high quantum efficiency and low bleaching rate. For cutting edge applications in bioimaging, the fluorescence imaging technique needs to break the optical diffraction limit allowing for sub-cellular structure to be visualized, leading to a better understanding of cellular function. In a nuclear microprobe this resolution requirement can be readily achieved utilizing low beam current techniques such as Scanning Transmission Ion Microscopy (STIM). In recent times, we have been able to extend this capability to fluorescence imaging through the development of a new high efficiency fluorescence detection system, and through the use of new novel fluorescent probes that are resistant to ion beam damage (bleaching). In this paper we demonstrate ion beam induced fluorescence imaging in several biological samples, highlighting the advantages and challenges associated with using this technique

  12. Damage induced in semiconductors by swift heavy ion irradiation

    International Nuclear Information System (INIS)

    Levalois, M.; Marie, P.

    1999-01-01

    The behaviour of semiconductors under swift heavy ion irradiation is different from that of metals or insulators: no spectacular effect induced by the inelastic energy loss has been reported in these materials. We present here a review of irradiation effects in the usual semiconductors (silicon, germanium and gallium arsenide). The damage is investigated by means of electrical measurements. The usual mechanisms of point defect creation can account for the experimental results. Besides, some results obtained on the wide gap semiconductor silicon carbide are reported. Concerning the irradiation effects induced by heavy ions in particle detectors, based on silicon substrate, we show that the deterioration of the detector performances can be explained from the knowledge of the substrate properties which are strongly perturbed after high doses of irradiation. Finally, some future ways of investigation are proposed. The silicon substrate is a good example to compare the irradiation effects with different particles such as electrons, neutrons and heavy ions. It is then necessary to use parameters which account for the local energy deposition, in order to describe the damage in the material

  13. Protection from ionizing radiation induced damages by phytoceuticals and nutraceuticals

    International Nuclear Information System (INIS)

    Nair, C.K.K.

    2012-01-01

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

  14. Correlation of simulated TEM images with irradiation induced damage

    International Nuclear Information System (INIS)

    Schaeublin, R.; Almeida, P. de; Almazouzi, A.; Victoria, M.

    2000-01-01

    Crystal damage induced by irradiation is investigated using transmission electron microscopy (TEM) coupled to molecular dynamics (MD) calculations. The displacement cascades are simulated for energies ranging from 10 to 50 keV in Al, Ni and Cu and for times of up to a few tens of picoseconds. Samples are then used to perform simulations of the TEM images that one could observe experimentally. Diffraction contrast is simulated using a method based on the multislice technique. It appears that the cascade induced damage in Al imaged in weak beam exhibits little contrast, which is too low to be experimentally visible, while in Ni and Cu a good contrast is observed. The number of visible clusters is always lower than the actual one. Conversely, high resolution TEM (HRTEM) imaging allows most of the defects contained in the sample to be observed, although experimental difficulties arise due to the low contrast intensity of the smallest defects. Single point defects give rise in HTREM to a contrast that is similar to that of cavities. TEM imaging of the defects is discussed in relation to the actual size of the defects and to the number of clusters deduced from MD simulations

  15. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    International Nuclear Information System (INIS)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G.; Castiglione, F.; Vanzi, E.; Bottoncetti, A.; Pupi, A.

    2011-01-01

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced

  16. Can ebselen prevent cisplatin-induced ovarian damage?

    Science.gov (United States)

    Soyman, Zeynep; Uzun, Hafize; Bayindir, Nihan; Esrefoglu, Mukaddes; Boran, Birtan

    2018-06-01

    The occurrence of ovarian damage is a major shortcoming in treating tumors with cisplatin (CP). The present study investigates the beneficial effects of ebselen-a seleno-organic compound with antioxidant and antiinflammatory properties-vis-à-vis CP-induced ovarian damage. Twenty-eight adult female rats were divided into four study groups. Group 1 received no treatment. The rats in Groups 2, 3, and 4 were intraperitoneally administered CP (2 mg/kg/day) twice per week, for 5 weeks. Those in Group 2 received 0.3 ml saline (0.9% NaCl) intraperitoneally 60 min before each CP treatment, while those in Group 3 received 0.2 ml dimethyl sulfoxide (DMSO) and 0.3 ml saline intraperitoneally 60 min before each CP treatment. The rats in Group 4 were pretreated with an intraperitoneal injection of 15 mg/kg/day ebselen 60 min before each CP treatment. Ovarian tissue malondialdehyde (MDA), total nitric oxide (NOx), glutathione (GSH), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and catalase levels, as well as histopathological damage scores (HDSs) and serum antimullerian hormone (AMH) levels, were assessed. Cu/Zn-SOD and GSH levels were significantly higher, and MDA and NOx levels significantly lower, in Group 4 than in Groups 2 and 3. Pretreatment with ebselen significantly improved serum AMH levels, relative to Groups 2 and 3. Additionally, HDS values were significantly lower in Group 4 than in Groups 2 and 3. Our results from using an experimental rat model of CP chemotherapy suggest that ebselen use may ameliorate ovarian damage by preventing oxidative injury.

  17. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

    2011-10-15

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced

  18. Curcumin Attenuates Gamma Radiation Induced Intestinal Damage in Rats

    International Nuclear Information System (INIS)

    EI-Tahawy, N.A.

    2009-01-01

    Small Intestine exhibits numerous morphological and functional alterations during radiation exposure. Oxidative stress, a factor implicated in the intestinal injury may contribute towards some of these alterations. The present work was designed to evaluate the efficacy of curcumin, a yellow pigment of turmeric on y-radiation-induced oxidative damage in the small intestine by measuring alterations in the level of thiobarbituric acid reactive substances (TSARS), serotonin metabolism, catecholamine levels, and monoamine oxidase (MAO) activity in parallel to changes in the architecture of intestinal tissues. In addition, monoamine level, MAO activity and TSARS level were determined in the serum. Curcumin was supplemented orally via gavages, to rats at a dose of (45 mg/ Kg body wt/ day) for 2 weeks pre-irradiation and the last supplementation was 30 min pre exposure to 6.5 Gy gamma radiations (applied as one shot dose). Animals were sacrificed on the 7th day after irradiation. The results demonstrated that, whole body exposure of rats to ionizing radiation has induced oxidative damage in small intestine obvious by significant increases of TSARS content, MAO activity and 5-hydroxy indole acetic acid (5-HIAA) and by significant decreases of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) levels. In parallel histopathological studies of the small intestine of irradiated rats through light microscopic showed significant decrease in the number of villi, villus height, mixed sub mucosa layer with more fibres and fibroblasts. Intestinal damage was in parallel to significant alterations of serum MAO activity, TBARS, 5-HT, DA, NE and EPI levels. Administration of curcumin before irradiation has significantly improved the levels of monoamines in small intestine and serum of irradiated rats, which was associated with significant amelioration in MAO activity and TBARS contents

  19. Defense mechanisms against radiation induced teratogenic damage in mice

    International Nuclear Information System (INIS)

    Kato, F.; Ootsuyama, A.; Nomoto, S.; Norimura, T.

    2002-01-01

    Experimental studies with mice have established that fetuses at midgestational stage are highly susceptible to malformation at high, but not low, doses of radiation. When DNA damage is produced by a small amount of radiation, it is efficiently eliminated by DNA repair. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. In order to elucidate the essential role of p53 gene in apoptotic tissue repair, we compared the incidence of radiation-induced malformations and deaths (deaths after day 10) in wild-type p53 (+/+) mice and null p53 (-/-) mice. For p53 (+/+) mice, an X-ray dose of 2 Gy given at a high dose-rate (450 mGy/min) to fetuses at 9.5 days of gestation was highly lethal and considerably teratogenic whereas it was only slightly lethal but highly teratogenic for p53 (-/-) fetuses. This reciprocal relationship of radiosensitivity to malformations and deaths supports the notion that fetal tissues have a p53 -dependent idguardianln of the tissue that aborts cells bearing radiation-induced teratogenic DNA damage. When an equal dose of 2 Gy given at a 400-fold lower dose-rate (1.2 mGy/min), this dose became not teratogenic for p53 (+/+) fetuses exhibiting p53 -dependent apoptosis, whereas this dose remained teratogenic for p53 (-/-) fetuses unable to carry out apoptosis. Furthermore, when the dose was divided into two equal dose fractions (1+1 Gy) at high dose rate, separated by 24 hours, the incidences of malformations were equal with control level for p53 (+/+), but higher for p53 (-/-) mice. Hence, complete elimination of teratogenic damage from irradiated tissues requires a concerted cooperation of two mechanisms; proficient DNA repair and p53-dependent apoptotic tissue repair

  20. Radiation-induced cross-link DNA damages: synthesis, measurement and insertion into oligonucleotides for replication and enzymatic repair studies

    International Nuclear Information System (INIS)

    Bellon, Sophie

    2003-01-01

    This research thesis addresses the synthesis, measurement and study of the biological impact of radio-induced DNA double damages. In the first part, the author reports the study of the reactivity and fate of the 5-(2'-desoxy-uridilyl)methyl radical which is one of the intermediates formed by oxidizing photo-sensitisation of thymine. The next part reports results of the formation and measurement of double damages of isolated and cellular DNA, notably in the case of γ irradiation. The third part reports the study of in vitro replication of one of the double damages. The behaviour of different polymerases with respect to the damage is reported. Finally, the modified oligonucleotide has been used as a substrate to highlight possible activities of enzymatic repair for this type of cross-link damages by purified proteins or proteins present within cellular extracts [fr

  1. Damage-free vibrational spectroscopy of biological materials in the electron microscope.

    Science.gov (United States)

    Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L; Dellby, Niklas; Lovejoy, Tracy C; Wolf, Sharon G; Cohen, Hagai

    2016-03-10

    Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an 'aloof' electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C-H, N-H and C=O vibrational signatures with no observable radiation damage. The technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ∼10 nm, simultaneously combined with imaging in the electron microscope.

  2. Progressive damage to rat skin induced by protons

    International Nuclear Information System (INIS)

    Molinari, Beatriz L.; Saint-Martin, Maria L.G.; Bernaola, Omar A.; Duran, Hebe; Policastro, Lucia L.; O'Connor, Silvia E.; Palmieri, Monica; Davidson, Miguel; Davidson, Jorge

    2003-01-01

    Wistar rats were locally irradiated with proton beams. Dorsal portions of the skin were irradiated to a dose of 20 Gy employing a plastic wedge as a variable thickness energy degrader. The animals were sacrificed 2,5,6,7,and 9 days post-irradiation. The doses were monitored with a transmission camera. Solid track detectors (Makrofold E) were placed on the area to be irradiated to determine spatial correlation with the dose. Tissue reactions were clearly observed and were quantitatively assessed as a function of dose. Track detectors proved to be valuable to determine the correlation between the dose and tissue damage . This biological experimental model proved useful to analyze the response of tissues to a gradient of doses yielded by a proton beam. (author)

  3. Quantitative assessment of the ion-beam irradiation induced direct damage of nucleic acid bases through FTIR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qing, E-mail: huangq@ipp.ac.cn [Key Laboratory of Ion Beam Bio-engineering, Institute of Technical Biology and Agriculture Engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences (China); University of Science and Technology of China, Hefei 230029, Anhui (China); Su, Xi; Yao, Guohua; Lu, Yilin; Ke, Zhigang; Liu, Jinghua; Wu, Yuejin; Yu, Zengliang [Key Laboratory of Ion Beam Bio-engineering, Institute of Technical Biology and Agriculture Engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences (China)

    2014-07-01

    Energetic particles exist ubiquitously in nature, and when they hit DNA molecules in organisms, they may induce critical biological effects such as mutation. It is however still a challenge to measure directly and quantitatively the damage imposed by the energetic ions on target DNA molecules. In this work we attempted to employ Fourier transformation infrared (FTIR) spectroscopy to assess the ion-induced direct damage of four nucleic acid bases, namely, thymine (T), cytosine (C), guanine (G), and adenine (A), which are the building blocks of DNA molecules. The samples were prepared as thin films, irradiated by argon ion-beams at raised ion fluences, and in the meantime measured by FTIR spectroscopy for the damage in a quasi-in-situ manner. It was found that the low-energy ion-beam induced radiosensitivity of the four bases shows the sequence G > T > C > A, wherein the possible mechanism was also discussed.

  4. Heavy ion induced damage to plasmid DNA : plateau region vs. spread out Bragg-peak

    NARCIS (Netherlands)

    Dang, H.M.; van Goethem, M.J.; van der Graaf, E.R.; Brandenburg, S.; Hoekstra, R.A.; Schlathölter, T.A.

    We have investigated the damage of synthetic plasmid pBR322 DNA in dilute aqueous solutions induced by fast carbon ions. The relative contribution of indirect damage and direct damage to the DNA itself is expected to vary with linear energy transfer along the ion track, with the direct damage

  5. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    Science.gov (United States)

    Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

    1991-01-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

  6. Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

    International Nuclear Information System (INIS)

    Cucinotta, F.A.; Katz, R.; Wilson, J.W.; Townsend, L.W.; Nealy, J.E.; Shinn, J.L.

    1991-02-01

    The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space

  7. Systems Biology of Saccharomyces cerevisiae Physiology and its DNA Damage Response

    DEFF Research Database (Denmark)

    Fazio, Alessandro

    The yeast Saccharomyces cerevisiae is a model organism in biology, being widely used in fundamental research, the first eukaryotic organism to be fully sequenced and the platform for the development of many genomics techniques. Therefore, it is not surprising that S. cerevisiae has also been widely...... used in the field of systems biology during the last decade. This thesis investigates S. cerevisiae growth physiology and DNA damage response by using a systems biology approach. Elucidation of the relationship between growth rate and gene expression is important to understand the mechanisms regulating...... set of growth dependent genes by using a multi-factorial experimental design. Moreover, new insights into the metabolic response and transcriptional regulation of these genes have been provided by using systems biology tools (Chapter 3). One of the prerequisite of systems biology should...

  8. Integration of Principles of Systems Biology and Radiation Biology: Toward Development of in silico Models to Optimize IUdR-Mediated Radiosensitization of DNA Mismatch Repair Deficient (Damage Tolerant) Human Cancers

    International Nuclear Information System (INIS)

    Kinsella, Timothy J.; Gurkan-Cavusoglu, Evren; Du, Weinan; Loparo, Kenneth A.

    2011-01-01

    Over the last 7 years, we have focused our experimental and computational research efforts on improving our understanding of the biochemical, molecular, and cellular processing of iododeoxyuridine (IUdR) and ionizing radiation (IR) induced DNA base damage by DNA mismatch repair (MMR). These coordinated research efforts, sponsored by the National Cancer Institute Integrative Cancer Biology Program (ICBP), brought together system scientists with expertise in engineering, mathematics, and complex systems theory and translational cancer researchers with expertise in radiation biology. Our overall goal was to begin to develop computational models of IUdR- and/or IR-induced base damage processing by MMR that may provide new clinical strategies to optimize IUdR-mediated radiosensitization in MMR deficient (MMR − ) “damage tolerant” human cancers. Using multiple scales of experimental testing, ranging from purified protein systems to in vitro (cellular) and to in vivo (human tumor xenografts in athymic mice) models, we have begun to integrate and interpolate these experimental data with hybrid stochastic biochemical models of MMR damage processing and probabilistic cell cycle regulation models through a systems biology approach. In this article, we highlight the results and current status of our integration of radiation biology approaches and computational modeling to enhance IUdR-mediated radiosensitization in MMR − damage tolerant cancers.

  9. Metoprolol induces oxidative damage in common carp (Cyprinus carpio).

    Science.gov (United States)

    Martínez-Rodríguez, Héctor; Donkor, Kingsley; Brewer, Sharon; Galar-Martínez, Marcela; SanJuan-Reyes, Nely; Islas-Flores, Hariz; Sánchez-Aceves, Livier; Elizalde-Velázquez, Armando; Gómez-Oliván, Leobardo Manuel

    2018-04-01

    During the last decade, β-blockers such as metoprolol (MTP) have been frequently detected in surface water, aquatic systems and municipal water at concentrations of ng/L to μg/L. Only a small number of studies exist on the toxic effects induced by this group of pharmaceuticals on aquatic organisms. Therefore, the present study aimed to evaluate the oxidative damage induced by MTP in the common carp Cyprinus carpio, using oxidative stress biomarkers. To this end, indicators of cellular oxidation such as hydroperoxide content (HPC), lipid peroxidation (LPX) and protein carbonyl content (PCC) were determined, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Also, concentrations of MTP and its metabolite O-desmethyl metoprolol were determined in water as well as carp gill, liver, kidney, brain and blood, along with the partial uptake pattern of these compounds. Results show that carp takes up MTP and its metabolite in the different organs evaluated, particularly liver and gill. The oxidative stress biomarkers, HPC, LPX, and PCC, as well as SOD and CAT activity all increased significantly at most exposure times in all organs evaluated. Results indicate that MTP and its metabolite induce oxidative stress on the teleost C. carpio and that the presence of these compounds may constitute a risk in water bodies for aquatic species. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Radiation and transposon-induced genetic damage in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Balter, H.; Griffith, C.S.; American Museum of Natural History, New York; Margulies, L.

    1992-01-01

    The interaction of X-ray-induced and transposon-induced damage was investigated in P-M hybrid dysgenesis in Drosophila melanogaster. X-ray dose-response of 330-1320 rad was monitored for sterility, fecundicity and partial X/Y chromosome loss among F 2 progeny derived from dysgenic cross of M strain females xP strain males (cross A) and its reciprocal (cross B), using a weaker and the standard Harwich P strain subline. The synergistic effect of P element activity and X-rays on sterility was observed only in cross A hybrids and the dose-response was nonlinear in hybrids derived from the strong standard reference Harwich subline, H W . This finding suggests that lesions induced by both mutator systems which produce the synergistic effects are 2-break events. Effect of increasing dose on the decline of fecundicity was synergistic, but linear, in hybrids of either subline. There was no interaction evident and thus no synergism in X/Y nondisjunction and partial Y chromosome loss measured by the loss of the B s marker alone or together with the y + marker. Interaction was detected in the loss of the y + marker alone from the X and Y chromosomes. The possible three-way interaction of X-rays (660 rad), post-replication repair deficiency and P elements mobility was assessed by measuring transmission distortion in dysgenic males derived from the Π 2 P strain. (author). 38 refs.; 5 tabs

  11. X-Ray induced DNA damage – why use plants?

    Directory of Open Access Journals (Sweden)

    John William Einset

    2015-06-01

    Full Text Available The comet assay was used to monitor DNA repair after X-ray exposures caused by 0.2-15 Gy. A clear distinction in the time course of DNA repair after 2 Gy was observed with an early ‘rapid phase’, lasting 20-40 minutes, being followed by a ‘slow phase’ which actually consists of a period of negligible repair and then rapid repair during 140-160 minutes. The fact that homozygous mutants for both ATM and BRCA1 fail to repair DNA completely during 3 hours after 2 Gy exposures indicates that repair processes occurring during the ‘slow phase’ involve ds breaks in DNA. Both BRCA1 and Rad51 expression are strongly upregulated by X-rays in Arabidopsis. Rye grass, Norway spruce and Sawara cypress also have ‘slow phase’ repair similar to Arabidopsis, suggesting that the requisite enzymes have to be induced in these plants as well. To look at the effect of genome size in relation to sensitivity to DNA damage, we exposed isolated nuclei from Norway spruce (19.2 Gbp genome, celery (14.1 Gbp, spinach (12.6 Gbp Sawara cypress (8.9 Gbp, lettuce (2.6 Gbp and Arabidopsis (0.135 Gbp to X-rays. After a 1 Gy exposure, a linear relationship was seen between % tails and genome size, confirming the idea that larger genomes are more sensitive to X-ray damage.

  12. Laser induced damage and fracture in fused silica vacuum windows

    International Nuclear Information System (INIS)

    Campbell, J.H.; Hurst, P.A.; Heggins, D.D.; Steele, W.A.; Bumpas, S.E.

    1996-11-01

    Laser-induced damage, that initiates catastrophic fracture, has been observed in large (≤61 cm dia) fused silica lenses that also serve as vacuum barriers in Nova and Beamlet lasers. If the elastic stored energy in the lens is high enough, the lens will fracture into many pieces (implosion). Three parameters control the degree of fracture in the vacuum barrier window: elastic stored energy (tensile stress), ratio of window thickness to flaw depth, and secondary crack propagation. Fracture experiments were conducted on 15-cm dia fused silica windows that contain surface flaws caused by laser damage. Results, combined with window failure data on Beamlet and Nova, were used to develop design criteria for a ''fail-safe'' lens (that may catastrophically fracture but not implode). Specifically, the window must be made thick enough so that the peak tensile stress is less than 500 psi (3.4 MPa) and the thickness/critical flaw size is less than 6. The air leak through the window fracture and into the vacuum must be rapid enough to reduce the load on the window before secondary crack growth occurs. Finite element stress calculations of a window before and immediately following fracture into two pieces show that the elastic stored energy is redistributed if the fragments ''lock'' in place and thereby bridge the opening. In such cases, the peak stresses at the flaw site can increase, leading to further (i.e. secondary) crack growth

  13. Long term radiological features of radiation-induced lung damage.

    Science.gov (United States)

    Veiga, Catarina; Landau, David; McClelland, Jamie R; Ledermann, Jonathan A; Hawkes, David; Janes, Sam M; Devaraj, Anand

    2018-02-01

    To describe the radiological findings of radiation-induced lung damage (RILD) present on CT imaging of lung cancer patients 12 months after radical chemoradiation. Baseline and 12-month CT scans of 33 patients were reviewed from a phase I/II clinical trial of isotoxic chemoradiation (IDEAL CRT). CT findings were scored in three categories derived from eleven sub-categories: (1) parenchymal change, defined as the presence of consolidation, ground-glass opacities (GGOs), traction bronchiectasis and/or reticulation; (2) lung volume reduction, identified through reduction in lung height and/or distortions in fissures, diaphragm, anterior junction line and major airways anatomy, and (3) pleural changes, either thickening and/or effusion. Six patients were excluded from the analysis due to anatomical changes caused by partial lung collapse and abscess. All remaining 27 patients had radiological evidence of lung damage. The three categories, parenchymal change, shrinkage and pleural change were present in 100%, 96% and 82% respectively. All patients had at least two categories of change present and 72% all three. GGOs, reticulation and traction bronchiectasis were present in 44%, 52% and 37% of patients. Parenchymal change, lung shrinkage and pleural change are present in a high proportion of patients and are frequently identified in RILD. GGOs, reticulation and traction bronchiectasis are common at 12 months but not diagnostic. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Limits for Beam Induced Damage: Reckless or too Cautious?

    CERN Document Server

    Bertarelli, A; Carra, F; Cerutti, F; Dallocchio, A; Mariani, N; Peroni, L; Scapin, M

    2011-01-01

    Accidental events implying direct beam impacts on collimators are of the utmost importance as they may lead to serious limitations of the overall LHC Performance. In order to assess damage threshold of components impacted by high energy density beams, entailing changes of phase and extreme pressures, state-of-the-art numerical simulation methods are required. In this paper, a review of the different dynamic response regimes induced by particle beams is given along with an indication of the most suited tools to treat each regime. Particular attention is paid to the most critical case, that of shock waves, for which standard Finite Element codes are totally unfit. A novel category of numerical tools, named Hydrocodes, has been adapted and used to analyse the consequences of an asynchronous beam abort on Phase 1 Tertiary Collimators (TCT). A number of simulations has been carried out with varying beam energy, number of bunches and bunch sizes allowing to identify different damage levels for the TCT up to catastr...

  15. Liposomal Antioxidants for Protection against Oxidant-Induced Damage

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2011-01-01

    Full Text Available Reactive oxygen species (ROS, including superoxide anion, hydrogen peroxide, and hydroxyl radical, can be formed as normal products of aerobic metabolism and can be produced at elevated rates under pathophysiological conditions. Overproduction and/or insufficient removal of ROS result in significant damage to cell structure and functions. In vitro studies showed that antioxidants, when applied directly and at relatively high concentrations to cellular systems, are effective in conferring protection against the damaging actions of ROS, but results from animal and human studies showed that several antioxidants provide only modest benefit and even possible harm. Antioxidants have yet to be rendered into reliable and safe therapies because of their poor solubility, inability to cross membrane barriers, extensive first-pass metabolism, and rapid clearance from cells. There is considerable interest towards the development of drug-delivery systems that would result in the selective delivery of antioxidants to tissues in sufficient concentrations to ameliorate oxidant-induced tissue injuries. Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and amphiphilic molecules. This paper focus on the use of liposomes for the delivery of antioxidants in the prevention or treatment of pathological conditions related to oxidative stress.

  16. Reversal of aflatoxin induced liver damage by turmeric and curcumin.

    Science.gov (United States)

    Soni, K B; Rajan, A; Kuttan, R

    1992-09-30

    The effect of certain food additives on aflatoxin production by Aspergillus parasiticus has been studied in vitro. Extracts of turmeric (Curcuma longa), garlic (Allium sativum) and asafoetida (Ferula asafoetida) inhibited the aflatoxin production considerably (more than 90%) at concentrations of 5-10 mg/ml. Similar results were also seen using butylated hydroxytoluene, butylated hydroxyanisole and ellagic acid at concentration 0.1 mM. Curcumin, the antioxidant principle from Curcuma longa did not have any effect on aflatoxin production. Turmeric and curcumin were also found to reverse the aflatoxin induced liver damage produced by feeding aflatoxin B1 (AFB1) (5 micrograms/day per 14 days) to ducklings. Fatty changes, necrosis and biliary hyperplasia produced by AFB1 were considerably reversed by these food additives.

  17. Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature

    Directory of Open Access Journals (Sweden)

    Abbaszadeh A.

    2017-06-01

    Full Text Available Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/ biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses

  18. Multi-scale approach to radiation damage induced by ion beams: complex DNA damage and effects of thermal spikes

    International Nuclear Information System (INIS)

    Surdutovich, E.; Yakubovich, A.V.; Solov'yov, A.V.; Surdutovich, E.; Yakubovich, A.V.; Solov'yov, A.V.

    2010-01-01

    We present the latest advances of the multi-scale approach to radiation damage caused by irradiation of a tissue with energetic ions and report the calculations of complex DNA damage and the effects of thermal spikes on biomolecules. The multi-scale approach aims to quantify the most important physical, chemical, and biological phenomena taking place during and following irradiation with ions and provide a better means for clinically-necessary calculations with adequate accuracy. We suggest a way of quantifying the complex clustered damage, one of the most important features of the radiation damage caused by ions. This quantification allows the studying of how the clusterization of DNA lesions affects the lethality of damage. We discuss the first results of molecular dynamics simulations of ubiquitin in the environment of thermal spikes, predicted to occur in tissue for a short time after an ion's passage in the vicinity of the ions' tracks. (authors)

  19. Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status

    Energy Technology Data Exchange (ETDEWEB)

    Lyckesvärd, Madeleine Nordén, E-mail: madeleine.lyckesvard@oncology.gu.se [Department of Oncology, Sahlgrenska Academy, University of Gothenburg (Sweden); Delle, Ulla; Kahu, Helena [Department of Oncology, Sahlgrenska Academy, University of Gothenburg (Sweden); Lindegren, Sture [Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg (Sweden); Jensen, Holger [The PET and Cyclotron Unit Copenhagen University Hospital, Rigshospitalet (Denmark); Bäck, Tom [Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg (Sweden); Swanpalmer, John [Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg (Sweden); Elmroth, Kecke [Department of Oncology, Sahlgrenska Academy, University of Gothenburg (Sweden)

    2014-07-15

    Highlights: • We study DNA damage response to low-LET photons and high-LET alpha particles. • Cycling primary thyrocytes are more sensitive to radiation than stationary cells. • Influence of radiation quality varies due to cell cycle status of normal cells. • High-LET radiation gives rise to a sustained DNA damage response. - Abstract: Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ({sup 211}At), concentrated in the thyroid by the same mechanism as {sup 131}I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ({sup 60}Co) and alpha particles from {sup 211}At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity levels of γH2AX decreased during the first 24 h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to {sup 211}At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels. Increasing ratios of micronuclei per cell nuclei were seen up to 1 Gy {sup 211}At. We found that primary thyrocytes were much more sensitive to alpha particle exposure compared with low-LET photons. Calculations of the relative biological effectiveness yielded higher RBE for cycling cells compared with stationary cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative

  20. The role of proteins in damage induced by free radicals

    International Nuclear Information System (INIS)

    Gebicki, J.M.

    1996-01-01

    The initial consequence of oxidative stress in living organisms is chemical modification of cell components. Recently increasing attention in this area has been paid to the modification of proteins. A form of protein modification which has been studied in some detail only recently is peroxidation. In the last 8 years, we and our collaborators have shown that a range of isolated proteins acquire hydroperoxide groups when exposed to a range of biologically plausible oxidants. These include HO free radicals generated by radiation or in the Fenton reaction, peroxyl radicals, oxidants released by activated neutrophils, and peroxynitrite. In more complex systems, we also found protein peroxides in the apo B component of LDL treated with 20 μM Cu ++ , and in irradiated blood serum. These observations suggest that the formation of protein peroxides is a possible consequence of oxidative stress in vivo. A remarkable feature of the process of protein peroxidation is its high efficiency. This is most easily measured with proteins oxidized by radiation-generated free radicals. It was found that, for some proteins, peroxide yields reached 40% of the numbers of HO radicals generated. Thus in effect, almost half of these radicals can be converted to the much more long-lived protein peroxide groups. If they, in turn, have the capacity to damage other molecules, the major oxidative pathway in vivo may have the sequence: free radical ? protein peroxide ? another oxidized molecule. This hypothesis was tested by studying the ability of protein peroxides to react with selected molecules and the results are briefly discussed. Clearly, these effects are specific to individual proteins. More generally, amino acid and protein peroxides were found to be a potential source of a range of free radicals when reduced by Fe ++ . If this turns out to be a common phenomenon, protein peroxides may prove to be a major source of oxidative damage

  1. The role of proteins in damage induced by free radicals

    Energy Technology Data Exchange (ETDEWEB)

    Gebicki, J.M. [Macquarie Univ., North Ryde, NSW (Australia). School of Biological Sciences

    1996-12-31

    The initial consequence of oxidative stress in living organisms is chemical modification of cell components. Recently increasing attention in this area has been paid to the modification of proteins. A form of protein modification which has been studied in some detail only recently is peroxidation. In the last 8 years, we and our collaborators have shown that a range of isolated proteins acquire hydroperoxide groups when exposed to a range of biologically plausible oxidants. These include HO free radicals generated by radiation or in the Fenton reaction, peroxyl radicals, oxidants released by activated neutrophils, and peroxynitrite. In more complex systems, we also found protein peroxides in the apo B component of LDL treated with 20 {mu}M Cu{sup ++}, and in irradiated blood serum. These observations suggest that the formation of protein peroxides is a possible consequence of oxidative stress in vivo. A remarkable feature of the process of protein peroxidation is its high efficiency. This is most easily measured with proteins oxidized by radiation-generated free radicals. It was found that, for some proteins, peroxide yields reached 40% of the numbers of HO radicals generated. Thus in effect, almost half of these radicals can be converted to the much more long-lived protein peroxide groups. If they, in turn, have the capacity to damage other molecules, the major oxidative pathway in vivo may have the sequence: free radical ? protein peroxide ? another oxidized molecule. This hypothesis was tested by studying the ability of protein peroxides to react with selected molecules and the results are briefly discussed. Clearly, these effects are specific to individual proteins. More generally, amino acid and protein peroxides were found to be a potential source of a range of free radicals when reduced by Fe{sup ++}. If this turns out to be a common phenomenon, protein peroxides may prove to be a major source of oxidative damage.

  2. Chromium-induced membrane damage: protective role of ascorbic acid.

    Science.gov (United States)

    Dey, S K; Nayak, P; Roy, S

    2001-07-01

    Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80-100 g body weight). It has been observed that the intoxication with chromium (i.p.) at the dose of 0.8 mg/100 g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospholipid of both liver and kidney. The alkaline phosphatase, total ATPase and Na(+)-K(+)-ATPase activities were significantly decreased in both liver and kidney after chromium treatment, except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid (i.p. at the dose of 0.5 mg/100 g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

  3. Exenatide Induces Impairment of Autophagy Flux to Damage Rat Pancreas.

    Science.gov (United States)

    Li, Zhiqiang; Huang, Lihua; Yu, Xiao; Yu, Can; Zhu, Hongwei; Li, Xia; Han, Duo; Huang, Hui

    2017-01-01

    The study aimed to explore the alteration of autophagy in rat pancreas treated with exenatide. Normal Sprague-Dawley rats and diabetes-model rats induced by 2-month high-sugar and high-fat diet and streptozotocin injection were subcutaneously injected with exenatide, respectively, for 10 weeks, with homologous rats treated with saline as control. Meanwhile, AR42J cells, pancreatic acinar cell line, were cultured with exenatide at doses of 5 pM for 3 days. The pancreas was disposed, and several sections were stained with hematoxylin-eosin. Immunohistochemistry was used to measure the expressions of glucagon-like peptide 1 receptor (GLP-1R) and cysteine-aspartic acid protease-3 in rat pancreas, and Western blot was used to test the expressions of GLP-1R, light chain 3B-I and -II, and p62 in rat pancreas and AR42J cells. The data were expressed as mean (standard deviation) and analyzed by unpaired Student's t-test. Exenatide can induce pathological changes in rat pancreas. The GLP-1R, p62, light chain 3B-II, and cysteine-aspartic acid protease-3 in rat pancreas and AR42J cells treated with exenatide were significantly overexpressed. Exenatide can activate and upregulate its receptor, GLP-1R, then impair autophagy flux and activate apoptosis in the pancreatic acinar cell, thus damaging rat pancreas.

  4. Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage.

    Science.gov (United States)

    Venditti, P; Pamplona, R; Ayala, V; De Rosa, R; Caldarone, G; Di Meo, S

    2006-03-01

    Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.

  5. Integrating plant and animal biology for the search of novel DNA damage biomarkers

    Czech Academy of Sciences Publication Activity Database

    Nikitaki, Z.; Holá, Marcela; Donà, M.; Pavlopoulou, A.; Michalopoulos, I.; Angelis, Karel; Georgakilas, A. G.; Macovei, I.; Balestrazzi, A.

    2018-01-01

    Roč. 775, JAN-MAR (2018), s. 21-38 ISSN 1383-5742 R&D Projects: GA ČR GA16-01137S Institutional support: RVO:61389030 Keywords : DNA damage response * Ionizing radiation * Radiation exposure monitoring * Radiotolerance * Ultraviolet radiation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 5.500, year: 2016

  6. The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

    International Nuclear Information System (INIS)

    Averbeck, D.; Boucher, D.

    2006-01-01

    Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using 137 Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage into

  7. The impact of locally multiply damaged sites (LMDS) induced by ionizing radiation in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Averbeck, D.; Boucher, D. [Institut Curie-Section de Recherche, UMR2027 CNRS, LCR-V28 du CEA, Centre Universitaire, 91405 Orsay Cedex (France)

    2006-07-01

    Monte Carlo calculations have shown that ionising radiations produce a specific type of clustered cell damage called locally multiply damaged sites or LMDS. These lesions consist of closely positioned single-strand breaks, (oxidative) base damage and DNA double-strand breaks (DSB) in between one helical turn of DNA. As specific markers of radiation-induced damage these lesions are likely to condition biological responses and are thus of great interest for radiation protection. Calculations indicate that there should be more LMDS induced by high than by low LET radiation, and they should be absent in un-irradiated cells. Processes like K-shell activation and local Auger electron emission can be expected to add complex DSB or LMDS, producing significant chromosomal damage. In the discussion of the specificity of ionising radiation in comparison to other genotoxic agents, many arguments have been put forward that these lesions should be particularly deleterious for living cells. Complex lesions of that type should represent big obstacles for DNA repair and give rise to high lethality. Moreover, cellular attempts to repair them could accentuate harm, leading to mutations, genetic instability and cancer. In vitro experiments with oligonucleotides containing an artificially introduced set of base damage and SSB in different combinations have shown that depending on the close positioning of the damage on DNA, repair enzymes, and even whole cell extracts, are unable to repair properly and may stimulate mis-repair. Pulsed field gel electrophoresis (PFGE) in conjunction with enzymatic treatments has been used to detect LMDS in mammalian cells after high and low LET radiation. In order to further define the importance of LMDS for radiation induced cellular responses, we studied the induction of LMDS as a function of radiation dose and dose rate in mammalian cells (CHO and MRC5) using {sup 137}Cs gamma-radiation. Using PFGE and specific glycosylases to convert oxidative damage

  8. Epithelial and endothelial damage induced by mechanical ventilation modes.

    Science.gov (United States)

    Suki, Béla; Hubmayr, Rolf

    2014-02-01

    The adult respiratory distress syndrome (ARDS) is a common cause of respiratory failure with substantial impact on public health. Patients with ARDS generally require mechanical ventilation, which risks further lung damage. Recent improvements in ARDS outcomes have been attributed to reductions in deforming stress associated with lung protective mechanical ventilation modes and settings. The following review details the mechanics of the lung parenchyma at different spatial scales and the response of its resident cells to deforming stress in order to provide the biologic underpinnings of lung protective care. Although lung injury is typically viewed through the lens of altered barrier properties and mechanical ventilation-associated immune responses, in this review, we call attention to the importance of heterogeneity and the physical failure of the load bearing cell and tissue elements in the pathogenesis of ARDS. Specifically, we introduce a simple elastic network model to better understand the deformations of lung regions, intra-acinar alveoli and cells within a single alveolus, and consider the role of regional distension and interfacial stress-related injury for various ventilation modes. Heterogeneity of stiffness and intercellular and intracellular stress failure are fundamental components of ARDS and their development also depends on the ventilation mode.

  9. A tissue phantom for visualization and measurement of ultrasound-induced cavitation damage.

    Science.gov (United States)

    Maxwell, Adam D; Wang, Tzu-Yin; Yuan, Lingqian; Duryea, Alexander P; Xu, Zhen; Cain, Charles A

    2010-12-01

    Many ultrasound studies involve the use of tissue-mimicking materials to research phenomena in vitro and predict in vivo bioeffects. We have developed a tissue phantom to study cavitation-induced damage to tissue. The phantom consists of red blood cells suspended in an agarose hydrogel. The acoustic and mechanical properties of the gel phantom were found to be similar to soft tissue properties. The phantom's response to cavitation was evaluated using histotripsy. Histotripsy causes breakdown of tissue structures by the generation of controlled cavitation using short, focused, high-intensity ultrasound pulses. Histotripsy lesions were generated in the phantom and kidney tissue using a spherically focused 1-MHz transducer generating 15 cycle pulses, at a pulse repetition frequency of 100 Hz with a peak negative pressure of 14 MPa. Damage appeared clearly as increased optical transparency of the phantom due to rupture of individual red blood cells. The morphology of lesions generated in the phantom was very similar to that generated in kidney tissue at both macroscopic and cellular levels. Additionally, lesions in the phantom could be visualized as hypoechoic regions on a B-mode ultrasound image, similar to histotripsy lesions in tissue. High-speed imaging of the optically transparent phantom was used to show that damage coincides with the presence of cavitation. These results indicate that the phantom can accurately mimic the response of soft tissue to cavitation and provide a useful tool for studying damage induced by acoustic cavitation. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  10. Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

    Science.gov (United States)

    Kim, Myung-Hee Y.; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

    2014-01-01

    The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ''biological Bragg curve'' is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta, et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called "overkill".

  11. Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

    International Nuclear Information System (INIS)

    Zheng, Juanjuan; Zhang, Yu; Xu, Wentao; Luo, YunBo; Hao, Junran; Shen, Xiao Li; Yang, Xuan; Li, Xiaohong; Huang, Kunlun

    2013-01-01

    Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ m ). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by OTA in

  12. Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Juanjuan; Zhang, Yu [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentaoboy@sina.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Luo, YunBo [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Hao, Junran [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Shen, Xiao Li [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Yang, Xuan [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Li, Xiaohong [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Huang, Kunlun, E-mail: hkl009@163.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

    2013-04-15

    Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by

  13. Biological significance of the focus on DNA damage checkpoint factors remained after irradiation of ionizing radiation

    International Nuclear Information System (INIS)

    Yamauchi, Motohiro; Suzuki, Keiji

    2005-01-01

    This paper reviews recent reports on the focus formation and participation to checkpoint of (such phosphorylated (P-d) as below) ATM and H2AX, MDC1, 53BP1 and NBS1, and discusses their role in DNA damage checkpoint induction mainly around authors' studies. When the cell is irradiated by ionizing radiation, the subtype histone like H2AX is P-d and the formed focus', seen in the nucleus on immuno-fluorographic observation, represents the P-d H2AX at the damaged site of DNA. The role of P-d ATM (the product of causative gene of ataxia-telangiectasia mutation, a protein kinase) has been first shown by laser beam irradiation. Described are discussions on the roles and functions after irradiation in focus formation and DNA damage checkpoint of P-d H2AX (a specific histone product by the radiation like γ-ray as above), P-d ATM, MDC1 (a mediator of DNA damage check point protein 1), 53BP1, (a p53 binding protein) and NBS1 (the product of the causative gene of Nijmegen Breakage Syndrome). Authors have come to point out the remained focal size increase as implications of the efficient repair of damaged DNA, and the second cycled p53 accumulation, of tumor suppression. Thus evaluation of biological significance of these aspects, scarcely noted hitherto, is concluded important. (S.I.)

  14. The biology of gall-inducing arthropods.

    Science.gov (United States)

    Gyuri Csoka; William J. Mattson; Graham N. Stone; Peter W. Price

    1998-01-01

    This proceedings explores many facets of the ever intriguing and enigmatic relationships between plants and their gall-forming herbivores. The research reported herein ranges from studies on classical biology and systematics of galling to molecular phylogeny, population genetics, and ecological and evolutionary theory. Human kind has much to learn and gain from...

  15. Molecular and sensory mechanisms to mitigate sunlight-induced DNA damage in treefrog tadpoles.

    Science.gov (United States)

    Schuch, André P; Lipinski, Victor M; Santos, Mauricio B; Santos, Caroline P; Jardim, Sinara S; Cechin, Sonia Z; Loreto, Elgion L S

    2015-10-01

    The increased incidence of solar ultraviolet B (UVB) radiation has been proposed as an environmental stressor, which may help to explain the enigmatic decline of amphibian populations worldwide. Despite growing knowledge regarding the UV-induced biological effects in several amphibian models, little is known about the efficacy of DNA repair pathways. In addition, little attention has been given to the interplay between these molecular mechanisms with other physiological strategies that avoid the damage induced by sunlight. Here, DNA lesions induced by environmental doses of solar UVB and UVA radiation were detected in genomic DNA samples of treefrog tadpoles (Hypsiboas pulchellus) and their DNA repair activity was evaluated. These data were complemented by monitoring the induction of apoptosis in blood cells and tadpole survival. Furthermore, the tadpoles' ability to perceive and escape from UV wavelengths was evaluated as an additional strategy of photoprotection. The results show that tadpoles are very sensitive to UVB light, which could be explained by the slow DNA repair rates for both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6,4PPs). However, they were resistant to UVA, probably as a result of the activation of photolyases during UVA irradiation. Surprisingly, a sensory mechanism that triggers their escape from UVB and UVA light avoids the generation of DNA damage and helps to maintain the genomic integrity. This work demonstrates the genotoxic impact of both UVB and UVA radiation on tadpoles and emphasizes the importance of the interplay between molecular and sensory mechanisms to minimize the damage caused by sunlight. © 2015. Published by The Company of Biologists Ltd.

