Effects of glutathione depletion using buthionine sulphoximine on the cytotoxicity of nitroaromatic compounds in mammalian cells in vitro.
The inhibitor of glutathione biosynthesis, buthionine sulphoximine (BSO) has been used to deplete endogenous thiols in mammalian cells in vitro. The effect of such depletion on the toxicity of nitroaromatic compounds has been investigated. Substantial enhancement of both aerobic and hypoxic toxicity of the 2-nitroimidazole, misonidazole is observed in thiol-depleted cells; the hypoxic toxicities of metronidazole, nitrofurantoin and nimorazole are also increased by thiol depletion. These data of significance for the potential combined use of BSO with nitroaromatic radiosensitizers to increase their radiosensitizing efficiency in radiotherapy, and as a potential method for enhancing the efficiency of anti-protozoal nitroaromatic drugs.
D000818:Animals; D019328:Buthionine Sulfoximine; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008920:Misonidazole / Q000633:toxicity*; D009582:Nitrofurantoin / Q000633:toxicity*; D009593:Nitroimidazoles / Q000633:toxicity*
D009593:Nitroimidazoles; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008920:Misonidazole; D009582:Nitrofurantoin; D005978:Glutathione