CELLULAR OXIDATIVE STRESS AND THE CONTROL OF APOPTOSIS BY WILD-TYPE P53, CYTOTOXIC COMPOUNDS, AND CYTOKINES

Apoptosis induced by wild-type p53 or cytotoxic compounds in myeloid l eukemic cells can be inhibited by the cytokines interleukin 6, interle ukin 3, granulocyte-macrophage colony-stimulating factor, and interfer on gamma and by antioxidants. The antioxidants and cytokines showed a cooperative protective effect against induction of apoptosis, Cells wi th a higher intrinsic level of peroxide production showed a higher sen sitivity to induction of apoptosis and required a higher cytokine conc entration to inhibit apoptosis, Decreasing the intrinsic oxidative str ess in cells by antioxidants thus inhibited apoptosis, whereas increas ing this intrinsic stress by adding H2O2 enhanced apoptosis, Induction of apoptosis by wild-type p53 was not preceded by increased peroxide production or lipid peroxidation and the protective effect of cytokine s was not associated with a decrease in these properties, The results indicate that the intrinsic degree of oxidative stress can regulate ce ll susceptibility to wild-type p53-dependent and p53-independent induc tion of apoptosis and the ability of cytokines to protect cells agains t apoptosis.