Changes in polyamine catabolism in HL-60 human promyelogenous leukaemic cells in response to etoposide-induced apoptosis

The topoisomerase II inhibitor etoposide induced apoptosis in HL-60 cells w ithin 4 h of exposure to the drug, as measured by changes in morphology, DN A fragmentation and cytotoxicity assays. Etoposide-induced apoptosis was ac companied by an increase in polyamine efflux from the cells and a decrease in total polyamine content during the first 24 h of exposure to the drug. A lthough both enzyme activities increased slightly, there were no significan t changes in spermidine/spermine N-1-acetyltransferase activity or polyamin e oxidase activity. After longer exposures (48-72 h), significant induction of spermidine/spermine N-1-acetyltransferase activity and loss of polyamin e content occurred. These results suggest that polyamine oxidation and the resultant hydrogen peroxide produced may be associated with the initiation of apoptosis, while induction of the acetyltransferase and overall loss of intracellular polyamines may be involved in the final, possibly necrotic, s tages of cell death.