Long-term buthionine-sulfoximine-mediated toxicity in cultured hepatoma cell lines.

The glutathione (GSH) biosynthesis inhibitor L-buthionine-S,R-sulfoximine (BSO) was applied at 100 microM to hepatoma cells in culture for periods up to 4 weeks. PLC/PRF/5 cells grew normally for 4 weeks, the GSH content remaining at a 12% level, but all Hep G2 cells died after 3 weeks, with a gradually decrease in GSH. BSO did not interfere with the trypsinization procedure. Simultaneous application of GSH with BSO for 3 days at least partly inhibited the BSO toxicity in the same cells and in Fa32 cells, but BW1 cells were not sensitive to BSO. GSH depletion was the reason of long-term toxicity of BSO. It is concluded that BSO should be used with great care as an inhibitor of GSH biosynthesis in long-term therapy.