CELL-DEATH PROTECTION BY 3-AMINOBENZAMIDE AND OTHER POLY(ADP-RIBOSE)POLYMERASE INHIBITORS - DIFFERENT EFFECTS ON HUMAN NATURAL-KILLER AND LYMPHOKINE-ACTIVATED KILLER-CELL ACTIVITIES

The death of target cells by cytotoxic effector cells is a relevant biological phenomenon, where cells are activated and a very quick apoptotic program occurs. In order to test the hypothesis that the nuclear enzyme poly(AD P-ribose)polymerase (PADPRP) plays a role in such a process, a variety of PADPRP inhibitors such as 3-aminobenzamide, nicotinamide, 4-aminobenzamide and luminol were used. All of them were able to strongly inhibit K562 target cell killing by human effector natural killer cells (NK) in a 4hr Cr-51 release assay. PADPRP inhibitors were much less effective in protecting target cells when lymphokine activated killer cells (LAK) were used as effecters. These substances were active only when both target and effector cells were mixed, being ineffective on target or effector cells alone. On the whole, these data indicate that PADPRP is involved in the death of target cells. Moreover, the different sensitivity of NK and LAK activities to PADPRP inhibitors suggests that the molecular mechanisms underlying these two types of cytotoxicity are at least partially different.