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 oxyradicals, or tert-butyl hydroperoxide (t-BOOH), which enters the cell and endogenously produces free radicals. Our data demonstrate that: (A) Using xanthine/xanthine oxidase system as a prooxidant, normal thymocytes are more sensitive than thymoma cells to oxidative damage, as their lactate dehydrogenase (LDH) and malondialdehyde (MDA) release is higher than that of tumor cells. By varying Fe3+/ADP ratios, a positive correlation can be established between LDH and MDA release only in normal thymocytes. While thymoma cells still show a very high level of vitamin E (80%) after 15 min of incubation with this prooxidant, normal thymocytes lose it after the same incubation time. (B) Using t-BOOH as 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 concentrations of the prooxidant, a correlation between LDH and MDA release 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 faster than thymoma cells. These data suggest that the role of lipid peroxidation in cell lethal injury is influenced by the source and the site of radical production as well as by the cell type. With t-BOOH 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 prooxidant. Moreover, whatever the prooxidant used in tumor thymocytes, membranes are more resistant to lipid peroxidation, suggesting that this mechanism is not causally related to cell death.
Institute of General Pathology, Catholic University, Rome, Italy.
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D000818:Animals; D000975:Antioxidants; D016923:Cell Death; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008223:Lymphoma / Q000201:enzymology / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction; D010545:Peroxides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000032:analysis; D013950:Thymus Gland / Q000201:enzymology / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000201:enzymology / Q000378:metabolism*; D014810:Vitamin E / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism; D020122:tert-Butylhydroperoxide
D000975:Antioxidants; D010545:Peroxides; D017382:Reactive Oxygen Species; D014970:Xanthines; D014810:Vitamin E; D019820:Xanthine; D008315:Malondialdehyde; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D005978:Glutathione