Induction and Repair of Single-strand DNA Breaks after X-irradiation of Human Fibroblasts Deficient in Glutathione

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Abstract
Using the unwinding technique in weak alkali, the induction and repair of DNA single-strand breaks was determined after aerobic and anaerobic X-irradiation of human fibroblasts, obtained from a patient suffering from 5-oxoprolinuria, and from a clinically healthy control. The metabolic disorder associated with 5-oxoprolinuria is a deficiency in glutathione synthetase activity resulting in a greatly reduced glutathione content in the cells. A small dose-modifying effect of oxygen (o.e.r. [O2 enhancement ratio] = 1.1) was found for these cells in comparison to an o.e.r. of 2.5 for control cells with normal glutathione content. No significant difference was found between the repair capacity of cells with normal and deficient glutathione content, and repair was nearly completed wtihin 60 min of anoxic irradiation in each case. In contrast, after aerobic irradiation the glutathione-deficient cells repaired less than 70% of the breaks during the same period. When the glutathione-deficient cells were incubated with either dithiothreitol or mercaptopropionyl-glycine directly after aerobic irradiation, almost complete repair was obtained within 60 min. The data are interpreted as indicating that the repair mechanism for oxically and anoxically induced single-strand breaks is qualitatively different, and requires glutathione in the former case.
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