Radiosensitization of hypoxic tumor cells by depletion of intracellular glutathione.
Depletion of glutathione in Chinese hamster ovary cells in vitro by diethyl maleate resulted in enhancement of the effect of x-rays on cell survival under hypoxic conditions but not under oxygenated conditions. Hypoxic EMT6 tumor cells were similarly sensitized in vivo. The action of diethyl maleate is synergistic with the effect of the electron-affinic radiosensitizer misonidazole, suggesting that the effectiveness of misonidazole in cancer radiotherapy may be improved by combining it with drugs that deplete intracellular glutathione.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism*; D000860:Hypoxia; D008298:Maleates / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008920:Misonidazole / Q000008:administration & dosage; D009374:Neoplasms, Experimental / Q000378:metabolism; D010101:Oxygen Consumption
D008298:Maleates; D008920:Misonidazole; C014476:diethyl maleate; D005978:Glutathione