Effects of an inhibitor and a mimic of superoxide dismutase on bleomycin mutagenesis in Chinese hamster ovary cells.
We have investigated the roles of reactive oxygen species (ROS) in bleomycin (BLM)-induced gene mutations in Chinese hamster ovary (CHO) cells using a superoxide dismutase (SOD) inhibitor, triethylenetetramine (TRIEN), and a SOD mimic, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEM-POL), to lower and increase intracellular 'SOD activity', respectively. Pretreatment of CHO cells with TRIEN (1 mM) for 1 h enhanced the mutagenic response of BLM (5-50 micrograms/ml, 1 h treatment) in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in CHO cell clone K1-BH4 (CHO/HPRT assay) and the xanthine-guanine phosphoribosyltransferase (gpt) gene in a CHO-K1 cell derivative AS52 (AS52/GPT assay). Pretreatment with TEMPOL (1 mM) for 1 h decreased the BLM (20-100 micrograms/ml, 1 h treatment) mutagenicity in the AS52/GPT assay. The mutagenic response of BLM appears to be modulated by the intracellular level of 'SOD activity' and hence the intracellular level of ROS. These data provide further evidence for the involvement of ROS in bleomycin mutagenesis in mammalian cells.
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Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77550.
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D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D016466:CHO Cells / Q000187:drug effects / Q000201:enzymology; D006224:Cricetinae; D003412:Cricetulus; D003497:Cyclic N-Oxides / Q000494:pharmacology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014266:Trientine / Q000494:pharmacology
D003497:Cyclic N-Oxides; D009153:Mutagens; D017382:Reactive Oxygen Species; D013113:Spin Labels; D001761:Bleomycin; D013482:Superoxide Dismutase; D007041:Hypoxanthine Phosphoribosyltransferase; D014266:Trientine; C001803:tempol