Status of glutathione and glutathione-metabolizing enzymes in menadione-resistant human cancer cells.
Cloned menadione (MD)-resistant human breast cancer cell lines have been developed and characterized with respect to glutathione (GSH) content and GSH-metabolizing enzymes. Increases in the activities of gamma-glutamyltranspeptidase and glutathione-S-transferase were demonstrated in the absence of alterations in the GSH content of two cloned MD-resistant cell lines. The MD-resistant cells also displayed alterations in their growth kinetics, possessing longer doubling times and increased fractions in the G1/O phase of the cell cycle as compared to parental MD-sensitive cells. The possible mechanisms for the resistance to MD, including an increase in repair of MD-induced DNA damage, are discussed.
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Department of Pharmacology, University of Minnesota, Minneapolis 55455.
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D002453:Cell Cycle / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004351:Drug Resistance; D005978:Glutathione / Q000032:analysis*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014812:Vitamin K / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D014812:Vitamin K; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D005978:Glutathione