Bimodal pattern of killing of Chinese hamster V79 variant cells by hydrogen peroxide.
To elucidate the mechanism of cytotoxicity of H2O2, we selected H2O2-resistant Chinese hamster V79 cells by single-step selection from a pool of spontaneous variants. The resistant cells showed bimodal sensitivity to H2O2 without exhibiting a significantly higher level of the detoxicating enzymes, catalase, glutathione peroxidase and superoxide dismutase. Mode-one and mode-two killing were observed at lower (< 300 microM) and higher (> 2 mM) H2O2 concentrations, respectively. Mode-one but not mode-two killing was prevented by iron chelators. Pretreatment with low concentrations of ascorbic acid preferentially enhanced the killing at higher H2O2 concentrations. These resistant cells were cross-resistant to t-butyl hydroperoxide and cumene hydroperoxide.
Kaneko
M
M
Biophysics Division, National Cancer Center Research Institute, Tokyo, Japan.
Kodama
M
M
Inoue
F
F
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology*; D002999:Clone Cells; D006224:Cricetinae; D003412:Cricetulus; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007700:Kinetics; D010545:Peroxides / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism; D020122:tert-Butylhydroperoxide
D001555:Benzene Derivatives; D002614:Chelating Agents; D010545:Peroxides; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003676:Deferoxamine; C007164:cumene hydroperoxide; D001205:Ascorbic Acid; C025205:1,10-phenanthroline