The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform

Hiroshi Ohshima - One of the best experts on this subject based on the ideXlab platform.

  • Induction of DNA Strand Breakage and base oxidation by nitroxyl anion through hydroxyl radical production.
    Free Radical Biology and Medicine, 1999
    Co-Authors: Hiroshi Ohshima, Isabelle Gilibert, Franca Bianchini
    Abstract:

    Nitroxyl anion (NO-), the one-electron reduction product of nitric oxide (NO*), has been reported to be formed under various physiological conditions and to be cytotoxic, although the mechanism responsible for the toxic effects has not been identified. We have studied the effects of NO- generated from Angeli's salt (sodium trioxodinitrate) or Piloty's acid (N-hydoxybenzenesulfonamide) on DNA Strand Breakage and DNA base oxidation in vitro. Induction of Strand Breakage was dose- and time-dependent upon incubation of plasmid pBR322 with Angeli's salt or Piloty's acid. Similarly, 8-oxo-2'-deoxyguanosine and malondialdehyde were formed when calf-thymus DNA or 2'-deoxyribose, respectively, were incubated with Angeli's salt. Electron acceptors (ferricyanide, 4-hydroxy-TEMPO), that convert NO to NO*, inhibited the reactions, indicating that NO , but not NO*, is responsible for the reactions. Furthermore, the reactions were also inhibited by the presence of hydroxyl radical (HO*) scavengers, antioxidants, metal chelators and superoxide dismutase and catalase, implying involvement of free HO*. These results suggest that NO- is a possible endogenous source of HO*, that may be formed either directly from the reaction product of NO- with NO* (N2O2*-) or indirectly through H2O2 formation. Thus NO may play an important role as a cause of diverse pathophysiological conditions such as inflammation and neurodegenerative diseases.

  • Synergistic Induction of DNA Strand Breakage by Catechol-Estrogen and Nitric Oxide: Implications for Hormonal Carcinogenesis
    Free radical biology & medicine, 1998
    Co-Authors: Yumiko Yoshie, Hiroshi Ohshima
    Abstract:

    Estrogen is a known risk factor for human breast cancer, although the mechanism by which estrogens induce cancer remains unestablished. We have demonstrated that DNA Strand Breakage is induced synergistically when pBR322 plasmid DNA is incubated in the presence of both a nitric oxide (NO)-releasing compound (diethylamine NONOate, etc.) and a catechol-estrogen (2- or 4-hydroxyestradiol or -hydroxyestrone). Either the NO-releasing compound or the catechol-estrogen alone induced much fewer Strand breaks. Estradiol, estrone, O-methylated catechol-estrogens, and diethylstilbestrol did not exert such DNA damaging effects. Strand Breakage induced by NO plus 2- or 4-hydroxyestradiol was inhibited by carboxy-PTIO (an NO-trapping agent) and, to a lesser extent, by superoxide dismutase. Antioxidants (e.g., N-acetylcysteine, ascorbate), but not HO. scavengers, exhibited inhibitory effects. A possible mechanism for this Strand Breakage would be: (1) NO mediates conversion of catechol-estrogens to quinones, (2) the quinone/hydroquinone redox system produces O2.-, and (3) O2.- reacts with NO to form peroxynitrite, which causes DNA Strand breaks. Our results imply that interaction of catechol-estrogens and NO, both known to be formed in human breast and uterus, leads to production of a potent oxidant(s), which could cause damage in cells and DNA, thus playing an important role in hormonal carcinogenesis.

  • Synergistic induction of DNA Strand Breakage by cigarette tar and nitric oxide.
    Carcinogenesis, 1997
    Co-Authors: Yumiko Yoshie, Hiroshi Ohshima
    Abstract:

    Cigarette smoking is a major cause of human cancer at a variety of sites, although its carcinogenic mechanisms remains unestablished. Cigarette smoke can be divided into two phases, gas phase and particulate matter (tar). Both phases contain high concentrations of oxidants and free radicals, especially nitric oxide (NO) and nitrogen oxides in the gas phase and quinone/hydroquinone complex in the tar. We have found that incubation of pBR322 plasmid DNA with aqueous extracts of cigarette tar and a NO-releasing compound (diethylamine NONOate) caused synergistic induction of DNA single-Strand Breakage, whereas either cigarette tar alone or NO alone induced much less Strand Breakage. This synergistic effect of cigarette tar and NO on DNA Strand Breakage was prevented by high concentrations of superoxide dismutase, carboxy-PTIO (an NO-trapping agent) or N-acetylcysteine, whereas hydroxyl radical scavengers such as dimethylsulfoxide, ethanol and D-mannitol did not show inhibitory effects. Possible mechanisms for this synergistic effect mediated by cigarette tar and NO are proposed, including involvement of peroxynitrite, which is a strong oxidant and nitrating agent formed rapidly by the reaction between NO and O 2 .- . NO is present in the gas phase of smoke and may be formed by a constitutive or inducible NO synthase in the lung, whereas O 2 .- is generated by auto-oxidation of polyhydroxyaromatic compounds such as catechol and 1,4-hydroquinone present in cigarette tar. Thus, potent reactive species including peroxynitrite formed by the interaction between cigarette tar and NO may play an important role in smoking-related diseases including lung cancer.

  • Synergistic Induction of DNA Strand Breakage Caused by Nitric Oxide Together with Catecholamine: Implications for Neurodegenerative Disease
    Chemical research in toxicology, 1997
    Co-Authors: Yumiko Yoshie, Hiroshi Ohshima
    Abstract:

    Oxidative damage in neuronal cells and DNA has been implicated in the pathogenesis of various neurodegenerative diseases. We have demonstrated that DNA Strand Breakage is induced synergistically when plasmid DNA is incubated in the presence of both an NO-releasing compound (diethylamine NONOate, spermine NONOate, sodium nitroprusside) and a catecholamine (e.g., L-DOPA, dopamine, etc.). Either an NO-releasing compound or a catecholamine alone induced much fewer Strand breaks. Tyrosine and tyramine as well as O-methylated derivatives of DOPA and dopamines did not exert this synergistic effect in the presence of NO. The DNA Strand Breakage induced by NO plus dopamine was inhibited by carboxy-PTIO (a trapping agent of NO and possibly other radicals), superoxide dismutase, and antioxidants such as N-acetylcysteine and ascorbate but not by HO. scavengers such as dimethyl sulfoxide, ethanol, and D-mannitol. These results suggest that the free HO. is not involved; rather a new oxidant(s) formed by the reaction between NO and catecholamine could be responsible for causing the DNA Strand Breakage. We propose that one of the responsible compounds is peroxynitrite (ONOO-), which is a strong oxidant and nitrating agent formed by the reaction between NO and O2.-. NO has been shown to oxidize catecholamines to form quinone derivatives, which lead to the generation of O2.- by the quinone/hydroquinone redox system. O2.- then reacts rapidly with NO to form peroxynitrite. However, it is also possible that other compounds such as NOx generated from catecholamines and NO may cause DNA damage. Our results implicate a synergistic interaction of catecholamines formed in dopaminergic neurons and NO formed by microglia or astrocytes or the two compounds produced within the same neuronal cells to produce a potent oxidant(s) which could cause damage in cells and DNA, thus playing an important role in the pathogenesis of various neurodegenerative diseases.

Barry Halliwell - One of the best experts on this subject based on the ideXlab platform.

  • OXIDATIVE DNA DAMAGE IN HUMAN RESPIRATORY TRACT EPITHELIAL CELLS. TIME COURSE IN RELATION TO DNA Strand Breakage
    Biochemical and biophysical research communications, 1996
    Co-Authors: Jeremy P. E. Spencer, Andrew M. Jenner, Okezie I. Aruoma, Carroll E. Cross, Barry Halliwell
    Abstract:

    When human respiratory tract epithelial cells were exposed to 100 μM H2O2, there was rapid induction of DNA Strand Breakage and chemical modifications to all 4 DNA bases suggestive of attack by OH•. The major products were FAPy-adenine, FAPy-guanine, and 8-OH-guanine. Some of the base modifications were removed very quickly from the DNA (e.g., 8-OH-guanine), whereas others persisted for longer (e.g., thymine glycol), probably due to differential activity of different repair enzymes. By contrast, Strand breaks continued to increase over the time course of the experiment, perhaps because Strand Breakage is also implicated in the repair process. One should therefore be cautious in using Strand Breakage as a sole measure of oxidative DNA damage, and when drawing conclusions about the pattern and biological significance of oxidative DNA damage in cells the relative persistence of different lesions must be considered.