  16. Beneficial effect of honokiol on lipopolysaccharide induced anxiety-like behavior and liver damage in mice.

    Science.gov (United States)

    Sulakhiya, Kunjbihari; Kumar, Parveen; Gurjar, Satendra S; Barua, Chandana C; Hazarika, Naba K

    2015-02-26

    Anxiety disorders are commonly occurring co-morbid neuropsychiatric disorders with chronic inflammatory conditions such as live damage. Numerous studies revealed that peripheral inflammation, oxidative stress and brain derived neurotrophic factor (BDNF) play important roles in the pathophysiology of anxiety disorders. Honokiol (HNK) is a polyphenol, possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and hepatoprotection. The present study was designed to investigate the effect of HNK, in lipopolysaccharide (LPS)-induced anxiety-like behavior and liver damage in mice. Mice (n=6-10/group) were pre-treated with different doses of HNK (2.5 and 5mg/kg; i.p.) for two days, and challenged with saline or LPS (0.83mg/kg; i.p.) on third day. Anxiety-like behavior was monitored using elevated plus maze (EPM) and open field test (OFT). Animals were sacrificed to evaluate various biochemical parameters in plasma and liver. HNK pre-treatment provided significant (P<0.01) protection against LPS-induced reduction in body weight, food and water intake in mice. HNK at higher dose significantly (P<0.05) attenuated LPS-induced anxiety-like behavior by increasing the number of entries and time spent in open arm in EPM test, and by increasing the frequency in central zone in OFT. HNK pre-treatment ameliorated LPS-induced peripheral inflammation by reducing plasma IL-1β, IL-6, TNF-α level, and also improved the plasma BDNF level, prevented liver damage via attenuating transaminases (AST, ALT), liver oxidative stress and TNF-α activity in LPS challenged mice. In conclusion, the current investigation suggests that HNK provided beneficial effect against LPS-induced anxiety-like behavior and liver damage which may be governed by inhibition of cytokines production, oxidative stress and depletion of plasma BDNF level. Our result suggests that HNK could be a therapeutic approach for the treatment of anxiety and other

  17. Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage

    OpenAIRE

    Venditti, Paola; Pamplona Gras, Reinald; Ayala, Victoria; Rosa, R. de; Caldarone, G.; Di Meo, S.

    2006-01-01

    Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T-3)- or thyroxine (T-4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most ex...

  18. Investigation on the correlation between energy deposition and clustered DNA damage induced by low-energy electrons.

    Science.gov (United States)

    Liu, Wei; Tan, Zhenyu; Zhang, Liming; Champion, Christophe

    2018-05-01

    This study presents the correlation between energy deposition and clustered DNA damage, based on a Monte Carlo simulation of the spectrum of direct DNA damage induced by low-energy electrons including the dissociative electron attachment. Clustered DNA damage is classified as simple and complex in terms of the combination of single-strand breaks (SSBs) or double-strand breaks (DSBs) and adjacent base damage (BD). The results show that the energy depositions associated with about 90% of total clustered DNA damage are below 150 eV. The simple clustered DNA damage, which is constituted of the combination of SSBs and adjacent BD, is dominant, accounting for 90% of all clustered DNA damage, and the spectra of the energy depositions correlating with them are similar for different primary energies. One type of simple clustered DNA damage is the combination of a SSB and 1-5 BD, which is denoted as SSB + BD. The average contribution of SSB + BD to total simple clustered DNA damage reaches up to about 84% for the considered primary energies. In all forms of SSB + BD, the SSB + BD including only one base damage is dominant (above 80%). In addition, for the considered primary energies, there is no obvious difference between the average energy depositions for a fixed complexity of SSB + BD determined by the number of base damage, but average energy depositions increase with the complexity of SSB + BD. In the complex clustered DNA damage constituted by the combination of DSBs and BD around them, a relatively simple type is a DSB combining adjacent BD, marked as DSB + BD, and it is of substantial contribution (on average up to about 82%). The spectrum of DSB + BD is given mainly by the DSB in combination with different numbers of base damage, from 1 to 5. For the considered primary energies, the DSB combined with only one base damage contributes about 83% of total DSB + BD, and the average energy deposition is about 106 eV. However, the

  19. Retinal Damage Induced by Internal Limiting Membrane Removal

    Directory of Open Access Journals (Sweden)

    Rachel Gelman

    2015-01-01

    Full Text Available The internal limiting membrane (ILM, the basement membrane of the Müller cells, serves as the interface between the vitreous body and the retinal nerve fiber layer. It has a fundamental role in the development, structure, and function of the retina, although it also is a pathologic component in the various vitreoretinal disorders, most notably in macular holes. It was not until understanding of the evolution of idiopathic macular holes and the advent of idiopathic macular hole surgery that the idea of adjuvant ILM peeling in the treatment of tractional maculopathies was explored. Today intentional ILM peeling is a commonly applied surgical technique among vitreoretinal surgeons as it has been found to increase the rate of successful macular hole closure and improve surgical outcomes in other vitreoretinal diseases. Though ILM peeling has refined surgery for tractional maculopathies, like all surgical procedures it is not immune to perioperative risk. The essential role of the ILM to the integrity of the retina and risk of trauma to retinal tissue spurs suspicion with regard to its routine removal. Several authors have investigated the retinal damage induced by ILM peeling and these complications have been manifested across many different diagnostic studies.

  20. Time evolution of damage in thermally induced creep rupture

    KAUST Repository

    Yoshioka, N.

    2012-01-01

    We investigate the time evolution of a bundle of fibers subject to a constant external load. Breaking events are initiated by thermally induced stress fluctuations followed by load redistribution which subsequently leads to an avalanche of breakings. We compare analytic results obtained in the mean-field limit to the computer simulations of localized load redistribution to reveal the effect of the range of interaction on the time evolution. Focusing on the waiting times between consecutive bursts we show that the time evolution has two distinct forms: at high load values the breaking process continuously accelerates towards macroscopic failure, however, for low loads and high enough temperatures the acceleration is preceded by a slow-down. Analyzing the structural entropy and the location of consecutive bursts we show that in the presence of stress concentration the early acceleration is the consequence of damage localization. The distribution of waiting times has a power law form with an exponent switching between 1 and 2 as the load and temperature are varied.

  1. Damage-induced permeability changes around underground excavations

    International Nuclear Information System (INIS)

    Coll, C.

    2005-07-01

    The storage of nuclear waste in deep geological formations is now considered more and more as a potential solution. During excavation, a disturbed zone develops in which damaging can be important and which can lead eventually to the failure of the rock. Fluid flow and permeability in the rock mass can be significantly modified producing a possible security risk. Our work consisted in an experimental study of the hydro-mechanical coupling of two argillaceous rocks: Boom clay (Mol, Belgium) and Opalinus clay (Mont-Terri, Switzerland). Triaxial tests were performed in a saturated state to study the permeability evolution of both clays with isotropic and deviatoric stresses. Argillaceous rocks are geo-materials with complex behaviour governed by numerous coupled processes. Strong physico-chemical interactions between the fluid and the solid particles and their very low permeability required the modification of the experimental set up. Moreover, specific procedures were developed to measure permeability and to detect strain localisation in shear bands. We show that for Boom Clay, permeability is not significantly influenced by strain localisation. For Opalinus clay, fracturing can induce an increase of the permeability at low confining pressure. (author)

  2. Reductive effects of poria cocos on radiation-induced damage

    International Nuclear Information System (INIS)

    Oh, Heon; Park, Hae-Ran; Jo, Sung-Kee; Kim, Sung-Ho

    2002-01-01

    In order to screen a radioprotective material from nontoxic natural products, the effects of Poria cocos (PC), known as a blood tonic of traditional Oriental herbs, were investigated in HL-60 cells and ICR mice. The water extract of PC was administrated to mice and then the mice were irradiated with - rays. The jejunal crypt survival, endogenous spleen colony formation and apoptosis in jejunal crypt cells were investigated in mice irradiated with 12 Gy, 6.5 Gy, 2 Gy of -rays, respectively. The administration of the PC extract protected the jejunal crypts (p<0.005) and decreased the apoptosis frequency (p<0.05). The formation of endogenous spleen colony was increased but not significantly. The micronuclei (MN) formation and the alkaline single-cell gel electrophoresis (SCGE; comet assay) were investigated in HL- 60 cells irradiated 2 Gy of -rays. The frequency of MN was decreased (p<0.001) and the tail movement, which was a marker of DNA strand breaks in the SCGE, was decreased in groups treated with PC extract (p<0.01) before exposure to-irradiation. These results indicated that PC protects stem cells and reduces DNA damage induced by -rays. Therefore, Poria cocos might be a useful radioprotector, especially since it is a relatively nontoxic product

  3. Physical analysis on laser-induced cerebral damage

    Science.gov (United States)

    Luo, Xiaosen; Liu, Jiangang; Tao, Chunkan; Lan, Xiufeng; Cao, Lingyan; Pan, Weimin; Shen, Zhonghua; Lu, Jian; Ni, Xiaowu

    2005-01-01

    Experimental investigation on cerebral damage of adult SD rats induced by 532nm CW laser was performed. Tissue heat conductive equation was set up based on two-layered structure model. Finite difference algorithm was utilized to numerically simulate the temperature distribution in the brain tissue. Allowing for tissue response to temperature variation, free boundary model was used to discuss tissue thermal coagulation formation in brain. Experimental observations show that thermal coagulation and necrosis can be caused due to laser light absorption. The result of the calculation shows that the process of the thermal coagulation of the given mode comprises two stages: fast and slow. At the first stage, necrosis domain grows fast. Then necrosis domain growth becomes slower because of the competition between the heat diffusion into the surrounding undamaged tissue and the heat dissipation caused by blood perfusion. At the center of coagulation area no neuron was observed and at the transitional zone few nervous cells were seen by microscope. The research can provide reference data for developing clinical therapy of some kind of encephalic diseases by using 532nm laser, and for making cerebral infarction models in animal experiment.

  4. SHI induced damage in electrical properties of silicon NPN BJTs

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, M. Vinay, E-mail: vkm288@gmail.com; Krishnaveni, S. [Department of studies in Physics, University of Mysore, Mysore (India); Kumar, Santhosh [Department of Physics, Regional Institute of Education, Mysore (India); Yashoda, T. [Department of Physics, AVK College for Women, Hassan (India)

    2016-05-23

    The investigation of radiation damage in Si microelectronic circuitry and devices are being carried out by various research groups globally. In particular the Si Bipolar junction transistors are very sensitive to high energetic radiation. In the present study, radiation response of NPN Bipolar junction transistor (2N3773) has been examined for 60 MeV B{sup 4+} ion. Key electrical properties like Gummel, dc current gain and capacitance – voltage (C-V) characteristics of 60 MeV B{sup 4+} ion irradiated transistor were studied before and after irradiation. Ion irradiation and subsequent electrical characterizations were performed at room temperature. Current voltage (I-V) measurements showed the increase in collector current for V{sub BE} ≤ 0.4 V as a function of fluence, which is due to B{sup 4+} ion induced surface leakage currents. Base current is observed to be more sensitive than collector current and gain appears to be degraded with ion fluence. Also, C-V measurements shows that both built in potential and doping concentration increased significantly after irradiation.

  5. Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.

    Science.gov (United States)

    Puche, Juan E; Muñoz, Úrsula; García-Magariño, Mariano; Sádaba, María C; Castilla-Cortázar, Inma

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. © 2016 International Union of Biochemistry and Molecular Biology.

  6. Robust optimization of the laser induced damage threshold of dielectric mirrors for high power lasers.

    Science.gov (United States)

    Chorel, Marine; Lanternier, Thomas; Lavastre, Éric; Bonod, Nicolas; Bousquet, Bruno; Néauport, Jérôme

    2018-04-30

    We report on a numerical optimization of the laser induced damage threshold of multi-dielectric high reflection mirrors in the sub-picosecond regime. We highlight the interplay between the electric field distribution, refractive index and intrinsic laser induced damage threshold of the materials on the overall laser induced damage threshold (LIDT) of the multilayer. We describe an optimization method of the multilayer that minimizes the field enhancement in high refractive index materials while preserving a near perfect reflectivity. This method yields a significant improvement of the damage resistance since a maximum increase of 40% can be achieved on the overall LIDT of the multilayer.

  7. Scopolamine methylbromide mitigates radiation induced damage and lethality in zebrafish

    International Nuclear Information System (INIS)

    Shrivastava, Nitisha; Joshi, Jayadev; Ghosh, Subhajit; Dimri, Manali; Prem Kumar, Indracanti; Sehgal, Neeta

    2014-01-01

    In view of the strategic importance radiation countermeasures hold, the present study was undertaken to screen a collection of small molecule clinical compounds for possible radioprotective action using zebrafish as a model system. Preliminary screening in developing zebrafish embryos (24 hour post fertilization, (hpf)) using damage manifestations and survival as end point identified scopolamine methylbromide (SMB), a muscarinic receptor antagonist, as a potential radiomitigator. It was found to be optimal (60% survival advantage after 6 th post irradiation day) at a dose of 80 μM when added 3 h post 20 Gy exposure. Mechanistic studies suggested that SMB though exhibited no significant antioxidant potential, but was found to limit radiation induced apoptosis (pre G1 population) quantified through flow cytometry (6 and 5% reduction after 8 or 24 h after treatments) and annexin V staining (8% reduction). Further, quantitative analysis, using caspase 3 assay, revealed a 2.46 fold increase in apoptosis in irradiated group and treatment of irradiated zebrafish embryos with SMB led to a significant reduction in global apoptosis (1.7 fold; p<0.05) when compared to irradiated group. In silico studies based on structural and functional similarity with known radioprotectors suggested similarities with atropine, a known anti-inflammatory agent with muscarinic antagonism and radioprotective potential. In view of this SMB was tested, in silico, for possible anti-inflammatory action. Molecular docking studies revealed that SMB interacts (B.E-8.0 Kcal/mole) with cycloxygenase-2 (COX-2). In lieu of this, anti-inflammation activity was assessed through ChIN (chemically induced inflammation) method in 3 dpf (days post fertilization) embryos and SMB was found to significantly inhibit inflammation at all doses studied from 20-200 μM at 3 and 6 hpi (hours post inflammation). Overall the result suggests that scopolamine methylbromide mitigates radiation induced injury and lethality in

  8. Laser-Induced Damage Growth on Larger-Aperture Fused Silica Optical Components at 351 nm

    International Nuclear Information System (INIS)

    Wan-Qing, Huang; Wei, Han; Fang, Wang; Yong, Xiang; Fu-Quan, Li; Bin, Feng; Feng, Jing; Xiao-Feng, Wei; Wan-Guo, Zheng; Xiao-Min, Zhang

    2009-01-01

    Laser-induced damage is a key lifetime limiter for optics in high-power laser facility. Damage initiation and growth under 351 nm high-fluence laser irradiation are observed on larger-aperture fused silica optics. The input surface of one fused silica component is damaged most severely and an explanation is presented. Obscurations and the area of a scratch on it are found to grow exponentially with the shot number. The area of damage site grows linearly. Micrographs of damage sites support the micro-explosion damage model which could be used to qualitatively explain the phenomena

  9. Clinical, biological, histological features and treatment of oral mucositis induced by radiation therapy: a literature review

    International Nuclear Information System (INIS)

    Bonan, Paulo Rogerio Ferreti; Lopes, Marcio Ajudarte; Almeida, Oslei Paes de; Alves, Fabio de Abreu

    2005-01-01

    The oral mucositis is a main side effect of radiotherapy on head and neck, initiating two weeks after the beginning of the treatment. It is characterized by sensation of local burning to intense pain, leading in several cases, to the interruption of the treatment. The purpose of this work is to review the main published studies that discuss the clinical, biological and histopathological features of oral mucositis induced by radiation therapy and to describe the main approaches recommended to prevent or to treat it. Although the clinical features of mucositis are intensively described in the literature, few studies address the histopathological alterations in oral mucositis and only recently, its biological processes have been investigated. The biological mechanisms involved in the radiation tissue damage have been only recently discussed and there is no consensus among treatment modalities. Yet, the progressive knowledge in the histopathology and biological characteristics of oral mucositis probably will lead to more effective in prevention and control strategies. (author)

  10. Basic molecular biology in radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Rytoemaa, T.

    1992-01-01

    The tumour suppressor gene p53 is 'guardian of the genome'. If a DNA molecule (each chromosome has one DNA molecule) is damaged by an external factor, such as ionizing radiation, the protein product of the p53 gene stops the cell's proliferative activity until the damage is repaired. If the repair fails, the p53 gene product normally triggers programmed death of the cell. P53 gene itself is commonly damaged by radiation (or by another DNA-damaging factor). The altered gene product fails to control the integrity of the genome, and it also prevents the guardian action of the protein which is produced by the intact allele (each cell has two p53 genes). Under these circumstances any subsequent damage to DNA, induced e.g. by a chemical, is easily 'fixed'. Potentially critical sites for an additional DNA damage are the proto-oncogens (when damaged these genes are called oncogens), which commonly act as components of the regulatory network in a cell. Permanent malfunction of the signal network may then lead to uncontrolled cell growth, resulting in a malignant clone (=cancer). This simplified molecular model seems to be the common mechanism in many (or most) human cancers. (orig.)

  11. Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage

    Directory of Open Access Journals (Sweden)

    Cheng Ji

    2015-06-01

    Full Text Available Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries.

  12. Relative biological effectiveness (RBE) and distal edge effects of proton radiation on early damage in vivo

    DEFF Research Database (Denmark)

    Sørensen, Brita Singers; Bassler, Niels; Nielsen, Steffen

    2017-01-01

    of the SOBP to behind the distal dose fall-off. Irradiations were performed with the same dose plan at all positions, corresponding to a dose of 31.25 Gy in the middle of the SOBP. Endpoint of the study was early skin damage of the foot, assessed by a mouse foot skin scoring system. RESULTS: The MDD50 values......, where LETd,z =1 was 3.3 keV/μm. CONCLUSIONS: Although there is a need to expand the current study to be able to calculate an exact enhancement ratio, an enhanced biological effect in vivo for early skin damage in the distal edge was demonstrated....

  13. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

    2012-01-01

    Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

  14. Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat

    Science.gov (United States)

    Dhibi, Sabah; Mbarki, Sakhria; Elfeki, Abdelfettah; Hfaiedh, Najla

    2014-01-01

    Plants have historically been used in treating many diseases. Eucalyptus globules, a rich source of bioactive compounds, and have been shown to possess antioxidative properties. The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of Eucalyptus globulus extract upon acetaminophen-induced damages in kidney. Our study is realized in the Department of Biology, Faculty of Sciences of Sfax (Tunisia). 32 Wistar male rats; were divided into 4 batches: a control group (n=8), a group of rats treated with acetaminophen (goomg/kg) by intraperitoneal injection during 4 days (n=8), a group receiving Eucalyptus globulus extract (130 mg of dry leaves/kg/day) in drinking water during 42 days after 2 hours of acetaminophen administration (during 4 days) (n=8) and group received only Eucalyptus (n=8) during 42 days. After 6 weeks, animals from each group were rapidly sacrificed by decapitation. Blood serum was obtained by centrifugation. Under our experimental conditions, acetaminophen poisoning resulted in an oxidative stress evidenced by statistically significant losses in the activities of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in lipids peroxidation level in renal tissue of acetaminophen-treated group compared with the control group. Acetaminophen also caused kidney damage as evident by statistically significant (p<0.05) increase in levels of creatinine and urea and decreased levels of uric acid and proteins in blood. Histological analysis demonstrated alteration of proximal tubules, atrophy of the glomerule and dilatation of urinary space. Previous administration of plant extract is found to alleviate this acetaminophen-induced damage. PMID:24856382

  15. Chromium-induced skin damage among Taiwanese cement workers.

    Science.gov (United States)

    Chou, Tzu-Chieh; Wang, Po-Chih; Wu, Jyun-De; Sheu, Shiann-Cherng

    2016-10-01

    Little research has been done on the relationships between chromium exposure, skin barrier function, and other hygienic habits in cement workers. Our purpose was to investigate chromium-induced skin barrier disruption due to cement exposure among cement workers. One hundred and eight cement workers were recruited in this study. Urinary chromium concentration was used to characterize exposure levels. The biological exposure index was used to separate high and low chromium exposure. Transepidermal water loss (TEWL) was used to assess the skin barrier function. TEWL was significantly increased in workers with high chromium exposure levels than those with low chromium exposure levels (p = 0.048). A positive correlation was also found between urinary chromium concentration and TEWL (R = 0.28, p = 0.004). After adjusting for smoking status and glove use, a significant correlation between urinary chromium concentrations and TEWL remained. Moreover, workers who smoked and had a high chromium exposure had significantly increased TEWL compared to nonsmokers with low chromium exposure (p = 0.01). Skin barrier function of cement workers may have been disrupted by chromium in cement, and smoking might significantly enhance such skin barrier perturbation with chromium exposure. Decreased chromium skin exposure and smoking cessation should be encouraged at work. © The Author(s) 2015.

  16. Involvement of inducible nitric oxide synthase in radiation-induced vascular endothelial damage

    International Nuclear Information System (INIS)

    Hong, Chang-Won; Lee, Joon-Ho; Kim, Suwan; Noh, Jae Myoung; Kim, Young-Mee; Pyo, Hongryull; Lee, Sunyoung

    2013-01-01

    The use of radiation therapy has been linked to an increased risk of cardiovascular disease. To understand the mechanisms underlying radiation-induced vascular dysfunction, we employed two models. First, we examined the effect of X-ray irradiation on vasodilation in rabbit carotid arteries. Carotid arterial rings were irradiated with 8 or 16 Gy using in vivo and ex vivo methods. We measured the effect of acetylcholine-induced relaxation after phenylephrine-induced contraction on the rings. In irradiated carotid arteries, vasodilation was significantly attenuated by both irradiation methods. The relaxation response was completely blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a potent inhibitor of soluble guanylate cyclase. Residual relaxation persisted after treatment with L-N ω -nitroarginine (L-NA), a non-specific inhibitor of nitric oxide synthase (NOS), but disappeared following the addition of aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS). The relaxation response was also affected by tetraethylammonium, an inhibitor of endothelium-derived hyperpolarizing factor activity. In the second model, we investigated the biochemical events of nitrosative stress in human umbilical-vein endothelial cells (HUVECs). We measured iNOS and nitrotyrosine expression in HUVECs exposed to a dose of 4 Gy. The expression of iNOS and nitrotyrosine was greater in irradiated HUVECs than in untreated controls. Pretreatment with AG, L-N 6 -(1-iminoethyl) lysine hydrochloride (a selective inhibitor of iNOS), and L-NA attenuated nitrosative stress. While a selective target of radiation-induced vascular endothelial damage was not definitely determined, these results suggest that NO generated from iNOS could contribute to vasorelaxation. These studies highlight a potential role of iNOS inhibitors in ameliorating radiation-induced vascular endothelial damage. (author)

  17. Complementing xeroderma pigmentosum fibroblasts restore biological activity to UV-damaged DNA

    International Nuclear Information System (INIS)

    Day, R.S. III; Kraemer, K.H.; Robbins, J.H.

    1975-01-01

    UV survival curves of adenovirus 2 using fused complementing xeroderma pigmentosum fibroblast strains as virus hosts showed a component with an inactivation slope identical to that given by normal cells. This component was not observed when the fibroblasts were not fused or when fusions involved strains in the same complementing group. Extrapolation to zero dose indicated that three percent of the viral plaque-forming units had infected cells capable of normal repair; this suggested that three percent of the cells were complementing heterokaryons. Thus, heterokaryons formed from xeroderma pigmentosum fibroblasts belonging to different complementation groups are as capable of restoring biological activity to UV-damaged adenovirus 2 as are normal cells

  18. Sunlight-induced DNA damage in human mononuclear cells

    DEFF Research Database (Denmark)

    Møller, Peter; Wallin, Hakan; Holst, Erik

    2002-01-01

    of sunlight was comparable to the interindividual variation, indicating that sunlight exposure and the individual's background were the two most important determinants for the basal level of DNA damage. Influence of other lifestyle factors such as exercise, intake of foods, infections, and age could......In this study of 301 blood samples from 21 subjects, we found markedly higher levels of DNA damage (nonpyrimidine dimer types) in the summer than in the winter detected by single-cell gel electrophoresis. The level of DNA damage was influenced by the average daily influx of sunlight ... to blood sampling. The 3 and 6 day periods before sampling influenced DNA damage the most. The importance of sunlight was further emphasized by a positive association of the DNA damage level to the amount of time the subjects had spent in the sun over a 3 day period prior to the sampling. The effect...

  19. UV-B induces DNA damage and DNA synthesis delay in the marine diatom Cyclotella sp

    NARCIS (Netherlands)

    Buma, A.G.J.; Van Hannen, E.J.; Veldhuis, M.; Gieskes, W.W.C.

    1996-01-01

    The effect of UV-B on the occurrence of DNA damage and consequences for the cell cycle were studied in the marine diatom Cyclotella sp. DNA damage was quantified by immunofluorescent detection of thymine dimers in nuclear DNA of single cells using flow cytometry. A total UV-B dose (biologically

  20. UV-B induces DNA damage and DNA synthesis delay in the marine diatom Cyclotella sp.

    NARCIS (Netherlands)

    Buma, A.G.J.; van Hannen, E.J; Veldhuis, M.J W; Gieskes, W.W C

    The effect of UV-B on the occurrence of DNA damage and consequences for the cell cycle were studied in the marine diatom Cyclotella sp. DNA damage was quantified by immunofluorescent detection of thymine dimers in nuclear DNA of single cells using flow cytometry. A total UV-B dose (biologically

  1. 2-Aminopurine hairpin probes for the detection of ultraviolet-induced DNA damage

    International Nuclear Information System (INIS)

    El-Yazbi, Amira F.; Loppnow, Glen R.

    2012-01-01

    Highlights: ► Molecular beacon with 2AP bases detects DNA damage in a simple mix-and-read assay. ► Molecular beacons with 2AP bases detect damage at a 17.2 nM limit of detection. ► The 2AP molecular beacon is linear over a 0–3.5 μM concentration range for damage. - Abstract: Nucleic acid exposure to radiation and chemical insults leads to damage and disease. Thus, detection and understanding DNA damage is important for elucidating molecular mechanisms of disease. However, current methods of DNA damage detection are either time-consuming, destroy the sample, or are too specific to be used for generic detection of damage. In this paper, we develop a fluorescence sensor of 2-aminopurine (2AP), a fluorescent analogue of adenine, incorporated in the loop of a hairpin probe for the quantification of ultraviolet (UV) C-induced nucleic acid damage. Our results show that the selectivity of the 2AP hairpin probe to UV-induced nucleic acid damage is comparable to molecular beacon (MB) probes of DNA damage. The calibration curve for the 2AP hairpin probe shows good linearity (R 2 = 0.98) with a limit of detection of 17.2 nM. This probe is a simple, fast and economic fluorescence sensor for the quantification of UV-induced damage in DNA.

  2. Heavy ion induced DNA transfer in biological cells

    International Nuclear Information System (INIS)

    Vilaithong, T.; Yu, L.D.; Apavatjrut, P.; Phanchaisri, B.; Sangyuenyongpipat, S.; Anuntalabhochai, S.; Brown, I.G.

    2004-01-01

    Low-energy ion beam bombardment of biological materials for genetic modification purposes has experienced rapid growth in the last decade, particularly for the direct DNA transfer into living organisms including both plants and bacteria. Attempts have been made to understand the mechanisms involved in ion-bombardment-induced direct gene transfer into biological cells. Here we summarize the present status of the application of low-energy ions for genetic modification of living sample materials

  3. Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage.

    Science.gov (United States)

    Shirazi, Alireza; Mihandoost, Ehsan; Ghobadi, Ghazale; Mohseni, Mehran; Ghazi-Khansari, Mahmoud

    2013-01-01

    Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system.The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study,thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin (30 mg/kg on the first day and 30 mg/kg on the following days), group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal (IP) injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde (MDA) and glutathione (GSH). Each data point represents mean ± standard error on the mean (SEM) of at least eight animals per group. A one-way analysis of variance (ANOVA) was performed to compare different groups, followed by Tukey's multiple comparison tests (p<0.05). The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin (30 mg/kg) were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation.

  4. A survey of chemicals inducing lipid peroxidation in biological systems.

    Science.gov (United States)

    Kappus, H

    1987-01-01

    A great number of drugs and chemicals are reviewed which have been shown to stimulate lipid peroxidation in any biological system. The underlying mechanisms, as far as known, are also dealt with. Lipid peroxidation induced by iron ions, organic hydroperoxides, halogenated hydrocarbons, redox cycling drugs, glutathione depleting chemicals, ethanol, heavy metals, ozone, nitrogen dioxide and a number of miscellaneous compounds, e.g. hydrazines, pesticides, antibiotics, are mentioned. It is shown that lipid peroxidation is stimulated by many of these compounds. However, quantitative estimates cannot be given yet and it is still impossible to judge the biological relevance of chemical-induced lipid peroxidation.

  5. The Protective Role of Hyaluronic Acid in Cr(VI-Induced Oxidative Damage in Corneal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Wei Wu

    2017-01-01

    Full Text Available Cr(VI exposure could produce kinds of intermediates and reactive oxygen species, both of which were related to DNA damage. Hyaluronan (HA has impressive biological functions and was reported to protect corneal epithelial cells against oxidative damage induced by ultraviolet B, benzalkonium chloride, and sodium lauryl sulfate. So the aim of our study was to investigate HA protection on human corneal epithelial (HCE cells against Cr(VI-induced toxic effects. The HCE cell lines were exposed to different concentrations of K2Cr2O7 (1.875, 3.75, 7.5, 15.0, and 30 μM or a combination of K2Cr2O7 and 0.2% HA and incubated with different times (15 min, 30 min, and 60 min. Our data showed that Cr(VI exposure could cause decreased cell viability, increased DNA damage, and ROS generation to the HCE cell lines. But incubation of HA increased HCE cell survival rates and decreased DNA damage and ROS generation induced by Cr(VI in a dose- and time-dependent manner. We report for the first time that HA can protect HCE cells against the toxicity of Cr(VI, indicating that it will be a promising therapeutic agent to corneal injuries caused by Cr(VI.

  6. Mining-induced surface damage and the study of countermeasures

    International Nuclear Information System (INIS)

    Cui Jixian

    1994-01-01

    Coal constitutes China's major energy resource. The majority of the coal is produced from underground mining operations. Surface subsidence may amount to 80% of the thickness of the seam mined, while the subsided volume is around 60% of the mined volume underground. An area of 20 hectares of land will be affected with each 1 million tons of coal mined, thereby causing severe surface damage. Following a description of the characteristics of surface damages due to underground mining disturbance, this paper elaborates on the damage prediction method, standards applied for evaluating the damages experienced by surface buildings, land reclamation methods in subsided area, measures for reinforcing and protecting buildings in mining-affected areas, and performance of antideformation buildings

  7. Chromatin remodeling in the UV-induced DNA damage response

    NARCIS (Netherlands)

    Ö.Z. Aydin (Özge)

    2014-01-01

    markdownabstract__Abstract__ DNA damage interferes with transcription and replication, causing cell death, chromosomal aberrations or mutations, eventually leading to aging and tumorigenesis (Hoeijmakers, 2009). The integrity of DNA is protected by a network of DNA repair and associated

  8. Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

    Science.gov (United States)

    Flores-Palacios, Alejandro; Corona-López, Angélica María; Rios, María Yolanda; Aguilar-Guadarrama, Berenice; Toledo-Hernández, Víctor Hugo; Rodríguez-López, Verónica; Valencia-Díaz, Susana

    2015-01-01

    Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC) 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound) and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load) that may be caused by a high load of epiphytes than to damage caused by the xylophages.

  9. Is Allelopathic Activity of Ipomoea murucoides Induced by Xylophage Damage?

    Directory of Open Access Journals (Sweden)

    Alejandro Flores-Palacios

    Full Text Available Herbivory activates the synthesis of allelochemicals that can mediate plant-plant interactions. There is an inverse relationship between the activity of xylophages and the abundance of epiphytes on Ipomoea murucoides. Xylophagy may modify the branch chemical constitution, which also affects the liberation of allelochemicals with defense and allelopathic properties. We evaluated the bark chemical content and the effect of extracts from branches subjected to treatments of exclusion, mechanical damage and the presence/absence of epiphytes, on the seed germination of the epiphyte Tillandsia recurvata. Principal component analysis showed that branches without any treatment separate from branches subjected to treatments; damaged and excluded branches had similar chemical content but we found no evidence to relate intentional damage with allelopathy; however 1-hexadecanol, a defense volatile compound correlated positively with principal component (PC 1. The chemical constitution of branches subject to exclusion plus damage or plus epiphytes was similar among them. PC2 indicated that palmitic acid (allelopathic compound and squalene, a triterpene that attracts herbivore enemies, correlated positively with the inhibition of seed germination of T. recurvata. Inhibition of seed germination of T. recurvata was mainly correlated with the increment of palmitic acid and this compound reached higher concentrations in excluded branches treatments. Then, it is likely that the allelopathic response of I. murucoides would increase to the damage (shade, load that may be caused by a high load of epiphytes than to damage caused by the xylophages.

  10. Photo-oxidative damage to isolated rat liver mitochondria induced by phenothiazines

    Directory of Open Access Journals (Sweden)

    T. RODRIGUES

    2009-01-01

    Full Text Available

    Photosensitization is a well-known side-effect of phenothiazines that could involve photochemically promoted oxidative damage to mitochondria, leading to the impairment of metabolic functions and apoptosis. In this work, for the first time, we investigated the effects of photoexcited thioridazine (TR, trifluoperazine (TFP and fluphenazine (FP on isolated rat liver mitochondria. Under UV irradiation, the presence of these phenothiazines led to a dose-dependent lack of the respiratory control ratio. These effects were not accompanied by significant swelling and oxidation of protein thiol groups but were accompanied by lipid peroxidation. Lycopene and sorbate, well-known quenchers of singlet oxygen and triplet species, respectively, were ineffective at protecting mitochondrial lipids against the damage promoted by the excited phenothiazines, suggesting that photochemically-produced cation radicals were the prooxidant species. Corroborating this proposal, butylated hydroxytoluene (BHT completely inhibited the lipid peroxidation induced by UV irradiation in the presence of phenothiazines. These novel results make a significant contribution to the understanding of the photochemical properties of phenothiazines in biological systems. Keywords: Trifluoperazine, thioridazine, fluphenazine, rat liver mitochondria, oxidative stress, photochemistry, photodamage, respiratory chain.

  11. Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway

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    Peter Belenky

    2013-02-01

    Full Text Available Amphotericin, miconazole, and ciclopirox are antifungal agents from three different drug classes that can effectively kill planktonic yeast, yet their complete fungicidal mechanisms are not fully understood. Here, we employ a systems biology approach to identify a common oxidative-damage cellular death pathway triggered by these representative fungicides in Candida albicans and Saccharomyces cerevisiae. This mechanism utilizes a signaling cascade involving the GTPases Ras1 and Ras2 and protein kinase A, and it culminates in death through the production of toxic reactive oxygen species in a tricarboxylic-acid-cycle- and respiratory-chain-dependent manner. We also show that the metabolome of C. albicans is altered by antifungal drug treatment, exhibiting a shift from fermentation to respiration, a jump in the AMP/ATP ratio, and elevated production of sugars; this coincides with elevated mitochondrial activity. Lastly, we demonstrate that DNA damage plays a critical role in antifungal-induced cellular death and that blocking DNA-repair mechanisms potentiates fungicidal activity.

  12. Excision of x-ray-induced thymine damage in chromatin from heated cells

    International Nuclear Information System (INIS)

    Warters, R.L.; Roti Roti, J.L.

    1979-01-01

    Experiments were performed to distinguish between two possible modes of hyperthermia-induced inhibition of thymine base damage excision from the DNA of CHO cells: (1) heat denaturation of excision enzyme(s) or (2) heat-induced alteration of the substrate for damage excision (chromatin). While hyperthermia (45 0 C, 15 min) had no apparent effect on the capacity of the excision enzymes to excise damage from DNA it had a dramatic effect (ca. 80% inhibition) on the ability of chromatin to serve as a substrate for unheated enzymes. These results suggest that hyperthermia-induced radiosensitization of CHO cells may be due primarily to lesions in the cellular chromatin

  13. Lightning Strike Induced Damage Mechanisms of Carbon Fiber Composites

    Science.gov (United States)

    Kawakami, Hirohide

    Composite materials have a wide application in aerospace, automotive, and other transportation industries, because of the superior structural and weight performances. Since carbon fiber reinforced polymer composites possess a much lower electrical conductivity as compared to traditional metallic materials utilized for aircraft structures, serious concern about damage resistance/tolerance against lightning has been rising. Main task of this study is to clarify the lightning damage mechanism of carbon fiber reinforced epoxy polymer composites to help further development of lightning strike protection. The research on lightning damage to carbon fiber reinforced polymer composites is quite challenging, and there has been little study available until now. In order to tackle this issue, building block approach was employed. The research was started with the development of supporting technologies such as a current impulse generator to simulate a lightning strike in a laboratory. Then, fundamental electrical properties and fracture behavior of CFRPs exposed to high and low level current impulse were investigated using simple coupon specimens, followed by extensive parametric investigations in terms of different prepreg materials frequently used in aerospace industry, various stacking sequences, different lightning intensity, and lightning current waveforms. It revealed that the thermal resistance capability of polymer matrix was one of the most influential parameters on lightning damage resistance of CFRPs. Based on the experimental findings, the semi-empirical analysis model for predicting the extent of lightning damage was established. The model was fitted through experimental data to determine empirical parameters and, then, showed a good capability to provide reliable predictions for other test conditions and materials. Finally, structural element level lightning tests were performed to explore more practical situations. Specifically, filled-hole CFRP plates and patch

  14. The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

    Science.gov (United States)

    George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

    2012-01-01

    Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

  15. Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells.

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    Luca A Petruccelli

    Full Text Available Histone deacetylase inhibitors (HDACi are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells. At clinically relevant concentrations, vorinostat induces double-strand breaks and oxidative DNA damage in AML cell lines. Additionally, AML patient blasts treated with vorinostat display increased DNA damage, followed by an increase in caspase-3/7 activity and a reduction in cell viability. Vorinostat-induced DNA damage is followed by a G2-M arrest and eventually apoptosis. We found that pre-treatment with the antioxidant N-acetyl cysteine (NAC reduces vorinostat-induced DNA double strand breaks, G2-M arrest and apoptosis. These data implicate DNA damage as an important mechanism in vorinostat-induced growth arrest and apoptosis in both AML cell lines and patient-derived blasts. This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents.

  16. Vorinostat Induces Reactive Oxygen Species and DNA Damage in Acute Myeloid Leukemia Cells

    Science.gov (United States)

    Pettersson, Filippa; Retrouvey, Hélène; Skoulikas, Sophia; Miller, Wilson H.

    2011-01-01

    Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML) cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells. At clinically relevant concentrations, vorinostat induces double-strand breaks and oxidative DNA damage in AML cell lines. Additionally, AML patient blasts treated with vorinostat display increased DNA damage, followed by an increase in caspase-3/7 activity and a reduction in cell viability. Vorinostat-induced DNA damage is followed by a G2-M arrest and eventually apoptosis. We found that pre-treatment with the antioxidant N-acetyl cysteine (NAC) reduces vorinostat-induced DNA double strand breaks, G2-M arrest and apoptosis. These data implicate DNA damage as an important mechanism in vorinostat-induced growth arrest and apoptosis in both AML cell lines and patient-derived blasts. This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents. PMID:21695163

  17. Impact induced damage assessment by means of Lamb wave image processing

    Science.gov (United States)

    Kudela, Pawel; Radzienski, Maciej; Ostachowicz, Wieslaw

    2018-03-01

    The aim of this research is an analysis of full wavefield Lamb wave interaction with impact-induced damage at various impact energies in order to find out the limitation of the wavenumber adaptive image filtering method. In other words, the relation between impact energy and damage detectability will be shown. A numerical model based on the time domain spectral element method is used for modeling of Lamb wave propagation and interaction with barely visible impact damage in a carbon-epoxy laminate. Numerical studies are followed by experimental research on the same material with an impact damage induced by various energy and also a Teflon insert simulating delamination. Wavenumber adaptive image filtering and signal processing are used for damage visualization and assessment for both numerical and experimental full wavefield data. It is shown that it is possible to visualize and assess the impact damage location, size and to some extent severity by using the proposed technique.

  18. The effect of 2-[(aminopropyl)amino] ethanethiol on fission-neutron-induced DNA damage and repair.

    Science.gov (United States)

    Grdina, D. J.; Sigdestad, C. P.; Dale, P. J.; Perrin, J. M.

    1989-01-01

    The effect(s) of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR 1065) on fission-neutron-induced DNA damage and repair in V79 Chinese hamster cells was determined by using a neutral filter elution procedure (pH 7.2). When required, WR1065, at a final working concentration of 4 mM, was added to the culture medium, either 30 min before and during irradiation with fission spectrum neutrons (beam energy of 0.85 MeV) from the JANUS research reactor, or for selected intervals of time following exposure. The frequency of neutron-induced DNA strand breaks as measured by neutral elution as a function of dose equalled that observed for 60Co gamma-ray-induced damage (relative biological effectiveness of one). In contrast to the protective effect exhibited by WR1065 in reducing 60Co-induced DNA damage, WR1065 was ineffective in reducing or protecting against induction of DNA strand breaks by JANUS neutrons. The kinetics of DNA double-strand rejoining were measured following neutron irradiation. In the absence of WR1065, considerable DNA degradation by cellular enzymes was observed. This process was inhibited when WR1065 was present. These results indicate that, under the conditions used, the quality (i.e. nature), rather than quantity, of DNA lesions (measured by neutral elution) formed by neutrons was significantly different from that formed by gamma-rays. PMID:2667608

  19. Detection, characterization and measure of a new radiation-induced damage in isolated and cellular DNA

    International Nuclear Information System (INIS)

    Regulus, P.

