Antimutagenicity of a low molecular weight superoxide dismutase mimic against oxidative mutagens.
A set of stable nitroxide free radicals that are used as spin labels have been shown to possess metal-independent superoxide dismutase-like activity. Unlike superoxide dismutase (SOD), these compounds are low molecular weight, and readily penetrate into the cell. A representative nitroxide, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (Tempol), was investigated for antimutagenic activity in the XPRT forward mutation assay in CHO AS52 cells. AS52 cells were exposed to hydrogen peroxide, or the hypoxanthine/xanthine oxidase superoxide generating system, in the presence or absence of 10 mM Tempol. Tempol itself was not mutagenic or toxic to AS52 cells. Tempol protected cells nearly completely from the cytotoxic and mutagenic effects of hydrogen peroxide and hypoxanthine/xanthine oxidase. We have previously shown that nitroxides do not alter the extracellular concentration of hydrogen peroxide, and that they are taken up by mammalian cells, suggesting that the antimutagenic activity of Tempol is an intracellular phenomenon.
DeGraff
W G
WG
Radiobiology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Krishna
M C
MC
Russo
A
A
Mitchell
J B
JB
D000818:Animals; D016587:Antimutagenic Agents; D016466:CHO Cells; D015197:Carcinogenicity Tests; D002374:Catalase / Q000494:pharmacology; D006224:Cricetinae; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity; D007700:Kinetics; D009152:Mutagenicity Tests; D009609:Nitrous Oxide / Q000633:toxicity; D012044:Regression Analysis; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000633:toxicity; D014969:Xanthine Oxidase / Q000633:toxicity
D016587:Antimutagenic Agents; D003497:Cyclic N-Oxides; D013113:Spin Labels; D013481:Superoxides; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D003676:Deferoxamine; D009609:Nitrous Oxide; C001803:tempol