  • DNA Strand Breakage and base modification induced by hydrogen peroxide treatment of human respiratory tract epithelial cells
    FEBS letters, 1995
    Co-Authors: Jeremy P. E. Spencer, Andrew M. Jenner, Ken Chimel, Okezie I. Aruoma, Carroll E. Cross, Barry Halliwell
    Abstract:

    Treatment of human respiratory tract epithelial cells with H2O2 led to concentration-dependent DNA Strand Breakage that was highly-correlated with multiple chemical modifications of all four DNA bases, suggesting that damage is due to hydroxyl radical, OH.. However, the major base damage occurred to adenine. Hence, conclusions made about the occurrence and the extent of oxidative DNA damage on the basis only of changes in 8-hydroxyguanine should be approached with caution.

Jeremy P. E. Spencer - One of the best experts on this subject based on the ideXlab platform.

  • OXIDATIVE DNA DAMAGE IN HUMAN RESPIRATORY TRACT EPITHELIAL CELLS. TIME COURSE IN RELATION TO DNA Strand Breakage
    Biochemical and biophysical research communications, 1996
    Co-Authors: Jeremy P. E. Spencer, Andrew M. Jenner, Okezie I. Aruoma, Carroll E. Cross, Barry Halliwell
    Abstract:

    When human respiratory tract epithelial cells were exposed to 100 μM H2O2, there was rapid induction of DNA Strand Breakage and chemical modifications to all 4 DNA bases suggestive of attack by OH•. The major products were FAPy-adenine, FAPy-guanine, and 8-OH-guanine. Some of the base modifications were removed very quickly from the DNA (e.g., 8-OH-guanine), whereas others persisted for longer (e.g., thymine glycol), probably due to differential activity of different repair enzymes. By contrast, Strand breaks continued to increase over the time course of the experiment, perhaps because Strand Breakage is also implicated in the repair process. One should therefore be cautious in using Strand Breakage as a sole measure of oxidative DNA damage, and when drawing conclusions about the pattern and biological significance of oxidative DNA damage in cells the relative persistence of different lesions must be considered.

  • DNA Strand Breakage and base modification induced by hydrogen peroxide treatment of human respiratory tract epithelial cells
    FEBS letters, 1995
    Co-Authors: Jeremy P. E. Spencer, Andrew M. Jenner, Ken Chimel, Okezie I. Aruoma, Carroll E. Cross, Barry Halliwell
    Abstract:

    Treatment of human respiratory tract epithelial cells with H2O2 led to concentration-dependent DNA Strand Breakage that was highly-correlated with multiple chemical modifications of all four DNA bases, suggesting that damage is due to hydroxyl radical, OH.. However, the major base damage occurred to adenine. Hence, conclusions made about the occurrence and the extent of oxidative DNA damage on the basis only of changes in 8-hydroxyguanine should be approached with caution.

Yumiko Yoshie - One of the best experts on this subject based on the ideXlab platform.

  • Synergistic Induction of DNA Strand Breakage by Catechol-Estrogen and Nitric Oxide: Implications for Hormonal Carcinogenesis
    Free radical biology & medicine, 1998
    Co-Authors: Yumiko Yoshie, Hiroshi Ohshima
    Abstract:

