Glutathione depletion and cytotoxicity of buthionine sulphoximine and SR2508 in rodent and human cells.
SR2508 (1 mM) increases the rate of glutathione (GSH) depletion by L-buthionine-S-R-sulphoximine (BSO) in hypoxic V79 rodent and A549 human cells. Specifically, the GSH content for V79 and A549 cells, after incubating for about 6 hr with 50 and 100 microM BSO, respectively, was lower by at least 10-fold when 1 mM SR2508 was present. In addition, 1 mM SR2508 is extremely toxic to hypoxic cells with lower GSH content. Survival probabilities of GSH-depleted V79 and A549 cells are about 10(-3) after 10 hr incubation with 1 mM SR2508. By itself, 1 mM SR2508 or 50-100 microM BSO decreased cellular viability by about 50% with a 10 hr treatment period. Both the phenomena described above are preferential towards hypoxic cells with minimal effect on aerobic cells.
Ling
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Department of Radiation Oncology, University of California, San Francisco 94143.
Wong
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Basas
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D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D004357:Drug Synergism; D017341:Etanidazole; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009593:Nitroimidazoles / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D000963:Antimetabolites; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D008717:Methionine Sulfoximine; D017341:Etanidazole; D019328:Buthionine Sulfoximine; D005978:Glutathione