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Opposing effects of nitroxide free radicals in Escherichia coli mutants deficient in DNA repair
Affiliation:3. Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts 01609;4. Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721;1. Laboratory of Environmental Pollution and Bioremediation, State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China;2. State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang 550002, China;3. University of Chinese Academy of Sciences, Beijing 100049, China;4. Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia;5. Department of Zoology, Faculty of Life and Earth Science, Rajshahi University, Rajshahi 6205, Bangladesh;1. Molecular Biology Section, Laboratory of Algal Biology, Center of Advanced Study in Botany, Banaras Hindu University, Varanasi 221005, India;2. Department of Biotechnology and Microbiology, Saaii College of Medical Science and Technology, Chaubeypur, Kanpur, India;1. College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR China;2. College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China;1. School of Metallurgy and Environment, Central South University, Changsha 410083, China;2. Chinese National Engineering Research Center for Control & Treatment of Heavy Metal Pollution, Changsha 410083, China;3. Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China;4. State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
Abstract:Nitroxide free radicals have been previously shown to function as superoxide dismutase (SOD) mimics and to protect bacterial and mammalian cells against oxidative damage, particularly from superoxide and hydrogen peroxide. Although nitroxides are generally considered to be non-toxic nor mutagenic, there is no agreement regarding their potential adverse effect. Some toxic effects were observed upon using high concentration of six-membered ring derivatives. Conflicting evidence has also been reported regarding the mutagenic activity of nitroxides toward Salmonella typhimurium. It was also demonstrated that nitroxides exert two opposing effects on exonuclease III deficient cells of Escherichia coli upon exposure to naphthoquinones. The attempts to use nitroxides as contrast agents in nuclear magnetic resonance imaging (MRI) and as a new class of anti-oxidants underscore the need to examine their potential adverse effects. Since nitroxides protected xthA cells from DNA scission caused by H2O2, it was anticipated that they would provide even greater t protection for recA DNA repair-deficient cells of E. coli, which are more sensitive to H2O2-induced oxidative stress. The results of the present study showed that: (1) nitroxides exert bactericidal and bacteriostatic effects on recA but not on xthA or wild-type E. coli K12 cells, (b) nitroxides and H2O2 act synergistically on recA cells, both under aerobic and hypoxic conditions; (c) the nitroxide-induced toxicity in recA cells and the synergistic effect with H2O2 were not accompanied by a decrease in the cellular level of reduced glutathione; (d) TEMPAMINE protected against DNA scission induced by H2O2 and 1,10-o-phenanthroline chelate of Cu(II) in xthA cells, but potentiated DNA double-strand breakage in recA cells.
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