Some effects of chlorambucil on enzymes of glutathione metabolism in drug-sensitive and -resistant strains of the Yoshida ascites sarcoma.

1. Yoshida ascites cells from a strain sensitive to chemotherapy with alkylating agents contained elevated activities of the two enzymes directly responsible for glutathione synthesis, in comparison with a resistant cell strain. The activities of the glutathione-degrading enzyme gamma-glutamyltranspeptidase were comparable in both cell strains. 2. After parenteral administration of chlorambucil to rats carrying either strain of tumour, the activities of the glutathione-synthetic enzymes increased in the sensitive cells, but remained unchanged in the resistant cells. Drug treatment was without effect on the gamma-glutamyltranspeptidase activity of either cell strain. 3. The activities of a number of enzymes concerned in the oxidoreduction of glutathione remained unchanged after the administration of chlorambucil to rats carrying either strain of cells.