EFFECT OF PROCAINAMIDE AND HYDRALAZINE ON POLY (ADP-RIBOSYLATION) IN CELL-LINES

The prescription drugs procainamide (PA) and hydralazine (HYD) are ass ociated with the induction of autoimmunity and a clinical syndrome cal led drug-induced lupus. Since PA- and HYD-induced autoantibodies are d irected primarily against histones and histones are prime acceptors of poly (ADP-ribose) (PADPR), we have investigated the effects of PA and HYD on the activity of poly (ADP-ribose) polymerase (PADPRP). Control substances, with structures similar to PA and HYD but not known to in duce lupus, included N-acetylprocainamide (NAPA) and the amino acids p henylalanine, tryptophan and proline, and their amide derivatives. Wil -2 cells were incubated in 0.5-50 muM PA, NAPA and HYD, which included therapeutic concentrations of these drugs. The mean enhancement of in corporation of [H-3]-nicotinamide adenine dinucleotide (NAD) into PADP R was 1.84 (P = 0.005) with PA, with HYD 1.48 (P = 0.029), and with NA PA 1.38 (P = 0.036). This increase was suppressed by 3-aminobenzamide, an inhibitor of PADPRP activity. Little or no increase in [H-3]-NAD i ncorporation was observed with equivalent concentrations of phenylalan ine, phenylalaninamide or tryptophan. However, a 1.29-fold increase wa s noted with 0.5 muM tryptophanamide, a 1.26-fold increase with 0.5 mu M prolinamide and a 1.4-fold increase with 50 muM proline. PA increase d PADPRP activity in B- and T-cell lines but not in promyelocytic leuk emia or epithelial cell lines. Since poly (ADP-ribosylation) is import ant in the cellular response to various agents, the increased ADP-ribo sylation of intracellular molecules may be a key event in the inductio n of autoantibodies.