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 γ-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.