STATUS OF GLUTATHIONE AND GLUTATHIONE-METABOLIZING ENZYMES IN MENADIONE-RESISTANT HUMAN CANCER-CELLS

Cloned menadione (MD)-resistant human breast cancer cell lines have be en developed and characterized with respect to glutathione (GSH) conte nt 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-res istant cell lines. The MD-resistant cells also displayed alterations i n their growth kinetics, possessing longer doubling times and increase d fractions in the G1/0 phase of the cell cycle as compared to parenta l MD-sensitive cells. The possible mechanisms for the resistance to MD , including an increase in repair of MD-induced DNA damage, are discus sed.