Intracellular glutathione as a determinant of responsiveness to antitumor drugs

The effect of glutathione depletion on cytotoxicity of the anthracycline daunorubicin, and of a copper:bis-thiosemicarbazone chelate, was examined in the P388 murine leukemia and its anthracycline-resistant subline, P388/ADR. Depletion of intracellular glutathione was accomplished through exposure to buthionine sulfoximine, a specific inhibitor of glutathione synthesis. Cytotoxicity of daunorubicin was not altered by glutathione depletion, while responsiveness to the bis-thiosemicarbazone chelate was thereby enhanced.