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 sensitive 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.
Wan
X S
XS
Graduate Center for Toxicology, University of Kentucky, Lexington 40506-0054.
St Clair
D K
DK
D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D019328:Buthionine Sulfoximine; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects*; D003958:Diamide / Q000633:toxicity; D005033:Ethylmaleimide / Q000633:toxicity; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008168:Lung; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000633:toxicity
D000964:Antimetabolites, Antineoplastic; D003958:Diamide; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D005033:Ethylmaleimide