Radiosensitivity of normal and polyunsaturated fatty acid supplemented fibroblasts after depletion of glutathione.

Abstract

Mouse fibroblast LM cells have been modified with respect to their phospholipid composition in all subcellular fractions, including the nuclear membrane. The content of polyunsaturated fatty acids (PUFA) was significantly increased but no difference in cell survival after X-irradiation could be observed between the normal and PUFA enriched cells. It is concluded that the radiosensitive PUFAs in the membranes are well protected against radiation damage. This protection of the PUFA cells could not be caused by vitamin E, because this membrane protector was not present in these fibroblasts. The content of glutathione (GSH) was about the same in the normal and the modified cells. Reduction of the cellular GSH content to less than 5 per cent of that for non-treated cells did not alter cellular survival after radiation of either normal or PUFA enriched cells under oxic or anoxic conditions. The radiosensitive lipids present in the membranes of the PUFA enriched cells proved to be vulnerable to radiation-induced lipid peroxidation when extracted from the cells and reconstituted into liposomes, indicating that the fatty acids per se are peroxidizable. It is concluded that the lipids in the membranes of mammalian cells are not the principal target in radiation-induced reproductive death, and that no generalization is permitted with respect to glutathione, as being the major hydrogen donating species in mammalian cells responsible for the repair of those target molecules responsible for cell survival after radiation.