Selenite-Induced Variation of Glutathione Peroxidase Activity in Mammalian Cells and Its Consequences for Cellular Radiation Resistance

Abstract

The current work was initiated upon the finding of a positive correlation (0.05<P<0.1) between the GSH peroxidase activities of seven human cell lines and their resistance against γ-irradiation (Marklund et al. 1984), as indicated by quasithreshold doses (D _q) and extrapolation numbers (n). The correlation between GSH peroxidase and D _q was particularly striking (Fig. 1). There was no correlation between GSH peroxidase and the general radiosensitivity (D ₀) of the cell lines. GSH peroxidase forms the primary intracellular enzymic defence against oxygen radicals (abundantly formed when water solutions are irradiated under oxic conditions) together with catalase, CuZn superoxide dismutase and Mn superoxide dismutase. No correlation with any survival parameter could be found for the latter enzymes. D ₀, D _q and n are parameters derived from the survival curve (Fig. 2) and are different measures of the size of the so-called shoulder of the survival curve. The size of the shoulder is thought to be the result of repair of radiation damage (Coggle 1983). There are mechanisms by which GSH peroxidase might contribute to this repair. Alkyl radicals are formed by ionizing radiation in target molecules. In the presence of oxygen, peroxy-radicals will be instantly formed, which subsequently form hydroperoxides by hydrogen abstraction. Such ionizing radiation-induced hydroperoxides have been found to be substrates for GSH peroxidase (Tan et al. 1987), which by reduction will form less toxic and probably more easily repaired alcohols.

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