    2006-10-01

    Deoxyribonucleic acid (DNA) contains the genetic information and chemical injury to this macromolecule may have severe biological consequences. We report here the detection of 4 new radiation-induced DNA lesions by using a high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) approach. For that purpose, the characteristic fragmentation of most 2'-deoxy-ribo nucleosides, the loss of 116 Da corresponding to the loss of the 2-deoxyribose moiety, was used in the so-called neutral loss mode of the HPLC-MS/MS. One of the newly detected lesions, named dCyd341 because it is a 2'-deoxycytidine modification exhibiting a molecular weight of 341 Da, was also detected in cellular DNA. Characterization of this modified nucleoside was performed using NMR and exact mass determination of the product obtained by chemical synthesis. A mechanism of formation was then proposed, in which the first event is the H-abstraction at the C4 position of a 2-deoxyribose moiety. Then, the sugar modification produced exhibits a reactive aldehyde that, through reaction with a vicinal cytosine base, gives rise to dCyd341. dCyd341 could be considered as a complex damage since its formation involves a DNA strand break and a cross-link between a damaged sugar residue and a vicinal cytosine base located most probably on the complementary DNA strand. In addition to its characterization, preliminary biological studies revealed that cells are able to remove the lesion from DNA. Repair studies have revealed the ability of cells to excise the lesion. Identification of the repair systems involved could represent an interesting challenge. (author)

  20. Exercise-Induced Muscle Damage and Hypertrophy: A Closer Look Reveals the Jury is Still Out

    OpenAIRE

    Schoenfeld, Brad; Contreras, Bret

    2018-01-01

    This letter is a response to the paper by Damas et al (2017) titled, “The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis,” which, in part, endeavored to review the role of exercise-induced muscle damage on muscle hypertrophy. We feel there are a number of issues in interpretation of research and extrapolation that preclude drawing the inference expressed in the paper that muscle damage neither explains nor potenti...

  1. Protective effects of rosmarinic acid on sepsis-induced DNA damage in the liver of Wistar albino rats

    Directory of Open Access Journals (Sweden)

    Hatice Gul Goktas

    2015-06-01

    Full Text Available Sepsis is an imbalance between pro and anti-inflammatory responses. Sepsis induced multiple organ failure that is associated with mortality is characterized by liver, renal, cardiovascular and pulmonary dysfunction and reactive oxygen species (ROS are believed to be involved in the development of sepsis. Plant polyphenols may act as antioxidants by different mechanisms such as free radical scavenging, metal chelation and protein binding. Data indicates possible beneficial effects of plant derived phenolic compounds against sepsis. Rosmarinic acid (RA (α-O-caffeoyl-3,4-dihydroxyphenyllactic acid is a phenolic compound commonly found in various plants such as Rosmarinus officinalis (rosemary, Origanum vulgare (oregano, Thymus vulgaris (thyme, Mentha spicata (spearmint, Perilla frutescens (perilla, Ocimum basilicum (sweet basil and several other medicinal plants. It has been shown that RA has many biological activities including antioxidant, anti-inflammatory, antiallergic, anticancer and actimicrobial and is widely used in cosmetic and food industry. In the present study, we aimed to determine the protective effects of RA against the oxidative DNA damage induced by sepsis in Wistar albino rats. The rats were divided into four groups; sham, sepsis induced, RA-treated, RA treated and sepsis induced groups. Wistar rats were subjected to sepsis by cecal ligation puncture. The liver tissues were carefully dissected from their attachments and totally excised. The concentrations of the hepatic tissue cells were adjusted to approximately 2 x 106 cells/ml. Standard and formamidopyrimidine-DNA glycosylase (Fpg modified comet assay described by Singh et al were used. There were no statistically significant differences in terms of tail length, tail intensity and tail moment between the sham group and the RA-treated groups (p>0.05. The DNA damage was found significantly higher in the sepsis-induced group compared to the sham group (p0.05, and the DNA damage

  2. Ceramide Production Mediates Aldosterone-Induced Human Umbilical Vein Endothelial Cell (HUVEC Damages.

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    Yumei Zhang

    Full Text Available Here, we studied the underlying mechanism of aldosterone (Aldo-induced vascular endothelial cell damages by focusing on ceramide. We confirmed that Aldo (at nmol/L inhibited human umbilical vein endothelial cells (HUVEC survival, and induced considerable cell apoptosis. We propose that ceramide (mainly C18 production might be responsible for Aldo-mediated damages in HUVECs. Sphingosine-1-phosphate (S1P, an anti-ceramide lipid, attenuated Aldo-induced ceramide production and following HUVEC damages. On the other hand, the glucosylceramide synthase (GCS inhibitor PDMP or the ceramide (C6 potentiated Aldo-induced HUVEC apoptosis. Eplerenone, a mineralocorticoid receptor (MR antagonist, almost completely blocked Aldo-induced C18 ceramide production and HUVEC damages. Molecularly, ceramide synthase 1 (CerS-1 is required for C18 ceramide production by Aldo. Knockdown of CerS-1 by targeted-shRNA inhibited Aldo-induced C18 ceramide production, and protected HUVECs from Aldo. Reversely, CerS-1 overexpression facilitated Aldo-induced C18 ceramide production, and potentiated HUVEC damages. Together, these results suggest that C18 ceramide production mediates Aldo-mediated HUVEC damages. MR and CerS-1 could be the two signaling molecule regulating C18 ceramide production by Aldo.

  3. DNA-damage response during mitosis induces whole-chromosome missegregation.

    Science.gov (United States)

    Bakhoum, Samuel F; Kabeche, Lilian; Murnane, John P; Zaki, Bassem I; Compton, Duane A

    2014-11-01

    Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

  4. Detection of base damage in DNA in human blood exposed to ionizing radiation at biologically relevant doses

    International Nuclear Information System (INIS)

    Loon, A.A.W.M. van; Lohman, P.H.M.; Groenendijk, R.H.; Schans, G.P. van der; Baan, R.A.

    1991-01-01

    The alkaline elution technique for the detection of DNA damage has been adapted to allow application on unlabelled blood cells. Both the induction and subsequent repair have been studied of two classes of DNA damage, viz. single-strand breaks and base damage recognized by the γ-endonuclease activity in a cell-free extract of Micrococcus luteus bacteria. The high sensitivity of the assay permitted the measurement of induction and repair of base damage after in vitro exposure of full blood under aerobic conditions to biologically relevant doses of γ-rays (1.5-4.5 Gy). After a radiation dose of 3 Gy about 50% of the base damage was removed within 1.5 h of repair. Base damage could still be detected at 24h after exposure to 15 Gy. (author)

  5. Cytomegalovirus-Induced Effector T Cells Cause Endothelial Cell Damage

    NARCIS (Netherlands)

    van de Berg, Pablo J. E. J.; Yong, Si-La; Remmerswaal, Ester B. M.; van Lier, René A. W.; ten Berge, Ineke J. M.

    2012-01-01

    Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases that involve vascular endothelial cell damage, but definitive proof for a direct cytopathic effect of CMV in these diseases is lacking. CMV infection is associated with a strong increase in both CD4(+) and CD8(+) T cells

  6. Experiment and numerical simulation of welding induced damage: stainless steel 15-5PH

    International Nuclear Information System (INIS)

    Wu, T.

    2007-11-01

    The objective of this study is the prediction of damage and residual stresses induced by hot processing which leads to phase transformation in martensitic stainless steel. This study firstly concerns the modelling of the damage of material induced by a complex history of thermo-elastoplastic multiphase in heat-affected-zone (HAZ) of welding. In this work, a two-scale mode of elastoplastic damage multiphase was developed in the framework of thermodynamics of irreversible process. The constitutive equations are coupling with ductile damage, elasto-plasticity, phase transformation, and transformation plasticity. Besides, a damage equation was proposed based on the Lemaitre's damage model in the framework of continuum damage mechanics. The experiments of 15-5PH were implemented for the identification of phase transformation, transformation plasticity and damage models. Tensile tests of round specimens were used to identify the parameters of damage model as well as mechanical behaviours at various temperatures. Tests of flat notched specimen were designed to provide the validation of damage model and strain localization using three dimensional image correlation technologies. In addition, microscopic analysis was performed to provide microstructure characterization of 15-5PH and to discover the damage mechanism. Finally the numerical simulation was performed in the code CAST3M of CEA. On the one hand, numerical verification of the flat notched plates was implemented and compared with experimental results. On the other hand, we used the two-scale model including phase transformation, transformation plasticity and damage to simulate the level of residual stresses of a disk made of 15-5PH metal heated by laser. The internal variables, such as strain, stress, damage, were successfully traced in the simulation of two-scale model. The simulation results showed the transformation plasticity changes the level of residual stresses and should not be negligible; damage decreases

  7. Modeling DNA?damage-induced pneumopathy in mice: insight from danger signaling cascades

    OpenAIRE

    Wirsd?rfer, Florian; Jendrossek, Verena

    2017-01-01

    Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. It is assumed that the initial radiation-induced damage to the resident cells triggers a multifaceted damage-signalling cascade in irradiated normal tissues including a multifactorial secr...

  8. The Role of Altered Nucleotide Excision Repair and UVB-Induced DNA Damage in Melanomagenesis

    Directory of Open Access Journals (Sweden)

    Timothy Budden

    2013-01-01

    Full Text Available UVB radiation is the most mutagenic component of the UV spectrum that reaches the earth’s surface and causes the development of DNA damage in the form of cyclobutane pyrimidine dimers and 6-4 photoproducts. UV radiation usually results in cellular death, but if left unchecked, it can affect DNA integrity, cell and tissue homeostasis and cause mutations in oncogenes and tumour-suppressor genes. These mutations, if unrepaired, can lead to abnormal cell growth, increasing the risk of cancer development. Epidemiological data strongly associates UV exposure as a major factor in melanoma development, but the exact biological mechanisms involved in this process are yet to be fully elucidated. The nucleotide excision repair (NER pathway is responsible for the repair of UV-induced lesions. Patients with the genetic disorder Xeroderma Pigmentosum have a mutation in one of eight NER genes associated with the XP complementation groups XP-A to XP-G and XP variant (XP-V. XP is characterized by diminished repair capacity, as well as a 1000-fold increase in the incidence of skin cancers, including melanoma. This has suggested a significant role for NER in melanoma development as a result of UVB exposure. This review discusses the current research surrounding UVB radiation and NER capacity and how further investigation of NER could elucidate the role of NER in avoiding UV-induced cellular death resulting in melanomagenesis.

  9. Radiation-induced normal tissue damage: implications for radiotherapy

    International Nuclear Information System (INIS)

    Prasanna, Pataje G.

    2014-01-01

    Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

  10. Long-term biological effects induced by ionizing radiation--implications for dose mediated risk.

    Science.gov (United States)

    Miron, S D; Astărăstoae, V

    2014-01-01

    Ionizing radiations are considered to be risk agents that are responsible for the effects on interaction with living matter. The occurring biological effects are due to various factors such as: dose, type of radiation, exposure time, type of biological tissue, health condition and the age of the person exposed. The mechanisms involved in the direct modifications of nuclear DNA and mitochondrial DNA are reviewed. Classical target theory of energy deposition in the nucleus that causes DNA damages, in particular DNA double-strand breaks and that explanation of the biological consequences of ionizing radiation exposure is a paradigm in radiobiology. Recent experimental evidences have demonstrated the existence of a molecular mechanism that explains the non-targeted effects of ionizing radiation exposure. Among these novel data, genomic instability and a variety of bystander effects are discussed here. Those bystander effects of ionizing radiation are fulfilled by cellular communication systems that give rise to non-targeted effects in the neighboring non irradiated cells. This paper provides also a commentary on the synergistic effects induced by the co-exposures to ionizing radiation and various physical agents such as electromagnetic fields and the co-exposures to ionizing radiation and chemical environmental contaminants such as metals. The biological effects of multiple stressors on genomic instability and bystander effects are also discussed. Moreover, a brief presentation of the methods used to characterize cyto- and genotoxic damages is offered.

  11. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

    Science.gov (United States)

    Bedarida, Tatiana; Domingues, Alison; Baron, Stephanie; Ferreira, Chrystophe; Vibert, Francoise; Cottart, Charles-Henry; Paul, Jean-Louis; Escriou, Virginie; Bigey, Pascal; Gaussem, Pascale; Leguillier, Teddy; Nivet-Antoine, Valerie

    2018-06-01

    Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIP fl/fl cdh5 cre ). Control (TXNIP fl/fl ) and TXNIP fl/fl cdh5 cre mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress. We found that TXNIP fl/fl and TXNIP fl/fl cdh5 cre mice on an HP-LC diet displayed impaired glucose tolerance and dyslipidemia concretizing the metabolic stress induced. We evaluated the impact of this metabolic stress on mice with reduced endothelial TXNIP expression with regard to arterial structure and function. TXNIP fl/fl cdh5 cre mice on an HP-LC diet exhibited less endothelial dysfunction than littermate mice on an HP-LC diet. These mice were protected from decreased aortic medial cell content, impaired aortic distensibility, and increased plasminogen activator inhibitor 1 secretion. This protective effect came with lower oxidative stress and lower inflammation, with a reduced NLRP3 inflammasome expression, leading to a decrease in cleaved IL-1β. We also show the major role of TXNIP in inflammation with a knockdown model, using a TXNIP-specific, small interfering RNA included in a lipoplex. These findings demonstrate a key role for endothelial TXNIP in arterial impairments induced by metabolic stress, making endothelial TXNIP a potential therapeutic target.-Bedarida, T., Domingues, A., Baron, S., Ferreira, C., Vibert, F., Cottart, C.-H., Paul, J.-L., Escriou, V., Bigey, P., Gaussem, P., Leguillier, T., Nivet-Antoine, V. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

  12. Towards a unified system for expression of biological damage by ionising radiation

    International Nuclear Information System (INIS)

    Watt, D.E.; Chen, C.Z.; Kadiri, L.; Younis, A.

    1987-01-01

    Limitations to current systems of radiation dosimetry are discussed. Analyses of a wide range of published data on inactivation of enzymes, viruses, bacteria, plant and mammalian cells by electrons, X and γ-rays, and accelerated ions leads to the conclusion that the main radiosensitive sites in higher cells are the double-stranded segments of DNA. The probability of damage is determined by the mean free path for ionization along the charged particle tracks and is optimum when the spacing matches the mean chord length (2 nm) through a DNA segment. Interpretation of these findings leads to the possibility of a more accurate unified system of dosimetry and to the specification of absolute biological effectiveness. (author)

  13. Investigation of radiation damage to biological specimens at water window wavelengths

    International Nuclear Information System (INIS)

    Foster, G.F.; Buckley, C.J.; Burge, R.E.; Bennett, P.M.

    1992-01-01

    This article reports the continuation of a series of experiments investigating the effects of soft x-ray radiation damage on the contractile elements of mammalian striated muscle (myofibrils), using their ability to contract as a functional assay. The myofibrils were exposed to 385 eV x rays. This energy is within the ''water window'' between the oxygen and carbon K edges, where the x-ray absorption coefficient of biological materials, such as protein, is about an order of magnitude greater than that for water. An exposure of 8x10 5 photons μm -1 was found to prevent contraction in the majority of myofibrils. Preliminary results indicate that it is possible to increase this exposure level by approximately 25% by adding the radioprotective dimethyl sulphoxide (DMSO), an OH radical scavenger to the myofibril buffer during irradiation. This suggests that OH radicals are important in the inactivation of myofibrils through irradiation

  14. RNA damage in biological conflicts and the diversity of responding RNA repair systems

    Science.gov (United States)

    Burroughs, A. Maxwell; Aravind, L.

    2016-01-01

    RNA is targeted in biological conflicts by enzymatic toxins or effectors. A vast diversity of systems which repair or ‘heal’ this damage has only recently become apparent. Here, we summarize the known effectors, their modes of action, and RNA targets before surveying the diverse systems which counter this damage from a comparative genomics viewpoint. RNA-repair systems show a modular organization with extensive shuffling and displacement of the constituent domains; however, a general ‘syntax’ is strongly maintained whereby systems typically contain: a RNA ligase (either ATP-grasp or RtcB superfamilies), nucleotidyltransferases, enzymes modifying RNA-termini for ligation (phosphatases and kinases) or protection (methylases), and scaffold or cofactor proteins. We highlight poorly-understood or previously-uncharacterized repair systems and components, e.g. potential scaffolding cofactors (Rot/TROVE and SPFH/Band-7 modules) with their respective cognate non-coding RNAs (YRNAs and a novel tRNA-like molecule) and a novel nucleotidyltransferase associating with diverse ligases. These systems have been extensively disseminated by lateral transfer between distant prokaryotic and microbial eukaryotic lineages consistent with intense inter-organismal conflict. Components have also often been ‘institutionalized’ for non-conflict roles, e.g. in RNA-splicing and in RNAi systems (e.g. in kinetoplastids) which combine a distinct family of RNA-acting prim-pol domains with DICER-like proteins. PMID:27536007

  15. Analysis of the Causes and Recommendations on Elimination of Biological Damage of Structures During the Repair and Reconstruction of the State Biological Museum in Moscow

    Directory of Open Access Journals (Sweden)

    Kamskov Viktor

    2017-01-01

    Full Text Available The article presents the results of mycological research on buildings of the State Biological Museum located in Moscow. Over time, the building maintenance conditions have worsened, in particular because of construction of high-rise buildings in the immediate vicinity of the museum, as well as construction of a greenhouse above the underground passage tunnel between buildings 1 and 2. Over the years, the temperature gradients, high humidity, wear and damage of wall waterproofing and foundations have caused leaks in the underpass tunnel and the biological corrosion of stone, wood and metal structures in indoor exhibition halls. In this connection, part of the survey was to determine the types and size of biological lesions in structures, determination of the causes of biological damage, and the development of measures to eliminate the mycological problems during repair and reconstruction works in the museum.

  16. Studies of cellular damage induced by X-rays and visible light

    International Nuclear Information System (INIS)

    Christensen, T.; Kinn, G.; Reitan, J.B.

    1989-01-01

    DNA-damage in cells has been studied by use of spectrophotometry and fluorometry. The method is based on the differential fluorescence quantum yield of the fluorochrome Hoechst 33258 when bound to single and double stranded DNA, respectively. DNA-damage by doses of X-rays below 2 Gy was clearly detectable. Blue light from phototherapy lamps induced DNA-damage in human TMG-1 glioblastoma, but no significant effect could be observed after irradiation with green lamps. In the presence of bilirubin the amount of DNA-damage was increased, notably at high bilirubin concentration and by blue light. 9 refs; 12 figs

  17. Theoretical research of multi-pulses laser induced damage in dielectrics

    International Nuclear Information System (INIS)

    Luo Jin; Liu Zhichao; Chen Songlin; Ma Ping

    2013-01-01

    The pulse width is different, the mechanism of the laser-matter interaction is different. Damage results from plasma formation and ablation forτ≤10 ps and from heat depositing and conventional melting for τ>100 ps. Two theoretical models of transparent dielectrics irradiated by multi-pulses laser are respectively developed based on the above-mentioned different mechanism. One is the dielectric breakdown model based on electron density evolution equation for femtosecond multi-pluses laser, the other is the dielectric heat-damage model based on Fourier's heat exchange equation for nanosecond multi-pluses laser. Using these models, the effects of laser parameters and material parameters on the laser-induced damage threshold of dielectrics are analyzed. The analysis results show that different parameters have different influence on the damage threshold. The effect of parameters on the multi -pulses damage threshold is not entirely the same to the single-pulse damage threshold. The multi-pulses damage mechanism of dielectrics is discussed in detail, considering the effect of different parameters. The discussion provides more information for understanding its damage process and more knowledge to improve its damage thresholds. And the relationship between damage threshold and pulse number is illustrated, it is in good agreement with experimental results. The illustration can help us to predict the multi-pulses damage threshold and the lifetime of optical components. (authors)

  18. Effect of Mercuric Nitrate on Repair of Radiation-induced DNA Damage

    Energy Technology Data Exchange (ETDEWEB)

    Paneka, Agnieszka; Antonina, Cebulska Wasilewska [The Henryk Niewodniczanski Institute of Nuclear Physics, Krakow (Poland); Han, Min; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2009-10-15

    High concentrations of mercury can cause serious damage to the nervous system, immune system, kidneys and liver in humans. And mercury is toxic to developing embryos because mercury ions can penetrate the blood.placenta barrier to reach the embryo. Studies from human monitoring of occupational exposure to mercury vapours have shown that mercury can alter the ability of lymphocytes to repair radiation-induced DNA damage. The aim of this in vitro study was to investigate, on the molecular and cytogenetic levels, the effect of exposure to mercury ions on the kinetics of the repair process of DNA damage induced by ionising radiation.

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

    International Nuclear Information System (INIS)

    Angermeier, Marita; Moertl, Simone

    2012-01-01

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

  20. Detection of UVR-induced DNA damage in mouse epidermis in vivo using alkaline elution

    International Nuclear Information System (INIS)

    Kinley, J.S.; Moan, J.; Brunborg, G.

    1995-01-01

    Alkaline elution has been used to detect ultraviolet radiation (UVR)-induced DNA damage in the epidermis of C3H/Tif hr/hr mice. This technique detects DNA damage in the form of single-strand breaks and alkali-labile sites (SSB) formed directly by UVA (320-400 nm) or indirectly by UVB (280-320 nm). The latter induces DNA damage such as cyclobutane pyrimidine dimers and pyrimidine-pyrimidone (6-4)-photoproducts, which are then converted into transient SSB by cellular endonucleases, during nucleotide excision repair (NER). (Author)

  1. Intensification of ultraviolet-induced dermal damage by infrared radiation

    International Nuclear Information System (INIS)

    Kligman, L.H.

    1982-01-01

    To assess the role of IR in actinic damage to the dermis, albino guinea pigs were irradiated for 45 weeks with UV-B and UV-A, with and without IR. Control animals received IR only or no irradiation at all. Unirradiated dermis contains small amounts of elastic fibers in the upper dermis with greater depositions around follicles and sebaceous glands. After irradiation with UV, the fibers became more numerous, thicker, and more twisted; IR alone producd many fine, feathery fibers. The addition of IR to UV resulted in dense matlike elastic fiber depositions that exceeded what was observed with either irradiation alone. In combination or alone UV and IR radiation produced a large increase in ground substance, a finding also seen in actinically damaged human skin. Infrared radiation, in the physiologic range, though pleasant is not innocuous. (orig./MG) [de

  2. Radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (Family: Poaceae), against radiation-induced cytogenetic damage

    International Nuclear Information System (INIS)

    Satish Rao, B.S.; Upadhya, D.; Adiga, S.K.

    2007-01-01

    The exposure of humans to ionizing radiations may be advertently by routine diagnostic and therapeutic purposes or inadvertently during natural, occupational and nuclear accident situations. Therefore, in order to overcome the deleterious biological effects of radiation several chemical agents have been studied for their radioprotective potential. The medicinal plants being one of the resources for such clinically important natural agents, used extensively in several drug discovery related research. Here the radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (Family: Poaceae), against radiation-induced cytogenetic damage was analyzed using Chinese hamster fibroblast cells (V79) and human peripheral blood lymphocytes (HPBLs) growing in vitro is reported

  3. Proton-induced direct and indirect damage of plasmid DNA

    Czech Academy of Sciences Publication Activity Database

    Vyšín, Luděk; Pachnerová Brabcová, Kateřina; Štěpán, V.; Moretto-Capelle, P.; Bugler, B.; Legube, G.; Cafarelli, P.; Casta, R.; Champeaux, J. P.; Sence, M.; Vlk, M.; Wagner, Richard; Štursa, Jan; Zach, Václav; Incerti, S.; Juha, Libor; Davídková, Marie

    2015-01-01

    Roč. 54, č. 3 (2015), s. 343-352 ISSN 0301-634X R&D Projects: GA ČR GA13-28721S; GA MŠk LD12008; GA MŠk LM2011019 Institutional support: RVO:68378271 ; RVO:61389005 Keywords : proton radiation * DNA plasmid * direct and indirect effects * clustered damage * repair enzymes Subject RIV: BO - Biophysics Impact factor: 1.923, year: 2015

  4. Ultraviolet induced DNA damage and hereditary skin cancer

    International Nuclear Information System (INIS)

    Regan, J.D.; Carrier, W.L.; Francis, A.A.

    1984-01-01

    Clearly, cells from normal individuals possess the ability to repair a variety of damage to DNA. Numerous studies indicate that defects in DNA repair may increase an individual's susceptibility to cancer. It is hoped that continued studies of the exact structural changes produced in the DNA by environmental insults, and the correlation of specific DNA changes with particulr cellular events, such as DNA repair, will lead to a better understanding of cell-killing, mutagenesis and carbinogenesis. 1 figure, 2 tables

  5. Tubular overexpression of gremlin induces renal damage susceptibility in mice.

    Directory of Open Access Journals (Sweden)

    Alejandra Droguett

    Full Text Available A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1 specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage

  6. Metformin (dimethyl-biguanide induced DNA damage in mammalian cells

    Directory of Open Access Journals (Sweden)

    Rubem R. Amador

    2012-01-01

    Full Text Available Metformin (dimethyl-biguanide is an insulin-sensitizing agent that lowers fasting plasma-insulin concentration, wherefore it's wide use for patients with a variety of insulin-resistant and prediabetic states, including impaired glucose tolerance. During pregnancy it is a further resource for reducing first-trimester pregnancy loss in women with the polycystic ovary syndrome. We tested metformin genotoxicity in cells of Chinese hamster ovary, CHO-K1 (chromosome aberrations; comet assays and in mice (micronucleus assays. Concentrations of 114.4 µg/mL and 572 µg/mL were used in in vitro tests, and 95.4 mg/kg, 190.8 mg/kg and 333.9 mg/kg in assaying. Although the in vitro tests revealed no chromosome aberrations in metaphase cells, DNA damage was detected by comet assaying after 24 h of incubation at both concentrations. The frequency of DNA damage was higher at concentrations of 114.4 µg/mL. Furthermore, although mortality was not observed in in vitro tests, the highest dose of metformin suppressed bone marrow cells. However, no statistically significant differences were noted in micronuclei frequencies between treatments. In vitro results indicate that chronic metformin exposure may be potentially genotoxic. Thus, pregnant woman undergoing treatment with metformin should be properly evaluated beforehand, as regards vulnerability to DNA damage.

  7. Ultrasound-induced cavitation damage to external epithelia of fish skin.

    Science.gov (United States)

    Frenkel, V; Kimmel, E; Iger, Y

    1999-10-01

    Transmission electron microscopy was used to show the effects of therapeutic ultrasound (fish skin. Exposures of up to 90 s produced damage to 5 to 6 of the outermost layers. Negligible temperature elevations and lack of damage observed when using degassed water indicated that the effects were due to cavitation. The minimal intensity was determined for inducing cellular damage, where the extent and depth of damage to the tissues was correlated to the exposure duration. The results may be interpreted as a damage front, advancing slowly from the outer cells inward, presumably in association with the slow replacement of the perforated cell contents with the surrounding water. This study illustrates that a controlled level of microdamage may be induced to the outer layers of the tissues.

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

    Science.gov (United States)

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

    2002-01-01

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

  9. Ethanolic extract of Moringa oleifera Lam. leaves protect the pre-pubertal spermatogonial cells from cyclophosphamide-induced damage.

    Science.gov (United States)

    Nayak, Guruprasad; Honguntikar, Sachin D; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Mutalik, Srinivas; Setty, Manjunath M; Kalyankumar, Raksha; Krishnamurthy, Hanumanthappa; Kalthur, Guruprasad; Adiga, Satish Kumar

    2016-04-22

    Moringa oleifera Lam. is widely cultivated in Asian and African countries for its medicinal and dietary significance. The leaves are highly nutritious and are known to possess various biological activities. Pre-pubertal Swiss albino male mice were injected with single dose of cyclophosphamide (CP, 200mg/kg body weight) or ethanolic extract of Moringa oleifera leaves (MOE, 100mg/kg body weight) intraperitoneally. In combination group, MOE was administered 24h prior to CP injection. CP induced a significant decrease in testicular weight (p<0.01) and depletion of germ cells (p<0.001) and higher level of DNA damage (p<0.001) compared to control. The expression of P53, Bax, Cytochrome C (Cyt C) was increased while there was a decrease in the expression of Bcl2, c-Kit and Oct4. Administration of MOE 24h prior to CP treatment ameliorated the depletion (p<0.001), DNA damage (p<0.001) and apoptosis (p<0.01) of germ cells induced by CP. The mitigating effect of MOE appears to be mediated by up-regulating the expression of c-Kit and Oct4 transcripts in P53-independent manner. MOE protects the spermatogonial cells from CP-induced damage by modulating the apoptotic response elicited by CP and therefore can be considered as an efficient method of male fertility preservation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Kombucha Tea Ameliorates Trichloroethylene Induced Hepatic Damages in Rats via Inhibition of Oxidative Stress and Free Radicals Induction

    International Nuclear Information System (INIS)

    Gharib, O.A.; Gharib, M.A.

    2008-01-01

    Kombucha Tea (KT) is reported to exhibit a wide variety of biological effects, including antioxidant. Evidence shows the important role of oxidative stress in the hepatic damage. The aim of this study is to investigate the possible protective effects of oral administration of KT in rats with trichloroethylene (TCE)-induced damage for ten consecutive days. Hepatic damage was evaluated by measuring total free radicals levels, biochemical and histological examinations. Serum gamma glutamyl transferase (GGT) activity (the hepatic damage marker), total protein, albumin and globulin as well as malonaldehyde (MDA), glutathione (GSH) content, nitric oxide (NO) concentration were evaluated in liver tissue homogenates. Total free radicals concentration in blood was examined by electron spin resonance (ESR). Total protein, DNA concentration, cell number and cell size in liver tissues were also examined. The rats orally administrated with TCE for ten days indicates hepatic damage changes, an increase in blood total free radicals concentration was observed, serum GGT activity, liver MDA, NO levels, total protein and decreased GSH content, DNA concentration and cell number. This accompanied with an increase in cell size of liver tissues, whereas KT reversed these effects. Furthermore, KT inhibits the concentration of total free radicals in blood and decreasing the increment of MDA and NO concentration. Histological studies reveal partial healing in those rats treated by KT after oral administration with TCE. The present results suggest that KT ameliorates TCE induced hepatic damage in rats probably due to its content of glucuronic, acetic acid and B vitamins via inhibition of oxidative stress and total free radicals

  11. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    International Nuclear Information System (INIS)

    Um, So Young; Park, Jung Hyun; Chung, Myeon Woo; Kim, Kyu-Bong; Kim, Seon Hwa; Choi, Ki Hwan; Lee, Hwa Jeong

    2012-01-01

    Highlights: ► NMR based metabolomics – gastric damage by indomethacin. ► Pattern recognition analysis was performed to biomarkers of gastric damage. ► 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. ► The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the 1 H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg −1 ) or co-administration with cimetidine (100 mg kg −1 ), which protects against GI damage. The 1 H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg −1 ) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a NMR based metabolomics approach.

  12. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Um, So Young [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Park, Jung Hyun [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Chung, Myeon Woo [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Kim, Kyu-Bong [College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Kim, Seon Hwa [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Choi, Ki Hwan, E-mail: hyokwa11@korea.kr [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Lee, Hwa Jeong, E-mail: hwalee@ewha.ac.kr [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer NMR based metabolomics - gastric damage by indomethacin. Black-Right-Pointing-Pointer Pattern recognition analysis was performed to biomarkers of gastric damage. Black-Right-Pointing-Pointer 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. Black-Right-Pointing-Pointer The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the {sup 1}H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg{sup -1}) or co-administration with cimetidine (100 mg kg{sup -1}), which protects against GI damage. The {sup 1}H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg{sup -1}) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by

  13. Could grape seed extract modulate nephritic damage induced by ...

    African Journals Online (AJOL)

    RBCs). Preadministration of GSO to Metho-induced rats revealed apparent normal renal parenchyma. The proximal convoluted tubules and collecting tubules appeared near to normal with their narrow lumen. Preadministration with GSO ...

  14. Influence of chromatin condensation on the number of direct DSB damages induced by ions studied using a Monte Carlo code

    International Nuclear Information System (INIS)

    Dos Santos, M.; Clairand, I.; Gruel, G.; Barquinero, J.F.; Villagrasa, C.; Incerti, S.

    2014-01-01

    The purpose of this work is to evaluate the influence of the chromatin condensation on the number of direct double-strand break (DSB) damages induced by ions. Two geometries of chromosome territories containing either condensed or de-condensed chromatin were implemented as biological targets in the Geant4 Monte Carlo simulation code and proton and alpha irradiation was simulated using the Geant4-DNA processes. A DBSCAN algorithm was used in order to detect energy deposition clusters that could give rise to single-strand breaks or DSBs on the DNA molecule. The results of this study show an increase in the number and complexity of DNA DSBs in condensed chromatin when compared with de-condensed chromatin. This work aims to evaluate the influence of the chromatin condensation in the number and complexity of direct DSB damages induced by proton and alpha irradiation. With the simulations of this study, the increase in the number and complexity of DSB-like clusters induced by ions in the heterochromatin when compared with euchromatin regions of the cell nucleus has been observed and quantified. These results suggest that condensed chromatin can be the location of more severe radiation-induced lesions, more difficult to repair, than de-condensed chromatin. On the other hand, it was also observed that, whatever the chromatin condensation, more possible damages are found after proton irradiation compared with alpha particles of the same LET. Nevertheless, as already remarked, this study concerns only the direct effect of ionising radiation that can be calculated from the results of the physical stage simulated with Geant4-DNA. To include indirect effects induced by radicals around the DNA molecule, the elements needed for simulating the chemical stage are being developed in the frame of the Geant4-DNA project(15, 16) and they are planned to be included in future work. With a complete calculation (direct + indirect damages) it would then be possible to estimate an energy

  15. Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Shikazono, Naoya, E-mail: shikazono.naoya@jaea.go.jp [Japan Atomic Energy Agency, Advanced Research Science Center, 2-4 Shirakata-Shirane, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); O' Neill, Peter [Gray Institute for Radiation Oncology and Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2009-10-02

    Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Using a plasmid-based assay in Escherichia coli, we previously found significantly higher mutation frequencies for bistranded clusters containing 7,8-dihydro-8-oxoguanine (8-oxoG) and 5,6-dihydrothymine (DHT) than for either a single 8-oxoG or a single DHT in wild type and in glycosylase-deficient strains of E. coli. This indicates that the removal of an 8-oxoG from a clustered damage site is most likely retarded compared to the removal of a single 8-oxoG. To gain further insights into the processing of bistranded base lesions, several potential repair intermediates following 8-oxoG removal were assessed. Clusters, such as DHT + apurinic/apyrimidinic (AP) and DHT + GAP have relatively low mutation frequencies, whereas clusters, such as AP + AP or GAP + AP, significantly reduce the number of transformed colonies, most probably through formation of a lethal double strand break (DSB). Bistranded AP sites placed 3' to each other with various interlesion distances also blocked replication. These results suggest that bistranded base lesions, i.e., single base lesions on each strand, but not clusters containing only AP sites and strand breaks, are repaired in a coordinated manner so that the formation of DSBs is avoided. We propose that, when either base lesion is initially excised from a bistranded base damage site, the remaining base lesion will only rarely be converted into an AP site or a single strand break in vivo.

  16. Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli

    International Nuclear Information System (INIS)

    Shikazono, Naoya; O'Neill, Peter

    2009-01-01

    Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Using a plasmid-based assay in Escherichia coli, we previously found significantly higher mutation frequencies for bistranded clusters containing 7,8-dihydro-8-oxoguanine (8-oxoG) and 5,6-dihydrothymine (DHT) than for either a single 8-oxoG or a single DHT in wild type and in glycosylase-deficient strains of E. coli. This indicates that the removal of an 8-oxoG from a clustered damage site is most likely retarded compared to the removal of a single 8-oxoG. To gain further insights into the processing of bistranded base lesions, several potential repair intermediates following 8-oxoG removal were assessed. Clusters, such as DHT + apurinic/apyrimidinic (AP) and DHT + GAP have relatively low mutation frequencies, whereas clusters, such as AP + AP or GAP + AP, significantly reduce the number of transformed colonies, most probably through formation of a lethal double strand break (DSB). Bistranded AP sites placed 3' to each other with various interlesion distances also blocked replication. These results suggest that bistranded base lesions, i.e., single base lesions on each strand, but not clusters containing only AP sites and strand breaks, are repaired in a coordinated manner so that the formation of DSBs is avoided. We propose that, when either base lesion is initially excised from a bistranded base damage site, the remaining base lesion will only rarely be converted into an AP site or a single strand break in vivo.

  17. Uranium bioaccumulation and biological disorders induced in zebrafish (Danio rerio) after a depleted uranium waterborne exposure

    International Nuclear Information System (INIS)

    Barillet, Sabrina; Adam-Guillermin, Christelle; Palluel, Olivier; Porcher, Jean-Marc; Devaux, Alain

    2011-01-01

    Because of its toxicity and its ubiquity within aquatic compartments, uranium (U) represents a significant hazard to aquatic species such as fish. In a previous study, we investigated some biological responses in zebrafish either exposed to depleted or to enriched U (i.e., to different radiological activities). However, results required further experiments to better understand biological responses. Moreover, we failed to clearly demonstrate a significant relationship between biological effects and U radiological activity. We therefore chose to herein examine U bioaccumulation and induced effects in zebrafish according to a chemical dose-response approach. Results showed that U is highly bioconcentrated in fish, according to a time- and concentration-dependent model. Additionally, hepatic antioxidant defenses, red blood cells DNA integrity and brain acetylcholinesterase activity were found to be significantly altered. Generally, the higher the U concentration, the sooner and/or the greater the effect, suggesting a close relationship between accumulation and effect. - Research highlights: → Depleted U bioconcentration factor is of about 1000 in zebrafish exposed to 20 μg/L. → Hepatic antioxidant disorders are noticed as soon as the first hours of exposure. → DNA damage is induced in red blood cells after 20 d of exposure to 500 μg DU/L. → The brain cholinergic system (AChE activity) is impacted. - This study demonstrates that U is highly bioaccumulated in fish, resulting in biological disorders such as hepatic oxidative stress as well as genotoxic and neurotoxic events.

  18. Uranium bioaccumulation and biological disorders induced in zebrafish (Danio rerio) after a depleted uranium waterborne exposure

    Energy Technology Data Exchange (ETDEWEB)

    Barillet, Sabrina, E-mail: sabrina.barillet@free.f [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Adam-Guillermin, Christelle, E-mail: christelle.adam-guillermin@irsn.f [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Palluel, Olivier, E-mail: olivier.palluel@ineris.f [Ecotoxicological Risk Assessment Unit, INERIS (National Institute for Industrial Environment and Risks), Parc technologique ALATA, 60 550 Verneuil-en-Halatte (France); Porcher, Jean-Marc, E-mail: jean-marc.porcher@ineris.f [Ecotoxicological Risk Assessment Unit, INERIS (National Institute for Industrial Environment and Risks), Parc technologique ALATA, 60 550 Verneuil-en-Halatte (France); Devaux, Alain, E-mail: alain.devaux@entpe.f [Universite de Lyon, INRA, EFPA-SA, Environmental Science Laboratory (LSE), ENTPE, 69518 Vaulx en Velin cedex (France)

    2011-02-15

    Because of its toxicity and its ubiquity within aquatic compartments, uranium (U) represents a significant hazard to aquatic species such as fish. In a previous study, we investigated some biological responses in zebrafish either exposed to depleted or to enriched U (i.e., to different radiological activities). However, results required further experiments to better understand biological responses. Moreover, we failed to clearly demonstrate a significant relationship between biological effects and U radiological activity. We therefore chose to herein examine U bioaccumulation and induced effects in zebrafish according to a chemical dose-response approach. Results showed that U is highly bioconcentrated in fish, according to a time- and concentration-dependent model. Additionally, hepatic antioxidant defenses, red blood cells DNA integrity and brain acetylcholinesterase activity were found to be significantly altered. Generally, the higher the U concentration, the sooner and/or the greater the effect, suggesting a close relationship between accumulation and effect. - Research highlights: Depleted U bioconcentration factor is of about 1000 in zebrafish exposed to 20 {mu}g/L. Hepatic antioxidant disorders are noticed as soon as the first hours of exposure. DNA damage is induced in red blood cells after 20 d of exposure to 500 {mu}g DU/L. The brain cholinergic system (AChE activity) is impacted. - This study demonstrates that U is highly bioaccumulated in fish, resulting in biological disorders such as hepatic oxidative stress as well as genotoxic and neurotoxic events.

  19. Radiation damage and induced tetraploidy in mulberry (Morus alba L.)

    International Nuclear Information System (INIS)

    Katagiri, K.

    1976-01-01

    Vigorously growing mulberry shoots were exposed to 5 kR of gamma rays at the rate of 0.2 kR/hr and 5.0 kR/hr and successively pruned three times in two growing seasons. The most radiosensitive part of both the apical and axillary meristems was the second cell layer. The younger axillary bud primordia were more sensitive to radiation then the older ones. Recovery from radiation damage was assumed to be from the flank meristem in the shoot apex. The frequency of mutations was much lower than that of tetraploidy. Among the tetraploids 50% were 2-4-4 chimeras. (author)

  20. Relationship between cross section measurements and understanding radiation induced damage to biomolecules

    International Nuclear Information System (INIS)

    DuBois, R.D.; Braby, L.A.

    1993-10-01

    Experimental research performed at the Pacific Northwest Laboratory relating to energy deposition by energetic charged particles is described. How cross section data obtained from gaseous- and condensed-phase studies are related to understanding damage to biomolecules is discussed. Studies to date stress the need for information about energy deposition in individual interactions and show that multiple ionization may play a very significant role in biological damage. Current efforts to relate this gas-phase information to condensed-phase processes and biologically relevant targets are outlined

  1. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

    Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

  2. p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage

    DEFF Research Database (Denmark)

    Borisova, Marina E; Voigt, Andrea; Tollenaere, Maxim A X

    2018-01-01

    quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway. We identify RNA-binding proteins......Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV-light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here we employ...

