Differential cytotoxicity of buthionine sulfoximine to "normal" and transformed human lung fibroblast cells

Glutathione (GSH) depletion has been studied extensively as a possible means to sensitize tumor cells to radiation treatment and chemotherapy. The present study was undertaken to compare the cytotoxicity of GSH depletion in normal and transformed cells. The results showed that specific inhibition of GSH synthesis by l-buthionine sulfoximine (BSO) caused significantly higher cytotoxicity in "normal" human-lung fibroblast cells than in their transformed counterparts. This finding suggests a possibility that depletion of GSH could be more harmful to normal cells than to transformed and/or tumor cells and that the selective cytotoxicity of BSO to normal cells could limit its potential as an effective sensitizer for cancer treatment.