The production of a reactive oxygen intermediate during the induction of apoptosis by cytotoxic insult.

We report the protective effects of two novel antioxidant compounds, 3 beta-doxyl-5 alpha cholestane and 2,2,6,6-tetramethyl-piperdinoxyl, in HL-60 and U937 leukemic cells subjected to a number of cytotoxic insults. In addition, the rapid production of peroxide is demonstrated as a general response to cytotoxic agents in these leukemic cell lines, indicating that changes in the redox status of a leukemic cell may contribute to the ultimate death of these cells. Closer examination of this peroxide production has identified enzymic production and/or disruption of resident antioxidants as possible sources. However, in contrast to recent reports from other model systems, mitochondrial transmembrane depolarization did not appear to be required for the production of peroxide in these cells. Finally, we demonstrated the activation of the redox-sensitive transcription factor, NF-kappa B, in response to these cytotoxic insults.