  3. Estimation of γ irradiation induced genetic damage by Ames test

    International Nuclear Information System (INIS)

    Hosoda, Eiko

    1999-01-01

    Mutation by 60 Co γ irradiation was studied in five different histidine-requiring auxotrophs of Salmonella typhimurium. The strains TA98 (sensitive to frameshift) and TA100 (sensitive to base-pair substitution) were irradiated (10-84 Gy and 45-317 Gy, respectively) and revertants were counted. TA98 exhibited radiation-induced revertants, 2.8 fold of spontaneous revertants, although no significant increase was detected in TA100. Then, three other frameshift-sensitive strains TA1537, TA1538 and TA94 were irradiated in a dose of 61-167 Gy. Only in TA94, revertants increased 3.5 fold. Since spontaneous revertants are known to be independent of cell density, a decrease of bacterial number by γ irradiation was confirmed not to affect the induced revertants by dilution test. Thus the standard Ames Salmonella assay identified γ irradiation was confirmed not to affect the induced revertants by dilution test. Thus the standard Ames Salmonella assay identified γ irradiation as a mutagenetic agent. The mutagenicity of dinitropyrene, a mutagen widely existing in food, and dismutagenicity of boiling water insoluble fraction of Hizikia fusiforme, edible marine alga, were tested on γ induced revertant formation in TA98 and TA94. Dinitropyrene synergistically increased γ induced revertants and Hizikia insoluble fraction reduced the synergistic effect of dinitropyrene dependently on the concentration. (author)

  4. Site specific X-ray induced changes in organic and metal organic compounds and their influence on global radiation damage

    International Nuclear Information System (INIS)

    Heintz, Desiree Ellen

    2012-07-01

    The aim of this work was to systematically investigate the effects of specific and global X-ray radiation damage to biological samples and obtain a conclusive model to describe the underlying principles. Based on the systematic studies performed in this work, it was possible to propose two conclusive mechanisms to describe X-ray induced photoreduction and global radiation damage. The influence of chemical composition, temperature and solvent on X-ray induced photoreduction was investigated by X-ray Absorption Near Edge Spectroscopy and single crystal X-ray diffraction of two B12 cofactors - cyano- and methylcobalamin - as well as iron(II) and iron(III) complexes. The obtained results revealed that X-ray induced photoreduction is a ligand dependent process, with a redox reaction taking place within the complex. It could further be shown that selective hydrogen abstraction plays an important role in the process of X-ray induced photoreduction. Based on the experimental results of this work, a model to describe X-ray induced photoreduction of metal organic complexes could be proposed. The process of X-ray induced hydrogen abstraction was further investigated in a combined X-ray and neutron diffraction study on the amino acids L-serine and L-alanine, which were used as model compounds for proteins, and the nucleoside deoxythymidine (thymidine) as a model for DNA. A damage mechanism for L-serine could be found. It involves the abstraction of two hydrogen atoms, one from the hydroxyl group and one from the adjacent methylene group. Such a hydrogen abstraction results in the formation of a carbonyl group. X-ray diffraction measurements on cyano- and methylcobalamin as well as on three metal amino acid complexes, containing nickel(II) and copper(II), respectively, were conducted to investigate the contribution of X-ray induced photoreduction to global radiation damage. Results from these measurements combined with the results from L-serine, L-alanine and thymidine allowed

  5. Site specific X-ray induced changes in organic and metal organic compounds and their influence on global radiation damage

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, Desiree Ellen

    2012-07-15

    The aim of this work was to systematically investigate the effects of specific and global X-ray radiation damage to biological samples and obtain a conclusive model to describe the underlying principles. Based on the systematic studies performed in this work, it was possible to propose two conclusive mechanisms to describe X-ray induced photoreduction and global radiation damage. The influence of chemical composition, temperature and solvent on X-ray induced photoreduction was investigated by X-ray Absorption Near Edge Spectroscopy and single crystal X-ray diffraction of two B12 cofactors - cyano- and methylcobalamin - as well as iron(II) and iron(III) complexes. The obtained results revealed that X-ray induced photoreduction is a ligand dependent process, with a redox reaction taking place within the complex. It could further be shown that selective hydrogen abstraction plays an important role in the process of X-ray induced photoreduction. Based on the experimental results of this work, a model to describe X-ray induced photoreduction of metal organic complexes could be proposed. The process of X-ray induced hydrogen abstraction was further investigated in a combined X-ray and neutron diffraction study on the amino acids L-serine and L-alanine, which were used as model compounds for proteins, and the nucleoside deoxythymidine (thymidine) as a model for DNA. A damage mechanism for L-serine could be found. It involves the abstraction of two hydrogen atoms, one from the hydroxyl group and one from the adjacent methylene group. Such a hydrogen abstraction results in the formation of a carbonyl group. X-ray diffraction measurements on cyano- and methylcobalamin as well as on three metal amino acid complexes, containing nickel(II) and copper(II), respectively, were conducted to investigate the contribution of X-ray induced photoreduction to global radiation damage. Results from these measurements combined with the results from L-serine, L-alanine and thymidine allowed

  6. Biological effects of laser-induced stress waves

    International Nuclear Information System (INIS)

    Doukas, A.; Lee, S.; McAuliffe, D.

    1995-01-01

    Laser-induced stress waves can be generated by one of the following mechanisms: Optical breakdown, ablation or rapid heating of an absorbing medium. These three modes of laser interaction with matter allow the investigation of cellular and tissue responses to stress waves with different characteristics and under different conditions. The most widely studied phenomena are those of the collateral damage seen in photodisruption in the eye and in 193 run ablation of cornea and skin. On the other hand, the therapeutic application of laser-induced stress waves has been limited to the disruption of noncellular material such as renal stones, atheromatous plaque and vitreous strands. The effects of stress waves to cells and tissues can be quite disparate. Stress waves can fracture tissue, damage cells, and increase the permeability of the plasma membrane. The viability of cell cultures exposed to stress waves increases with the peak stress and the number of pulses applied. The rise time of the stress wave also influences the degree of cell injury. In fact, cell viability, as measured by thymidine incorporation, correlates better with the stress gradient than peak stress. Recent studies have also established that stress waves induce a transient increase of the permeability of the plasma membrane in vitro. In addition, if the stress gradient is below the damage threshhold, the cells remain viable. Thus, stress waves can be useful as a means of drug delivery, increasing the intracellular drug concentration and allowing the use of drugs which are impermeable to the cell membrane. The present studies show that it is important to create controllable stress waves. The wavelength tunability and the micropulse structure of the free electron laser is ideal for generating stress waves with independently adjustable parameters, such as rise time, duration and peak stress

  7. Hypoxic pretreatment protects against neuronal damage of the rat hippocampus induced by severe hypoxia.

    Science.gov (United States)

    Gorgias, N; Maidatsi, P; Tsolaki, M; Alvanou, A; Kiriazis, G; Kaidoglou, K; Giala, M

    1996-04-01

    The present study investigates whether under conditions of successive hypoxic exposures pretreatment with mild (15% O(2)) or moderate (10% O(2)) hypoxia, protects hippocampal neurones against damage induced by severe (3% O(2)) hypoxia. The ultrastructural findings were also correlated with regional superoxide dismutase (SOD) activity changes. In unpretreated rats severe hypoxia induced ultrastructural changes consistent with the aspects of delayed neuronal death (DND). However, in preexposed animals hippocampal damage was attenuated in an inversely proportional way with the severity of the hypoxic pretreatment. The ultrastructural hypoxic tolerance findings were also closely related to increased regional SOD activity levels. Thus the activation of the endogenous antioxidant defense by hypoxic preconditioning, protects against hippocampal damage induced by severe hypoxia. The eventual contribution of increased endogenous adenosine and/or reduced excitotoxicity to induce hypoxic tolerance is discussed.

  8. Beam-Induced Damage Mechanisms and their Calculation

    CERN Document Server

    Bertarelli, A

    2016-01-01

    The rapid interaction of highly energetic particle beams with matter induces dynamic responses in the impacted component. If the beam pulse is sufficiently intense, extreme conditions can be reached, such as very high pressures, changes of material density, phase transitions, intense stress waves, material fragmentation and explosions. Even at lower intensities and longer time-scales, significant effects may be induced, such as vibrations, large oscillations, and permanent deformation of the impacted components. These lectures provide an introduction to the mechanisms that govern the thermomechanical phenomena induced by the interaction between particle beams and solids and to the analytical and numerical methods that are available for assessing the response of impacted components. An overview of the design principles of such devices is also provided, along with descriptions of material selection guidelines and the experimental tests that are required to validate materials and components exposed to interactio...

  9. Effects of fatigue induced damage on the longitudinal fracture resistance of cortical bone.

    Science.gov (United States)

    Fletcher, Lloyd; Codrington, John; Parkinson, Ian

    2014-07-01

    As a composite material, cortical bone accumulates fatigue microdamage through the repetitive loading of everyday activity (e.g. walking). The accumulation of fatigue microdamage is thought to contribute to the occurrence of fragility fractures in older people. Therefore it is beneficial to understand the relationship between microcrack accumulation and the fracture resistance of cortical bone. Twenty longitudinally orientated compact tension fracture specimens were machined from a single bovine femur, ten specimens were assigned to both the control and fatigue damaged groups. The damaged group underwent a fatigue loading protocol to induce microdamage which was assessed via fluorescent microscopy. Following fatigue loading, non-linear fracture resistance tests were undertaken on both the control and damaged groups using the J-integral method. The interaction of the crack path with the fatigue induced damage and inherent toughening mechanisms were then observed using fluorescent microscopy. The results of this study show that fatigue induced damage reduces the initiation toughness of cortical bone and the growth toughness within the damage zone by three distinct mechanisms of fatigue-fracture interaction. Further analysis of the J-integral fracture resistance showed both the elastic and plastic component were reduced in the damaged group. For the elastic component this was attributed to a decreased number of ligament bridges in the crack wake while for the plastic component this was attributed to the presence of pre-existing fatigue microcracks preventing energy absorption by the formation of new microcracks.

  10. Quantification of stress-induced damage and post-fire response of 5083 aluminum alloy

    International Nuclear Information System (INIS)

    Chen, Y.; Puplampu, S.B.; Summers, P.T.; Lattimer, B.Y.; Penumadu, D.; Case, S.W.

    2015-01-01

    One of the major concerns regarding the use of lightweight materials in ship construction is the response of those materials to fire scenarios, including the residual structural performance after a fire event. This paper presents a study on creep damage evolution in 5083 marine-grade aluminum alloy and its impact on residual mechanical behavior. Tests conducted at 400 °C and pre-selected tensile stress levels were interrupted at target amplitudes of accumulated engineering creep strains to investigate the stress-induced damage using ex-situ characterization. Two-dimensional optical and electron microscopy and three-dimensional X-ray tomography were utilized on samples extracted from these test specimens to characterize the external and internal creep damage. The stress-induced damage is primarily manifested as cavitation and dynamic microstructural evolution. Cavitation morphology, orientation and grain structure evolution were investigated on three perpendicular sample surfaces. A 3D examination of the damage state provided consistent damage information to that obtained from the 2D analysis. The post-fire mechanical properties were also evaluated and linked to the microstructural change. The competing processes of cavitation and grain structure evolution were investigated to develop an understanding of the stress-induced damage associated with high temperature creep

  11. Quantification of stress-induced damage and post-fire response of 5083 aluminum alloy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y., E-mail: yanyun@vt.edu [Department of Engineering Science & Mechanics, Virginia Tech, Blacksburg, VA 24061 (United States); Puplampu, S.B. [Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Summers, P.T.; Lattimer, B.Y. [Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061 (United States); Penumadu, D. [Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Case, S.W. [Department of Engineering Science & Mechanics, Virginia Tech, Blacksburg, VA 24061 (United States)

    2015-08-12

    One of the major concerns regarding the use of lightweight materials in ship construction is the response of those materials to fire scenarios, including the residual structural performance after a fire event. This paper presents a study on creep damage evolution in 5083 marine-grade aluminum alloy and its impact on residual mechanical behavior. Tests conducted at 400 °C and pre-selected tensile stress levels were interrupted at target amplitudes of accumulated engineering creep strains to investigate the stress-induced damage using ex-situ characterization. Two-dimensional optical and electron microscopy and three-dimensional X-ray tomography were utilized on samples extracted from these test specimens to characterize the external and internal creep damage. The stress-induced damage is primarily manifested as cavitation and dynamic microstructural evolution. Cavitation morphology, orientation and grain structure evolution were investigated on three perpendicular sample surfaces. A 3D examination of the damage state provided consistent damage information to that obtained from the 2D analysis. The post-fire mechanical properties were also evaluated and linked to the microstructural change. The competing processes of cavitation and grain structure evolution were investigated to develop an understanding of the stress-induced damage associated with high temperature creep.

  12. Radition-induced genetic damage in plutella xylostella

    International Nuclear Information System (INIS)

    Ismail bin Bahari; Mahani binti Mohamad

    1993-01-01

    Radiation-induced chromosomal aberrations in progenies of irradiated Plutella xylostella was determined in a F1 sterility study. A total of 4 types of crosses (irradiated males against unirradiated females, irradiated females against unirradiated males, both parents irradiated and normal) were made following gamma irradiation at the pupal stage. Testes squash preparations made from F1 male larvae revealed 3 main types of chromosomal abberations induced by doses of 100, 150 and 200 Gy. Results obtained indicate the possibility of using chromosome translocations as the genetic marker

  13. Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

    Science.gov (United States)

    Griko, Y. V.; Yan, Xiaoli

    2016-01-01

    Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing

  14. Cytogenetic Damages Induced by Chronic Exposure to Microwave Non-Ionizing Radiofrequency Fields

    Directory of Open Access Journals (Sweden)

    Boris Đinđić

    2013-12-01

    Full Text Available Non-ionizing radiation has a significant and positive impact on modern society through a number of uses. There is increasing public concern regarding the health risks of radio-frequency (RF radiation, particularly that produced by mobile phones. Concern regarding the potential risks of exposure to EMFs has led to many epidemiological investigations, but the effects of EMF exposure on human and other mammalian cells are still unclear. One of the most frequently asked questions about the effects of microwave radiation on biological systems is whether they produce genotoxic effects and could be there a possible link with oncogenic processes. It is most difficult to get accurate and reproducible results for the studies that tell us most about the effects of EMF on humans. Based on some “weak” evidence suggesting an association between exposure to radiofrequency fields (RF emitted from mobile phones and two types of brain cancer, glioma and acoustic neuroma, the International Agency for Research on Cancer has classified RF as ‘possibly carcinogenic to humans’ in group 2B. Literature results suggest that pulsed microwaves from working environment can be the cause of genetic and cell alterations. Taken together, the increased frequency of DNA damages, increased intensity of oxydative stress and production of reactive oxygen species as well as prolonged disruption in DNA repair mechanisms could be possible mechanisms for microwave induced cytogenetic damages even at low-level electromagnetic fields. Although there were contradictory results about harmful effects of electromagnetic fields we recommend that the mobile phone should be kept as far as possible from the body during conversations and also during usual daily activities to reduce the absorption of radiation by cells. In addition, the appropriate intake of antioxidant-rich food or drugs may be helpful for preventing the genotoxic effects that could be caused by mobile phone use.

  15. Calibration curves for biological dosimetry by drug-induced prematurely condensed chromosomes in human lymphocytes

    International Nuclear Information System (INIS)

    Kang, C. M.; Chung, H. C.; Cho, C. K.

    2002-01-01

    To develop the cytogenetic tool to detect chromosome damages after high dose exposure with 60 Coγ- rays, dose-response curves were measured for induction of prematurely condensed chromosomes (PCC) in peripheral lymphocytes. Blood was obtained from 10 different healthy donors, and given okadaic acid (OA) 500nM in cultured lymphocytes 1h after radiation exposure. Cells were analyzed by the frequencies of OA-induced PCC rings because it is difficult to obtain mitotic chromosomes using a conventional chromosome aberration (CA). PCC-rings were scored in cells exposed in the dose range of 0.2-16Gy. The frequency of the cells with PCC and the dose-response relationship for the yield of PCC rings were examined in the irradiated lymphocytes. The yield of PCC-rings increased with dose dependent-manner up to 16Gy. The observed dose-effect relationship for the percentage of cells with PCC-rings was calculated by linear-quadratic model. This technique can be applied to biological dosimetry of radiation exposures involving whole body irradiation to allow damaged chromosomes to be detected with great sensitivity. Detection of okadaic acid-induced PCC rings is a useful method up to 16Gy or more doses in estimating the absorbed doses of victims after high dose exposure. Calibration curves described in this paper will be used in our laboratory for biological dosimetry by PCC-ring after a high dose exposure

  16. Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G., E-mail: lhudson@salud.unm.edu

    2013-06-01

    Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the Hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. - Highlights: • Low levels of arsenite enhance UV-induced DNA damage in human keratinocytes. • UV-initiated HPRT mutation frequency is enhanced by arsenite. • Zinc supplementation offsets DNA damage and mutation frequency enhanced by arsenite. • Zinc-dependent reduction of arsenite enhanced DNA damage is confirmed in vivo.

  17. Prevention of Severe Hypoglycemia-Induced Brain Damage and Cognitive Impairment with Verapamil.

    Science.gov (United States)

    Jackson, David A; Michael, Trevin; Vieira de Abreu, Adriana; Agrawal, Rahul; Bortolato, Marco; Fisher, Simon J

    2018-05-03

    People with insulin-treated diabetes are uniquely at risk for severe hypoglycemia-induced brain damage. Since calcium influx may mediate brain damage, we tested the hypothesis that the calcium channel blocker, verapamil, would significantly reduce brain damage and cognitive impairment caused by severe hypoglycemia. Ten-week-old Sprague-Dawley rats were randomly assigned to one of three treatments; 1) control hyperinsulinemic (200 mU.kg -1 min -1 ) euglycemic (80-100mg/dl) clamps (n=14), 2) hyperinsulinemic hypoglycemic (10-15mg/dl) clamps (n=16), or 3) hyperinsulinemic hypoglycemic clamps followed by a single treatment with verapamil (20mg/kg) (n=11). As compared to euglycemic controls, hypoglycemia markedly increased dead/dying neurons in the hippocampus and cortex, by 16-fold and 14-fold, respectively. Verapamil treatment strikingly decreased hypoglycemia-induced hippocampal and cortical damage, by 87% and 94%, respectively. Morris Water Maze probe trial results demonstrated that hypoglycemia induced a retention, but not encoding, memory deficit (noted by both abolished target quadrant preference and reduced target quadrant time). Verapamil treatment significantly rescued spatial memory as noted by restoration of target quadrant preference and target quadrant time. In summary, a one-time treatment with verapamil following severe hypoglycemia prevented neural damage and memory impairment caused by severe hypoglycemia. For people with insulin treated diabetes, verapamil may be a useful drug to prevent hypoglycemia-induced brain damage. © 2018 by the American Diabetes Association.

  18. High-Density Plasma-Induced Etch Damage of GaN

    International Nuclear Information System (INIS)

    Baca, A.G.; Han, J.; Lester, L.F.; Pearton, S.J.; Ren, F.; Shul, R.J.; Willison, C.G.; Zhang, L.; Zolper, J.C.

    1999-01-01

    Anisotropic, smooth etching of the group-III nitrides has been reported at relatively high rates in high-density plasma etch systems. However, such etch results are often obtained under high de-bias and/or high plasma flux conditions where plasma induced damage can be significant. Despite the fact that the group-III nitrides have higher bonding energies than more conventional III-V compounds, plasma-induced etch damage is still a concern. Attempts to minimize such damage by reducing the ion energy or increasing the chemical activity in the plasma often result in a loss of etch rate or anisotropy which significantly limits critical dimensions and reduces the utility of the process for device applications requiring vertical etch profiles. It is therefore necessary to develop plasma etch processes which couple anisotropy for critical dimension and sidewall profile control and high etch rates with low-damage for optimum device performance. In this study we report changes in sheet resistance and contact resistance for n- and p-type GaN samples exposed to an Ar inductively coupled plasma (ICP). In general, plasma-induced damage was more sensitive to ion bombardment energies as compared to plasma flux. In addition, p-GaN was typically more sensitive to plasma-induced damage as compared to n-GaN

  19. Radiation-induced DNA damage as a function of DNA hydration

    International Nuclear Information System (INIS)

    Swarts, S.G.; Miao, L.; Wheeler, K.T.; Sevilla, M.D.; Becker, D.

    1995-01-01

    Radiation-induced DNA damage is produced from the sum of the radicals generated by the direct ionization of the DNA (direct effect) and by the reactions of the DNA with free radicals formed in the surrounding environment (indirect effect). The indirect effect has been believed to be the predominant contributor to radiation-induced intracellular DNA damage, mainly as the result of reactions of bulk water radicals (e.g., OH·) with DNA. However, recent evidence suggests that DNA damage, derived from the irradiation of water molecules that are tightly bound in the hydration layer, may occur as the result of the transfer of electron-loss centers (e.g. holes) and electrons from these water molecules to the DNA. Since this mechanism for damaging DNA more closely parallels that of the direct effect, the irradiation of these tightly bound water molecules may contribute to a quasi-direct effect. These water molecules comprise a large fraction of the water surrounding intracellular DNA and could account for a significant proportion of intracellular radiation-induced DNA damage. Consequently, the authors have attempted to characterize this quasi-direct effect to determine: (1) the extent of the DNA hydration layer that is involved with this effect, and (2) what influence this effect has on the types and quantities of radiation-induced DNA damage

  20. Chemically induced aneuploidy in mammalian cells: mechanisms and biological significance in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oshimura, M.; Barrett, J.C.

    1986-01-01

    A literature review with over 200 references examines the growing body of evidence from human and animal cancer cytogenetics that aneuploidy is an important chromosome change in carcinogenesis. Evidence from in vitro cell transformation studies supports the idea that aneuploidy has a direct effect on the conversion of a normal cell to a preneoplastic or malignant cell. Induction of an aneuploid state in a preneoplastic or neoplastic cell could have any of the following four biological effects: a change in gene dosage, a change in gene balance, expression of a recessive mutation, or a change in genetic instability (which could secondarily lead to neoplasia). There are a number of possible mechanisms by which chemicals might induce aneuploidy, including effects on microtubules, damage to essential elements for chromosome function reduction in chromosome condensation or pairing, induction of chromosome interchanges, unresolved recombination structures, increased chromosome stickiness, damage to centrioles, impairment of chromosome alignment ionic alterations during mitosis, damage to the nuclear membrane, and a physical disruption of chromosome segregation. Therefore, a number of different targets exist for chemically induced aneuploidy.

  1. Electronic-excitation induced radiation damage in glasses

    Energy Technology Data Exchange (ETDEWEB)

    Vigouroux, J P

    1985-01-01

    In order to understand the microscopic nature of radiation induced defects in insulators, we have studied localization of negative and positive charges in amorphous and monocrystalline SiO2. The behaviour of these charges is linked to creation of point defects by electronic excitation. The role of intense electric fields under irradiation is pointed out.

  2. Terbium fluorescence as a sensitive, inexpensive probe for UV-induced damage in nucleic acids

    International Nuclear Information System (INIS)

    El-Yazbi, Amira F.; Loppnow, Glen R.

    2013-01-01

    Graphical abstract: -- Highlights: •Simple, inexpensive, mix-and-read assay for positive detection of DNA damage. •Recognition of undamaged DNA via hybridization to a hairpin probe. •Terbium(III) fluorescence reports the amount of damage by binding to ssDNA. •Tb/hairpin is a highly selective and sensitive fluorescent probe for DNA damage. -- Abstract: Much effort has been focused on developing methods for detecting damaged nucleic acids. However, almost all of the proposed methods consist of multi-step procedures, are limited, require expensive instruments, or suffer from a high level of interferences. In this paper, we present a novel simple, inexpensive, mix-and-read assay that is generally applicable to nucleic acid damage and uses the enhanced luminescence due to energy transfer from nucleic acids to terbium(III) (Tb 3+ ). Single-stranded oligonucleotides greatly enhance the Tb 3+ emission, but duplex DNA does not. With the use of a DNA hairpin probe complementary to the oligonucleotide of interest, the Tb 3+ /hairpin probe is applied to detect ultraviolet (UV)-induced DNA damage. The hairpin probe hybridizes only with the undamaged DNA. However, the damaged DNA remains single-stranded and enhances the intrinsic fluorescence of Tb 3+ , producing a detectable signal directly proportional to the amount of DNA damage. This allows the Tb 3+ /hairpin probe to be used for sensitive quantification of UV-induced DNA damage. The Tb 3+ /hairpin probe showed superior selectivity to DNA damage compared to conventional molecular beacons probes (MBs) and its sensitivity is more than 2.5 times higher than MBs with a limit of detection of 4.36 ± 1.2 nM. In addition, this probe is easier to synthesize and more than eight times cheaper than MBs, which makes its use recommended for high-throughput, quantitative analysis of DNA damage

  3. Cardiac c-Kit Biology Revealed by Inducible Transgenesis.

    Science.gov (United States)

    Gude, Natalie A; Firouzi, Fareheh; Broughton, Kathleen M; Ilves, Kelli; Nguyen, Kristine P; Payne, Christina R; Sacchi, Veronica; Monsanto, Megan M; Casillas, Alexandria R; Khalafalla, Farid G; Wang, Bingyan J; Ebeid, David E; Alvarez, Roberto; Dembitsky, Walter P; Bailey, Barbara A; van Berlo, Jop; Sussman, Mark A

    2018-06-22

    Biological significance of c-Kit as a cardiac stem cell marker and role(s) of c-Kit+ cells in myocardial development or response to pathological injury remain unresolved because of varied and discrepant findings. Alternative experimental models are required to contextualize and reconcile discordant published observations of cardiac c-Kit myocardial biology and provide meaningful insights regarding clinical relevance of c-Kit signaling for translational cell therapy. The main objectives of this study are as follows: demonstrating c-Kit myocardial biology through combined studies of both human and murine cardiac cells; advancing understanding of c-Kit myocardial biology through creation and characterization of a novel, inducible transgenic c-Kit reporter mouse model that overcomes limitations inherent to knock-in reporter models; and providing perspective to reconcile disparate viewpoints on c-Kit biology in the myocardium. In vitro studies confirm a critical role for c-Kit signaling in both cardiomyocytes and cardiac stem cells. Activation of c-Kit receptor promotes cell survival and proliferation in stem cells and cardiomyocytes of either human or murine origin. For creation of the mouse model, the cloned mouse c-Kit promoter drives Histone2B-EGFP (enhanced green fluorescent protein; H2BEGFP) expression in a doxycycline-inducible transgenic reporter line. The combination of c-Kit transgenesis coupled to H2BEGFP readout provides sensitive, specific, inducible, and persistent tracking of c-Kit promoter activation. Tagging efficiency for EGFP+/c-Kit+ cells is similar between our transgenic versus a c-Kit knock-in mouse line, but frequency of c-Kit+ cells in cardiac tissue from the knock-in model is 55% lower than that from our transgenic line. The c-Kit transgenic reporter model reveals intimate association of c-Kit expression with adult myocardial biology. Both cardiac stem cells and a subpopulation of cardiomyocytes express c-Kit in uninjured adult heart

  4. Chromatin damage induced by fast neutrons or UV laser radiation

    Energy Technology Data Exchange (ETDEWEB)

    Radu, L.; Constantinescu, B.; Gazdaru, D.; Mihailescu, I

    2002-07-01

    Chromatin samples from livers of Wistar rats were subjected to fast neutron irradiation in doses of 10-100 Gy or to a 248 nm excimer laser radiation, in doses of 0.5-3 MJ.m{sup -2}. The action of the radiation on chromatin was monitored by chromatin intrinsic fluorescence and fluorescence lifetimes (of bound ethidium bromide to chromatin) and by analysing fluorescence resonance energy transfer between dansyl chloride and acridine orange coupled to chromatin. For the mentioned doses of UV excimer laser radiation, the action on chromatin was more intense than in the case of fast neutrons. The same types of damage are produced by the two radiations: acidic and basic destruction of chromatin protein structure, DNA strand breaking and the increase of the distance between DNA and proteins in chromatin. (author)

  5. Chromatin damage induced by fast neutrons or UV laser radiation

    International Nuclear Information System (INIS)

    Radu, L.; Constantinescu, B.; Gazdaru, D.; Mihailescu, I.

    2002-01-01

    Chromatin samples from livers of Wistar rats were subjected to fast neutron irradiation in doses of 10-100 Gy or to a 248 nm excimer laser radiation, in doses of 0.5-3 MJ.m -2 . The action of the radiation on chromatin was monitored by chromatin intrinsic fluorescence and fluorescence lifetimes (of bound ethidium bromide to chromatin) and by analysing fluorescence resonance energy transfer between dansyl chloride and acridine orange coupled to chromatin. For the mentioned doses of UV excimer laser radiation, the action on chromatin was more intense than in the case of fast neutrons. The same types of damage are produced by the two radiations: acidic and basic destruction of chromatin protein structure, DNA strand breaking and the increase of the distance between DNA and proteins in chromatin. (author)

  6. Zicam-induced damage to mouse and human nasal tissue.

    Directory of Open Access Journals (Sweden)

    Jae H Lim

    Full Text Available Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc, a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

  7. Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

    Science.gov (United States)

    Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

    2011-01-01

    It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

  8. Feasibility of OCT to detect radiation-induced esophageal damage in small animal models (Conference Presentation)

    Science.gov (United States)

    Jelvehgaran, Pouya; Alderliesten, Tanja; Salguero, Javier; Borst, Gerben; Song, Ji-Ying; van Leeuwen, Ton G.; de Boer, Johannes F.; de Bruin, Daniel M.; van Herk, Marcel B.

    2016-03-01

    Lung cancer survival is poor and radiotherapy patients often suffer serious treatment side effects. The esophagus is particularly sensitive leading to reduced food intake or even fistula formation. Only few direct techniques exist to measure radiation-induced esophageal damage, for which knowledge is needed to improve the balance between risk of tumor recurrence and complications. Optical coherence tomography (OCT) is a minimally-invasive imaging technique that obtains cross-sectional, high-resolution (1-10µm) images and is capable of scanning the esophageal wall up to 2-3mm depth. In this study we investigated the feasibility of OCT to detect esophageal radiation damage in mice. In total 30 mice were included in 4 study groups (1 main and 3 control groups). Mice underwent cone-beam CT imaging for initial setup assessment and dose planning followed by single-fraction dose delivery of 4, 10, 16, and 20Gy on 5mm spots, spaced 10mm apart. Mice were repeatedly imaged using OCT: pre-irradiation and up to 3 months post-irradiation. The control groups received either OCT only, irradiation only, or were sham-operated. We used histopathology as gold standard for radiation-induced damage diagnosis. The study showed edema in both the main and OCT-only groups. Furthermore, radiation-induced damage was primarily found in the highest dose region (distal esophagus). Based on the histopathology reports we were able to identify the radiation-induced damage in the OCT images as a change in tissue scattering related to the type of induced damage. This finding indicates the feasibility and thereby the potentially promising role of OCT in radiation-induced esophageal damage assessment.

  9. Synchrotron radiation. 4. Analyses of biological samples using synchrotron radiation. 3. Research on radiation damage to DNA using synchrotron radiation

    International Nuclear Information System (INIS)

    Takakura, Kaoru

    1998-01-01

    This review described how the synchrotron radiation (SR) is used to solve problems unknown hitherto in radiation biology. Historically, the target substance of UV light in bacterial death was suggested to be nucleic acid in 1930. Researches on the radiation damage to DNA were begun at around 1960 and have mainly used UV light, X-ray and γray. Soft X-ray and vacuum UV whose energy covering from several eV to scores of keV have not been used since UV and X-ray lack the energy of this range. This is one of reasons why detailed process leading to radiation-induced death, carcinogenicity and mutation has not been known hitherto. RS possesses wide range of energy, i.e., from UV to hard X-ray, of high intensity, which is helpful for studying the unknown problems. The RS studies were begun in nineteen-seventies. Those include the action spectrum studies and atomic target studies. In the former, the course of the effect, e.g., the mechanism of DNA double strand breakage, can be elucidated. In the latter, photon of known energy can be irradiated to the specified atom like phosphorus in DNA which elucidating the precise physicochemical process of the breakage. Use of RS in these studies is thought still meaningful in future. (K.H.) 62 refs

  10. Hydrogen induced plastic damage in pressure vessel steel of 2.25Cr-1Mo

    International Nuclear Information System (INIS)

    Han, G.W.; Song, Y.J.

    1995-01-01

    2.25Cr-1Mo steel is generally employed as a hydrogenation reaction vessel material used at elevated temperature and in a hydrogen containing environment. During service of the reaction vessel, a large number of hydrogen atoms would enter its wall. When the reaction vessel is shutdown and the temperature reduces to about ambient temperature, the hydrogen atoms remaining in the wall would induce plastic damage in the steel. The mechanism of hydrogen induced plastic damage is different for various materials with different microstructures. Investigations have demonstrated that the hydrogen induced plastic damage in carbide annealed carbon steels is caused by hydrogen accelerating the initiating and growing of microvoids from the carbide particles. However, SEM examination on the fracture surface of hydrogen charged tensile specimen of 2.25Cr-1Mo steel show that a large number of fisheyes appear on the fracture surface. This indicates that hydrogen induced plastic damage in 2.25Cr-1Mo steel is related to the occurrence of fisheye cracks during plastic deformation. By means of micro-fracture mechanics to analyze fisheye crack occurrence from the first generation microvoid, the mechanism of hydrogen induced plastic damage in the pressure vessel steel is investigated

  11. Organic honey supplementation reverses pesticide-induced genotoxicity by modulating DNA damage response.

    Science.gov (United States)

    Alleva, Renata; Manzella, Nicola; Gaetani, Simona; Ciarapica, Veronica; Bracci, Massimo; Caboni, Maria Fiorenza; Pasini, Federica; Monaco, Federica; Amati, Monica; Borghi, Battista; Tomasetti, Marco

    2016-10-01

    Glyphosate (GLY) and organophosphorus insecticides such as chlorpyrifos (CPF) may cause DNA damage and cancer in exposed individuals through mitochondrial dysfunction. Polyphenols ubiquitously present in fruits and vegetables, have been viewed as antioxidant molecules, but also influence mitochondrial homeostasis. Here, honey containing polyphenol compounds was evaluated for its potential protective effect on pesticide-induced genotoxicity. Honey extracts from four floral organic sources were evaluated for their polyphenol content, antioxidant activity, and potential protective effects on pesticide-related mitochondrial destabilization, reactive oxygen and nitrogen species formation, and DNA damage response in human bronchial epithelial and neuronal cells. The protective effect of honey was, then evaluated in a residential population chronically exposed to pesticides. The four honey types showed a different polyphenol profile associated with a different antioxidant power. The pesticide-induced mitochondrial dysfunction parallels ROS formation from mitochondria (mtROS) and consequent DNA damage. Honey extracts efficiently inhibited pesticide-induced mtROS formation, and reduced DNA damage by upregulation of DNA repair through NFR2. Honey supplementation enhanced DNA repair activity in a residential population chronically exposed to pesticides, which resulted in a marked reduction of pesticide-induced DNA lesions. These results provide new insight regarding the effect of honey containing polyphenols on pesticide-induced DNA damage response. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Treatment of Radiation Induced Biological Changes by Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    El-Missiry, M.A.; Shehata, G.; Roushdy, H.M; Fayed, Th.A.

    1999-01-01

    Preventing the propagation of radiation induced oxidative damage has been a subject of considerable investigations. The ultimate goal of the present study is to use bone marrow cells to ameliorate or to treat the radiation sickness. Transplantation of bone marrow cell has shown promising results in the present experimental radiation treatment. In this report, suspension of bone marrow cells was injected into rats 12 h. after exposure to 4.5 Gy whole body gamma irradiation. Significant results were recorded on the successful control of the radiation induced disorders in a number of biochemical parameters including certain enzymatic and nonenzymatic antioxidants (superoxide dismutase and glutathione) and certain parameters related to kidney function including creatinine, urea as well as Atpase Activity in blood serum, urine and kidney tissue

  13. Effect of melatonin and time of administration on irradiation-induced damage to rat testes

    Directory of Open Access Journals (Sweden)

    G. Take

    2009-07-01

    Full Text Available The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol or melatonin administered 24 h before (10 mg/kg, immediately before (20 mg/kg and 24 h after irradiation (10 mg/kg, all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05. Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05. Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

  14. Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    N.B.R. Colombo

    2015-01-01

    Full Text Available The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

  15. Plastic Strain Induced Damage Evolution and Martensitic Transformation in Ductile Materials at Cryogenic Temperatures

    CERN Document Server

    Garion, C

    2002-01-01

    The Fe-Cr-Ni stainless steels are well known for their ductile behaviour at cryogenic temperatures. This implies development and evolution of plastic strain fields in the stainless steel components subjected to thermo-mechanical loads at low temperatures. The evolution of plastic strain fields is usually associated with two phenomena: ductile damage and strain induced martensitic transformation. Ductile damage is described by the kinetic law of damage evolution. Here, the assumption of isotropic distribution of damage (microcracks and microvoids) in the Representative Volume Element (RVE) is made. Formation of the plastic strain induced martensite (irreversible process) leads to the presence of quasi-rigid inclusions of martensite in the austenitic matrix. The amount of martensite platelets in the RVE depends on the intensity of the plastic strain fields and on the temperature. The evolution of the volume fraction of martensite is governed by a kinetic law based on the accumulated plastic strain. Both of thes...

  16. Extract from Armoracia rusticana and Its Flavonoid Components Protect Human Lymphocytes against Oxidative Damage Induced by Hydrogen Peroxide

    Directory of Open Access Journals (Sweden)

    Michala Gafrikova

    2014-03-01

    Full Text Available DNA damage prevention is an important mechanism involved in cancer prevention by dietary compounds. Armoracia rusticana is cultivated mainly for its roots that are used in the human diet as a pungent spice. The roots represent rich sources of biologically active phytocompounds, which are beneficial for humans. In this study we investigated the modulation of H2O2 genotoxicity using the A. rusticana root aqueous extract (AE and two flavonoids (kaempferol or quercetin. Human lymphocytes pre-treated with AE, kaempferol and quercetin were challenged with H2O2 and the DNA damage was assessed by the comet assay. At first we assessed a non-genotoxic concentration of AE and flavonoids, respectively. In lymphocytes challenged with H2O2 we proved that the 0.0025 mg·mL−1 concentration of AE protected human DNA. It significantly reduced H2O2-induced oxidative damage (from 78% to 35.75%. Similarly, a non-genotoxic concentration of kaempferol (5 μg·mL−1 significantly diminished oxidative DNA damage (from 83.3% to 19.4%, and the same concentration of quercetin also reduced the genotoxic effect of H2O2 (from 83.3% to 16.2%. We conclude that AE, kaempferol and quercetin probably act as antimutagens. The molecular mechanisms underlying their antimutagenic activity might be explained by their antioxidant properties.

  17. Extract from Armoracia rusticana and its flavonoid components protect human lymphocytes against oxidative damage induced by hydrogen peroxide.

    Science.gov (United States)

    Gafrikova, Michala; Galova, Eliska; Sevcovicova, Andrea; Imreova, Petronela; Mucaji, Pavel; Miadokova, Eva

    2014-03-14

    DNA damage prevention is an important mechanism involved in cancer prevention by dietary compounds. Armoracia rusticana is cultivated mainly for its roots that are used in the human diet as a pungent spice. The roots represent rich sources of biologically active phytocompounds, which are beneficial for humans. In this study we investigated the modulation of H₂O₂ genotoxicity using the A. rusticana root aqueous extract (AE) and two flavonoids (kaempferol or quercetin). Human lymphocytes pre-treated with AE, kaempferol and quercetin were challenged with H₂O₂ and the DNA damage was assessed by the comet assay. At first we assessed a non-genotoxic concentration of AE and flavonoids, respectively. In lymphocytes challenged with H₂O₂ we proved that the 0.0025 mg·mL⁻¹ concentration of AE protected human DNA. It significantly reduced H₂O₂-induced oxidative damage (from 78% to 35.75%). Similarly, a non-genotoxic concentration of kaempferol (5 μg·mL⁻¹) significantly diminished oxidative DNA damage (from 83.3% to 19.4%), and the same concentration of quercetin also reduced the genotoxic effect of H₂O₂ (from 83.3% to 16.2%). We conclude that AE, kaempferol and quercetin probably act as antimutagens. The molecular mechanisms underlying their antimutagenic activity might be explained by their antioxidant properties.

  18. Modulation of DNA-induced damage and repair capacity in humans after dietary intervention with lutein-enriched fermented milk.

    Science.gov (United States)

    Herrero-Barbudo, Carmen; Soldevilla, Beatriz; Pérez-Sacristán, Belén; Blanco-Navarro, Inmaculada; Herrera, Mercedes; Granado-Lorencio, Fernando; Domínguez, Gemma

    2013-01-01

    Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers.

  19. Modulation of DNA-induced damage and repair capacity in humans after dietary intervention with lutein-enriched fermented milk.

    Directory of Open Access Journals (Sweden)

    Carmen Herrero-Barbudo

    Full Text Available Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers.

  20. Temozolomide-induced liver damage. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Becker, F.; Hecht, M.; Schmidtner, J.; Semrau, S.; Fietkau, R. [University of Erlangen-Nuremberg, Department of Radiation Oncology, Erlangen (Germany)

    2014-04-15

    Temozolomide (TMZ) is an alkylating agent used in chemoradiotherapy and adjuvant chemotherapy regimens for treatment of newly diagnosed or recurrent glioblastoma. In Germany alone, 900,000 daily doses of the drug are prescribed each year. Therefore, all severe side effects of TMZ, even those rarely observed, are relevant to radiotherapists. We report a case of severe drug-induced toxic hepatitis that developed during chemoradiotherapy with TMZ in a patient with glioblastoma multiforme. Transaminase elevation was observed after 5 weeks of TMZ treatment, followed by severe jaundice symptoms which only subsided 2 months later. These findings were consistent with diagnosis of the mixed hepatic/cholestatic type of drug-induced toxic hepatitis. Due to the early termination of treatment, no life-threatening complications occurred in our patient. However, rare reports of encephalopathy and fatality as complications of TMZ therapy can be found in the literature. When using TMZ for treatment of glioblastoma, monitoring of liver enzyme levels should be performed twice weekly to prevent fatal toxic hepatitis. In the case of any drug-induced hepatitis, TMZ must be discontinued immediately. (orig.)

  1. Photoprotection beyond ultraviolet radiation--effective sun protection has to include protection against infrared A radiation-induced skin damage.

    Science.gov (United States)

    Schroeder, P; Calles, C; Benesova, T; Macaluso, F; Krutmann, J

    2010-01-01

    Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more than one third of the solar energy that reaches human skin. While infrared radiation of longer wavelengths (IRB and IRC) does not penetrate deeply into the skin, more than 65% of the shorter wavelength (IRA) reaches the dermis. IRA radiation has been demonstrated to alter the collagen equilibrium of the dermal extracellular matrix in at least two ways: (a) by leading to an increased expression of the collagen-degrading enzyme matrix metalloproteinase 1, and (b) by decreasing the de novo synthesis of the collagen itself. IRA radiation exposure therefore induces similar biological effects to UV radiation, but the underlying mechanisms are substantially different, specifically, the cellular response to IRA irradiation involves the mitochondrial electron transport chain. Effective sun protection requires specific strategies to prevent IRA radiation-induced skin damage. 2010 S. Karger AG, Basel.

  2. In vitro and in vivo assay of radio-induced damage in Escherichia Coli, DNA labelled on thymidilic fragment

    International Nuclear Information System (INIS)

    Bonicel, A.

    1977-01-01

    A technique of rapid assay for a particular and very important damage, N-formamido (DNA), is described. Using this technique, the importance of radio-induced DNA damage can be evaluated before the repair enzymatic system takes place [fr

  3. DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase

    Czech Academy of Sciences Publication Activity Database

    Bražina, Jan; Švadlenka, Jan; Macůrek, Libor; Anděra, Ladislav; Hodný, Zdeněk; Bartek, Jiří; Hanzlíková, Hana

    2015-01-01

    Roč. 14, č. 3 (2015), s. 375-387 ISSN 1538-4101 R&D Projects: GA ČR GPP305/11/P683 Institutional support: RVO:68378050 Keywords : ATM * DAXX * DNA damage * p53 * Wip1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.952, year: 2015

  4. (WASHINGTON, DC) A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

    Science.gov (United States)

    Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

  5. The contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore

    International Nuclear Information System (INIS)

    Jacobs, G.P.; Samuni, A.; Czapski, G.

