EFFECT OF GLUTATHIONE-MODULATING COMPOUNDS ON HYDROGEN PEROXIDE-INDUCED CYTOTOXICITY IN HUMAN GLIOBLASTOMA AND GLIOMA CELL-LINES

The relation between the intracellular glutathione (GSH) concentration and hydrogen-peroxide(H2O2)-induced cytotoxicity was investigated. Th e intracellular GSH concentration in human glioblastoma (T98G, U87MG) and glioma (KGlC) cell lines was one or two orders of magnitude higher than that in a human myelogenous leukemic cell line (HL-60), which sh owed higher sensitivity to H2O2. Pretreatment of these cell lines with L-buthionine-[S,R]-sulfoximine, which significantly reduced the intra cellular GSH concentration, increased their sensitivity against H2O2, whereas pretreatment with N-acetyl-L-cysteine, which did not significa ntly change the intracellular GSH concentration, only marginally prote cted the cells from the cytotoxic effect of H2O2. The results suggest that drug sensitivity of tumor cells can be modified by glutathione-mo dulating compounds.