Apoptotic death of lymphocytes upon treatment with 2-chloro-2'-deoxyadenosine (2-CdA)

In this work we addressed the question if the difference in the mechanism by which 2-CdA kills resting and proliferating cells could be responsible for the therapeutic window of the drug. We show that 2-CdA triggers programmed cell death in proliferating human promyelocytic cell line, HL-60, human lymphocytic cell line, MOLT-4, and human peripheral blood lymphocytes stimulated to proliferation by PHA. Under our experimental conditions 2-CdA failed to induce apoptosis in the resting human peripheral blood lymphocytes despite induction of massive apoptosis in the same lymphocytes stimulated to proliferation by PHA. We also show that 2-CdA-induced apoptosis in HL-60 and MOLT-4 cells can not be prevented by addition of nicotinamide or inhibiting poly(ADP-ribose) synthetase by 3-aminobenzamide. In the case of HL-60 cells apoptosis is specific to the S phase of the cell cycle. Taking together these data suggest that selective induction of apoptosis in proliferating cells may be responsible for the therapeutic value of 2-CdA.