    1985-01-01

    Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia. (author)

  6. Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Zamansky, G B

    1986-08-01

    The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells.

  7. Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

    International Nuclear Information System (INIS)

    Zamansky, G.B.

    1986-01-01

    The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells. (author)

  8. Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging?

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available Accumulation of DNA damage leading to stem cell exhaustion has been proposed to be a principal mechanism of aging. Using 53BP1-foci as a marker for DNA double-strand breaks (DSBs, hair follicle stem cells (HFSCs in mouse epidermis were analyzed for age-related DNA damage response (DDR. We observed increasing amounts of 53BP1-foci during the natural aging process independent of telomere shortening and after protracted low-dose radiation, suggesting substantial accumulation of DSBs in HFSCs. Electron microscopy combined with immunogold-labeling showed multiple small 53BP1 clusters diffusely distributed throughout the highly compacted heterochromatin of aged HFSCs, but single large 53BP1 clusters in irradiated HFSCs. These remaining 53BP1 clusters did not colocalize with core components of non-homologous end-joining, but with heterochromatic histone modifications. Based on these results we hypothesize that these lesions were not persistently unrepaired DSBs, but may reflect chromatin rearrangements caused by the repair or misrepair of DSBs. Flow cytometry showed increased activation of repair proteins and damage-induced chromatin modifications, triggering apoptosis and cellular senescence in irradiated, but not in aged HFSCs. These results suggest that accumulation of DNA damage-induced chromatin alterations, whose structural dimensions reflect the complexity of the initial genotoxic insult, may lead to different DDR events, ultimately determining the biological outcome of HFSCs. Collectively, our findings support the hypothesis that aging might be largely the remit of structural changes to chromatin potentially leading to epigenetically induced transcriptional deregulation.

  9. Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

    Science.gov (United States)

    Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

    2017-06-01

    Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. DNA Damage Induced by Alkylating Agents and Repair Pathways

    Science.gov (United States)

    Kondo, Natsuko; Takahashi, Akihisa; Ono, Koji; Ohnishi, Takeo

    2010-01-01

    The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine. PMID:21113301

  11. Root damage induced by intraosseous anesthesia. An in vitro investigation.

    Science.gov (United States)

    Graetz, Christian; Fawzy-El-Sayed, Karim-Mohamed; Graetz, Nicole; Dörfer, Christof-Edmund

    2013-01-01

    The principle of the intraosseous anesthesia (IOA) relies on the perforation of the cortical plate of the bone for direct application of the local anesthetic solution into the underlying cancellous structures. During this procedure, IOA needles might accidentally come in contact with the tooth roots. The aim of the current in vitro study was to examine the consequences of this 'worst case scenario' comparing five commercially available IOA systems. Extracted human roots were randomly perforated using five different IOA systems with a drilling time ≤5s. To simulate normal in vivo conditions, the roots were kept humid during the drilling procedure. Data was statistically evaluated using F-test (SPSS16, SPSS Inc., Chicago, USA) and the significance level was set at p ≤ 0.05. All examined systems resulted in root perforation. Drill fractures occurred in either none 0% (Quicksleeper, Anesto, Intraflow, Stabident) or 100% (X-Tip) of the applications. Excessive heat generation, as evident by combustion odor as well as metal and tooth discoloration, appeared in 30% (Quicksleeper), 40% (Anesto), 60% (Intraflow), 90% (Stabident) and 100% (X-Tip) of all perforations. Within the limits of in-vitro studies, the results show a potential for irreversible root damage that might be inflicted by an improper use of IOA systems.

  12. Mechanically induced tube damage in the artificial hydrosalpinx.

    Science.gov (United States)

    Kleinstein, J; Neubüser, D; Mussmann, J

    1982-01-01

    One-sided artificial hydrosalpinx was caused in mature New Zealand rabbits by proximal and distal ligature. After 2 weeks the average secretion accumulation was 2.1 ml, after 8 weeks 6.3 ml. A fold relief could no longer be detected after 8 weeks. The light-microscopical study of the epithelium showed signs of cell degeneration with cell dedifferentiation, pyknosis of the nucleus, and perinuclear aerolae. The ciliation of 66% ciliated cells for the normal oviduct (pars ampullaris) was reduced to 15% after 8 weeks of artificial hydrosalpinx. Based on the hypertrophy of the muscularis the percentage loss of E2 receptors within 4 weeks was smaller in comparison with the percentage reduction of the ciliation during the same time. Finally, after 8 weeks an amount of 15% for the estrogen receptors as well as for the ciliation was achieved--both compared to the untreated oviduct. It is possible that the oviduct damage, caused only by the mechanical influence of the secretion congestion, is the reason for the unfavorable pregnancy rate after salpingoneostomy of a chronic atrophied hydrosalpinx.

  13. Laser-induced damage in dielectrics with nanosecond to subpicosecond pulses. I. Experimental. Part 1

    International Nuclear Information System (INIS)

    Stuart, B.C.; Herman, S.; Perry, M.D.

    1994-12-01

    The authors report extensive laser-induced damage threshold measurements on pure and multilayer dielectrics at 1053 and 526 mm for pulse durations, τ, ranging from 140 fs to 1 ns. Qualitative differences in the morphology of damage and a departure from the diffusion-dominated τ 1/2 scaling indicate that damage results from plasma formation and ablation for τ≤10 ps and from conventional melting and boiling for τ>50 ps. A theoretical model based on electron production via multiphoton ionization, Joule heating, and collisional (avalanche) ionization is in good agreement with both the pulsewidth and wavelength scaling of experimental results

  14. Reduction of damage threshold in dielectric materials induced by negatively chirped laser pulses

    International Nuclear Information System (INIS)

    Louzon, E.; Henis, Z.; Pecker, S.; Ehrlich, Y.; Fisher, D.; Fraenkel, M.; Zigler, A.

    2005-01-01

    The threshold fluence for laser induced damage in wide band gap dielectric materials, fused silica and MgF 2 , is observed to be lower by up to 20% for negatively (down) chirped pulses than for positively (up) chirped, at pulse durations ranging from 60 fs to 1 ps. This behavior of the threshold fluence for damage on the chirp direction was not observed in semiconductors (silicon and GaAs). Based on a model including electron generation in the conduction band and Joule heating, it is suggested that the decrease in the damage threshold for negatively chirped pulse is related to the dominant role of multiphoton ionization in wide gap materials

  15. Modification of radiation-induced oxidative damage in liposomal and microsomal membrane by eugenol

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, B.N. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Lathika, K.M. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Mishra, K.P. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: kpm@magnum.barc.ernet.in

    2006-03-15

    Radiation-induced membrane oxidative damage, and their modification by eugenol, a natural antioxidant, was investigated in liposomes and microsomes. Liposomes prepared with DPH showed decrease in fluorescence after {gamma}-irradiation, which was prevented significantly by eugenol and correlated with magnitude of oxidation of phospholipids. Presence of eugenol resulted in substantial inhibition in MDA formation in irradiated liposomes/microsomes, which was less effective when added after irradiation. Similarly, the increase in phospholipase C activity observed after irradiation in microsomes was inhibited in samples pre-treated with eugenol. Results suggest association of radio- oxidative membrane damage with alterations in signaling molecules, and eugenol significantly prevented these membrane damaging events.

  16. Inductively Coupled Plasma-Induced Etch Damage of GaN p-n Junctions

    International Nuclear Information System (INIS)

    SHUL, RANDY J.; ZHANG, LEI; BACA, ALBERT G.; WILLISON, CHRISTI LEE; HAN, JUNG; PEARTON, S.J.; REN, F.

    1999-01-01

    Plasma-induced etch damage can degrade the electrical and optical performance of III-V nitride electronic and photonic devices. We have investigated the etch-induced damage of an Inductively Coupled Plasma (ICP) etch system on the electrical performance of mesa-isolated GaN pn-junction diodes. GaN p-i-n mesa diodes were formed by Cl 2 /BCl 3 /Ar ICP etching under different plasma conditions. The reverse leakage current in the mesa diodes showed a strong relationship to chamber pressure, ion energy, and plasma flux. Plasma induced damage was minimized at moderate flux conditions (≤ 500 W), pressures ≥2 mTorr, and at ion energies below approximately -275 V

  17. A tan in a test tube - in vitro models for investigating ultraviolet radiation-induced damage in skin.

    Science.gov (United States)

    Fernandez, Tara L; Dawson, Rebecca A; Van Lonkhuyzen, Derek R; Kimlin, Michael G; Upton, Zee

    2012-06-01

    Presently, global rates of skin cancers induced by ultraviolet radiation (UVR) exposure are on the rise. In view of this, current knowledge gaps in the biology of photocarcinogenesis and skin cancer progression urgently need to be addressed. One factor that has limited skin cancer research has been the need for a reproducible and physiologically-relevant model able to represent the complexity of human skin. This review outlines the main currently-used in vitro models of UVR-induced skin damage. This includes the use of conventional two-dimensional cell culture techniques and the major animal models that have been employed in photobiology and photocarcinogenesis research. Additionally, the progression towards the use of cultured skin explants and tissue-engineered skin constructs, and their utility as models of native skin's responses to UVR are described. The inherent advantages and disadvantages of these in vitro systems are also discussed. © 2012 John Wiley & Sons A/S.

  18. Sestrin2 protects the myocardium against radiation-induced damage

    International Nuclear Information System (INIS)

    Zeng, Yue-Can; Chi, Feng; Xing, Rui; Gao, Song; Chen, Jia-Jia; Duan, Qiong-Yu; Sun, Yu-Nan; Niu, Nan; Tang, Mei-Yue; Wu, Rong; Zeng, Jing; Wang, Hong-Mei

    2016-01-01

    The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury. (orig.)

  19. Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom

    Directory of Open Access Journals (Sweden)

    Cinthya Kimori Okamoto

    2017-03-01

    Full Text Available Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP. Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism.

  20. Sestrin2 protects the myocardium against radiation-induced damage

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Yue-Can; Chi, Feng; Xing, Rui; Gao, Song; Chen, Jia-Jia; Duan, Qiong-Yu; Sun, Yu-Nan; Niu, Nan; Tang, Mei-Yue; Wu, Rong [Shengjing Hospital of China Medical University, Department of Medical Oncology, Cancer Center, Shenyang (China); Zeng, Jing [University of Washington School of Medicine, Department of Radiation Oncology, Seattle, WA (United States); Wang, Hong-Mei [Nanfang Hospital of Southern Medical University, Department of Radiation Oncology, Guangzhou (China)

    2016-05-15

    The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury. (orig.)

  1. DNA-damage-inducible (din) loci are transcriptionally activated in competent Bacillus subtilis

    International Nuclear Information System (INIS)

    Love, P.E.; Lyle, M.J.; Yasbin, R.E.

    1985-01-01

    DNA damage-inducible (din) operon fusions were generated in Bacillus subtilis by transpositional mutagenesis. These YB886(din::Tn917-lacZ) fusion isolates produced increased β-galactosidase when exposed to mitomycin C, UV radiation, or ethyl methanesulfonate, indicating that the lacZ structural gene had inserted into host transcriptional units that are induced by a variety of DNA-damaging agents. One of the fusion strains was DNA-repair deficient and phenotypically resembled a UV-sensitive mutant of B. subtilis. Induction of β-galactosidase also occurred in the competent subpopulation of each of the din fusion strains, independent of exposure to DNA-damaging agents. Both the DNA-damage-inducible and competence-inducible components of β-galactosidase expression were abolished by the recE4 mutation, which inhibits SOS-like (SOB) induction but does not interfere with the development of the component state. The results indicate that gene expression is stimulated at specific loci within the B. subtilis chromosome both by DNA-damaging agents and by the development of competence and that this response is under the control of the SOB regulatory system. Furthermore, they demonstrate that at the molecular level SOB induction and the development of competence are interrelated cellular events

  2. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage?

    International Nuclear Information System (INIS)

    Wallace, J.L.; Beck, P.L.; Morris, G.P.

    1988-01-01

    The role of leukotriene (LT) C 4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC 4 synthesis. LTC 4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT 4 synthesis paralleled the changes in LTC 4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC 4 synthesis does not confer protection to the mucosa, suggesting that LTC 4 does not play an important role in the etiology of ethanol-induced gastric damage

  3. Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice.

    Science.gov (United States)

    Alvarenga, T A; Ribeiro, D A; Araujo, P; Hirotsu, C; Mazaro-Costa, R; Costa, J L; Battisti, M C; Tufik, S; Andersen, M L

    2011-09-01

    The purpose of the present study was to characterize the genetic damage induced by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the platform technique for 72 hours, followed by drug administration and evaluation of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to induce genetic damage in the blood, brain and liver cells of sleep-deprived mice at the majority of the doses evaluated. Ecstasy also induced increased DNA migration in peripheral blood cells for all concentrations tested. Analysis of damaged cells by the tail moment data suggests that ecstasy is a genotoxic chemical at the highest concentrations tested, inducing damage in liver or brain cells after sleep deprivation in mice. Taken together, our results suggest that cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when associated with sleep loss.

  4. Protection of vanillin derivative VND3207 on plasmid DNA damage induced by different LET ionizing radiation

    International Nuclear Information System (INIS)

    Xu Huihui; Wang Li; Sui Li; Guan Hua; Wang Yu; Liu Xiaodan; Zhang Shimeng; Xu Qinzhi; Wang Xiao; Zhou Pingkun

    2011-01-01

    Objective: To evaluate the radioprotective effect of vanillin derivative VND3207 on DNA damage induced by different LET ionizing radiation. Methods: The plasmid DNA in liquid was irradiated by 60 Co γ-rays, proton or 7 Li heavy ion with or without VND3207. The conformation changes of plasmid DNA were assessed by agarose gel electrophoresis and the quantification was done using gel imaging system. Results: The DNA damage induced by proton and 7 Li heavy ion was much more serious as compared with that by 60 Co γ-rays, and the vanillin derivative VND3207 could efficiently decrease the DNA damage induced by all three types of irradiation sources, which was expressed as a significantly reduced ratio of open circular form (OC) of plasmid DNA. The radioprotective effect of VND3207 increased with the increasing of drug concentration. The protective efficiencies of 200 μmol/L VND3207 were 85.3% (t =3.70, P=0.033), 73.3% (t=10.58, P=0.017) and 80.4% (t=8.57, P=0.008) on DNA damage induction by 50 Gy of γ-rays, proton and 7 Li heavy ion, respectively. It seemed that the radioprotection of VND3207 was more effective on DNA damage induced by high LET heavy ion than that by proton. Conclusions: VND3207 has a protective effect against the genotoxicity of different LET ionizing radiation, especially for γ-rays and 7 Li heavy ion. (authors)

  5. Decrease of FIB-induced lateral damage for diamond tool used in nano cutting

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Wei [State Key Laboratory of Precision Measuring Technology and Instruments, Centre of MicroNano Manufacturing Technology, Tianjin University, Tianjin 300072 (China); Xu, Zongwei, E-mail: zongweixu@163.com [State Key Laboratory of Precision Measuring Technology and Instruments, Centre of MicroNano Manufacturing Technology, Tianjin University, Tianjin 300072 (China); Fang, Fengzhou, E-mail: fzfang@gmail.com [State Key Laboratory of Precision Measuring Technology and Instruments, Centre of MicroNano Manufacturing Technology, Tianjin University, Tianjin 300072 (China); Liu, Bing; Xiao, Yinjing; Chen, Jinping [State Key Laboratory of Precision Measuring Technology and Instruments, Centre of MicroNano Manufacturing Technology, Tianjin University, Tianjin 300072 (China); Wang, Xibin [School of Mechanical Engineering, Beijing Institute of Technology, Beijing 100081 (China); Liu, Hongzhong [State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an 710049 (China)

    2014-07-01

    Highlights: • We mainly aim to characterize and decrease the FIB-induced damage on diamond tool. • Raman and XPS methods were used to characterize the nanoscale FIB-induced damage. • Lower energy FIB can effectively lessen the FIB-induced damage on diamond tool. • The diamond tools’ performance was greatly improved after FIB process optimization. • 6 nm chip thickness of copper was achieved by diamond tool with 22 nm edge radius. - Abstract: Diamond cutting tools with nanometric edge radius used in ultra-precision machining can be fabricated by focused ion beam (FIB) technology. However, due to the nanoscale effects, the diamond tools performance and the cutting edge lifetime in nano cutting would be degraded because of the FIB-induced nanoscale lateral damage. In this study, the methods of how to effectively characterize and decrease the FIB-induced lateral damage for diamond tool are intensively studied. Based on the performance optimization diamond machining tools, the controllable chip thickness of less than 10 nm was achieved on a single-crystal copper in nano cutting. In addition, the ratio of minimum thickness of chip (MTC) to tool edge radius of around 0.3–0.4 in nano cutting is achieved. Methods for decreasing the FIB-induced damage on diamond tools and adding coolant during the nano cutting are very beneficial in improving the research of nano cutting and MTC. The nano cutting experiments based on the sharp and high performance of diamond tools would validate the nano cutting mechanisms that many molecular dynamic simulation studies have put forward and provide new findings for nano cutting.

  6. The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2016-02-01

    Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide and destroys primordial and primary follicles potentially by DNA damage induction. The temporal pattern by which PM induces DNA damage and initiation of the ovarian response to DNA damage has not yet been well characterized. This study investigated DNA damage initiation, the DNA repair response, as well as induction of follicular demise using a neonatal rat ovarian culture system. Additionally, to delineate specific mechanisms involved in the ovarian response to PM exposure, utility was made of PKC delta (PKCδ) deficient mice as well as an ATM inhibitor (KU 55933; AI). Fisher 344 PND4 rat ovaries were cultured for 12, 24, 48 or 96 h in medium containing DMSO ± 60 μM PM or KU 55933 (48 h; 10 nM). PM-induced activation of DNA damage repair genes was observed as early as 12 h post-exposure. ATM, PARP1, E2F7, P73 and CASP3 abundance were increased but RAD51 and BCL2 protein decreased after 96 h of PM exposure. PKCδ deficiency reduced numbers of all follicular stages, but did not have an additive impact on PM-induced ovotoxicity. ATM inhibition protected all follicle stages from PM-induced depletion. In conclusion, the ovarian DNA damage repair response is active post-PM exposure, supporting that DNA damage contributes to PM-induced ovotoxicity. - Highlights: • PM exposure induces DNA damage repair gene expression. • Inhibition of ATM prevented PM-induced follicle depletion. • PKCδ deficiency did not impact PM-induced ovotoxicity.

  7. The protective effect of hypoxia and dithiothreitol on X-ray-induced genetic damage in Arabidopsis

    International Nuclear Information System (INIS)

    Sree Ramulu, K.; Veen, J.H. van der

    1987-01-01

    A study was made on the protective effect of hypoxia and dithiothreitol (DTT) on X-ray-induced ovule sterility and embryonic lethality in Arabidopsis. Both hypoxia and DTT gave a pronounced and additive reduction of radiation-induced genetic damage. The reduction was significantly higher for ovule sterility than for embryonic lethals. It is suggested that non-fertilized ovules contain a higher ratio of strand breaks/other damage than embryonic lethals do, for hypoxia and DTT are known specifically to give a reduction of strand breaks. (Auth.)

  8. Strain-dependent Damage Evolution and Velocity Reduction in Fault Zones Induced by Earthquake Rupture

    Science.gov (United States)

    Zhong, J.; Duan, B.

    2009-12-01

    Low-velocity fault zones (LVFZs) with reduced seismic velocities relative to the surrounding wall rocks are widely observed around active faults. The presence of such a zone will affect rupture propagation, near-field ground motion, and off-fault damage in subsequent earth-quakes. In this study, we quantify the reduction of seismic velocities caused by dynamic rup-ture on a 2D planar fault surrounded by a low-velocity fault zone. First, we implement the damage rheology (Lyakhovsky et al. 1997) in EQdyna (Duan and Oglesby 2006), an explicit dynamic finite element code. We further extend this damage rheology model to include the dependence of strains on crack density. Then, we quantify off-fault continuum damage distribution and velocity reduction induced by earthquake rupture with the presence of a preexisting LVFZ. We find that the presence of a LVFZ affects the tempo-spatial distribu-tions of off-fault damage. Because lack of constraint in some damage parameters, we further investigate the relationship between velocity reduction and these damage prameters by a large suite of numerical simulations. Slip velocity, slip, and near-field ground motions computed from damage rheology are also compared with those from off-fault elastic or elastoplastic responses. We find that the reduction in elastic moduli during dynamic rupture has profound impact on these quantities.

  9. Thyroid hormone-induced oxidative damage on lipids, glutathione and DNA in the mouse heart.

    Science.gov (United States)

    Gredilla, R; Barja, G; López-Torres, M

    2001-10-01

    Oxygen radicals of mitochondrial origin are involved in oxidative damage. In order to analyze the possible relationship between metabolic rate, oxidative stress and oxidative damage, OF1 female mice were rendered hyper- and hypothyroid by chronic administration of 0.0012% L-thyroxine (T4) and 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water for 5 weeks. Hyperthyroidism significantly increased the sensitivity to lipid peroxidation in the heart, although the endogenous levels of lipid peroxidation were not altered. Thyroid hormone-induced oxidative stress also resulted in higher levels of GSSG and GSSG/GSH ratio. Oxidative damage to mitochondrial DNA was greater than that to genomic DNA. Hyperthyroidism decreased oxidative damage to genomic DNA. Hypothyroidism did not modify oxidative damage in the lipid fraction but significantly decreased GSSG and GSSG/GSH ratio and oxidative damage to mitochondrial DNA. These results indicate that thyroid hormones modulate oxidative damage to lipids and DNA, and cellular redox potential in the mouse heart. A higher oxidative stress in the hyperthyroid group is presumably neutralized in the case of nuclear DNA by an increase in repair activity, thus protecting this key molecule. Treatment with PTU, a thyroid hormone inhibitor, reduced oxidative damage in the different cell compartments.

  10. Relation between four types of radiation damage and induced repair

    International Nuclear Information System (INIS)

    Radar, M.L.

    1977-08-01

    Four strains of Escherichia coli were exposed to uv and gamma radiation. Procedures are described for mutational studies, classification of revertants, inhibition of postirradiation DNA degradation and radioresistance. Comparisons were made of induction of the error-prone repair (epr) system with four mutagens; uv radiation, near uv radiation, gamma radiation, and DNA-protein crosslinks. An increase in the number of mutations was shown in every case. The observation that induction of mutagenesis, induction of inhibition of post-irradiation DNA degradation, and induction of radioresistance are closely parallel phenomena led to the investigation of the possibility that DNA-protein crosslinks which were known mutagens were also inducers of the epr system. The significance of the results is discussed

  11. Yields of clustered DNA damage induced by charged-particle radiations of similar kinetic energy per nucleon: LET dependence in different DNA microenvironments

    International Nuclear Information System (INIS)

    Keszenman, D.J.; Sutherland, B.M.

    2010-01-01

    To determine the linear energy transfer (LET) dependence of the biological effects of densely ionizing radiation in relation to changes in the ionization density along the track, we measured the yields and spectrum of clustered DNA damages induced by charged particles of different atomic number but similar kinetic energy per nucleon in different DNA microenvironments. Yeast DNA embedded in agarose in solutions of different free radical scavenging capacity was irradiated with 1 GeV protons, 1 GeV/nucleon oxygen ions, 980 MeV/nucleon titanium ions or 968 MeV/nucleon iron ions. The frequencies of double-strand breaks (DSBs), abasic sites and oxypurine clusters were quantified. The total DNA damage yields per absorbed dose induced in non-radioquenching solution decreased with LET, with minor variations in radioquenching conditions being detected. However, the total damage yields per particle fluence increased with LET in both conditions, indicating a higher efficiency per particle to induce clustered DNA damages. The yields of DSBs and non-DSB clusters as well as the damage spectra varied with LET and DNA milieu, suggesting the involvement of more than one mechanism in the formation of the different types of clustered damages.

  12. Ginsenoside Rg3 induces DNA damage in human osteosarcoma cells and reduces MNNG-induced DNA damage and apoptosis in normal human cells.

    Science.gov (United States)

    Zhang, Yue-Hui; Li, Hai-Dong; Li, Bo; Jiang, Sheng-Dan; Jiang, Lei-Sheng

    2014-02-01

    Panax ginseng is a Chinese medicinal herb. Ginsenosides are the main bioactive components of P. ginseng, and ginsenoside Rg3 is the primary ginsenoside. Ginsenosides can potently kill various types of cancer cells. The present study was designed to evaluate the potential genotoxicity of ginsenoside Rg3 in human osteosarcoma cells and the protective effect of ginsenoside Rg3 with respect to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced DNA damage and apoptosis in a normal human cell line (human fibroblasts). Four human osteosarcoma cell lines (MG-63, OS732, U-2OS and HOS cells) and a normal human cell line (human fibroblasts) were employed to investigate the cytotoxicity of ginsenosides Rg3 by MTT assay. Alkaline comet assay and γH2AX focus staining were used to detect the DNA damage in MG-63 and U-2OS cells. The extent of cell apoptosis was determined by flow cytometry and a DNA ladder assay. Our results demonstrated that the cytotoxicity of ginsenoside Rg3 was dose-dependent in the human osteosarcoma cell lines, and MG-63 and U-2OS cells were the most sensitive to ginsenoside Rg3. As expected, compared to the negative control, ginsenoside Rg3 significantly increased DNA damage in a concentration-dependent manner. In agreement with the comet assay data, the percentage of γH2AX-positive MG-63 and U-2OS cells indicated that ginsenoside Rg3 induced DNA double-strand breaks in a concentration-dependent manner. The results also suggest that ginsenoside Rg3 reduces the extent of MNNG-induced DNA damage and apoptosis in human fibroblasts.

  13. Radiation-induced DNA damage and cellular lethality

    International Nuclear Information System (INIS)

    Sakai, K.; Okada, S.

    1984-01-01

    Radiation-induced DNA scissions and their repair were investigated in mammalian cells using an alkaline separation method. DNA breaks in mouse L5178Y cells and Chinese hamster V79 cells were grouped into three in terms of their repair profile; fast-reparable breaks (FRBs; T1/2 = 5 min), slow-reparable breaks (SRBs; T1/2 = 70 min) and non-reparable breaks (NRBs). The three types of DNA lesions were studied under conditions where cellular radiosensitivity was modified. The authors obtained the following results: 1. Cell cycle fluctuation: L5178Y showed maximum sensitivity at M and G/sub 1/-S boundary, and minimum sensitivity at G/sub 1/ and late S. Cycle dependency was not found for FRBs or SRBs, but NRBs showed bimodal fluctuation with peaks at M and G/sub 1/-S, and with bottoms at G/sub 1/ and late S. 2. Different sensitivity of L5178Y and V79: L5178Y cells were more sensitive to X-rays (D/sub ο/ = 0.9 Gy) than V79 (D/sub ο/ = 1.8 Gy). The amount of FRBs or SRBs was identical in the two cell lines. However, the amount of NRBs in L5178Y was greater than that in V79. 3. Split dose irradiation: The time interval between two doses resulted in a gradual decrease of NRBs. The time course of the decrease was similar to the split dose recovery in terms of cell death. The parallel relationship between NRBs and cell killing implies that NRBs could play an important role in radiation-induced cell death

  14. Radioprotective effects of sodium arginate on radiation induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Nakatsugawa, Shigekazu; Yukawa, Yutaka; Abe, Mitsuyuki.

    1988-05-01

    Effects of sodium arginate were examined on radiation-induced intestinal death of mice and on the pathological changes of the ileum after whole or partial abdominal X-irradiation. BALB/c male mice (SPF, 7 approx. 8 week old, 21 approx. 28 g body weight) were irradiated with various doses of 10 MV of X-rays under general anesthesia (dose rate : 4 Gy/min). A radiation field covers either 2.5 or 5.0 cm width of abdomen from the anus. Sterilized water or 5 % sodium arginate solution (0.2 ml/body) was daily given per os through a stomach tube until the death of mice or 15 approx. 21 days after X-ray exposure. Intestinal death was examined daily. In another experiment, mice were daily sacrificed and pathological specimens were made. In order to study the effects of sodium arginate on peripheral blood circulation in the ileum after X-ray exposure, the microangiograms with Ba contrast media were also taken. Sodium arginate showed statistically significant radioprotective effects on intestinal death after 14.5 approx. 15.0 Gy of X-ray irradiation to the abdomen through a radiation field of 5.0 cm width or after 18.0 Gy of X-irradiation to the abdomen through a field of 2.5 cm width. The pathological studies suggest that the drug may protect the surface of the intestine against infection and potentiate the recovery processes of the mucosal membrane. This may elucidate the possible mechanisms of radioprotective effects of sodium arginate on esophagitis or on rectal ulcer induced by radiotherapy.

  15. Sulforaphane protects against cytokine- and streptozotocin-induced β-cell damage by suppressing the NF-κB pathway

    International Nuclear Information System (INIS)

    Song, Mi-Young; Kim, Eun-Kyung; Moon, Woo-Sung; Park, Jin-Woo; Kim, Hyung-Jin; So, Hong-Seob; Park, Raekil; Kwon, Kang-Beom; Park, Byung-Hyun

    2009-01-01

    Sulforaphane (SFN) is an indirect antioxidant that protects animal tissues from chemical or biological insults by stimulating the expression of several NF-E2-related factor-2 (Nrf2)-regulated phase 2 enzymes. Treatment of RINm5F insulinoma cells with SFN increases Nrf2 nuclear translocation and expression of phase 2 enzymes. In this study, we investigated whether the activation of Nrf2 by SFN treatment or ectopic overexpression of Nrf2 inhibited cytokine-induced β-cell damage. Treatment of RIN cells with IL-1β and IFN-γ induced β-cell damage through a NF-κB-dependent signaling pathway. Activation of Nrf2 by treatment with SFN and induction of Nrf2 overexpression by transfection with Nrf2 prevented cytokine toxicity. The mechanism by which Nrf2 activation inhibited NF-κB-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H 2 O 2 production. The protective effect of SFN was further demonstrated by the restoration of normal insulin secreting responses to glucose in cytokine-treated rat pancreatic islets. Furthermore, pretreatment with SFN blocked the development of type 1 diabetes in streptozotocin-treated mice

  16. Ultrasound-induced DNA damage and signal transductions indicated by gammaH2AX

    Science.gov (United States)

    Furusawa, Yukihiro; Fujiwara, Yoshisada; Zhao, Qing-Li; Hassan, Mariame Ali; Ogawa, Ryohei; Tabuchi, Yoshiaki; Takasaki, Ichiro; Takahashi, Akihisa; Ohnishi, Takeo; Kondo, Takashi

    2011-09-01

    Ultrasound (US) has been shown to induce cancer cell death via different forms including apoptosis. Here, we report the potential of low-intensity pulsed US (LIPUS) to induce genomic DNA damage and subsequent DNA damage response. Using the ionizing radiation-induced DNA double-strand breaks (DSBs) as the positive control, we were able to observe the induction of DSBs (as neutral comet tails) and the subsequent formation of gammaH2AX-positive foci (by immunofluorescence detection) in human leukemia cells following exposure to LIPUS. The LIPUS-induced DNA damage arose most likely from the mechanical, but not sonochemical, effect of cavitation, based on our observation that the suppression of inertial cavitation abrogated the gammH2AX foci formation, whereas scavenging of free radical formation (e.g., hydroxyl radical) had no protective effect on it. Treatment with the specific kinase inhibitor of ATM or DNA-PKcs, which can phosphorylate H2AX Ser139, revealed that US-induced gammaH2AX was inhibited more effectively by the DNA-PK inhibitor than ATM kinase inhibitor. Notably, these inhibitor effects were opposite to those with radiation-induced gammH2AX. In conclusion, we report, for the first time that US can induce DNA damage and the DNA damage response as indicated by gammaH2AX was triggered by the cavitational mechanical effects. Thus, it is expected that the data shown here may provide a better understanding of the cellular responses to US.

  17. The effect of dithiothreitol on radiation-induced genetic damage in Arabidopsis thaliana (L) Heynh

    International Nuclear Information System (INIS)

    Dellaert, L.M.W.

    1980-01-01

    A study was made on the effect of dithiothreitol (DTT; present during irradiation) on M 1 ovule sterility, M 2 embryonic lethals, M 2 chlorophyll mutants and M 2 viable mutants induced with fast neutrons or X-rays in Arabidopsis thaliana. DTT provides considerable protection against both fast-neutron and X-ray induced genetic damage. However, a higher protection was observed against M 1 ovule sterility, than against embryonic lethals, chlorophylls and viable mutants. This implies a significant DTT-induced spectral shift (0.01 < p < 0.05), i.e. a shift in the relative frequencies of the different genetic parameters. This spectral shift is explained on the basis of a specific DTT protection against radiation-induced strand breaks, and by differences in the ratio strand breaks/base damage for the genetic parameters concerned, i.e. a higher ratio for ovule sterility than for the other parameters. The induction of the genetic damage by ionizing radiation, either with or without DTT, is described by a mathematical model, which includes both strand breaks and base damage. The model shows that the resolving power of a test for a 'mutation'spectral shift depends on the relative values of the strandbreak reduction factor of -SH compounds and on the ratio strand breaks/base damage of the genetic parameters. For each genetic parameter the DTT damage reduction factor (DRF) is calculated per irradiation dose, and in addition the average (over-all doses) ratio strand breaks/base damage. (orig.)

  18. Assessment of radiation damage - the need for a multi-parametric and integrative approach with the help of both clinical and biological dosimetry

    International Nuclear Information System (INIS)

    Meineke, Viktor

    2008-01-01

    Full text: Accidental exposure to ionising radiation leads to a damage on different levels of the biological organization of the organism. Depending on exposure conditions, such as nature of radiation, time and affected organs and organ systems, the clinical endpoint of radiation damage and the resulting acute and chronic radiation syndromes may vary to a great extent. Exposure situations range from pure localised radiation scenarios and partial body exposures up to whole body exposures. Therefore clinical pictures vary from localized radiation injuries up to the extreme situation of a radiation-induced multi-organ involvement and failure requiring immediate, intensive and interdisciplinary medical treatment. These total different and complex clinical situations not only show up most different clinical diagnostic and therapeutic aspects but necessarily due to different levels of the underlying biological damage, biological indicators of effects may vary to a wide extent. This fact means that an exact assessment of the extent of radiation damage within individual patients can only be performed when taking into consideration both clinical signs and symptoms as well as different biological indicators. Among the clinical indicators, routine laboratory parameters such as blood counts and the documentation of clinical signs and symptoms (such as the METREPOL system) are the key parameters, whereas the dicentric assay, the gold standard for biological dosimetry, but also methods under development such as the gamma-H2Ax focus assay or the estimation of variations of gene expression have to be taken into account. Each method provides best results in different situations, or in other words, there are methods that work better in a specific exposure condition or at a given time of examination (e.g. time after exposure) than others. Some methods show up results immediately, others require days to weeks until results are available for clinical decision making. Therefore to

  19. Analysis of the causes and recommendations on elimination of biological damage of structures during the repair and reconstruction of the State Biological Museum in Moscow.

    Directory of Open Access Journals (Sweden)

    Kamskov Victor

    2017-01-01

    Full Text Available The article presents the results of mycological research on buildings of the State Biological Museum located in Moscow. The problems have been considered as for a complex of buildings of the State Biological Museum built in the late nineteenth century which, to the present time, has been operated almost in its original form. Over time, the building maintenance conditions have worsened, in particular because of construction of high-rise buildings in the immediate vicinity of the museum, as well as construction of a greenhouse above the underground passage tunnel between buildings 1 and 2. Over the years, the temperature gradients, high humidity, wear and damage of wall waterproofing and foundations have caused leaks in the underpass tunnel and the biological corrosion of stone, wood and metal structures in indoor exhibition halls. In this connection, part of the survey was to determine the types and size of biological lesions in structures, determination of the causes of biological damage, and the development of measures to eliminate the mycological problems during repair and reconstruction works in the museum.

  20. Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis

    International Nuclear Information System (INIS)

    Ma, Jiali; Hui, Pingping; Meng, Wenying; Wang, Na; Xiang, Shihao

    2017-01-01

    The current study focused on the role of Ku70, a DNA-dependent protein kinase (DNA-PK) complex protein, in pancreatic cancer cell resistance to gemcitabine. In both established cell lines (Mia-PaCa-2 and PANC-1) and primary human pancreatic cancer cells, shRNA/siRNA-mediated knockdown of Ku70 significantly sensitized gemcitabine-induced cell death and proliferation inhibition. Meanwhile, gemcitabine-induced DNA damage and subsequent pancreatic cancer cell apoptosis were also potentiated with Ku70 knockdown. On the other hand, exogenous overexpression of Ku70 in Mia-PaCa-2 cells suppressed gemcitabine-induced DNA damage and subsequent cell apoptosis. In a severe combined immune deficient (SCID) mice Mia-PaCa-2 xenograft model, gemcitabine-induced anti-tumor activity was remarkably pontificated when combined with Ku70 shRNA knockdown in the xenografts. The results of this preclinical study imply that Ku70 might be a primary resistance factor of gemcitabine, and Ku70 silence could significantly chemo-sensitize gemcitabine in pancreatic cancer cells. - Highlights: • Ku70 knockdown sensitizes gemcitabine-induced killing of pancreatic cancer cells. • Ku70 knockdown facilitates gemcitabine-induced DNA damage and cell apoptosis. • Ku70 overexpression deceases gemcitabine's sensitivity in pancreatic cancer cells. • Ku70 knockdown sensitizes gemcitabine-induced anti-tumor activity in vivo.

  1. Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage.

    Science.gov (United States)

    Chen, Liming; Liu, Yinghui; Dong, Liangliang; Chu, Xiaoxia

    2015-03-01

    Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p edaravone offers protection from radiation-induced cytogenetic alterations.

  2. A decrease in cyclin B1 levels leads to polyploidization in DNA damage-induced senescence.

    Science.gov (United States)

    Kikuchi, Ikue; Nakayama, Yuji; Morinaga, Takao; Fukumoto, Yasunori; Yamaguchi, Naoto

    2010-05-04

    Adriamycin, an anthracycline antibiotic, has been used for the treatment of various types of tumours. Adriamycin induces at least two distinct types of growth repression, such as senescence and apoptosis, in a concentration-dependent manner. Cellular senescence is a condition in which cells are unable to proliferate further, and senescent cells frequently show polyploidy. Although abrogation of cell division is thought to correlate with polyploidization, the mechanisms underlying induction of polyploidization in senescent cells are largely unclear. We wished, therefore, to explore the role of cyclin B1 level in polyploidization of Adriamycin-induced senescent cells. A subcytotoxic concentration of Adriamycin induced polyploid cells having the features of senescence, such as flattened and enlarged cell shape and activated beta-galactosidase activity. In DNA damage-induced senescent cells, the levels of cyclin B1 were transiently increased and subsequently decreased. The decrease in cyclin B1 levels occurred in G2 cells during polyploidization upon treatment with a subcytotoxic concentration of Adriamycin. In contrast, neither polyploidy nor a decrease in cyclin B1 levels was induced by treatment with a cytotoxic concentration of Adriamycin. These results suggest that a decrease in cyclin B1 levels is induced by DNA damage, resulting in polyploidization in DNA damage-induced senescence.

  3. Involvement of DNA-PK and ATM in radiation- and heat-induced DNA damage recognition and apoptotic cell death

    International Nuclear Information System (INIS)

    Tomita, Masanori

    2010-01-01

    Exposure to ionizing radiation and hyperthermia results in important biological consequences, e.g. cell death, chromosomal aberrations, mutations, and DNA strand breaks. There is good evidence that the nucleus, specifically cellular DNA, is the principal target for radiation-induced cell lethality. DNA double-strand breaks (DSBs) are considered to be the most serious type of DNA damage induced by ionizing radiation. On the other hand, verifiable mechanisms which can lead to heat-induced cell death are damage to the plasma membrane and/or inactivation of heat-labile proteins caused by protein denaturation and subsequent aggregation. Recently, several reports have suggested that DSBs can be induced after hyperthermia because heat-induced phosphorylated histone H2AX (γ-H2AX) foci formation can be observed in several mammalian cell lines. In mammalian cells, DSBs are repaired primarily through two distinct and complementary mechanisms: non-homologous end joining (NHEJ), and homologous recombination (HR) or homology-directed repair (HDR). DNA-dependent protein kinase (DNA-PK) and ataxia-telangiectasia mutated (ATM) are key players in the initiation of DSB repair and phosphorylate and/or activate many substrates, including themselves. These phosphorylated substrates have important roles in the functioning of cell cycle checkpoints and in cell death, as well as in DSB repair. Apoptotic cell death is a crucial cell suicide mechanism during development and in the defense of homeostasis. If DSBs are unrepaired or misrepaired, apoptosis is a very important system which can protect an organism against carcinogenesis. This paper reviews recently obtained results and current topics concerning the role of DNA-PK and ATM in heat- or radiation-induced apoptotic cell death. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

  5. Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis

    Science.gov (United States)

    Caputo, Fanny; de Nicola, Milena; Sienkiewicz, Andrzej; Giovanetti, Anna; Bejarano, Ignacio; Licoccia, Silvia; Traversa, Enrico; Ghibelli, Lina

    2015-09-01

    Efficient inorganic UV shields, mostly based on refracting TiO2 particles, have dramatically changed the sun exposure habits. Unfortunately, health concerns have emerged from the pro-oxidant photocatalytic effect of UV-irradiated TiO2, which mediates toxic effects on cells. Therefore, improvements in cosmetic solar shield technology are a strong priority. CeO2 nanoparticles are not only UV refractors but also potent biological antioxidants due to the surface 3+/4+ valency switch, which confers anti-inflammatory, anti-ageing and therapeutic properties. Herein, UV irradiation protocols were set up, allowing selective study of the extra-shielding effects of CeO2vs. TiO2 nanoparticles on reporter cells. TiO2 irradiated with UV (especially UVA) exerted strong photocatalytic effects, superimposing their pro-oxidant, cell-damaging and mutagenic action when induced by UV, thereby worsening the UV toxicity. On the contrary, irradiated CeO2 nanoparticles, via their Ce3+/Ce4+ redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer. Interestingly, CeO2 nanoparticles also protect cells from the damage induced by irradiated TiO2, suggesting that these two particles may also complement their effects in solar lotions. CeO2 nanoparticles, which intrinsically couple UV shielding with biological and genetic protection, appear to be ideal candidates for next-generation sun shields.

