Effect of ADP-ribosyl transferase inhibitors on the survival of human lymphocytes after exposure to different DNA-damaging agents

ADP-ribosyl transferase (ADPRT) is a nuclear enzyme activated by single (SSB) and double (DSB) DNA strand breaks which synthesizes ADP-ribose homopolymers bound to nuclear proteins. The physiological role of ADPRT is still poorly understood, although it has been suggested that it plays a role in DNA repair and cell proliferation and differentiation. Excessive activation of the enzyme can exhaust intracellular NAD⁺ and ATP pools, thereby contributing to the so-called suicide response of extensively damaged cells. We asked whether ADPRT inhibitors, such as 3-aminobenzamide (3-ABA) and nicotinamide (NAM), would prevent the suicide response of human lymophocyte damaged by gamma rays in the same way as in lymphocytes damaged by oxygen radicals, taking into account that cells damaged by both agents show increased ADPRT activity and DNA strand breaks.