Lack of oxygen effect in glutathione-deficient human cells in culture.
The frequency of X-ray-induced DNA breaks was determined in human cell lines which are deficient in glutathione synthetase and have a greatly reduced glutathione content. Hydroxyapatite chromatography was used for the estimation of the DNA breaks in cell cultures, which were derived either from lymphoblasts transformed by infection with EB virus or from fibroblasts. The dose-effect relationship for the induction of breaks when radiation exposure was made in argon, was similar to that found when exposure was made in air. In control cultures with normal glutathione content, the induction of breaks was enhanced when irradiation was made under aerobic, instead of anaerobic, conditions. Treatment of the glutathione-deficient cells with the hypoxic radiosensitizer misonidazole did not enhance the induction of breaks by radiation delivered either in air or in argon. In control cultures, radiation induction of breaks was enhanced by misonidazole under anaerobic but not under aerobic conditions. When the glutathione-deficient cells were pretreated with cysteamine however, irradiation in the absence of oxygen resulted in a decreased frequency of DNA breaks.
D002478:Cells, Cultured; D003543:Cysteamine / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005978:Glutathione / Q000172:deficiency*; D005981:Glutathione Synthase / Q000172:deficiency / Q000235:genetics; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000378:metabolism; D009154:Mutation; D010100:Oxygen; D011836:Radiation Tolerance; D014965:X-Rays
D003543:Cysteamine; D004247:DNA; D005981:Glutathione Synthase; D005978:Glutathione; D010100:Oxygen