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

    International Nuclear Information System (INIS)

    Spigoti, Geyza; Bartolini, Paolo; Okazaki, Kayo; Tsutsumi, Shiguetoshi

    2009-01-01

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

  7. Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis

    KAUST Repository

    Caputo, Fanny

    2015-08-20

    Efficient inorganic UV shields, mostly based on refracting TiO2 particles, have dramatically changed the sun exposure habits. Unfortunately, health concerns have emerged from the pro-oxidant photocatalytic effect of UV-irradiated TiO2, which mediates toxic effects on cells. Therefore, improvements in cosmetic solar shield technology are a strong priority. CeO2 nanoparticles are not only UV refractors but also potent biological antioxidants due to the surface 3+/4+ valency switch, which confers anti-inflammatory, anti-ageing and therapeutic properties. Herein, UV irradiation protocols were set up, allowing selective study of the extra-shielding effects of CeO2vs. TiO2 nanoparticles on reporter cells. TiO2 irradiated with UV (especially UVA) exerted strong photocatalytic effects, superimposing their pro-oxidant, cell-damaging and mutagenic action when induced by UV, thereby worsening the UV toxicity. On the contrary, irradiated CeO2 nanoparticles, via their Ce3+/Ce4+ redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer. Interestingly, CeO2 nanoparticles also protect cells from the damage induced by irradiated TiO2, suggesting that these two particles may also complement their effects in solar lotions. CeO2 nanoparticles, which intrinsically couple UV shielding with biological and genetic protection, appear to be ideal candidates for next-generation sun shields. © The Royal Society of Chemistry 2015.

  8. The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence.

    Science.gov (United States)

    Khoe, Clairine V; Chung, Long H; Murray, Vincent

    2018-06-01

    The sequence specificity of UV-induced DNA damage was investigated in a specifically designed DNA plasmid using two procedures: end-labelling and linear amplification. Absorption of UV photons by DNA leads to dimerisation of pyrimidine bases and produces two major photoproducts, cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). A previous study had determined that two hexanucleotide sequences, 5'-GCTC*AC and 5'-TATT*AA, were high intensity UV-induced DNA damage sites. The UV clone plasmid was constructed by systematically altering each nucleotide of these two hexanucleotide sequences. One of the main goals of this study was to determine the influence of single nucleotide alterations on the intensity of UV-induced DNA damage. The sequence 5'-GCTC*AC was designed to examine the sequence specificity of 6-4PPs and the highest intensity 6-4PP damage sites were found at 5'-GTTC*CC nucleotides. The sequence 5'-TATT*AA was devised to investigate the sequence specificity of CPDs and the highest intensity CPD damage sites were found at 5'-TTTT*CG nucleotides. It was proposed that the tetranucleotide DNA sequence, 5'-YTC*Y (where Y is T or C), was the consensus sequence for the highest intensity UV-induced 6-4PP adduct sites; while it was 5'-YTT*C for the highest intensity UV-induced CPD damage sites. These consensus tetranucleotides are composed entirely of consecutive pyrimidines and must have a DNA conformation that is highly productive for the absorption of UV photons. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  9. Oxidative damage to biological macromolecules in Prague bus drivers and garagemen: impact of air pollution and genetic polymorphisms.

    Science.gov (United States)

    Bagryantseva, Yana; Novotna, Bozena; Rossner, Pavel; Chvatalova, Irena; Milcova, Alena; Svecova, Vlasta; Lnenickova, Zdena; Solansky, Ivo; Sram, Radim J

    2010-11-10

    DNA integrity was investigated in the lymphocytes of 50 bus drivers, 20 garagemen and 50 controls using the comet assay with excision repair enzymes. In parallel, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 15-F(2t)-isoprostane levels in the urine and protein carbonyl levels in the plasma were assessed as markers of oxidative damage to DNA, lipids and proteins. Exposure to carcinogenic polycyclic aromatic hydrocarbons (cPAHs) and volatile compounds was measured by personal samplers for 48 and 24h, respectively, before the collection of biological specimens. Both exposed groups exhibited a higher levels of DNA instability and oxidative damage to biological macromolecules than the controls. The incidence of oxidized lesions in lymphocyte DNA, but not the urinary levels of 8-oxodG, correlated with exposure to benzene and triglycerides increased this damage. Oxidative damage to lipids and proteins was associated with exposure to cPAHs and the lipid peroxidation levels positively correlated with age and LDL cholesterol, and negatively with vitamin C. The carriers of at least one variant hOGG1 (Cys) allele tended to higher oxidative damage to lymphocyte DNA than those with the wild genotype, while XPD23 (Gln/Gln) homozygotes were more susceptible to the induction of DNA strand breaks. In contrast, GSTM1 null variant seemed to protect DNA integrity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Perinatal radiation-induced renal damage in the beagle

    International Nuclear Information System (INIS)

    Jaenke, R.S.; Angleton, G.M.

    1990-01-01

    The developing perinatal kidney is particularly sensitive to radiation. The pathogenesis of the radiation-induced lesion is related to the destruction of outer cortical developing nephrons and direct radiation injury with secondary hemodynamic alterations in remnant nephrons. In this study, which is part of a life span investigation of the effects of whole-body gamma radiation during prenatal and early postnatal life, dogs were given 0, 0.16, 0.83, or 1.25 Gy irradiation at either 55 days postcoitus or 2 days postpartum and were examined morphometrically and histopathologically at 70 days of age. Although irradiated dogs showed no reduction in the total number of nephrons per kidney, there was a significant increase in the total number and relative percentage of immature, dysplastic glomeruli. In addition, deeper cortical glomeruli of irradiated kidneys exhibited mesangial sclerosis similar to that associated with progressive renal failure in our previous studies. These findings are in accord with those reported at doses of 2.24 to 3.57 Gy and demonstrate that the perinatal kidney is affected by radiation doses much lower than previously demonstrated

  11. Urea-induced oxidative damage in Elodea densa leaves.

    Science.gov (United States)

    Maleva, Maria; Borisova, Galina; Chukina, Nadezda; Prasad, M N V

    2015-09-01

    Urea being a fertilizer is expected to be less toxic to plants. However, it was found that urea at 100 mg L(-1) caused the oxidative stress in Elodea leaves due to the formation of reactive oxygen species (ROS) and lipid peroxidation that are known to stimulate antioxidant pathway. Urea at a concentration of 500 and 1000 mg L(-1) decreased low-molecular-weight antioxidants. In this case, the antioxidant status of plants was supported by the activity of antioxidant enzymes such as superoxide dismutase and guaiacol peroxidase. A significant increase in the soluble proteins and -SH groups was observed with high concentrations of urea (30-60 % of control). Thus, the increased activity of antioxidant enzymes, low-molecular-weight antioxidants, and induced soluble protein thiols are implicated in plant resistance to oxidative stress imposed by urea. We found that guaiacol peroxidase plays an important role in the removal of the peroxide in Elodea leaves exposed to 1000 mg L(-1)of urea.

  12. Effects of ionizing radiation on laser-induced damage in SiO/sub 2/

    Energy Technology Data Exchange (ETDEWEB)

    Soileau, M J; Mansour, N; Canto, E; Griscom, D L

    1988-05-01

    The effects of radiation damage on bulk laser-induced damage in SiO/sub 2/ were investigated. Samples studied included Spectrasil A, B, and WF (water free). Measurements of laser-induced breakdown were conducted with 532 and 1064 nm laser pulses of approximately 20 ns duration. Reductions of up to 40% in the laser-induced breakdown threshold were observed at 532 nm for samples exposed to 10/sup 8/ rad of ..gamma..-radiation. The decrease in breakdown threshold for irradiated SiO/sub 2/ samples at 532 nm was found to be proportional to the linear absorption of the specimen at 266 nm. These results are in good agreement with a proposed model which suggests that two-photon absorption initiated avalanche process is responsible for laser-induced breakdown for these materials.

  13. Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

    Science.gov (United States)

    Calvo, Jennifer A; Moroski-Erkul, Catherine A; Lake, Annabelle; Eichinger, Lindsey W; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T; Christiani, David C; Meira, Lisiane B; Samson, Leona D

    2013-04-01

    Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

  14. Aag DNA glycosylase promotes alkylation-induced tissue damage mediated by Parp1.

    Directory of Open Access Journals (Sweden)

    Jennifer A Calvo

    2013-04-01

    Full Text Available Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag⁻/⁻ mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage.

  15. Non-destructive evaluation of UV pulse laser-induced damage performance of fused silica optics.

    Science.gov (United States)

    Huang, Jin; Wang, Fengrui; Liu, Hongjie; Geng, Feng; Jiang, Xiaodong; Sun, Laixi; Ye, Xin; Li, Qingzhi; Wu, Weidong; Zheng, Wanguo; Sun, Dunlu

    2017-11-24

    The surface laser damage performance of fused silica optics is related to the distribution of surface defects. In this study, we used chemical etching assisted by ultrasound and magnetorheological finishing to modify defect distribution in a fused silica surface, resulting in fused silica samples with different laser damage performance. Non-destructive test methods such as UV laser-induced fluorescence imaging and photo-thermal deflection were used to characterize the surface defects that contribute to the absorption of UV laser radiation. Our results indicate that the two methods can quantitatively distinguish differences in the distribution of absorptive defects in fused silica samples subjected to different post-processing steps. The percentage of fluorescence defects and the weak absorption coefficient were strongly related to the damage threshold and damage density of fused silica optics, as confirmed by the correlation curves built from statistical analysis of experimental data. The results show that non-destructive evaluation methods such as laser-induced fluorescence and photo-thermal absorption can be effectively applied to estimate the damage performance of fused silica optics at 351 nm pulse laser radiation. This indirect evaluation method is effective for laser damage performance assessment of fused silica optics prior to utilization.

  16. Nano-ranged low-energy ion-beam-induced DNA transfer in biological cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, L.D., E-mail: yuld@fnrf.science.cmu.ac.th [Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Wongkham, W. [Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Prakrajang, K. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Sangwijit, K.; Inthanon, K. [Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thongkumkoon, P. [Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Wanichapichart, P. [Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Membrane Science and Technology Research Center, Department of Physics, Faculty of Science, Prince of Songkla University, Hat Yai, Songkla 90112 (Thailand); Anuntalabhochai, S. [Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand)

    2013-06-15

    Low-energy ion beams at a few tens of keV were demonstrated to be able to induce exogenous macromolecules to transfer into plant and bacterial cells. In the process, the ion beam with well controlled energy and fluence bombarded living cells to cause certain degree damage in the cell envelope in nanoscales to facilitate the macromolecules such as DNA to pass through the cell envelope and enter the cell. Consequently, the technique was applied for manipulating positive improvements in the biological species. This physical DNA transfer method was highly efficient and had less risk of side-effects compared with chemical and biological methods. For better understanding of mechanisms involved in the process, a systematic study on the mechanisms was carried out. Applications of the technique were also expanded from DNA transfer in plant and bacterial cells to DNA transfection in human cancer cells potentially for the stem cell therapy purpose. Low-energy nitrogen and argon ion beams that were applied in our experiments had ranges of 100 nm or less in the cell envelope membrane which was majorly composed of polymeric cellulose. The ion beam bombardment caused chain-scission dominant damage in the polymer and electrical property changes such as increase in the impedance in the envelope membrane. These nano-modifications of the cell envelope eventually enhanced the permeability of the envelope membrane to favor the DNA transfer. The paper reports details of our research in this direction.

  17. Nano-ranged low-energy ion-beam-induced DNA transfer in biological cells

    International Nuclear Information System (INIS)

    Yu, L.D.; Wongkham, W.; Prakrajang, K.; Sangwijit, K.; Inthanon, K.; Thongkumkoon, P.; Wanichapichart, P.; Anuntalabhochai, S.

    2013-01-01

    Low-energy ion beams at a few tens of keV were demonstrated to be able to induce exogenous macromolecules to transfer into plant and bacterial cells. In the process, the ion beam with well controlled energy and fluence bombarded living cells to cause certain degree damage in the cell envelope in nanoscales to facilitate the macromolecules such as DNA to pass through the cell envelope and enter the cell. Consequently, the technique was applied for manipulating positive improvements in the biological species. This physical DNA transfer method was highly efficient and had less risk of side-effects compared with chemical and biological methods. For better understanding of mechanisms involved in the process, a systematic study on the mechanisms was carried out. Applications of the technique were also expanded from DNA transfer in plant and bacterial cells to DNA transfection in human cancer cells potentially for the stem cell therapy purpose. Low-energy nitrogen and argon ion beams that were applied in our experiments had ranges of 100 nm or less in the cell envelope membrane which was majorly composed of polymeric cellulose. The ion beam bombardment caused chain-scission dominant damage in the polymer and electrical property changes such as increase in the impedance in the envelope membrane. These nano-modifications of the cell envelope eventually enhanced the permeability of the envelope membrane to favor the DNA transfer. The paper reports details of our research in this direction.

  18. Repair of radiation-induced DNA damage in rat epidermis as a function of age

    International Nuclear Information System (INIS)

    Sargent, E.V.; Burns, F.J.

    1985-01-01

    The rate of repair of radiation-induced DNA damage in proliferating rat epidermal cells diminished progressively with increasing age of the animal. The dorsal skin was irradiated with 1200 rad of 0.8 MeV electrons at various ages, and the amount of DNA damage was determined as a function of time after irradiation by the method of alkaline unwinding followed by S 1 nuclease digestion. The amount of DNA damage immediately after irradiation was not age dependent, while the rate of damage removal from the DNA decreased with increasing age. By fitting an exponential function to the relative amount of undamaged DNA as a function of time after irradiation, DNA repair halftimes of 20, 27, 69, and 107 min were obtained for 28, 100-, 200-, and 400-day-old animals, respectively

  19. Estimate of the damage in organs induced by neutrons in three-dimensional conformal radiotherapy

    International Nuclear Information System (INIS)

    Benites R, J. L.; Vega C, H. R.; Uribe, M. del R.

    2014-08-01

    By means of Monte Carlo methods was considered the damage in the organs, induced by neutrons, of patients with cancer that receive treatment in modality of three-dimensional conformal radiotherapy (3D-CRT) with lineal accelerator Varian Ix. The objective of this work was to estimate the damage probability in radiotherapy patients, starting from the effective dose by neutrons in the organs and tissues out of the treatment region. For that a three-dimensional mannequin of equivalent tissue of 30 x 100 x 30 cm 3 was modeled and spherical cells were distributed to estimate the Kerma in equivalent tissue and the absorbed dose by neutrons. With the absorbed dose the effective dose was calculated using the weighting factors for the organ type and radiation type. With the effective dose and the damage factors, considered in the ICRP 103, was considered the probability of damage induction in organs. (Author)

  20. Quantitative measurement of ultraviolet-induced damage in cellular DNA by an enzyme immunodot assay

    International Nuclear Information System (INIS)

    Wakizaka, A.; Nishizawa, Y.; Aiba, N.; Okuhara, E.; Takahashi, S.

    1989-01-01

    A simple enzyme immunoassay procedure was developed for the quantitative determination of 254-nm uv-induced DNA damage in cells. With the use of specific antibodies to uv-irradiated DNA and horseradish peroxidase-conjugated antibody to rabbit IgG, the extent of damaged DNA in uv-irradiated rat spleen mononuclear cells was quantitatively measurable. Through the use of this method, the amount of damaged DNA present in 2 X 10(5) cells irradiated at a dose of 75 J/m2 was estimated to be 7 ng equivalents of the standard uv-irradiated DNA. In addition, when the cells, irradiated at 750 J/m2, were incubated for 1 h, the antigenic activity of DNA decreased by 40%, suggesting that a repair of the damaged sites in DNA had proceeded to some extent in the cells

  1. Photodynamic DNA damage induced by phycocyanin and its repair in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    M. Pádula

    1999-09-01

    Full Text Available In the present study, we analyzed DNA damage induced by phycocyanin (PHY in the presence of visible light (VL using a set of repair endonucleases purified from Escherichia coli. We demonstrated that the profile of DNA damage induced by PHY is clearly different from that induced by molecules that exert deleterious effects on DNA involving solely singlet oxygen as reactive species. Most of PHY-induced lesions are single strand breaks and, to a lesser extent, base oxidized sites, which are recognized by Nth, Nfo and Fpg enzymes. High pressure liquid chromatography coupled to electrochemical detection revealed that PHY photosensitization did not induce 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo at detectable levels. DNA repair after PHY photosensitization was also investigated. Plasmid DNA damaged by PHY photosensitization was used to transform a series of Saccharomyces cerevisiae DNA repair mutants. The results revealed that plasmid survival was greatly reduced in rad14 mutants, while the ogg1 mutation did not modify the plasmid survival when compared to that in the wild type. Furthermore, plasmid survival in the ogg1 rad14 double mutant was not different from that in the rad14 single mutant. The results reported here indicate that lethal lesions induced by PHY plus VL are repaired differently by prokaryotic and eukaryotic cells. Morever, nucleotide excision repair seems to play a major role in the recognition and repair of these lesions in Saccharomyces cerevisiae.

  2. Damage to cellular and isolated DNA induced by a metabolite of aspirin

    Energy Technology Data Exchange (ETDEWEB)

    Oikawa, Shinji [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan)], E-mail: s-oikawa@doc.medic.mie-u.ac.jp; Kobayashi, Hatasu; Tada-Oikawa, Saeko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); JSPS Research Fellow (Japan); Isono, Yoshiaki [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Kawanishi, Shosuke [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie 514-8507 (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan)

    2009-02-10

    Aspirin has been proposed as a possible chemopreventive agent. On the other hand, a recent cohort study showed that aspirin may increase the risk for pancreatic cancer. To clarify whether aspirin is potentially carcinogenic, we investigated the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is correlated with the incidence of cancer, in cultured cells treated with 2,3-dihydroxybenzoic acid (2,3-DHBA), a metabolite of aspirin. 2,3-DHBA induced 8-oxodG formation in the PANC-1 human pancreatic cancer cell line. 2,3-DHBA-induced DNA single-strand breaks were also revealed by comet assay using PANC-1 cells. Flow cytometric analyses showed that 2,3-DHBA increased the levels of intracellular reactive oxygen species (ROS) in PANC-1 cells. The 8-oxodG formation and ROS generation were also observed in the HL-60 leukemia cell line, but not in the hydrogen peroxide (H{sub 2}O{sub 2})-resistant clone HP100 cells, suggesting the involvement of H{sub 2}O{sub 2}. In addition, an hprt mutation assay supported the mutagenicity of 2,3-DHBA. We investigated the mechanism underlying the 2,3-DHBA-induced DNA damage using {sup 32}P-labeled DNA fragments of human tumor suppressor genes. 2,3-DHBA induced DNA damage in the presence of Cu(II) and NADH. DNA damage induced by 2,3-DHBA was enhanced by the addition of histone peptide-6 [AKRHRK]. Interestingly, 2,3-DHBA and histone peptide-6 caused base damage in the 5'-ACG-3' and 5'-CCG-3' sequences, hotspots of the p53 gene. Bathocuproine, a Cu(I) chelator, and catalase inhibited the DNA damage. Typical hydroxyl radical scavengers did not inhibit the DNA damage. These results suggest that ROS derived from the reaction of H{sub 2}O{sub 2} with Cu(I) participate in the DNA damage. In conclusion, 2,3-DHBA induces oxidative DNA damage and mutations, which may result in carcinogenesis.

  3. Damage to cellular and isolated DNA induced by a metabolite of aspirin

    International Nuclear Information System (INIS)

    Oikawa, Shinji; Kobayashi, Hatasu; Tada-Oikawa, Saeko; Isono, Yoshiaki; Kawanishi, Shosuke

    2009-01-01

    Aspirin has been proposed as a possible chemopreventive agent. On the other hand, a recent cohort study showed that aspirin may increase the risk for pancreatic cancer. To clarify whether aspirin is potentially carcinogenic, we investigated the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is correlated with the incidence of cancer, in cultured cells treated with 2,3-dihydroxybenzoic acid (2,3-DHBA), a metabolite of aspirin. 2,3-DHBA induced 8-oxodG formation in the PANC-1 human pancreatic cancer cell line. 2,3-DHBA-induced DNA single-strand breaks were also revealed by comet assay using PANC-1 cells. Flow cytometric analyses showed that 2,3-DHBA increased the levels of intracellular reactive oxygen species (ROS) in PANC-1 cells. The 8-oxodG formation and ROS generation were also observed in the HL-60 leukemia cell line, but not in the hydrogen peroxide (H 2 O 2 )-resistant clone HP100 cells, suggesting the involvement of H 2 O 2 . In addition, an hprt mutation assay supported the mutagenicity of 2,3-DHBA. We investigated the mechanism underlying the 2,3-DHBA-induced DNA damage using 32 P-labeled DNA fragments of human tumor suppressor genes. 2,3-DHBA induced DNA damage in the presence of Cu(II) and NADH. DNA damage induced by 2,3-DHBA was enhanced by the addition of histone peptide-6 [AKRHRK]. Interestingly, 2,3-DHBA and histone peptide-6 caused base damage in the 5'-ACG-3' and 5'-CCG-3' sequences, hotspots of the p53 gene. Bathocuproine, a Cu(I) chelator, and catalase inhibited the DNA damage. Typical hydroxyl radical scavengers did not inhibit the DNA damage. These results suggest that ROS derived from the reaction of H 2 O 2 with Cu(I) participate in the DNA damage. In conclusion, 2,3-DHBA induces oxidative DNA damage and mutations, which may result in carcinogenesis

  4. Oxidative damage and cell-programmed death induced in Zea mays L. by allelochemical stress.

    Science.gov (United States)

    Ciniglia, Claudia; Mastrobuoni, Francesco; Scortichini, Marco; Petriccione, Milena

    2015-05-01

    The allelochemical stress on Zea mays was analyzed by using walnut husk washing waters (WHWW), a by-product of Juglans regia post-harvest process, which possesses strong allelopathic potential and phytotoxic effects. Oxidative damage and cell-programmed death were induced by WHWW in roots of maize seedlings. Treatment induced ROS burst, with excess of H2O2 content. Enzymatic activities of catalase were strongly increased during the first hours of exposure. The excess in malonildialdehyde following exposure to WHWW confirmed that oxidative stress severely damaged maize roots. Membrane alteration caused a decrease in NADPH oxidase activity along with DNA damage as confirmed by DNA laddering. The DNA instability was also assessed through sequence-related amplified polymorphism assay, thus suggesting the danger of walnut processing by-product and focusing the attention on the necessity of an efficient treatment of WHWW.

  5. Spontaneous perseverative turning in rats with radiation-induced hippocampal damage

    International Nuclear Information System (INIS)

    Mickley, G.A.; Ferguson, J.L.; Nemeth, T.J.; Mulvihill, M.A.; Alderks, C.E.

    1989-01-01

    This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage

  6. Impact of environmental contamination on laser induced damage of silica optics in Laser MegaJoule

    International Nuclear Information System (INIS)

    Bien-Aime, K.

    2009-11-01

    Laser induced damage impact of molecular contamination on fused polished silica samples in a context of high power laser fusion facility, such as Laser MegaJoule (LMJ) has been studied. One of the possible causes of laser induced degradation of optical component is the adsorption of molecular or particular contamination on optical surfaces. In the peculiar case of LMJ, laser irradiation conditions are a fluence of 10 J/cm 2 , a wavelength of 351 nm, a pulse duration of 3 ns for a single shot/days frequency. Critical compounds have been identified thanks to environmental measurements, analysis of material outgassing, and identification of surface contamination in the critical environments. Experiments of controlled contamination involving these compounds have been conducted in order to understand and model mechanisms of laser damage. Various hypotheses are proposed to explain the damage mechanism. (author)

  7. Summary of the mechanism of U-induced renal damage and its biochemical studies

    International Nuclear Information System (INIS)

    Chen Rusong

    1994-05-01

    In China studies on the toxicology of uranium were systematically conducted from the 1960's. Among them the studies of the change of biochemical indicators of U-induced renal damage were involved. On the basis of summarizing the relevant information of our country and the study progress of biochemical methods in recent years, the mechanism of U-induced renal damage and its biochemical basis, the behavior of uranium in kidney and the recent progress to detect renal damage with several biochemical indexes (such as α 1 -or β 2 -microglobulin, N-acetyl-β-D-glucosaminidase and alanine aminopeptidase etc.) are introduced respectively. Finally, the evaluation on the biochemical basis for acquired tolerance to U in kidney is performed. It should be noted that from the clinical viewpoint the tolerance cannot be considered as a practical measure of protection

  8. Flow cytometric determination of radiation-induced chromosome damage and its correlation with cell survival

    International Nuclear Information System (INIS)

    Welleweerd, J.; Wilder, M.E.; Carpenter, S.G.; Raju, M.R.

    1984-01-01

    Chinese hamster M3-1 cells were irradiated with several doses of x rays or α particles from 238 Pu. Propidium iodide-stained chromosome suspensions were prepared at different times after irradiation; cells were also assayed for survival. The DNA histograms of these chromosomes showed increased background counts with increased doses of radiation. This increase in background was cell-cycle dependent and was correlated with cell survival. The correlation between radiation-induced chromosome damage and cell survival was the same for X rays and α particles. Data are presented which indicate that flow cytometric analysis of chromosomes of irradiated cell populations can be a useful adjunct to classical cytogenic analysis of irradiation-induced chromosomal damage by virtue of its ability to express and measure chromosomal damage not seen by classical cytogenic methods

  9. Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

    Directory of Open Access Journals (Sweden)

    José A. Hernández

    2016-01-01

    Full Text Available The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol-related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms.

  10. Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients

    International Nuclear Information System (INIS)

    Pinar, Beatriz; Henríquez-Hernández, Luis Alberto; Lara, Pedro C; Bordon, Elisa; Rodriguez-Gallego, Carlos; Lloret, Marta; Nuñez, Maria Isabel; De Almodovar, Mariano Ruiz

    2010-01-01

    DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed. Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radio-induced apoptosis at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Radiation-induced apoptosis increased in order to radiation dose and data fitted to a semi logarithmic mathematical model. A positive correlation was found among radio-induced apoptosis values at different radiation doses: 1, 2 and 8 Gy (p < 0.0001 in all cases). Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). A statistically significant inverse correlation was found between initial damage to DNA and radio-induced apoptosis at 1 Gy (p = 0.034). A trend toward 2 Gy (p = 0.057) and 8 Gy (p = 0.067) was observed after 24 hours of incubation. An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity

  11. Biomarkers of DNA and cytogenetic damages induced by environmental chemicals or radiation

    International Nuclear Information System (INIS)

    1999-01-01

    This paper presents and discusses results from the studies on various biomarkers of the DNA and cytogenetic damages induced by environmental chemicals or radiation. Results of the biomonitoring studies have shown that particularly in the condition of Poland, health hazard from radiation exposure is overestimated in contradistinction to the environmental hazard

  12. Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2 activity

    DEFF Research Database (Denmark)

    Köpper, Frederik; Bierwirth, Cathrin; Schön, Margarete

    2013-01-01

    knockdown of the MAP kinase-activated protein kinase 2 (MK2), a kinase currently implicated in p38 stress signaling and G2 arrest. Depletion or inhibition of MK2 also protected cells from DNA damage-induced cell death, and mice deficient for MK2 displayed decreased apoptosis in the skin upon UV irradiation...

  13. Imitation of radiation-induced damages to DNA with a radionuclide incorporated into polynucleotides

    International Nuclear Information System (INIS)

    Korolev, V.G.

    1984-01-01

    Because of a great variety and different reparability of radiation-induced DNA lesions it is difficult to evaluate the radiobiologacal significance of certain individual alterations. It is suggested that the radionuclides incorporated anto DNA can be used to imitate different types of radiation damages to DNA. Both qualitative and quantitative aspects of the problem are discussed

  14. Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

    NARCIS (Netherlands)

    Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

    Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

  15. Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin

    NARCIS (Netherlands)

    Middelkamp-Hup, Maritza A.; Pathak, Madhu A.; Parrado, Concepcion; Goukassian, David; Rius-Díaz, Francisca; Mihm, Martín C.; Fitzpatrick, Thomas B.; González, Salvador

    2004-01-01

    BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL). METHODS: A

  16. Antagonist Effects of Veratric Acid against UVB-Induced Cell Damages

    OpenAIRE

    Deokhoon Park; Jong-Kyung Youm; Kyung-Eun Lee; Seungbeom Kim; Eunsun Jung; Seoung Woo Shin

    2013-01-01

    Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, ...

  17. Modeling of combined physical-mechanical moisture induced damage in asphaltic mixes

    NARCIS (Netherlands)

    Kringos, N.

    2007-01-01

    Moisture induced damage in asphaltic mixes is recognized as a major issue, resulting to the need for frequent maintenance operations. This does not only imply high maintenance costs, but also temporary closure of traffic and hence increased road congestion. Given the high costs for the road

  18. Free methionine supplementation limits alcohol-induced liver damage in rats

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Bode, C.; Bode, J.C.

    1998-01-01

    Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has been shown to result in liver damage being comparable with alcohol-induced liver disease in man. In the present study, a striking effect of free methionine consumption on histological liver injury, triglyceride accu...

  19. Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation.

    Science.gov (United States)

    Kang, Kyoung Ah; Lee, Kyoung Hwa; Chae, Sungwook; Zhang, Rui; Jung, Myung Sun; Ham, Young Min; Baik, Jong Seok; Lee, Nam Ho; Hyun, Jin Won

    2006-02-15

    We investigated the cytoprotective effect of phloroglucinol, which was isolated from Ecklonia cava (brown alga), against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Phloroglucinol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H(2)O(2)), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, phloroglucinol reduced H(2)O(2) induced apoptotic cells formation in V79-4 cells. In addition, phloroglucinol inhibited cell damage induced by serum starvation and radiation through scavenging ROS. Phloroglucinol increased the catalase activity and its protein expression. In addition, catalase inhibitor abolished the protective effect of phloroglucinol from H(2)O(2) induced cell damage. Furthermore, phloroglucinol increased phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that phloroglucinol protects V79-4 cells against oxidative damage by enhancing the cellular catalase activity and modulating ERK signal pathway. (c) 2005 Wiley-Liss, Inc.

  20. Efficient photoreactivation of UVBR-induced DNA damage in the sublittoral macroalga Rhodymenia pseudopalmata (Rhodophyta)

    NARCIS (Netherlands)

    Pakker, H; Beekman, C.A C; Breeman, Arno

    Repair of DNA damage induced by ultraviolet-B radiation (UVBR) was investigated in the sublittoral red alga Rhodymenia pseudopalmata at different temperatures, using immunofluorescent detection of thymine dimers. Photoreactivation of thymine dimers was completed within about 3 h at 6, 12 and 18

  1. Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2015-11-27

    Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

  2. Repair of DNA damage induced by ionizing radiation and benzo[a]pyrene in mammalian cells

    International Nuclear Information System (INIS)

    Cerutti, P.; Shinohara, K.; Remsen, J.

    1977-01-01

    The biological effects of DNA-damaging agents are codetermined by the structural characteristics of the lesions, the quality and extent of the local distortion of DNA and chromatin structure, and the mode(s) of damage processing used by a given type of cell. Persistent damage (i.e., damage that is not removed before it is reached by DNA replication) may be mostly responsible for mutagenesis and carcinogenesis. To understand the effects of environmental physical and chemical DNA-damaging agents on human health, the mechanisms of damage processing used by human cells have to be elucidated. We report our studies of the excision of gamma-ray products of the 5,6-dihydroxydihydrothymine type (t 0 /sub 2//sup γ/) in normal human fibroblasts and in fibroblasts from patients with the hereditary diseases Fanconi's anemia (FA) and ataxia telangiectasia (AT). Both diseases are characterized by chromosomal instability and increased susceptibility for the development of cancer. Formation and repair of DNA-benzo[a]pyrene adducts were studied in baby hamster kidney cells, secondary mouse embryo cells, and human lymphoma. The relative persistence of DNA-B[a]P may explain the high mutagenicity of the 7,8-dihydroxy-9,10-epoxy-tetrahydrobenzo[a]pyrene metabolites in rodent cells that has been observed by several investigators

  3. Coagulin-L ameliorates TLR4 induced oxidative damage and immune response by regulating mitochondria and NOX-derived ROS

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Sukka Santosh [Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Chauhan, Parul [Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Maurya, Preeti [Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Academy of Scientific and Innovative Research, New Delhi 110025 (India); Saini, Deepika [Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Yadav, Prem Prakash, E-mail: pp_yadav@cdri.res.in [Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Barthwal, Manoj Kumar, E-mail: manojbarthwal@cdri.res.in [Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India)

    2016-10-15

    Withanolides possess diverse biological and pharmacological activity but their immunomodulatory function is less realized. Hence, coagulin-L, a withanolide isolated from Withania coagulans Dunal has been studied for such an effect in human and murine cells, and mice model. Coagulin-L (1, 3, 10 μM) exhibited immunomodulatory effect by suppressing TLR4 induced immune mediators such as cytokines (GMCSF, IFNα, IFNγ, IL-1α, IL-1Rα, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17), chemokines (IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10, KC, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, eotaxin/CCL11), growth factors (FGF-basic, VEGF), nitric oxide and intracellular superoxide. Mechanistically, coagulin-L abrogated LPS induced total and mitochondrial ROS generation, NOX2, NOX4 mRNA expression, IRAK and MAPK (p38, JNK, ERK) activation. Coagulin-L also attenuated IκBα degradation, which prevented NFκB downstream iNOS expression and pro-inflammatory cytokine release. Furthermore, coagulin-L (10, 25, 50 mg/kg, p.o.), undermined the LPS (10 mg/kg, i.p.) induced endotoxemia response in mice as evinced from diminished cytokine release, nitric oxide, aortic p38 MAPK activation and endothelial tissue impairment besides suppressing NOX2 and NOX4 expression in liver and aorta. Moreover, coagulin-L also alleviated the ROS mediated oxidative damage which was assessed through protein carbonyl, lipid hydroperoxide, 8-isoprostane and 8-hydroxy-2-deoxyguanosine quantification. To extend, coagulin-L also suppressed carrageenan-induced paw edema and thioglycollate-induced peritonitis in mice. Therefore, coagulin-L can be of therapeutic importance in pathological conditions induced by oxidative damage. - Highlights: • Coagulin-L demonstrates immunomodulatory effects in vivo and in vitro by modulating ROS. • Coagulin-L modulates TH1/TH2/TH17 immunokines. • Coagulin-L exerts immunomodulatory effect by regulating TLR4-IRAK- ROS

  4. Modeling marrow damage from response data: Morphallaxis from radiation biology to benzene toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T.D.; Morris, M.D.; Hasan, J.S.

    1995-12-01

    Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between {approximately} 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is ``critical`` to hematopoietic recovery does not resemble stem-like cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD{sub 50} and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in the fitting of model coefficients.

  5. Modeling marrow damage from response data: Morphallaxis from radiation biology to benzene toxicity

    International Nuclear Information System (INIS)

    Jones, T.D.; Morris, M.D.; Hasan, J.S.

    1995-01-01

    Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between ∼ 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is ''critical'' to hematopoietic recovery does not resemble stem-like cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD 50 and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in the fitting of model coefficients

  6. Cellular and molecular mechanisms of cigarette smoke-induced lung damage and prevention by vitamin C

    Directory of Open Access Journals (Sweden)

    Roy Siddhartha

    2008-11-01

    Full Text Available Abstract Background Cigarette smoke-induced cellular and molecular mechanisms of lung injury are not clear. Cigarette smoke is a complex mixture containing long-lived radicals, including p-benzosemiquinone that causes oxidative damage. Earlier we had reported that oxidative protein damage is an initial event in smoke-induced lung injury. Considering that p-benzosemiquinone may be a causative factor of lung injury, we have isolated p-benzosemiquinone and compared its pathophysiological effects with cigarette smoke. Since vitamin C is a strong antioxidant, we have also determined the modulatory effect of vitamin C for preventing the pathophysiological events. Methods Vitamin C-restricted guinea pigs were exposed to cigarette smoke (5 cigarettes/day; 2 puffs/cigarette for 21 days with and without supplementation of 15 mg vitamin C/guinea pig/day. Oxidative damage, apoptosis and lung injury were assessed in vitro, ex vivo in A549 cells as well as in vivo in guinea pigs. Inflammation was measured by neutrophilia in BALF. p-Benzosemiquinone was isolated from freshly prepared aqueous extract of cigarette smoke and characterized by various physico-chemical methods, including mass, NMR and ESR spectroscopy. p-Benzosemiquinone-induced lung damage was examined by intratracheal instillation in guinea pigs. Lung damage was measured by increased air spaces, as evidenced by histology and morphometric analysis. Oxidative protein damage, MMPs, VEGF and VEGFR2 were measured by western blot analysis, and formation of Michael adducts using MALDI-TOF-MS. Apoptosis was evidenced by TUNEL assay, activation of caspase 3, degradation of PARP and increased Bax/Bcl-2 ratio using immunoblot analysis and confocal microscopy. Results Exposure of guinea pigs to cigarette smoke resulted in progressive protein damage, inflammation, apoptosis and lung injury up to 21 days of the experimental period. Administration of 15 mg of vitamin C/guinea pig/day prevented all these

  7. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Science.gov (United States)

    Gruel, Gaëtan; Villagrasa, Carmen; Voisin, Pascale; Clairand, Isabelle; Benderitter, Marc; Bottollier-Depois, Jean-François; Barquinero, Joan Francesc

    2016-01-01

    Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF) per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This comparison allowed us to

  8. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Directory of Open Access Journals (Sweden)

    Gaëtan Gruel

    Full Text Available Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This

  9. Effective protection of biological membranes against photo-oxidative damage: Polymeric antioxidant forming a protecting shield over the membrane.

    Science.gov (United States)

    Mertins, Omar; Mathews, Patrick D; Gomide, Andreza B; Baptista, Mauricio S; Itri, Rosangela

    2015-10-01

    We have prepared a chitosan polymer modified with gallic acid in order to develop an efficient protection strategy biological membranes against photodamage. Lipid bilayers were challenged with photoinduced damage by photosensitization with methylene blue, which usually causes formation of hydroperoxides, increasing area per lipid, and afterwards allowing leakage of internal materials. The damage was delayed by a solution of gallic acid in a concentration dependent manner, but further suppressed by the polymer at very low concentrations. The membrane of giant unilamellar vesicles was covered with this modified macromolecule leading to a powerful shield against singlet oxygen and thus effectively protecting the lipid membrane from oxidative stress. The results have proven the discovery of a promising strategy for photo protection of biological membranes. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Mixed martial arts induces significant fatigue and muscle damage up to 24 hours post-combat.

    Science.gov (United States)

    Ghoul, Nihel; Tabben, Montassar; Miarka, Bianca; Tourny, Claire; Chamari, Karim; Coquart, Jeremy

    2017-06-22

    This study investigates the physiological/physical responses to a simulated mixed martial arts (MMA) competition over 24 hr. Twelve fighters performed a simulated MMA competition, consisting of three 5-min MMA matches. Physiological/physical data were assessed before (Trest), directly after round 1 (Trd1), round 2 (Trd2) and round 3 (Trd3), and then 30-min (Trecovery30min) and/or 24-hr (Trecovery24h) post-competition. Heart rate (HR), rating of perceived exertion (RPE) and blood lactate concentration ([La]) were assessed at Trest, Trd1, Trd2 and Trd3. Biological data were collected at Trest, Trd3, Trecovery30min and Trecovery24h. Physical tests were performed at Trest, Trecovery30min and Trecovery24h. HR, RPE and [La] were high during competition. Leukocytes, hemoglobin, total protein and glycemia were increased at Trd3 compared with all other time points (p<0.05). Cortisol was increased at Trd3 compared with Trest and Trecovery24h (p<0.05). Testosterone was higher at Trd3 and Trecovery30min than Trest (p<0.001). Higher values of uric acid were noted during recovery periods (p<0.001). Lactate dehydrogenase was lower at Trest compared with Trd3, Trecovery30min and Trecovery24h (p<0.05). Countermovement jump was higher at Trest than Trecovery30min (p=0.020). Consequently, MMA is a high-intensity intermittent combat sport that induces significant fatigue and muscle damage, both of which are still present 24-hr post-competition.

  11. Alpha Particles and X Rays Interact in Inducing DNA Damage in U2OS Cells.

    Science.gov (United States)

    Sollazzo, Alice; Brzozowska, Beata; Cheng, Lei; Lundholm, Lovisa; Haghdoost, Siamak; Scherthan, Harry; Wojcik, Andrzej

    2017-10-01

    Survivors of the atomic bombings of Hiroshima and Nagasaki are monitored for health effects within the Life Span Study (LSS). The LSS results represent the most important source of data about cancer effects from ionizing radiation exposure, which forms the foundation for the radiation protection system. One uncertainty connected to deriving universal risk factors from these results is related to the problem of mixed radiation qualities. The A-bomb explosions generated a mixed beam of the sparsely ionizing gamma radiation and densely ionizing neutrons. However, until now the possible interaction of the two radiation types of inducing biological effects has not been taken into consideration. The existence of such interaction would suggest that the application of risk factors derived from the LSS to predict cancer effects after pure gamma-ray irradiation (such as in the Fukushima prefecture) leads to an overestimation of risk. To analyze the possible interaction of radiation types, a mixed-beam exposure facility was constructed where cells can be exposed to sparsely ionizing X rays and densely ionizing alpha particles. U2OS cells were used, which are stably transfected with a plasmid coding for the DNA repair gene 53BP1 coupled to a gene coding for the green fluorescent protein (GFP). The induction and repair of DNA damage, which are known to be related to cancer induction, were analyzed. The results suggest that alpha particles and X rays interact, leading to cellular and possibly cancer effects, which cannot be accurately predicted based on assuming simple additivity of the individual mixed-beam components.

  12. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    Directory of Open Access Journals (Sweden)

    Mónica Millán

    2008-01-01

    Full Text Available Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA.

  13. 'Nothing of chemistry disappears in biology': the Top 30 damage-prone endogenous metabolites.

    Science.gov (United States)

    Lerma-Ortiz, Claudia; Jeffryes, James G; Cooper, Arthur J L; Niehaus, Thomas D; Thamm, Antje M K; Frelin, Océane; Aunins, Thomas; Fiehn, Oliver; de Crécy-Lagard, Valérie; Henry, Christopher S; Hanson, Andrew D

    2016-06-15

    Many common metabolites are intrinsically unstable and reactive, and hence prone to chemical (i.e. non-enzymatic) damage in vivo Although this fact is widely recognized, the purely chemical side-reactions of metabolic intermediates can be surprisingly hard to track down in the literature and are often treated in an unprioritized case-by-case way. Moreover, spontaneous chemical side-reactions tend to be overshadowed today by side-reactions mediated by promiscuous ('sloppy') enzymes even though chemical damage to metabolites may be even more prevalent than damage from enzyme sloppiness, has similar outcomes, and is held in check by similar biochemical repair or pre-emption mechanisms. To address these limitations and imbalances, here we draw together and systematically integrate information from the (bio)chemical literature, from cheminformatics, and from genome-scale metabolic models to objectively define a 'Top 30' list of damage-prone metabolites. A foundational part of this process was to derive general reaction rules for the damage chemistries involved. The criteria for a 'Top 30' metabolite included predicted chemical reactivity, essentiality, and occurrence in diverse organisms. We also explain how the damage chemistry reaction rules ('operators') are implemented in the Chemical-Damage-MINE (CD-MINE) database (minedatabase.mcs.anl.gov/#/top30) to provide a predictive tool for many additional potential metabolite damage products. Lastly, we illustrate how defining a 'Top 30' list can drive genomics-enabled discovery of the enzymes of previously unrecognized damage-control systems, and how applying chemical damage reaction rules can help identify previously unknown peaks in metabolomics profiles. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  14. Surfactant Protein D is a candidate biomarker for subclinical tobacco smoke-induced lung damage

    DEFF Research Database (Denmark)

    Lock Johansson, Sofie; Tan, Qihua; Holst, Rene

    2014-01-01

    Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage. The associat......Variation in Surfactant Protein D (SP-D) is associated with lung function in tobacco smoke-induced chronic respiratory disease. We hypothesized that the same association exists in the general population and could be used to identify individuals sensitive to smoke-induced lung damage...... or haplotypes, and expiratory lung function were assessed using twin study methodology and mixed-effects models. Significant inverse associations were evident between sSP-D and the forced expiratory volume in 1 second and forced vital capacity in the presence of current tobacco smoking but not in non...... with lung function measures in interaction with tobacco smoking. The obtained data suggest sSP-D as a candidate biomarker in risk assessments for subclinical tobacco smoke-induced lung damage. The data and derived conclusion warrant confirmation in a longitudinal population following chronic obstructive...

