REACTIVE OXYGEN INTERMEDIATE(S) (ROI) - COMMON MEDIATOR(S) OF POLY(ADP-RIBOSE)POLYMERASE (PARP) CLEAVAGE AND APOPTOSIS

HL-60 acute myeloblastic and U937 monoblastoid leukaemic cell lines bo th cleave poly(ADP-ribose)polymerase (PARP), at the onset of apoptosis , in response to a wide range of cytotoxic agents. This appears to be a common feature of leukaemic cell apoptosis, However, in the chronic myelogenous leukaemic (CML) derived cell line, K562, no such cleavage was detectable. This correlated with previous findings that this cell line is particularly resistant to apoptosis induced by cytotoxic agent s. Proteolytic cleavage of PARP and the subsequent progression to apop tosis was inhibited by two protease inhibitors NEM and IOD. As both PA RP cleavage and DNA fragmentation appeared closely Linked in these cel l lines, anti-oxidants (previously shown to be effective inhibitors of DNA fragmentation and apoptosis) were also demonstrated to prevent PA RP cleavage. These results combine to suggest that ROI may mediate PAR P cleavage, DNA fragmentation and the eventual apoptosis of these cell s following cytotoxic insult.