    Estrogen is a known risk factor for human breast cancer, although the mechanism by which estrogens induce cancer remains unestablished. We have demonstrated that DNA Strand Breakage is induced synergistically when pBR322 plasmid DNA is incubated in the presence of both a nitric oxide (NO)-releasing compound (diethylamine NONOate, etc.) and a catechol-estrogen (2- or 4-hydroxyestradiol or -hydroxyestrone). Either the NO-releasing compound or the catechol-estrogen alone induced much fewer Strand breaks. Estradiol, estrone, O-methylated catechol-estrogens, and diethylstilbestrol did not exert such DNA damaging effects. Strand Breakage induced by NO plus 2- or 4-hydroxyestradiol was inhibited by carboxy-PTIO (an NO-trapping agent) and, to a lesser extent, by superoxide dismutase. Antioxidants (e.g., N-acetylcysteine, ascorbate), but not HO. scavengers, exhibited inhibitory effects. A possible mechanism for this Strand Breakage would be: (1) NO mediates conversion of catechol-estrogens to quinones, (2) the quinone/hydroquinone redox system produces O2.-, and (3) O2.- reacts with NO to form peroxynitrite, which causes DNA Strand breaks. Our results imply that interaction of catechol-estrogens and NO, both known to be formed in human breast and uterus, leads to production of a potent oxidant(s), which could cause damage in cells and DNA, thus playing an important role in hormonal carcinogenesis.

  • Synergistic induction of DNA Strand Breakage by cigarette tar and nitric oxide.
    Carcinogenesis, 1997
    Co-Authors: Yumiko Yoshie, Hiroshi Ohshima
    Abstract:

    Cigarette smoking is a major cause of human cancer at a variety of sites, although its carcinogenic mechanisms remains unestablished. Cigarette smoke can be divided into two phases, gas phase and particulate matter (tar). Both phases contain high concentrations of oxidants and free radicals, especially nitric oxide (NO) and nitrogen oxides in the gas phase and quinone/hydroquinone complex in the tar. We have found that incubation of pBR322 plasmid DNA with aqueous extracts of cigarette tar and a NO-releasing compound (diethylamine NONOate) caused synergistic induction of DNA single-Strand Breakage, whereas either cigarette tar alone or NO alone induced much less Strand Breakage. This synergistic effect of cigarette tar and NO on DNA Strand Breakage was prevented by high concentrations of superoxide dismutase, carboxy-PTIO (an NO-trapping agent) or N-acetylcysteine, whereas hydroxyl radical scavengers such as dimethylsulfoxide, ethanol and D-mannitol did not show inhibitory effects. Possible mechanisms for this synergistic effect mediated by cigarette tar and NO are proposed, including involvement of peroxynitrite, which is a strong oxidant and nitrating agent formed rapidly by the reaction between NO and O 2 .- . NO is present in the gas phase of smoke and may be formed by a constitutive or inducible NO synthase in the lung, whereas O 2 .- is generated by auto-oxidation of polyhydroxyaromatic compounds such as catechol and 1,4-hydroquinone present in cigarette tar. Thus, potent reactive species including peroxynitrite formed by the interaction between cigarette tar and NO may play an important role in smoking-related diseases including lung cancer.

  • Synergistic Induction of DNA Strand Breakage Caused by Nitric Oxide Together with Catecholamine: Implications for Neurodegenerative Disease
    Chemical research in toxicology, 1997
    Co-Authors: Yumiko Yoshie, Hiroshi Ohshima
    Abstract:

    Oxidative damage in neuronal cells and DNA has been implicated in the pathogenesis of various neurodegenerative diseases. We have demonstrated that DNA Strand Breakage is induced synergistically when plasmid DNA is incubated in the presence of both an NO-releasing compound (diethylamine NONOate, spermine NONOate, sodium nitroprusside) and a catecholamine (e.g., L-DOPA, dopamine, etc.). Either an NO-releasing compound or a catecholamine alone induced much fewer Strand breaks. Tyrosine and tyramine as well as O-methylated derivatives of DOPA and dopamines did not exert this synergistic effect in the presence of NO. The DNA Strand Breakage induced by NO plus dopamine was inhibited by carboxy-PTIO (a trapping agent of NO and possibly other radicals), superoxide dismutase, and antioxidants such as N-acetylcysteine and ascorbate but not by HO. scavengers such as dimethyl sulfoxide, ethanol, and D-mannitol. These results suggest that the free HO. is not involved; rather a new oxidant(s) formed by the reaction between NO and catecholamine could be responsible for causing the DNA Strand Breakage. We propose that one of the responsible compounds is peroxynitrite (ONOO-), which is a strong oxidant and nitrating agent formed by the reaction between NO and O2.-. NO has been shown to oxidize catecholamines to form quinone derivatives, which lead to the generation of O2.- by the quinone/hydroquinone redox system. O2.- then reacts rapidly with NO to form peroxynitrite. However, it is also possible that other compounds such as NOx generated from catecholamines and NO may cause DNA damage. Our results implicate a synergistic interaction of catecholamines formed in dopaminergic neurons and NO formed by microglia or astrocytes or the two compounds produced within the same neuronal cells to produce a potent oxidant(s) which could cause damage in cells and DNA, thus playing an important role in the pathogenesis of various neurodegenerative diseases.