  15. Membrane damage induced in cultured human skin fibroblasts by UVA irradiation

    International Nuclear Information System (INIS)

    Gaboriau, F.; Morliere, P.; Marquis, I.; Moysan, A.; Geze, M.; Dubertret, L.

    1993-01-01

    Irradiation of cultured human skin fibroblasts with ultraviolet light from 320 to 400 nm (UVA) leads to a decrease in the membrane fluidity exemplified by an enhanced fluorescence anisotropy of the lipophilic fluorescent probe 1-[4-trimethylamino)-phenyl]-6-phenylhexa-1,3,5-triene. This UVA-induced decrease in fluidity is associated with lactate dehydrogenase leakage in the supernatant. Vitamin E, an inhibitor of lipid peroxidation, exerts a protective effect on both phenomena. Therefore, this UVA-induced damage in membrane properties may be related to lipid peroxidation processes. Moreover, exponentially growing cells are more sensitive to these UVA-induced alterations than confluent cells. (Author)

  16. Heavy Metal-Induced Oxidative DNA Damage in Earthworms: A Review

    Directory of Open Access Journals (Sweden)

    Takeshi Hirano

    2010-01-01

    Full Text Available Earthworms can be used as a bio-indicator of metal contamination in soil, Earlier reports claimed the bioaccumulation of heavy metals in earthworm tissues, while the metal-induced mutagenicity reared in contaminated soils for long duration. But we examined the metal-induced mutagenicity in earthworms reared in metal containing culture beddings. In this experiment we observed the generation of 8-oxoguanine (8-oxo-Gua in earthworms exposed to cadmium and nickel in soil. 8-oxo-Gua is a major premutagenic form of oxidative DNA damage that induces GC-to-TA point mutations, leading to carcinogenesis.

  17. Comparison of damage induced by mercury chloride and ionizing radiation in the susceptible rat model

    International Nuclear Information System (INIS)

    Kim, Ji Hyang; Yoon, Yong Dal; Kim, Jin Kyu

    2003-01-01

    Mercury (Hg), one of the most diffused and hazardous organ-specific environmental contaminants, exists in a wide variety of physical and chemical states. Although the reports indicate that mercury induces a deleterious damage, little has been reported from the investigations of mercury effects in living things. The purpose of this study is to evaluate the effects of mercury chloride and ionizing radiation. Prepubertal male F-344 rats were administered mercury chloride in drinking water throughout the experimental period. Two weeks after whole body irradiation, organs were collected for measuring the induced injury. Serum levels of GOT, GPT, ALP, and LDH were checked in the experimental groups and the hematological analysis was accomplished in plasma. In conclusion, the target organ of mercury chloride seems to be urinary organs and the pattern of damage induced by mercury differs from that of the irradiated group

  18. Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage

    Directory of Open Access Journals (Sweden)

    Jiaxiang Shao

    2016-03-01

    Full Text Available Abstract SIRT6 is a NAD+-dependent histone deacetylase and has been implicated in the regulation of genomic stability, DNA repair, metabolic homeostasis and several diseases. The effect of SIRT6 in cerebral ischemia and oxygen/glucose deprivation (OGD has been reported, however the role of SIRT6 in oxidative stress damage remains unclear. Here we used SH-SY5Y neuronal cells and found that overexpression of SIRT6 led to decreased cell viability and increased necrotic cell death and reactive oxygen species (ROS production under oxidative stress. Mechanistic study revealed that SIRT6 induced autophagy via attenuation of AKT signaling and treatment with autophagy inhibitor 3-MA or knockdown of autophagy-related protein Atg5 rescued H2O2-induced neuronal injury. Conversely, SIRT6 inhibition suppressed autophagy and reduced oxidative stress-induced neuronal damage. These results suggest that SIRT6 might be a potential therapeutic target for neuroprotection.

  19. Muscle damage and repeated bout effect induced by enhanced eccentric squats.

    Science.gov (United States)

    Coratella, Giuseppe; Chemello, Alessandro; Schena, Federico

    2016-12-01

    Muscle damage and repeated bout effect have been studied after pure eccentric-only exercise. The aim of this study was to evaluate muscle damage and repeated bout effect induced by enhanced eccentric squat exercise using flywheel device. Thirteen healthy males volunteered for this study. Creatine kinase blood activity (CK), quadriceps isometric peak torque and muscle soreness were used as markers of muscle damage. The dependent parameters were measured at baseline, immediately after and each day up to 96 hours after the exercise session. The intervention consisted of 100 repetitions of enhanced eccentric squat exercise using flywheel device. The same protocol was repeated after 4 weeks. After the first bout, CK and muscle soreness were significantly greater (P0.05), while isometric peak torque and muscle soreness returned to values similar to baseline after respectively 48 and 72 hours. All muscle damage markers were significantly lower after second compared to first bout. The enhanced eccentric exercise induced symptoms of muscle damage up to 96 hours. However, it provided muscle protection after the second bout, performed four weeks later. Although it was not eccentric-only exercise, the enhancement of eccentric phase provided muscle protection.

  20. Investigation on the effect of developed product and new food for radiation-induced skin damage

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Ho; Kim, Jong Chun; Bae, Chun Sik; Kim, Se Ra; Lee, Hae Jun; Bang, Dae Won; Lee, Jin Hee; Kim, Joong Sun; Ki, Sun Ah; Song, Myung Seop [Chonnam National University, Gwangju (Korea, Republic of)

    2007-07-15

    In vivo evaluation of the developed pilot product on the skin protection against UV irradiation and screening of new candidate materials. Project Results are Establishment of experimental methods for 3 morphological indices of UV-induced skin damages -Establishment of experimental methods for whitening effect evaluation -Evaluation of HemoHIM administration on the skin damage indices -Evaluation of HemoHIM skin application on the skin damage indices -Evaluation of HemoTonic administration on the skin damage indices -Evaluation of HemoTonic skin application on the skin damage indices -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 1 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 2 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 3 -Evaluation of HemoHIM on the antiinflamatory effects in the TNBS-induced colitis -Evaluation of HemoHIM on the anti-wrinkle effects in the skin -Evaluation of HemoHIM on the protective effects on the skin tissue (epidermal thickening, dermal cellularity, dermal cyst) -Evaluation of HemoHIM on the protective effects on the skin tumor development

  1. Investigation on the effect of developed product and new food for radiation-induced skin damage

    International Nuclear Information System (INIS)

    Kim, Sung Ho; Kim, Jong Chun; Bae, Chun Sik; Kim, Se Ra; Lee, Hae Jun; Bang, Dae Won; Lee, Jin Hee; Kim, Joong Sun; Ki, Sun Ah; Song, Myung Seop

    2007-07-01

    In vivo evaluation of the developed pilot product on the skin protection against UV irradiation and screening of new candidate materials. Project Results are Establishment of experimental methods for 3 morphological indices of UV-induced skin damages -Establishment of experimental methods for whitening effect evaluation -Evaluation of HemoHIM administration on the skin damage indices -Evaluation of HemoHIM skin application on the skin damage indices -Evaluation of HemoTonic administration on the skin damage indices -Evaluation of HemoTonic skin application on the skin damage indices -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 1 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 2 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 3 -Evaluation of HemoHIM on the antiinflamatory effects in the TNBS-induced colitis -Evaluation of HemoHIM on the anti-wrinkle effects in the skin -Evaluation of HemoHIM on the protective effects on the skin tissue (epidermal thickening, dermal cellularity, dermal cyst) -Evaluation of HemoHIM on the protective effects on the skin tumor development

  2. The neuroprotective effect of hyperbaric oxygen treatment on laser-induced retinal damage in rats

    Science.gov (United States)

    Vishnevskia-Dai, Victoria; Belokopytov, Mark; Dubinsky, Galina; Nachum, Gal; Avni, Isaac; Belkin, Michael; Rosner, Mordechai

    2005-04-01

    Retinal damage induced by mechanical trauma, ischemia or laser photocoagulation increases considerably by secondary degeneration processes. The spread of damage may be ameliorated by neuroprotection that is aimed at reducing the extent of the secondary degeneration and promote healing processes. Hyperbaric oxygen (HBO) treatment consists of inspiration of oxygen at higher than one absolute atmospheric pressure. Improved neural function was observed in patients with acute brain trauma or ischemia treated with HBO. This study was designed to evaluate the neuroprotective effect of hyperbaric oxygen (HBO) on laser induced retinal damage in a rat model. Standard argon laser lesions were created in 25 pigmented rats divided into three groups: Ten rats were treated immediately after the irradiation with HBO three times during the first 24 hr followed by 12 consecutive daily treatments. Five rats received a shorter treatment regimen of 10 consecutive HBO treatments. The control group (10 rats) underwent the laser damage with no additional treatment. The retinal lesions were evaluated 20 days after the injury. All outcome measures were improved by the longer HBO treatment (Ptreatment was less effective, showing an increase only in nuclei density at the central area of lesion (Pretinal damage in a rat model. In the range of HBO exposures studied, longer exposure provides more neuroprotection. These results encourage further evaluation of the potential therapeutic use of hyperbaric oxygen in diseases and injuries of the retina.

  3. Human lymphocyte damage and phosphorylation of H2AX and ATM induced by γ-rays

    International Nuclear Information System (INIS)

    Tian Mei; Pan Yan; Liu Jianxiang; Ruan Jianlei; Su Xu

    2011-01-01

    Objective: To investigate 60 Co γ-ray induced damage in lymphocytes and the relationship between doses of 60 Co γ-ray irradiation and the levels of phosphorylated H2AX and ATM. Methods: Cells were irradiated with 60 Co γ-rays in the range of 0-8 Gy. The levels of phosphorylated H2AX and ATM were detected by Western blot and FACScan,respectively. The micronucleus(MN)was analyzed by CB method to evaluate DNA damage. Results: FACScan results showed the dose-effect relationship of γ-H2AX expression were linear.square at 0.5 h post-irradiation to different doses, and the fitting curve was shown as Y=3.96+11.29D-0.45D 2 . The level of phosphorylated ATM (p-ATM) was not changed significantly by using the same method. Western blot showed that p-ATM protein expression was significantly increased after irradiation compared with sham, irradiated group. The MN assay which represented DNA damage was sensitive to different doses. Conclusions: γ-ray irradiation could induce the phosphorylation of H2AX and ATM, which may play an important role in indicating DNA damage. Both of H2AX and ATM have the potential as sensitive biomarker and biodosimeter for radiation damage. (authors)

  4. Use of 2-color flow cytometry to assess radiation induced geotoxic damage on CHO-KI cells

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Luma Ramirez de; Bonfim, Leticia; Vieira, Daniel Perez, E-mail: lrcarvalho@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2017-11-01

    The micronucleus assay is an important technique used to evaluate genotoxic damage of chemical or physical agents (as ionizing radiations) on cells, based on quantification of cells bearing micronuclei, which are fragments derived from damage (breakage) of the DNA. Currently, this technique was updated to an automated approach that relies on plasma membrane dissolution to analyze fluorescent dye-labelled nuclei and micronuclei by flow cytometry. Cell suspensions were irradiated in PBS by a {sup 60}Co source in doses between 0 and 16Gy, and incubated by 48h. Cell membranes were lysed in the presence of SYTOX Green and EMA dyes, so EMA-stained nuclei could be discriminated as from dead cells, and nuclei and micronuclei could be quantified. Amounts of micronuclei (percent of events) in the samples, were found to be proportional to radiation doses, and could be fitted to a linear-quadratic model (R² = 0.993). Only higher doses (8 and 16Gy) and positive control could induce relevant increases in micronucleus amounts. The incorporation EMA showed an increase in irradiated cells. Mid to high doses (4, 8 and 16Gy) induced reduction of cell proliferation. Experiments showed the suitability of the technique to replace traditional microscopy analysis in evaluation of the effects of ionizing radiations on cells, with possibility to use in biological dosimetry. (author)

  5. The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, F. A.

    2011-01-01

    Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, Ti-48-ions with energies ranging from 240 to 1000 MeV/u, or to Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Si beams in this study ranged from 48 to 158 keV/ m, the LET of the Ti ions ranged from 107 to 240 keV/micron, and the LET of the Fe-ions ranged from 145 to 440 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosome damage with respect to gamma-rays. The estimates of RBEmax values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, 21.4+/-1.7 to 28.3+/-2.4 for Ti ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBEmax value for Fe ions was obtained with the 600 MeV/u beam, the highest RBEmax value for Ti ions was obtained 1000 MeV/u beam, and the highest RBEmax value for Si ions was obtained with the 170 MeV/u beam. For Si and Fe ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreasing with further increase in LET. Additional studies for low doses Si-28-ions down to 0.02 Gy will be discussed.

  6. Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage

    Directory of Open Access Journals (Sweden)

    Srivastava AK

    2013-04-01

    Full Text Available Amit Kumar Srivastava,1 Priyanka Bhatnagar,2 Madhulika Singh,1 Sanjay Mishra,1 Pradeep Kumar,2 Yogeshwer Shukla,1 Kailash Chand Gupta1,2 1Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR, Lucknow, India; 2Nucleic Acid Research Laboratory, Institute of Genomics and Integrative Biology (CSIR, Delhi University Campus, India Abstract: In spite of proficient results of several phytochemicals in preclinical settings, the conversion rate from bench to bedside is not very encouraging. Many reasons are attributed to this limited success, including inefficient systemic delivery and bioavailability under in vivo conditions. To achieve improved efficacy, polyphenolic constituents of black (theaflavin [TF] and green (epigallocatechin-3-gallate [EGCG] tea in poly(lactide-co-glycolide nanoparticles (PLGA-NPs were entrapped with entrapment efficacy of ~18% and 26%, respectively. Further, their preventive potential against 7,12-dimethylbenzanthracene (DMBA-induced DNA damage in mouse skin using DNA alkaline unwinding assay was evaluated. Pretreatment (topically of mouse skin with either TF or EGCG (100 µg/mouse doses exhibits protection of 45.34% and 28.32%, respectively, against DMBA-induced DNA damage. However, pretreatment with TF-loaded PLGA-NPs protects against DNA damage 64.41% by 1/20th dose of bulk, 71.79% by 1/10th dose of bulk, and 72.46% by 1/5th dose of bulk. Similarly, 51.28% (1/20th of bulk, 57.63% (1/10th of bulk, and 63.14% (1/5th of bulk prevention was noted using EGCG-loaded PLGA-NP doses. These results showed that tea polyphenol-loaded PLGA-NPs have ~30-fold dose-advantage than bulk TF or EGCG doses. Additionally, TF- or EGCG-loaded PLGA-NPs showed significant potential for induction of DNA repair genes (XRCC1, XRCC3, and ERCC3 and suppression of DNA damage responsive genes (p53, p21, MDM2, GADD45α, and COX-2 as compared with respective bulk TF or EGCG doses. Taken together, TF- or EGCG-loaded PLGA-NPs showed a superior

  7. Effect of SOS-induced levels of imuABC on spontaneous and damage-induced mutagenesis in Caulobacter crescentus.

    Science.gov (United States)

    Alves, Ingrid R; Lima-Noronha, Marco A; Silva, Larissa G; Fernández-Silva, Frank S; Freitas, Aline Luiza D; Marques, Marilis V; Galhardo, Rodrigo S

    2017-11-01

    imuABC (imuAB dnaE2) genes are responsible for SOS-mutagenesis in Caulobacter crescentus and other bacterial species devoid of umuDC. In this work, we have constructed operator-constitutive mutants of the imuABC operon. We used this genetic tool to investigate the effect of SOS-induced levels of these genes upon both spontaneous and damage-induced mutagenesis. We showed that constitutive expression of imuABC does not increase spontaneous or damage-induced mutagenesis, nor increases cellular resistance to DNA-damaging agents. Nevertheless, the presence of the operator-constitutive mutation rescues mutagenesis in a recA background, indicating that imuABC are the only genes required at SOS-induced levels for translesion synthesis (TLS) in C. crescentus. Furthermore, these data also show that TLS mediated by ImuABC does not require RecA, unlike umuDC-dependent mutagenesis in E. coli. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Induction of the Wnt antagonist Dickkopf-1 is involved in stress-induced hippocampal damage.

    Directory of Open Access Journals (Sweden)

    Francesco Matrisciano

    Full Text Available The identification of mechanisms that mediate stress-induced hippocampal damage may shed new light into the pathophysiology of depressive disorders and provide new targets for therapeutic intervention. We focused on the secreted glycoprotein Dickkopf-1 (Dkk-1, an inhibitor of the canonical Wnt pathway, involved in neurodegeneration. Mice exposed to mild restraint stress showed increased hippocampal levels of Dkk-1 and reduced expression of β-catenin, an intracellular protein positively regulated by the canonical Wnt signalling pathway. In adrenalectomized mice, Dkk-1 was induced by corticosterone injection, but not by exposure to stress. Corticosterone also induced Dkk-1 in mouse organotypic hippocampal cultures and primary cultures of hippocampal neurons and, at least in the latter model, the action of corticosterone was reversed by the type-2 glucocorticoid receptor antagonist mifepristone. To examine whether induction of Dkk-1 was causally related to stress-induced hippocampal damage, we used doubleridge mice, which are characterized by a defective induction of Dkk-1. As compared to control mice, doubleridge mice showed a paradoxical increase in basal hippocampal Dkk-1 levels, but no Dkk-1 induction in response to stress. In contrast, stress reduced Dkk-1 levels in doubleridge mice. In control mice, chronic stress induced a reduction in hippocampal volume associated with neuronal loss and dendritic atrophy in the CA1 region, and a reduced neurogenesis in the dentate gyrus. Doubleridge mice were resistant to the detrimental effect of chronic stress and, instead, responded to stress with increases in dendritic arborisation and neurogenesis. Thus, the outcome of chronic stress was tightly related to changes in Dkk-1 expression in the hippocampus. These data indicate that induction of Dkk-1 is causally related to stress-induced hippocampal damage and provide the first evidence that Dkk-1 expression is regulated by corticosteroids in the central

  9. Purine receptor P2Y_6 mediates cellular response to γ-ray-induced DNA damage

    International Nuclear Information System (INIS)

    Ide, Shunta; Nishimaki, Naoko; Tsukimoto, Mitsutoshi; Kojima, Shuji

    2014-01-01

    We previously showed that nucleotide P2 receptor agonists such as ATP and UTP amplify γ-ray-induced focus formation of phosphorylated histone H2A variant H2AX (γH2AX), which is considered to be an indicator of DNA damage so far, by activating purine P2Y_6 and P2Y_1_2 receptors. Therefore, we hypothesized that these P2 receptors play a role in inducing the repair response to γ-ray-induced DNA damage. In the present study, we tested this idea by using human lung cancer A549 cells. First, reverse-transcription polymerase chain reaction (RT-PCR) showed that P2Y_6 receptor is highly expressed in A549 cells, but P2Y_1_2 receptor is only weakly expressed. Next, colony formation assay revealed that P2Y_6 receptor antagonist MRS2578 markedly reduced the survival rate of γ-ray-exposed A549 cells. The survival rate was also significantly reduced in P2Y_6-knock-down cells, compared with scramble siRNA-transfected cells. Since it has reported that phosphorylation of ERK1/2 after activation of EGFR via P2Y_6 and P2Y_1_2 receptors is involved in the repair response to γ-ray-induced DNA damage, we next examined whether γ-ray-induced phosphorylation of ERK1/2 was also inhibited by MRS2578 in A549 cells. We found that it was. Taken together, these findings indicate that purinergic signaling through P2Y_6 receptor, followed by ERK1/2 activation, promotes the cellular repair response to γ-ray-induced DNA damage. (author)

  10. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anthony Skipper

    2016-01-01

    Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

  11. DNA damage responses in human induced pluripotent stem cells and embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Olga Momcilovic

    2010-10-01

    Full Text Available Induced pluripotent stem (iPS cells have the capability to undergo self-renewal and differentiation into all somatic cell types. Since they can be produced through somatic cell reprogramming, which uses a defined set of transcription factors, iPS cells represent important sources of patient-specific cells for clinical applications. However, before these cells can be used in therapeutic designs, it is essential to understand their genetic stability.Here, we describe DNA damage responses in human iPS cells. We observe hypersensitivity to DNA damaging agents resulting in rapid induction of apoptosis after γ-irradiation. Expression of pluripotency factors does not appear to be diminished after irradiation in iPS cells. Following irradiation, iPS cells activate checkpoint signaling, evidenced by phosphorylation of ATM, NBS1, CHEK2, and TP53, localization of ATM to the double strand breaks (DSB, and localization of TP53 to the nucleus of NANOG-positive cells. We demonstrate that iPS cells temporary arrest cell cycle progression in the G(2 phase of the cell cycle, displaying a lack of the G(1/S cell cycle arrest similar to human embryonic stem (ES cells. Furthermore, both cell types remove DSB within six hours of γ-irradiation, form RAD51 foci and exhibit sister chromatid exchanges suggesting homologous recombination repair. Finally, we report elevated expression of genes involved in DNA damage signaling, checkpoint function, and repair of various types of DNA lesions in ES and iPS cells relative to their differentiated counterparts.High degrees of similarity in DNA damage responses between ES and iPS cells were found. Even though reprogramming did not alter checkpoint signaling following DNA damage, dramatic changes in cell cycle structure, including a high percentage of cells in the S phase, increased radiosensitivity and loss of DNA damage-induced G(1/S cell cycle arrest, were observed in stem cells generated by induced pluripotency.

  12. Photoelectrochemical Sensors for the Rapid Detection of DNA Damage Induced by Some Nanoparticles

    Directory of Open Access Journals (Sweden)

    M. Jamaluddin Ahmed

    2010-06-01

    Full Text Available Photoelectrochemcal sensors were developed for the rapid detection of oxidative DNA damage induced by titanium dioxide and polystyrene nanoparticles. Each sensor is a multilayer film prepared on a tin oxide nanoparticle electrode using layer- by-layer self assembly and is composed of separate layer of a photoelectrochemical indicator, DNA. The organic compound and heavy metals represent genotoxic chemicals leading two major damaging mechanisms, DNA adduct formation and DNA oxidation. The DNA damage is detected by monitoring the change of photocurrent of the indicator. In one sensor configuration, a DNA intercalator, Ru(bpy2 (dppz2+ [bpy=2, 2′ -bipyridine, dppz=dipyrido( 3, 2-a: 2′ 3′-c phenazine], was employed as the photoelectrochemical indicator. The damaged DNA on the sensor bound lesser Ru(bpy2 (dppz2+ than the intact DNA, resulting in a drop in photocurrent. In another configuration, ruthenium tris(bipyridine was used as the indicator and was immobilized on the electrode underneath the DNA layer. After oxidative damage, the DNA bases became more accessible to photoelectrochemical oxidation than the intact DNA, producing a rise in photocurrent. Both sensors displayed substantial photocurrent change after incubation in titanium dioxide / polystyrene solution in a time – dependent manner. According to the data, damage of the DNA film was completed in 1h in titanium dioxide / polystyrene solution. In addition, the titanium dioxide induced much more sever damage than polysterene. The results were verified independently by gel electrophoresis and UV-Vis absorbance experiments. The photoelectrochemical reaction can be employed as a new and inexpensive screening tool for the rapid assessment of the genotoxicity of existing and new chemicals.

  13. Cellular Response to Bleomycin-Induced DNA Damage in Human Fibroblast Cells in Space

    Science.gov (United States)

    Lu, Tao; Zhang, Ye; Wong, Michael; Stodieck, Louis; Karouia, Fathi; Wu, Honglu

    2015-01-01

    Outside the protection of the geomagnetic field, astronauts and other living organisms are constantly exposed to space radiation that consists of energetic protons and other heavier charged particles. Whether spaceflight factors, microgravity in particular, have effects on cellular responses to DNA damage induced by exposure to radiation or cytotoxic chemicals is still unknown, as is their impact on the radiation risks for astronauts and on the mutation rate in microorganisms. Although possible synergistic effects of space radiation and other spaceflight factors have been investigated since the early days of the human space program, the published results were mostly conflicting and inconsistent. To investigate effects of spaceflight on cellular responses to DNA damages, human fibroblast cells flown to the International Space Station (ISS) were treated with bleomycin for three hours in the true microgravity environment, which induced DNA damages including double-strand breaks (DSB) similar to the ionizing radiation. Damages in the DNA were measured by the phosphorylation of a histone protein H2AX (g-H2AX), which showed slightly more foci in the cells on ISS than in the ground control. The expression of genes involved in DNA damage response was also analyzed using the PCR array. Although a number of the genes, including CDKN1A and PCNA, were significantly altered in the cells after bleomycin treatment, no significant difference in the expression profile of DNA damage response genes was found between the flight and ground samples. At the time of the bleomycin treatment, the cells on the ISS were found to be proliferating faster than the ground control as measured by the percentage of cells containing positive Ki-67 signals. Our results suggested that the difference in g-H2AX focus counts between flight and ground was due to the faster growth rate of the cells in space, but spaceflight did not affect initial transcriptional responses of the DNA damage response genes to

  14. Photoelectrochemical sensors for the rapid detection of DNA damage Induced by some nanoparticles

    International Nuclear Information System (INIS)

    Ahmed, M.J.; Zhang, B.T.; Guo, L.H.

    2010-01-01

    Photoelectrochemical sensors were developed for the rapid detection of oxidative DNA damage induced by titanium dioxide and polystyrene nanoparticles. Each sensor is a multilayer film prepared on a tin oxide nanoparticle electrode using layer- by-layer self assembly and is composed of separate layer of a photoelectrochemical indicator, DNA. The organic compound and heavy metals represent genotoxic chemicals leading two major damaging mechanisms, DNA adduct formation and DNA oxidation. The DNA damage is detected by monitoring the change of photocurrent of the indicator. In one sensor configuration, a DNA intercalator, Ru(bpy)2 (dppz)2+ [bpy=2, 2' -bipyridine, dppz=dipyrido (3, 2-a: 2' 3'-c) phenazine], was employed as the photoelectrochemical indicator. The damaged DNA on the sensor bound lesser Ru(bpy)2 (dppz)2+ than the intact DNA, resulting in a drop in photocurrent. In another configuration, ruthenium tris(bipyridine) was used as the indicator and was immobilized on the electrode underneath the DNA layer. After oxidative damage, the DNA bases became more accessible to photoelectrochemical oxidation than the intact DNA, producing a rise in photocurrent. Both sensors displayed substantial photocurrent change after incubation in titanium dioxide / polystyrene solution in a time . dependent manner. According to the data, damage of the DNA film was completed in 1h in titanium dioxide / polystyrene solution. In addition, the titanium dioxide induced much more sever damage than polystyrene. The results were verified independently by gel electrophoresis and UV-Vis absorbance experiments. The photoelectrochemical reaction can be employed as a new and inexpensive screening tool for the rapid assessment of the genotoxicity of existing and new chemicals. (author)

  15. Multiple repair pathways mediate cellular tolerance to resveratrol-induced DNA damage.

    Science.gov (United States)

    Liu, Ying; Wu, Xiaohua; Hu, Xiaoqing; Chen, Ziyuan; Liu, Hao; Takeda, Shunichi; Qing, Yong

    2017-08-01

    Resveratrol (RSV) has been reported to exert health benefits for the prevention and treatment of many diseases, including cancer. The anticancer mechanisms of RSV seem to be complex and may be associated with genotoxic potential. To better understand the genotoxic mechanisms, we used wild-type (WT) and a panel of isogenic DNA-repair deficient DT40 cell lines to identify the DNA damage effects and molecular mechanisms of cellular tolerance to RSV. Our results showed that RSV induced significant formation of γ-H2AX foci and chromosome aberrations (CAs) in WT cells, suggesting direct DNA damage effects. Comparing the survival of WT with isogenic DNA-repair deficient DT40 cell lines demonstrated that single strand break repair (SSBR) deficient cell lines of Parp1 -/- , base excision repair (BER) deficient cell lines of Polβ -/- , homologous recombination (HR) mutants of Brca1 -/- and Brca2 -/- and translesion DNA synthesis (TLS) mutants of Rev3 -/- and Rad18 -/- were more sensitive to RSV. The sensitivities of cells were associated with enhanced DNA damage comparing the accumulation of γ-H2AX foci and number of CAs of isogenic DNA-repair deficient DT40 cell lines with WT cells. These results clearly demonstrated that RSV-induced DNA damage in DT40 cells, and multiple repair pathways including BER, SSBR, HR and TLS, play critical roles in response to RSV- induced genotoxicity. Copyright © 2017. Published by Elsevier Ltd.

  16. The effect of phytosterol protects rats against 4-nitrophenol-induced liver damage.

    Science.gov (United States)

    Chen, Jiaqin; Song, Meiyan; Li, Yansen; Zhang, Yonghui; Taya, Kazuyoshi; Li, ChunMei

    2016-01-01

    We investigated the effect of phytosterol (PS) in regard to liver damage induced by 4-nitrophenol (PNP). Twenty rats were randomly divided into four groups (Control, PS, PNP, and PNP+PS). The PS and PNP+PS groups were pretreated with PS for one week. The PNP and PNP+PS groups were injected subcutaneously with PNP for 28 days. The control group received a basal diet and was injected with vehicle alone. Treatment with PS prevented the elevation of the total bilirubin levels, as well as an increase in serum alkaline transaminase and aspartate transaminase, which are typically caused by PNP-induced liver damage. Histopathologically showed that liver damage was significantly mitigated by PS treatment. However, there was no significant change in antioxidant enzyme activities, and the Nrf2-antioxidant system was not activated after treatment with PS. These results suggest that PS could mitigate liver damage induced by PNP, but does not enhance antioxidant capacity. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage

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    Jie Deng

    2018-04-01

    Full Text Available Oxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX. However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine, a special antioxidant with acrolein-sequestering ability, on CTX-induced bone marrow cell suppression. Our results show that carnosine treatment (100 and 200 mg/kg, i.p. significantly inhibited the generation of reactive oxygen species (ROS and 8-hydroxy-2′-deoxyguanosine (8-oxo-dG, and decreased chromosomal abnormalities in the bone marrow cells of mice treated with CTX (20 mg/kg, i.v., 24 h. Furthermore, carnosine evidently mitigated CTX-induced G2/M arrest in murine bone marrow cells, accompanied by reduced ratios of p-Chk1/Chk1 and p-p53/p53 as well as decreased p21 expression. In addition, cell apoptosis caused by CTX was also suppressed by carnosine treatment, as assessed by decreased TUNEL-positive cell counts, down-regulated expressions of Bax and Cyt c, and reduced ratios of cleaved Caspase-3/Caspase-3. These results together suggest that carnosine can protect murine bone marrow cells from CTX-induced DNA damage via its antioxidant activity. Keywords: Carnosine, Cyclophosphamide, Oxidative DNA damage, Sister chromatid exchange, Apoptosis, Cell cycle arrest

  18. Edaravone Protect against Retinal Damage in Streptozotocin-Induced Diabetic Mice

    Science.gov (United States)

    Liu, Xiaoyi; Chen, Xi; Xie, Ping; Yuan, Songtao; Zhang, Weiwei; Lin, Xiaojun; Liu, Qinghuai

    2014-01-01

    Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is used for the clinical treatment of retinal injury. In this study, we investigated the protective effects of edaravone against diabetic retinal damage in the mouse. Diabetic retinopathy in the mouse was induced by injection of streptozotocin. Edaravone was given once-daily and was intraperitoneally (i.p.) treated at a dose of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes. Retinal ganglion cells (RGCs) damage was evaluated by recording the pattern electroretinogram (ERG). RGCs damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of reactive oxygen species (ROS) were determined fluorometrically. The expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expression of BDNF was significantly decreased in the retinas of diabetic mice, compared to nondiabetic mice. Administration of edaravone significantly attenuated diabetes induced RGCs death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF. These findings suggest that oxidative stress plays a pivotal role in diabetic retinal damage and that systemic administration of edaravone may slow the progression of retinal neuropathy induced by diabetes. PMID:24897298

  19. Edaravone protect against retinal damage in streptozotocin-induced diabetic mice.

    Directory of Open Access Journals (Sweden)

    Dongqing Yuan

    Full Text Available Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, a free radical scavenger, is used for the clinical treatment of retinal injury. In this study, we investigated the protective effects of edaravone against diabetic retinal damage in the mouse. Diabetic retinopathy in the mouse was induced by injection of streptozotocin. Edaravone was given once-daily and was intraperitoneally (i.p. treated at a dose of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes. Retinal ganglion cells (RGCs damage was evaluated by recording the pattern electroretinogram (ERG. RGCs damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining, and the levels of reactive oxygen species (ROS were determined fluorometrically. The expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expression of BDNF was significantly decreased in the retinas of diabetic mice, compared to nondiabetic mice. Administration of edaravone significantly attenuated diabetes induced RGCs death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF. These findings suggest that oxidative stress plays a pivotal role in diabetic retinal damage and that systemic administration of edaravone may slow the progression of retinal neuropathy induced by diabetes.

  20. Solar ultraviolet radiation-induced DNA damage in aquatic organisms: potential environmental impact

    International Nuclear Information System (INIS)

    Haeder, Donat-P.; Sinha, Rajeshwar P.

    2005-01-01

    Continuing depletion of stratospheric ozone and subsequent increases in deleterious ultraviolet (UV) radiation at the Earth's surface have fueled the interest in its ecological consequences for aquatic ecosystems. The DNA is certainly one of the key targets for UV-induced damage in a variety of aquatic organisms. UV radiation induces two of the most abundant mutagenic and cytotoxic DNA lesions, cyclobutane pyrimidine dimers (CPDs) and pyrimidine pyrimidone photoproducts (6-4PPs) and their Dewar valence isomers. However, aquatic organisms have developed a number of repair and tolerance mechanisms to counteract the damaging effects of UV on DNA. Photoreactivation with the help of the enzyme photolyase is one of the most important and frequently occurring repair mechanisms in a variety of organisms. Excision repair, which can be distinguished into base excision repair (BER) and nucleotide excision repair (NER), also play an important role in DNA repair in several organisms with the help of a number of glycosylases and polymerases, respectively. In addition, mechanisms such as mutagenic repair or dimer bypass, recombinational repair, cell-cycle checkpoints, apoptosis and certain alternative repair pathways are also operative in various organisms. This review deals with the UV-induced DNA damage and repair in a number of aquatic organisms as well as methods of detecting DNA damage

  1. Mild hyperthermia can induce adaptation to cytogenetic damage caused by subsequent X irradiation

    International Nuclear Information System (INIS)

    Cai, Lu.; Jiang, Jie.

    1995-01-01

    Many low-level environmental agents are able to induce an increased resistance to subsequent mutagenic effects induced by ionizing radiation. In this paper, an induced cytogenetic adaptation to radiation in human lymphocytes was studied with mild hyperthermia as the adaptive treatment and compared with that induced by low-dose radiation. We found that this adaptation could be induced not only in PHA-stimulated human lymphocytes (at 14, 38 and 42 h after addition of PHA), but also in unstimulated G 0 -phase cells (before addition of PHA) by mild hyperthermia (41 degrees C for 1 h) as well as 50 mGy X rays. When the two adaptive treatments were combined, no additive effects on the magnitude of the adaptation induced were observed, suggesting that low-dose radiation and hyperthermia may share one mechanism of induction of adaptation to cytogenetic damage. Some mechanisms which may be involved in the induction of adaptation to cytogenetic damage by low-dose radiation are discussed and compared with the effects of mild hyperthermia in inducing thermotolerance and radioresistance. 56 refs., 4 figs., 3 tabs

  2. Delayed repair of radiation induced clustered DNA damage: Friend or foe?

    Science.gov (United States)

    Eccles, Laura J.; O’Neill, Peter; Lomax, Martine E.

    2011-01-01

    A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a “friend”, leading to cell killing in tumour cells or as a “foe”, resulting in the formation of mutations and genetic instability in normal tissue. PMID:21130102

  3. Delayed repair of radiation induced clustered DNA damage: Friend or foe?

    International Nuclear Information System (INIS)

    Eccles, Laura J.; O'Neill, Peter; Lomax, Martine E.

    2011-01-01

    A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a 'friend', leading to cell killing in tumour cells or as a 'foe', resulting in the formation of mutations and genetic instability in normal tissue.

  4. Apple Flavonoids Suppress Carcinogen-Induced DNA Damage in Normal Human Bronchial Epithelial Cells

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    Vazhappilly Cijo George

    2017-01-01

    Full Text Available Scope. Human neoplastic transformation due to DNA damage poses an increasing global healthcare concern. Maintaining genomic integrity is crucial for avoiding tumor initiation and progression. The present study aimed to investigate the efficacy of an apple flavonoid fraction (AF4 against various carcinogen-induced toxicity in normal human bronchial epithelial cells and its mechanism of DNA damage response and repair processes. Methods and Results. AF4-pretreated cells were exposed to nicotine-derived nitrosamine ketones (NNK, NNK acetate (NNK-Ae, methotrexate (MTX, and cisplatin to validate cytotoxicity, total reactive oxygen species, intracellular antioxidants, DNA fragmentation, and DNA tail damage. Furthermore, phosphorylated histone (γ-H2AX and proteins involved in DNA damage (ATM/ATR, Chk1, Chk2, and p53 and repair (DNA-PKcs and Ku80 mechanisms were evaluated by immunofluorescence and western blotting, respectively. The results revealed that AF4-pretreated cells showed lower cytotoxicity, total ROS generation, and DNA fragmentation along with consequent inhibition of DNA tail moment. An increased level of γ-H2AX and DNA damage proteins was observed in carcinogen-treated cells and that was significantly (p≤0.05 inhibited in AF4-pretreated cells, in an ATR-dependent manner. AF4 pretreatment also facilitated the phosphorylation of DNA-PKcs and thus initiation of repair mechanisms. Conclusion. Apple flavonoids can protect in vitro oxidative DNA damage and facilitate repair mechanisms.

  5. Study of the laser-induced damage of reflective components in the sub-picosecond regime

    International Nuclear Information System (INIS)

    Sozet, Martin

    2016-01-01

    In this thesis, laser-induced damage phenomenon of reflective components is investigated in the sub-picosecond regime. These components, made of stacks of dielectric materials, are widely used in powerful laser facilities such as PETAL laser. PETAL laser has been built at the CEA-CESTA in France to deliver multi-kJ/500 fs pulses at 1053 nm and reach a power higher than 6 PW. For this kind of laser systems, reflective components are commonly used instead of optics operating in transmission to limit the accumulation of non-linear phase along the beam propagation due to the high intensities. Optical components irradiated by the highest power densities are the pulse compression gratings, transport mirrors and the focusing parabola, located at the end of the laser chain. Nowadays, laser-induced damage is the main factor that limits the overall performances of powerful laser systems. This manuscript presents three study axes to better understand and control damage phenomenon. The first one concerns the conception of reflective optics for the peta-watt applications. The design of new structures has been investigated to reach high diffraction efficiencies in the case of pulse compression gratings and a high reflectivity in the case of mirrors, while reducing the Electric-field enhancement which is one of the causes of the laser-induced damage. The second axis deals with the development of a precise damage metrology with new testing tools which brings new perspectives and a new viewpoint for the assessment of the laser resistance of optical components. Finally, the third axis concerns the study the damage growth after several irradiations in the sub-picosecond regime. The evolution of the damage area during growth sequences is observed and compared to numerical simulations. It enables to improve the understanding in the growth phenomenon. In the end, these studies will allow to develop predictive models of the laser-induced damage and new tools for the conception of

  6. Radiation degradation of polysaccharides and induced biological activity

    Energy Technology Data Exchange (ETDEWEB)

    Nagasawa, Naotsugu; Yoshii, Fumio; Makuuchi Keizo; Kume Tamikazu [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment; Mitomo, Hiroshi [Gunma Univ., Kiryu (Japan). Faculty of Engineering

    1999-09-01

    Relationship between irradiation effect of polysaccharides and induced biological activity for plants has been investigated. Sodium alginate was irradiated by gamma-rays from a Co-60 source in liquid state (aqueous solution) and in solid state (powder form). Measurement of molecular weight and analysis of UV spectra of irradiated sodium alginate have been carried out. The molecular weight was decreased by irradiation in both conditions. New absorbance peak derived from double bond or/and carbonyl group was appeared at close to 267 nm by irradiation in UV spectra. It was found that alginate having molecular weight about 10,000 is most suitable to used as growth promoter in plants. To obtain the molecular weight of 10,000 by irradiation, the necessary doses are 100 kGy in liquid state and 500 kGy in solid state, respectively. (author)

  7. Endomorphin 1 effectively protects cadmium chloride-induced hepatic damage in mice

    International Nuclear Information System (INIS)

    Gong Pin; Chen Fuxin; Ma Guofen; Feng Yun; Zhao Qianyu; Wang Rui

    2008-01-01

    The antioxidative capacity of endomorphin 1 (EM1), an endogenous μ-opioid receptor agonist, has been demonstrated by in vivo assays. The present study reports the effect of EM1 on hepatic damage induced by cadmium chloride (Cd(II)) in adult male mouse. Mouse were given intraperitoneally (i.p.) a single dose of Cd(II) (1 mg/kg body weight per day) and the animals were co-administrated with a dose of EM1 (50 μM/kg body weight per day) for 6 days. Since hepatic damage induced by Cd(II) is related to oxidative stress, lipid peroxidation (LPO), protein carbonyl (PCO), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were evaluated. The parameter indicating tissue damage such as liver histopathology was also determined. In addition, the concentrations of Cd and zinc (Zn) in the liver were analyzed. The intoxication of Cd(II) lead to the enhanced production of LPO and PCO, treatment with EM1 can effectively ameliorate the increase of LPO and PCO compared to the Cd(II) group. The increased activities of CAT, SOD and the elevated GSH induced by Cd(II) may relate to an adaptive-response to the oxidative damage, the effect of EM1 can restore the elevated antioxidant defense. Our results suggested that the structure features and the ability of chelating metal of EM1 may play a major role in the antioxidant effect of EM1 in vivo and opioid receptors may be involved in the protection of hepatic damage induced by Cd(II)

  8. Studies of multi-wavelength laser-induced damage on KDP crystals in the nanosecond regime

    International Nuclear Information System (INIS)

    Reyne, Stephane

    2011-01-01

    This thesis interests in the laser-induced damage mechanisms of KDP and DKDP crystals in the nanosecond regime. KDP is a non-linear material particularly used in the frequency converters of the Laser MegaJoule, which is under construction at the CEA-Cesta in France. For this facility, the KDP laser damage resistance is one of the keystones and is still under investigations to fix this problem. This is why this manuscript presents different studies which highlight the two main aspects of the nanosecond laser-induced damage of KDP frequency converters: the precursor defects and the mechanisms to initiate damage. First, we propose a study based on the analysis of several photos obtained by DIC microscopy of damage initiated by different wavelengths. A comparison with a code coupling the energy deposition and hydrodynamic is also done. Then, we interest in the influence of the defects geometry through a study based on the laser polarization effect on the laser damage resistance. By the comparison with a CEA home-made code, this study particularly underlines the possibility to define a new geometry for the precursor defects. This geometry proposed has the shape of an ellipsoid and is supposed to keep the crystal structure properties. Finally, we enlarge on the physical mechanisms initiating laser damage with pump-pump experiments. These tests consist in combining two radiations of different wavelengths which impacting the crystal simultaneously or are delayed one by the other. We then observe the influence of this wavelengths mixing on the KDP laser damage resistance. In particular, a coupling effect between the wavelengths of the mixture may occur as a function of the fluences combination. Finally, the goal of these specific studies is to accumulate new data in order to improve the understanding in the initiation of the laser damage in KDP and DKDP crystals in the nanosecond regime. In the end, these data will allow us to develop predictive models to simulate the laser

  9. Hydrocortisone Increases the Vinblastine-Induced Chromosomal Damages in L929 Cells Investigated by the Micronucleus Assay on Cytokinesis-Blocked Binucleated Cells

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    Tahere Ebrahimipour

    2017-03-01

    Full Text Available Background: Stress may cause damages to DNA or/and change the ability of the cells to overcome these damages. It may also cause irregularities in the cell cycle and induce abnormal cell divisions through glucocorticoid-dependent functions. The abnormal cell divisions, in turn, lead to chromosomal mal-segregation and aneuploidy. In this study, the effects of the stress hormone, hydrocortisone (HYD, were investigated on the induced chromosomal abnormalities by vinblastine (VIN during cell cycle in L929 cells. Methods: This work was performed in winter 2013 at Department of Biology, University of Ferdowsi, Mashhad, Iran. Cultured cells were divided into different groups including control, VIN-treated, HYD treated and VIN+HYD co-treated cells. The induced chromosomal damages were investigated by micronucleus assay in cytokinesis-blocked binucleated cells. Results: Although HYD by itself did not increase the micronuclei (Mn frequency, co-treatment of cells with VIN and HYD led to significant increase (P<0.05 in the frequency of Mn in comparison to control and VIN treated groups. Conclusion: Cells treated with stress hormone are more sensitive to damages induced by VIN. Therefore, stress may not directly result in genetic instability, it can increase the harmful effects associated with other genotoxic agents.

