Compartmentalised depletion of glutathione in cells treated with buthionine sulphoximine

Abstract

Evidence obtained in different types of experiments has indicated that glutathione (GSH) can function as an inherent protector of cells against treatment with radiation and many chemotherapeutic agents (Arrick & Nathan, 1984). In an attempt to enhance the effect of such treatments, efforts have been made to control the cellular GSH content artificially. In many of the recent studies, buthionine sulphoximine (BSO) has been used to deplete cellular GSH (Chemical Modifiers of Cancer Treatment, 1986). This substance inhibits the synthesis of gamma-glutamyl-cysteine, a precursor of GSH, by specifically blocking the synthesising enzyme. Edgren (1987) reported observations which suggest that depletion of GSH by BSO occurs to different extents in the nucleus and the cytoplasm. The experiments reported here confirm the earlier observations either when treatment is made with BSO at a single concentration for varying time periods, or at varying concentrations for a fixed period.