DIFFERENT ROLE OF LIPID-PEROXIDATION IN OXIDATIVE STRESS-INDUCED LETHAL INJURY IN NORMAL AND TUMOR THYMOCYTES

In the present work, the role of lipid peroxidation in cellular lethal injury induced by various types of oxidative stress has been studied in both normal and tumor thymocytes. The prooxidants included either a xanthine/xanthine oxidase system, which is an exogenous source of oxy radicals, or tert-butyl hydroperoxide (t-BOOB), which enters the cell and endogenously produces free radicals. Our data demonstrate that: (A ) Using xanthine/xanthine oxidase system as a prooxidant, normal thymo cytes are more sensitive than thymoma cells to oxidative damage, as th eir lactate dehydrogenase (LDH) and malondialdehyde (MDA) release is h igher than that of tumor cells. By varying Fe3+/ADP ratios, a positive correlation can be established between LDH and MDA release only in no rmal thymocytes. While thymoma cells still show a very high level of v itamin E (80%) after 15 min of incubation with this prooxidant, normal thymocytes lose it after the same incubation time. (B) Using t-BOOH a s a prooxidant, normal thymocytes release a higher amount of MDA but a lower amount of LDH than thymoma cells. In agreement with the results obtained with the xanthine/xanthine oxidase system, by varying the co ncentrations of the prooxidant, a correlation between LDH and MDA rele ase can be established only in normal thymocytes. Although high levels of the antioxidant are still present in both kinds of cells after 15 min of incubation with t-BOOH, normal thymocytes consume vitamin E fas ter than thymoma cells. These data suggest that the role of lipid pero xidation in cell lethal injury is influenced by the source and the sit e of radical production as well as by the cell type. With t-BOOB as a prooxidant in normal thymocytes, lipid peroxidation is only partially involved in the induction of irreversible cell injury, but it plays a crucial role when the xanthine/xanthine oxidase system is used as a pr ooxidant. Moreover, whatever the prooxidant used in tumor thymocytes, membranes are more resistant to lipid peroxidation, suggesting that th is mechanism is not causally related to cell death. (C) 1994 Academic Press,Ino.