Induction of cell differentiation potentiates apoptosis triggered by prior exposure to DNA-damaging drugs

At the end of their life span, differentiated cells die by apoptosis. Subsets of cells also die, in some cell systems, shortly after exposure to differentiating agents. This suggests that early during differentiation the cells may undergo “priming, ” during which synthesis and/or activation and accumulation of effectors of apoptosis occurs. The objective of the present study was to test the hypothesis that the signal for apoptosis provided by DNA-damaging drugs given prior to induction of differentiation will be more effective in triggering apoptosis than when given following induction of differentiation. Human promyelocytic HL-60 cells were treated with the topoisomerase I inhibitor camptothecin, the alkylating agent nitrogen mustard, or 5’-azacytidine