Radioprotection by glutathione esters and cysteamine in normal and glutathione-depleted mammalian cells.
Monoethyl (MEE) and diethyl (DEE) esters of glutathione (GSH) had the capacity to provide some protection of normal and buthionine sulfoximine (BSO) pretreated cells against X-irradiation. Both compounds appeared to be transported through the cell membrane into the cells. MEE was intracellularly partly hydrolysed to GSH and caused a limited rise of intracellular GSH. DEE was intracellularly mainly converted into MEE and partly into GSH. DEE caused a larger rise of the intracellular GSH content than MEE; it also provided a better radioprotection. Radioprotection by the GSH esters may be explained by an increase of intracellular GSH as well as by the presence of the esters themselves. Cysteamine caused no rise of the intracellular GSH content, thus its radioprotection could not be mediated by an increase of intracellular GSH. When the radiosensitivity of GSH-depleted cells protected by cysteamine was compared with the radiosensitivity of non-GSH-depleted cells similarly protected by cysteamine, it appeared that the GSH-depleted cells remained more sensitive to irradiation. Thus, it seems that in this respect cysteamine cannot fully substitute for endogenous GSH.
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TNO, Medical Biological Laboratory, Rijswijk, The Netherlands.
Roos-Verhey
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D000818:Animals; D019328:Buthionine Sulfoximine; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D003543:Cysteamine / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D011837:Radiation-Protective Agents; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D003543:Cysteamine; C042431:S-ethyl glutathione; D005978:Glutathione