  10. The Extract of D. dasycarpus Ameliorates Oxazolone-Induced Skin Damage in Mice by Anti-Inflammatory and Antioxidant Mechanisms

    Directory of Open Access Journals (Sweden)

    Tsong-Min Chang

    2018-06-01

    Full Text Available Dictamni dasycarpus is a type of Chinese medicine made from the root bark of D. dasycarpus. It has been reported to show a wide spectrum of biological and pharmacological effects, for example, it has been used widely for the treatment of rheumatism, nettle rash, itching, jaundice, chronic hepatitis and skin diseases. In the current study, D. dasycarpus extract was investigated for its antioxidant and anti-inflammatory effects, as well as its capability to alleviate oxazolone-induced skin damage in mice. The possible anti-inflammatory mechanism of D. dasycarpus extract against oxidative challenge was elucidated by measuring the levels of reactive oxygen species (ROS production, interleukin-6, Tumor necrosis factor-α, NLRP3 (NACHT, LRR and PYD domains-containing protein 3 (NALP3 inflammasome and interleukin-1β in HaCaT cells. D. dasycarpus extract did not affect cell viability in basal conditions. The extract significantly reduced oxazolone-induced epidermal swelling compared to untreated animal in the hairless albino mice (ICR mice model. At the molecular level, Western blot assays indicated that the D. dasycarpus extract attenuated oxazolone-induced activation of apoptosis-associated speck-like protein containing CARD (ASC, procaspase-1, NF-κB and mitogen-activated protein kinase (MAPKs such as c-Jun N-terminal protein kinase (JNK and p38. This study demonstrates that D. dasycarpus extract could protect skin cells against oxidative and inflammatory insult by modulating the intracellular levels of ROS, TNF-α, interleukin-1, interleukin-6, NLR family pyrin domain containing 3 (NLRP3 inflammasome generation, antioxidant enzyme activity and cell signaling pathways. D. dasycarpus extract also attenuated the expression of NF-κB in HaCaT keratinocytes and thereby effectively downregulated inflammatory responses in the skin. Furthermore, D. dasycarpus extract alleviated oxazolone-induced damage in mice. Our results suggest the potential application

  11. The Extract of D. dasycarpus Ameliorates Oxazolone-Induced Skin Damage in Mice by Anti-Inflammatory and Antioxidant Mechanisms.

    Science.gov (United States)

    Chang, Tsong-Min; Yang, Ting-Ya; Niu, Yu-Lin; Huang, Huey-Chun

    2018-06-15

    Dictamni dasycarpus is a type of Chinese medicine made from the root bark of D. dasycarpus . It has been reported to show a wide spectrum of biological and pharmacological effects, for example, it has been used widely for the treatment of rheumatism, nettle rash, itching, jaundice, chronic hepatitis and skin diseases. In the current study, D. dasycarpus extract was investigated for its antioxidant and anti-inflammatory effects, as well as its capability to alleviate oxazolone-induced skin damage in mice. The possible anti-inflammatory mechanism of D. dasycarpus extract against oxidative challenge was elucidated by measuring the levels of reactive oxygen species (ROS) production, interleukin-6, Tumor necrosis factor-α, NLRP3 (NACHT, LRR and PYD domains-containing protein 3 (NALP3)) inflammasome and interleukin-1β in HaCaT cells. D. dasycarpus extract did not affect cell viability in basal conditions. The extract significantly reduced oxazolone-induced epidermal swelling compared to untreated animal in the hairless albino mice (ICR mice) model. At the molecular level, Western blot assays indicated that the D. dasycarpus extract attenuated oxazolone-induced activation of apoptosis-associated speck-like protein containing CARD (ASC), procaspase-1, NF-κB and mitogen-activated protein kinase (MAPKs) such as c-Jun N-terminal protein kinase (JNK) and p38. This study demonstrates that D. dasycarpus extract could protect skin cells against oxidative and inflammatory insult by modulating the intracellular levels of ROS, TNF-α, interleukin-1, interleukin-6, NLR family pyrin domain containing 3 (NLRP3) inflammasome generation, antioxidant enzyme activity and cell signaling pathways. D. dasycarpus extract also attenuated the expression of NF-κB in HaCaT keratinocytes and thereby effectively downregulated inflammatory responses in the skin. Furthermore, D. dasycarpus extract alleviated oxazolone-induced damage in mice. Our results suggest the potential application of D

  12. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

    Energy Technology Data Exchange (ETDEWEB)

    Tang, J.; Jiang, Y. [Southern Medical University, Nanfang Hospital, Department of Anesthesia, Guangzhou, China, Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou (China); Tang, Y.; Chen, B. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China); Sun, X. [Laboratory of Traditional Chinese Medicine Syndrome, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou (China); Su, L.; Liu, Z. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China)

    2013-06-25

    Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries.

  13. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

    International Nuclear Information System (INIS)

    Tang, J.; Jiang, Y.; Tang, Y.; Chen, B.; Sun, X.; Su, L.; Liu, Z.

    2013-01-01

    Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries

  14. Nrf2 deficiency potentiates methamphetamine-induced dopaminergic axonal damage and gliosis in the striatum.

    Science.gov (United States)

    Granado, Noelia; Lastres-Becker, Isabel; Ares-Santos, Sara; Oliva, Idaira; Martin, Eduardo; Cuadrado, Antonio; Moratalla, Rosario

    2011-12-01

    Oxidative stress that correlates with damage to nigrostriatal dopaminergic neurons and reactive gliosis in the basal ganglia is a hallmark of methamphetamine (METH) toxicity. In this study, we analyzed the protective role of the transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2), a master regulator of redox homeostasis, in METH-induced neurotoxicity. We found that Nrf2 deficiency exacerbated METH-induced damage to dopamine neurons, shown by an increase in loss of tyrosine hydroxylase (TH)- and dopamine transporter (DAT)-containing fibers in striatum. Consistent with these effects, Nrf2 deficiency potentiated glial activation, indicated by increased striatal expression of markers for microglia (Mac-1 and Iba-1) and astroglia (GFAP) one day after METH administration. At the same time, Nrf2 inactivation dramatically potentiated the increase in TNFα mRNA and IL-15 protein expression in GFAP+ cells in the striatum. In sharp contrast to the potentiation of striatal damage, Nrf2 deficiency did not affect METH-induced dopaminergic neuron death or expression of glial markers or proinflammatory molecules in the substantia nigra. This study uncovers a new role for Nrf2 in protection against METH-induced inflammatory and oxidative stress and striatal degeneration. Copyright © 2011 Wiley‐Liss, Inc.

  15. Evaluation of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage

    Directory of Open Access Journals (Sweden)

    R Sunil Kumar

    2017-01-01

    Full Text Available Objective: The present study aims to evaluate antioxidants and protective role of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage. Materials and Methods: The total and profiles of flavonoids were identified and quantified through reversed-phase high-performance liquid chromatography. In vitro antioxidant activity was determined using standard antioxidant assays. The protective role of C. tora extracts against oxidative stress-induced DNA and cell membrane damage was examined by electrophoretic and scanning electron microscopic studies, respectively. Results: The total flavonoid content of CtEA was 106.8 ± 2.8 mg/g d.w.QE, CtME was 72.4 ± 1.12 mg/g d.w.QE, and CtWE was 30.4 ± 0.8 mg/g d.w.QE. The concentration of flavonoids present in CtEA in decreasing order: quercetin >kaempferol >epicatechin; in CtME: quercetin >rutin >kaempferol; whereas, in CtWE: quercetin >rutin >kaempferol. The CtEA inhibited free radical-induced red blood cell hemolysis and cell membrane morphology better than CtME as confirmed by a scanning electron micrograph. CtEA also showed better protection than CtME and CtWE against free radical-induced DNA damage as confirmed by electrophoresis. Conclusion: C. tora contains flavonoids and inhibits oxidative stress and can be used for many health benefits and pharmacotherapy.

  16. Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality

    Directory of Open Access Journals (Sweden)

    Ruei-Tang Cheng

    2010-01-01

    Full Text Available When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4∘C±0.3∘C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15 and reduced the hypothermia (core temperature, 37.3∘C. The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediatedαUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality.

  17. Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

    Directory of Open Access Journals (Sweden)

    Tobias Eggert

    Full Text Available Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL, while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

  18. Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

    Science.gov (United States)

    Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J; Korangy, Firouzeh; Greten, Tim F

    2014-01-01

    Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

  19. Impact of TLR4 on behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage.

    Science.gov (United States)

    Pascual, María; Baliño, Pablo; Alfonso-Loeches, Silvia; Aragón, Carlos M G; Guerri, Consuelo

    2011-06-01

    Toll-like receptors (TLRs) play an important role in the innate immune response, and emerging evidence indicates their role in brain injury and neurodegeneration. Our recent results have demonstrated that ethanol is capable of activating glial TLR4 receptors and that the elimination of these receptors in mice protects against ethanol-induced glial activation, induction of inflammatory mediators and apoptosis. This study was designed to assess whether ethanol-induced inflammatory damage causes behavioral and cognitive consequences, and if behavioral alterations are dependent of TLR4 functions. Here we show in mice drinking alcohol for 5months, followed by a 15-day withdrawal period, that activation of the astroglial and microglial cells in frontal cortex and striatum is maintained and that these events are associated with cognitive and anxiety-related behavioral impairments in wild-type (WT) mice, as demonstrated by testing the animals with object memory recognition, conditioned taste aversion and dark and light box anxiety tasks. Mice lacking TLR4 receptors are protected against ethanol-induced inflammatory damage, and behavioral associated effects. We further assess the possibility of the epigenetic modifications participating in short- or long-term behavioral effects associated with neuroinflammatory damage. We show that chronic alcohol treatment decreases H4 histone acetylation and histone acetyltransferases activity in frontal cortex, striatum and hippocampus of WT mice. Alterations in chromatin structure were not observed in TLR4(-/-) mice. These results provide the first evidence of the role that TLR4 functions play in the behavioral consequences of alcohol-induced inflammatory damage and suggest that the epigenetic modifications mediated by TLR4 could contribute to short- or long-term alcohol-induced behavioral or cognitive dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Protection against UVA-induced photooxidative damage in mammalian cell lines expressing increased levels of metallothionein

    International Nuclear Information System (INIS)

    Dudek, E.J.; Roth, R.M.

    1990-01-01

    Metallothionein (MT) is an endogenous low molecular weight protein that is inducible in a variety of eukaryotic cells and has the ability to selectivity bind heavy metal ions such as zinc and the cadmium. Although the exact physiological role of MT is still not understood, there is strong evidence that MT is involved in providing cellular resistance against the damaging effects of heavy metals and in the regulation of intracellular zinc and copper. Recently, it has been demonstrated that MT can scavenge radiation-induced reactive oxygen intermediates in vitro, specifically hydroxyl and superoxide radicals, and because of these observations it has been suggested that MT may provide protection against radiation-induced oxidative stress in vivo. Cell lines expressing increased levels of MT have demonstrated resistance to ionizing radiation, to ultraviolet radiation, and also to various DNA damaging agents including melphalan and cis-diaminedichloroplatinum. It is therefore important to gain some insight into the relationship between cellular MT content and cellular resistance to radiation and other DNA damaging agents. In this study we investigated the role of MT in providing protection against monochromatic 365-nm UVA radiation, which is known to generate intracellular reactive oxygen species that are involved in both DNA damage and cell killing. For this purpose, we used zinc acetate, a potent inducer of MT, to elevate MT levels in V79 Chinese hamster fibroblasts prior to UVA exposure and determined cell survival for uninduced and induced cultures. In order to eliminate any zinc effects other than MT induction, we also isolated and characterized cadmium chloride-resistant clones of V79 cells that have increased steady-state levels of both MT mRNA and protein, and we examined their survival characteristics against 365-nm radiation in the absence of zinc acetate. 14 refs., 3 figs

  1. NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage.

    Science.gov (United States)

    Tang, Li-li; Wu, Yuan-bo; Fang, Chuan-qin; Qu, Ping; Gao, Zong-liang

    2016-01-15

    Microglia microvesicles (MVs) has shown to have significant biological functions under normal conditions. A diversity of miRNAs is involved in neuronal development, survival, function, and plasticity, but the exact functional role of NDRG2 and secreted miR-375 in MVs in neuron damage is poorly understood. We investigated the effect of NDRG2 and secreted miR-375 in MVs shed from M1 microglia on neuron damage. Expression of Nos2, Arg-1, miR-375, syntaxin-1A, NDRG2 and Pdk 1 were evaluated using RT-PCR or western blotting. Cell viability of N2A neuron was quantified by a MTT assay. Microglia can be polarized into different functional phenotypes. Expression of NDRG2 and Nos2 were significantly increased by LPS treatment on N9 cells, whereas treatment with IL-4 dramatically suppressed the expression of NDRG2 and remarkably elevated expression of Arg-1. Besides, MVs shed from LPS-treated N9 microglia significantly inhibited cell viability of N2A neurons and expression of syntaxin-1A, and NDRG2 interference reversed the up-regulated miR-375 in LPS-treated N9 microglia and MVs shed from LPS-treated N9 cells. Furthermore, NDRG2 could modulate miR-375 expression in N9 microglia and MVs. And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons. Finally, miR-375 inhibitor could reverse suppression effect of NDRG2 overexpression on cell viability of N2A neurons and expression of syntaxin-1A. Our results demonstrated that NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. The suppression of NDRG2 and secreted miR-375 in MVs shed from M1 microglia may be potential targets for alleviation of neuron damage. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents.

    Science.gov (United States)

    Paiva, C; Godbersen, J C; Berger, A; Brown, J R; Danilov, A V

    2015-07-09

    Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-κB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents.

  3. Chromosomal damages and mutagenesis in mammalian and human cells induced by ionizing radiations with different LET

    International Nuclear Information System (INIS)

    Govorun, R.D.

    1997-01-01

    On the basis of literature and proper data the inference was made about essential role of structural chromosomal (and gene) damages in spontaneous and radiation-induced mutagenesis of mammalian and human cells on HPRT-loci. The evidences of increasing role of these damages in the mutagenesis after the influence of ionizing radiations with high LET are adduced. The consequences of HPRT-gene damages have been examined hypothetically. The geterogeneity of mutant subclones on their cytogenetical properties were revealed experimentally. The data reflect a phenomenon of the reproductive chromosomal instability in many generations of mutant cell. The mutagenesis of mammalian cells is also accompanied by the impairment of chromosome integrity with high probability as a stage of appropriate genome reorganization because of changed vital conditions

  4. DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations

    Directory of Open Access Journals (Sweden)

    Mankgopo Magdeline Kgatle

    2017-01-01

    Full Text Available Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV, hepatitis B virus (HBV, and Epstein-Barr virus (EBV. Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.

  5. Laser-induced damage of materials in bulk, thin-film, and liquid forms

    International Nuclear Information System (INIS)

    Natoli, Jean-Yves; Gallais, Laurent; Akhouayri, Hassan; Amra, Claude

    2002-01-01

    Accurate threshold curves of laser-induced damage (7-ns single shot at 1.064 μm) are measured in bulk and at the surfaces of optical components such as substrates, thin films, multilayers, and liquids. The shapes and the slopes of the curves are related to the spot size and to the densities of the nanodefects that are responsible for damage. First, these densities are reported for bulk substrates. In surfaces and films the recorded extrinsic and intrinsic threshold curves permit the discrimination of the effects of microdefects and nanodefects. In all cases the density of nanocenters is extracted by means of a phenomenological approach. Then we test liquids and mixtures of liquids with controlled defect densities. The results emphasize the agreement between measurement and prediction and demonstrate the validity of the presence of different kinds of nanocenter as the precursors of laser damage

  6. Effects of focused ion beam induced damage on the plasticity of micropillars

    International Nuclear Information System (INIS)

    El-Awady, Jaafar A.; Woodward, Christopher; Dimiduk, Dennis M.; Ghoniem, Nasr M.

    2009-01-01

    The hardening effects of focused ion beam (FIB) induced damage produced during the fabrication of micropillars are examined by introducing a surface layer of nanosized obstacles into a dislocation dynamics simulation. The influence of the depth and strength of the obstacles as a function of pillar diameter is assessed parametrically. We show that for a selected set of sample sizes between 0.5 and 1.0 μm, the flow strength can increase by 10-20 %, for an obstacle strength of 750 MPa, and damage depth of 100 nm. On the other hand, for sizes larger and smaller than this range, the effect of damage is negligible. Results show that the obstacles formed during the FIB milling may be expected to alter the microstructure of micropillars, however, they have a negligible effect on the observed size-strength scaling laws.

  7. Experimental setup and first measurement of DNA damage induced along and around an antiproton beam

    DEFF Research Database (Denmark)

    Kavanagh, J. N.; Currell, F. J.; Timson, D. J.

    2010-01-01

    a further enhancement due to their annihilation at the end of the path. The work presented here aimed to establish and validate an experimental procedure for the quantification of plasmid and genomic DNA damage resulting from antiproton exposure. Immunocytochemistry was used to assess DNA damage in directly......Radiotherapy employs ionizing radiation to induce lethal DNA lesions in cancer cells while minimizing damage to healthy tissues. Due to their pattern of energy deposition, better therapeutic outcomes can, in theory, be achieved with ions compared to photons. Antiprotons have been proposed to offer...... and indirectly exposed human fibroblasts irradiated in both plateau and Bragg peak regions of a 126 MeV antiproton beam at CERN. Cells were stained post irradiation with an anti-γ-H2AX antibody. Quantification of the γ-H2AX foci-dose relationship is consistent with a linear increase in the Bragg peak region...

  8. Growth behavior of laser-induced damage on fused silica optics under UV, ns laser irradiation.

    Science.gov (United States)

    Negres, Raluca A; Norton, Mary A; Cross, David A; Carr, Christopher W

    2010-09-13

    The growth behavior of laser-induced damage sites is affected by a large number of laser parameters as well as site morphology. Here we investigate the effects of pulse duration on the growth rate of damage sites located on the exit surface of fused silica optics. Results demonstrate a significant dependence of the growth parameters on laser pulse duration at 351 nm from 1 ns to 15 ns, including the observation of a dominant exponential versus linear, multiple-shot growth behavior for long and short pulses, respectively. These salient behaviors are tied to the damage morphology and suggest a shift in the fundamental growth mechanisms for pulses in the 1-5 ns range.

  9. Gravity-induced rock mass damage related to large en masse rockslides: Evidence from Vajont

    Science.gov (United States)

    Paronuzzi, Paolo; Bolla, Alberto

    2015-04-01

    The Vajont landslide is a well-known, reservoir-induced slope failure that occurred on 9 October 1963 and was characterized by an 'en masse' sliding motion that triggered various large waves, determining catastrophic consequences for the nearby territory and adjacent villages. During the Vajont dam construction, and especially after the disaster, some researchers identified widespread field evidence of heavy rock mass damage involving the presumed prehistoric rockslide and/or the 1963 failed mass. This paper describes evidence of heavy gravitational damage, including (i) folding, (ii) fracturing, (iii) faulting, and (iv) intact rock disintegration. The gravity-induced rock mass damage (GRMD) characterizes the remnants of the basal shear zone, still resting on the large detachment surface, and the 1963 failed rock mass. The comprehensive geological study of the 1963 Vajont landslide, based on the recently performed geomechanical survey (2006-present) and on the critical analysis of the past photographic documentation (1959-1964), allows us to recognize that most GRMD evidence is related to the prehistoric multistage Mt. Toc rockslide. The 1963 catastrophic en masse remobilization induced an increase to the prehistoric damage, reworking preexisting structures and creating additional gravity-driven features (folds, fractures, faults, and rock fragmentation). The gravity-induced damage was formed during the slope instability phases that preceded the collapse (static or quasi-static GRMD) and also as a consequence of the sliding motion and of the devastating impact between the failed blocks (dynamic GRMD). Gravitational damage originated various types of small drag folds such as flexures, concentric folds, chevron, and kink-box folds, all having a radius of 1-5 m. Large buckle folds (radius of 10-50 m) are related to the dynamic damage and were formed during the en masse motion as a consequence of deceleration and impact processes that involved the sliding mass. Prior

  10. Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Slininger Patricia J

    2010-01-01

    Full Text Available Abstract Background Biofuels offer a viable alternative to petroleum-based fuel. However, current methods are not sufficient and the technology required in order to use lignocellulosic biomass as a fermentation substrate faces several challenges. One challenge is the need for a robust fermentative microorganism that can tolerate the inhibitors present during lignocellulosic fermentation. These inhibitors include the furan aldehyde, furfural, which is released as a byproduct of pentose dehydration during the weak acid pretreatment of lignocellulose. In order to survive in the presence of furfural, yeast cells need not only to reduce furfural to the less toxic furan methanol, but also to protect themselves and repair any damage caused by the furfural. Since furfural tolerance in yeast requires a functional pentose phosphate pathway (PPP, and the PPP is associated with reactive oxygen species (ROS tolerance, we decided to investigate whether or not furfural induces ROS and its related cellular damage in yeast. Results We demonstrated that furfural induces the accumulation of ROS in Saccharomyces cerevisiae. In addition, furfural was shown to cause cellular damage that is consistent with ROS accumulation in cells which includes damage to mitochondria and vacuole membranes, the actin cytoskeleton and nuclear chromatin. The furfural-induced damage is less severe when yeast are grown in a furfural concentration (25 mM that allows for eventual growth after an extended lag compared to a concentration of furfural (50 mM that prevents growth. Conclusion These data suggest that when yeast cells encounter the inhibitor furfural, they not only need to reduce furfural into furan methanol but also to protect themselves from the cellular effects of furfural and repair any damage caused. The reduced cellular damage seen at 25 mM furfural compared to 50 mM furfural may be linked to the observation that at 25 mM furfural yeast were able to exit the furfural-induced

  11. Spatiotemporal kinetics of γ-H2AX protein on charged particles induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Niu, H., E-mail: hniu@mx.nthu.edu.tw [Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu, Taiwan (China); Chang, H.C. [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan (China); Cho, I.C. [Institute for Radiological Research, Chang Gung University and Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Chen, C.H. [Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu, Taiwan (China); Liu, C.S. [Cancer Center of Taipei Veterans General Hospital, Taipei, Taiwan (China); Chou, W.T. [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan (China)

    2014-08-15

    Highlights: • Charged particles can induce more complex DNA damages, and these complex damages have higher ability to cause the cell death or cell carcinogenesis. • In this study, we used γ-H2AX protein to investigate the spatiotemporal kinetics of DNA double strand breaks in particle irradiated HeLa cells. • The HeLa cells were irradiated by 400 keV alpha-particles in four different dosages. • The result shows that a good linear relationship can be observed between foci number and radiation dose. • The data shows that the dissolution rate of γ-H2AX foci agree with the two components DNA repairing model, and it was decreasing as the radiation dose increased. • These results suggest that charged particles can induce more complex DNA damages and causing the retardation of DNA repair. - Abstract: In several researches, it has been demonstrated that charged particles can induce more complex DNA damages. These complex damages have higher ability to cause the cell death or cell carcinogenesis. For this reason, clarifying the DNA repair mechanism after charged particle irradiation plays an important role in the development of charged particle therapy and space exploration. Unfortunately, the detail spatiotemporal kinetic of DNA damage repair is still unclear. In this study, we used γ-H2AX protein to investigate the spatiotemporal kinetics of DNA double strand breaks in alpha-particle irradiated HeLa cells. The result shows that the intensity of γ-H2AX foci increased gradually, and reached to its maximum at 30 min after irradiation. A good linear relationship can be observed between foci intensity and radiation dose. After 30 min, the γ-H2AX foci intensity was decreased with time passed, but remained a large portion (∼50%) at 48 h passed. The data show that the dissolution rate of γ-H2AX foci agreed with two components DNA repairing model. These results suggest that charged particles can induce more complex DNA damages and causing the retardation of DNA

  12. Acute hydrodynamic damage induced by SPLITT fractionation and centrifugation in red blood cells.

    Science.gov (United States)

    Urbina, Adriana; Godoy-Silva, Ruben; Hoyos, Mauricio; Camacho, Marcela

    2016-05-01

    Though blood bank processing traditionally employs centrifugation, new separation techniques may be appealing for large scale processes. Split-flow fractionation (SPLITT) is a family of techniques that separates in absence of labelling and uses very low flow rates and force fields, and is therefore expected to minimize cell damage. However, the hydrodynamic stress and possible consequent damaging effects of SPLITT fractionation have not been yet examined. The aim of this study was to investigate the hydrodynamic damage of SPLITT fractionation to human red blood cells, and to compare these effects with those induced by centrifugation. Peripheral whole blood samples were collected from healthy volunteers. Samples were diluted in a buffered saline solution, and were exposed to SPLITT fractionation (flow rates 1-10 ml/min) or centrifugation (100-1500 g) for 10 min. Cell viability, shape, diameter, mean corpuscular hemoglobin, and membrane potential were measured. Under the operating conditions employed, both SPLITT and centrifugation maintained cell viability above 98%, but resulted in significant sublethal damage, including echinocyte formation, decreased cell diameter, decreased mean corpuscular hemoglobin, and membrane hyperpolarization which was inhibited by EGTA. Wall shear stress and maximum energy dissipation rate showed significant correlation with lethal and sublethal damage. Our data do not support the assumption that SPLITT fractionation induces very low shear stress and is innocuous to cell function. Some changes in SPLITT channel design are suggested to minimize cell damage. Measurement of membrane potential and cell diameter could provide a new, reliable and convenient basis for evaluation of hydrodynamic effects on different cell models, allowing identification of optimal operating conditions on different scales. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Topical application of ST266 reduces UV-induced skin damage

    Directory of Open Access Journals (Sweden)

    Guan L

    2017-11-01

    Full Text Available Linna Guan,1 Amanda Suggs,1 Emily Galan,1 Minh Lam,1 Elma D Baron1,2 1Department of Dermatology, Case Western Reserve University, 2Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA Abstract: Ultraviolet radiation (UVR has a significant impact on human skin and is the major environmental factor for skin cancer formation. It is also believed that 80% of the signs of skin aging are attributed to UVR. UVR induces inflammatory changes in the skin via the increase in oxidative stress, DNA damage vascular permeability, and fluctuation in a myriad of cytokines. Acutely, UVR causes skin inflammation and DNA damage, which manifest as sunburn (erythema. ST266 is the secretome of proprietary amnion-derived cells that have been shown to reduce inflammation and accelerate healing of various wounds by promoting migration of keratinocytes and fibroblasts in preclinical animal studies. We hypothesized that ST266 has anti-inflammatory effects that can be used to reduce ultraviolet (UV erythema and markers of inflammation. In this study, we examined the in vivo effects of ST266 on post UV-irradiated skin by measuring erythema, level of cyclobutane pyrimidine dimer (CPD, and expression level of xeroderma pigmentosum, complementation group A (XPA. We demonstrated that ST266 has the potential to reduce the acute effects of UV-induced skin damage when applied immediately after the initial exposure. In addition, ST266 is shown to reduce erythema, increase XPA DNA repair protein, and decrease damaged DNA. Keywords: ST266, photoaging, erythema, CPD, XPA, UV-induced DNA damage

  14. Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

    Science.gov (United States)

    Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

    2015-12-01

    Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  15. Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish.

    Science.gov (United States)

    Lisse, Thomas S; Middleton, Leah J; Pellegrini, Adriana D; Martin, Paige B; Spaulding, Emily L; Lopes, Olivia; Brochu, Elizabeth A; Carter, Erin V; Waldron, Ashley; Rieger, Sandra

    2016-04-12

    Paclitaxel is a microtubule-stabilizing chemotherapeutic agent that is widely used in cancer treatment and in a number of curative and palliative regimens. Despite its beneficial effects on cancer, paclitaxel also damages healthy tissues, most prominently the peripheral sensory nervous system. The mechanisms leading to paclitaxel-induced peripheral neuropathy remain elusive, and therapies that prevent or alleviate this condition are not available. We established a zebrafish in vivo model to study the underlying mechanisms and to identify pharmacological agents that may be developed into therapeutics. Both adult and larval zebrafish displayed signs of paclitaxel neurotoxicity, including sensory axon degeneration and the loss of touch response in the distal caudal fin. Intriguingly, studies in zebrafish larvae showed that paclitaxel rapidly promotes epithelial damage and decreased mechanical stress resistance of the skin before induction of axon degeneration. Moreover, injured paclitaxel-treated zebrafish skin and scratch-wounded human keratinocytes (HEK001) display reduced healing capacity. Epithelial damage correlated with rapid accumulation of fluorescein-conjugated paclitaxel in epidermal basal keratinocytes, but not axons, and up-regulation of matrix-metalloproteinase 13 (MMP-13, collagenase 3) in the skin. Pharmacological inhibition of MMP-13, in contrast, largely rescued paclitaxel-induced epithelial damage and neurotoxicity, whereas MMP-13 overexpression in zebrafish embryos rendered the skin vulnerable to injury under mechanical stress conditions. Thus, our studies provide evidence that the epidermis plays a critical role in this condition, and we provide a previously unidentified candidate for therapeutic interventions.

  16. Plastic strain induced damage evolution and martensitic transformation in ductile materials at cryogenic temperatures

    International Nuclear Information System (INIS)

    Garion, C.; Skoczen, B.T.

    2002-01-01

    The Fe-Cr-Ni stainless steels are well known for their ductile behavior at cryogenic temperatures. This implies development and evolution of plastic strain fields in the stainless steel components subjected to thermo-mechanical loads at low temperatures. The evolution of plastic strain fields is usually associated with two phenomena: ductile damage and strain induced martensitic transformation. Ductile damage is described by the kinetic law of damage evolution. Here, the assumption of isotropic distribution of damage (microcracks and microvoids) in the Representative Volume Element (RVE) is made. Formation of the plastic strain induced martensite (irreversible process) leads to the presence of quasi-rigid inclusions of martensite in the austenitic matrix. The amount of martensite platelets in the RVE depends on the intensity of the plastic strain fields and on the temperature. The evolution of the volume fraction of martensite is governed by a kinetic law based on the accumulated plastic strain. Both of these irreversible phenomena, associated with the dissipation of plastic power, are included into the constitutive model of stainless steels at cryogenic temperatures. The model is tested on the thin-walled corrugated shells (known as bellows expansion joints) used in the interconnections of the Large Hadron Collider, the new proton storage ring being constructed at present at CERN

  17. Histone peptide AKRHRK enhances H2O2-induced DNA damage and alters its site specificity

    International Nuclear Information System (INIS)

    Midorikawa, Kaoru; Murata, Mariko; Kawanishi, Shosuke

    2005-01-01

    Histone proteins are involved in compaction of DNA and the protection of cells from oxygen toxicity. However, several studies have demonstrated that the metal-binding histone reacts with H 2 O 2 , leading to oxidative damage to a nucleobase. We investigated whether histone can accelerate oxidative DNA damage, using a minimal model for the N-terminal tail of histone H4, CH 3 CO-AKRHRK-CONH 2 , which has a metal-binding site. This histone peptide enhanced DNA damage induced by H 2 O 2 and Cu(II), especially at cytosine residues, and induced additional DNA cleavage at the 5'-guanine of GGG sequences. The peptide also enhanced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine and ESR spin-trapping signal from H 2 O 2 and Cu(II). Cyclic redox reactions involving histone-bound Cu(II) and H 2 O 2 , may give rise to multiple production of radicals leading to multiple hits in DNA. It is noteworthy that the histone H4 peptide with specific sequence AKRHRK can cause DNA damage rather than protection under metal-overloaded condition

  18. Benefits of dietary phytochemical supplementation on eccentric exercise-induced muscle damage: Is including antioxidants enough?

    Science.gov (United States)

    Pereira Panza, Vilma Simões; Diefenthaeler, Fernando; da Silva, Edson Luiz

    2015-09-01

    The purpose of this review was to critically discuss studies that investigated the effects of supplementation with dietary antioxidant phytochemicals on recovery from eccentric exercise-induced muscle damage. The performance of physical activities that involve unaccustomed eccentric muscle actions-such as lowering a weight or downhill walking-can result in muscle damage, oxidative stress, and inflammation. These events may be accompanied by muscle weakness and delayed-onset muscle soreness. According to the current evidences, supplementation with dietary antioxidant phytochemicals appears to have the potential to attenuate symptoms associated with eccentric exercise-induced muscle damage. However, there are inconsistencies regarding the relationship between muscle damage and blood markers of oxidative stress and inflammation. Furthermore, the effectiveness of strategies appear to depend on a number of aspects inherent to phytochemical compounds as well as its food matrix. Methodological issues also may interfere with the proper interpretation of supplementation effects. Thus, the study may contribute to updating professionals involved in sport nutrition as well as highlighting the interest of scientists in new perspectives that can widen dietary strategies applied to training. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Temporal scaling law and intrinsic characteristic of laser induced damage on the dielectric coating

    Science.gov (United States)

    Zhou, Li; Jiang, Youen; Wang, Chao; Wei, Hui; Zhang, Peng; Fan, Wei; Li, Xuechun

    2018-01-01

    High power laser is essential for optical manipulation and fabrication. When the laser travels through optics and to the target finally, irreversible damage on the dielectric coating is always accompanied without knowing the law and principle of laser induced damage. Here, an experimental study of laser induced damage threshold (LIDT) Fth of the dielectric coating under different pulse duration t is implemented. We observe that the temporal scaling law of square pulse for high-reflectivity (HR) coating and anti-reflectivity (AR) coating are Fth = 9.53t0.47 and Fth = 6.43t0.28 at 1064 nm, respectively. Moreover, the intrinsic LIDT of HR coating is 62.7 J/cm2 where the coating is just 100% damaged by gradually increasing the fluence densities of a 5ns-duration pulse, which is much higher than the actual LIDT of 18.6 J/cm2. Thus, a more robust and reliable high power laser system will be a reality, even working at very high fluence, if measures are taken to improve the actual LIDT to a considerable level near the intrinsic value.

  20. Beam-induced damage to the Tevatron components and what has been done about it

    International Nuclear Information System (INIS)

    Mokhov, N.V.; Czarapata, P.C.; Drozhdin, A.I.; Still, D.A.; Samulyak, R.V.

    2007-01-01

    A beam-induced damage to the Tevatron collimators happened in December 2003 was induced by a failure in the CDF Roman Pot detector positioning during the collider run. Possible scenarios of this failure resulted in an excessive halo generation and superconducting magnet quench have been studied via realistic simulations using the STRUCT and MARS14 codes. It is shown that the interaction of a misbehaved proton beam with the collimators result in a rapid local heating and a possible damage. A detailed consideration is given to the ablation process for the collimator material taking place in high vacuum. It is shown that ablation of tungsten (primary collimator) and stainless steel (secondary collimator) jaws results in creation of a groove in the jaw surface as was observed after the December's accident. The actions undertaken to avoid such an accident in future are described in detail. (author)

  1. Beam-induced damage to the Tevatron components and what has been done about it

    International Nuclear Information System (INIS)

    Mokhov, N.V.; Czarapata, P.C.; Drozhdin, A.I.; Still, D.A.; Samulyak, R.V.

    2006-01-01

    A beam-induced damage to the Tevatron collimators happened in December 2003 was induced by a failure in the CDF Roman Pot detector positioning during the collider run. Possible scenarios of this failure resulted in an excessive halo generation and superconducting magnet quench have been studied via realistic simulations using the STRUCT and MARS14 codes. It is shown that the interaction of a misbehaved proton beam with the collimators result in a rapid local heating and a possible damage. A detailed consideration is given to the ablation process for the collimator material taking place in high vacuum. It is shown that ablation of tungsten (primary collimator) and stainless steel (secondary collimator) jaws results in creation of a groove in the jaw surface as was observed after the December's accident. The actions undertaken to avoid such an accident in future are described in detail

  2. Analytical studies into radiation-induced starch damage in black and white peppers

    International Nuclear Information System (INIS)

    Farkas, J.; Sharif, M.M.; Barabassy, S.

    1990-01-01

    In order to develop detection methods of radiation treatment, ground black pepper samples equilibrated to water activity levels of 0.25, 0.50 and 0.75 a w , respectively, were irradiated with gamma radiation doses of 0, 4, 8, 16 or 32 kGy, and their damaged starch content, reduced sugar content and alcohol induced turbidity of their aqueous extracts were investigated. The colorimetric method and the alcohol-induced turbidity showed statistically significant increase of starch damage at 4 kGy or higher dose levels. However, all investigated analytical indices of starch radio-depolymerization were changed less dramatically by irradiation than the apparent viscosity of the gelatinized suspensions of spices reported previously. (author) 15 refs.; 4 tabs

  3. Repair of ultraviolet-light-induced DNA damage in Vibrio cholerae

    International Nuclear Information System (INIS)

    Das, G.; Sil, K.; Das, J.

    1981-01-01

    Repair of ultraviolet-light-induced DNA damage in a highly pathogenic Gram-negative bacterium, Vibrio cholerae, has been examined. All three strains of V. cholerae belonging to two serotypes, Inaba and Ogawa, are very sensitive to ultraviolet irradiation, having inactivation cross-sections ranging from 0.18 to 0.24 m 2 /J. Although these cells are proficient in repairing the DNA damage by a photoreactivation mechanism, they do not possess efficient dark repair systems. The mild toxinogenic strain 154 of classical Vibrios presumably lacks any excision repair mechanism and studies of irradiated cell DNA indicate that the ultraviolet-induced pyrimidine dimers may not be excised. Ultraviolet-irradiated cells after saturation of dark repair can be further photoreactivated. (Auth.)

  4. Plasma induced DNA damage: Comparison with the effects of ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lazović, S.; Maletić, D.; Puač, N.; Malović, G.; Petrović, Z. Lj. [Institute of Physics, University of Belgrade, Pregrevica 118, 11080 Belgrade (Serbia); Leskovac, A.; Filipović, J.; Joksić, G. [Department of Physical Chemistry, Vinča Institute of Nuclear Sciences, University of Belgrade, 11001 Belgrade (Serbia)

    2014-09-22

    We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2 Gy. Tailoring the effective dose through plasma power and duration of the treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei.

  5. Ellipticine induces apoptosis in T-cell lymphoma via oxidative DNA damage

    DEFF Research Database (Denmark)

    Savorani, Cecilia; Manfé, Valentina; Biskup, Edyta

    2015-01-01

    (CTCL), a disease that is progressive, chemoresistant and refractory to treatment. We tested the effect of ellipticine in three cell lines with different p53 status: MyLa2000 (p53(wt/wt)), SeAx ((G245S)p53) and Hut-78 ((R196Stop)p53). Ellipticine caused apoptosis in MyLa2000 and SeAx and restored...... the transcriptional activity of (G245S)p53 in SeAx. However, p53 siRNA knockdown experiments revealed that p53 was not required for ellipticine-induced apoptosis in CTCL. The lipophilic antioxidant α-tocopherol inhibited ellipticine-dependent apoptosis and we linked the apoptotic response to the oxidative DNA damage....... Our results provide evidence that ellipticine-induced apoptosis is exerted through DNA damage and does not require p53 activation in T-cell lymphoma....

  6. Equivalence of displacement radiation damage in superluminescent diodes induced by protons and heavy ions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xingji, E-mail: lxj0218@hit.edu.cn [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Liu, Chaoming [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China); Lan, Mujie; Xiao, Liyi [Center of Micro-electronics, Harbin Institute of Technology, Harbin 150001 (China); Liu, Jianchun; Ding, Dongfa [Beijing Aerospace Times Optical-electronic Technology Co.Ltd, Beijing 100854 (China); Yang, Dezhuang; He, Shiyu [School of Materials Science and Engineering, Harbin Institute of Technology, Harbin 150001 (China)

    2013-07-11

    The degradation of optical power for superluminescent diodes is in situ measured under exposures of protons with various energies (170 keV, 3 MeV