W. Popp - One of the best experts on this subject based on the ideXlab platform.

  • DNA Strand Breakage and DNA adducts in lymphocytes of oral cancer patients
    Carcinogenesis, 1993
    Co-Authors: W. Popp, C. Schell, R. Kraus, C. Vahrenholz, R. Wolf, J. Radtke, K. Bierwirth, K. Norpoth
    Abstract:

    In lymphocytes of 12 oral cancer patients (and two control groups) the frequencies of DNA single-Strand breaks and DNA-protein cross-linking were determined by alkaline filter elution. We found elevated DNA elution rates, which must be interpreted as an increased Strand Breakage frequency. There were significant correlations between the DNA Strand Breakage frequency and smoking habits. Using the 32P-postlabelling assay we determined the DNA adduct level in lymphocytes of 23 oral cancer patients (and two control groups). No significant influence of smoking habit on the DNA adduct level could be detected. There was a significant correlation between the DNA adduct level and the gamma-glutamyltranspeptidase (GGT) value, suggesting systemic influences of alcohol drinking habits on the adduct level.

  • Investigations of the frequency of DNA Strand Breakage and cross-linking and of sister chromatid exchange frequency in the lymphocytes of female workers exposed to benzene and toluene.
    Carcinogenesis, 1992
    Co-Authors: W. Popp, C. Vahrenholz, K. Norpoth, W. Schmieding, S. Yaman, C. Müller, G. Müller, R. Fahnert
    Abstract:

    Peripheral lymphocyte DNA damage as measured by the method of alkaline filter elution and the frequency of sister chromatid exchange (SCE) in lymphocytes was investigated for a group of 20 female workers of a shoemaking plant who were exposed to benzene and toluene, primarily below the German threshold limit value of 5 and 100 p.p.m. respectively; the results were compared with those from a control group. In the female workers significantly raised (P less than 0.05) SCE values were found. The relative DNA elution rate through polycarbonate filters was significantly increased (P less than 0.001). The elution rate through polyvinylidene fluoride (HVLP) filters showed a tendency to increase (P = 0.052), which must be interpreted as indicating increased DNA Strand Breakage. The SCE rates of the female workers were significantly correlated (P less than 0.01) with the relative DNA elution rate through HVLP filters. There was no correlation with the actual benzene and toluene uptake measured by personal air monitoring. Four months after cessation of work, DNA Strand Breakage decreased significantly (P less than 0.05) in blood samples of six reinvestigated female workers.

  • Investigations of the frequency of DNA Strand Breakage and cross-linking and of sister chromatid exchange in the lymphocytes of electric welders exposed to chromium- and nickel-containing fumes.
    International archives of occupational and environmental health, 1991
    Co-Authors: W. Popp, C. Vahrenholz, W. Schmieding, E. Krewet, K. Norpoth
    Abstract:

    A total of 39 electric welders exposed to chromium and nickel were compared with 18 controls standardized for age, smoking habits and sex with respect to the frequency of sister chromatid exchange (SCE) and of DNA Strand Breakage and cross-linking (measured by the method of alkaline filter elution) in their blood lymphocytes. A significant correlation was found between the frequency of SCE and of individual DNA Strand Breakage and the concentration of chromium in the urine. Less DNA from the welders than from the control group was eluted through the two filter types used (polycarbonate and polyvinylidene fluoride filters). This must be interpreted as resulting from the presence of DNA-protein cross-links, which has the secondary effect of leading to a relative reduction in the measurable frequency of Strand Breakage amongst the welders. The present results are in good agreement with in vitro and in vivo investigations that confirm the importance of DNA-protein cross-links for the carcinogenic effect of chromium.