Lack of Oxygen Effect in Glutathione-deficient Human Cells in Culture

Abstract
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 from lymphoblasts transformed by infection EB [Epstein-Barr] virus or from fibroblasts. The dose-effect relationship for the induction of breaks when radiation exposure was made in Ar was similar to exposure 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 in air or in Ar. In control cultures radiation induction of breaks was enhanced by misonidazole under anaerobic but not aerobic conditions. When the glutathione-deficient cells were pretreated with cysteamine, irradiation in the absence of O2 produced a decreased frequency of DNA breaks.