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Effect of Procainamide and Hydralazine on Poly (ADP-ribosylation) in Cell Lines

Joint Injury and Arthritis Research Group, University of Calgary, Calgary, Alberta, Canada

Steven M. Edworthy

Joint Injury and Arthritis Research Group, University of Calgary, Calgary, Alberta, Canada

Marvin J. Fritzler

Joint Injury and Arthritis Research Group, University of Calgary, Calgary, Alberta, Canada

The prescription drugs procainamide (PA) and hydralazine (HYD) are associated with the induction of autoimmunity and a clinical syndrome called drug-induced lupus. Since PA- and HYD-induced autoantibodies are directed 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 induce lupus, included N-acetylprocainamide (NAPA) and the amino acids phenylalanine, tryptophan and proline, and their amide derivatives. Wil-2 cells were incubated in 0.5-50 µM PA, NAPA and HYD, which included therapeutic concentrations of these drugs. The mean enhancement of incorporation of [³H]-nicotinamide adenine dinucleotide (NAD) into PADPR was 1.84 (P = 0.005) with PA, with HYD 1.48 (P = 0.029), and with NAPA 1.38 (P = 0.036). This increase was suppressed by 3-aminobenzamide, an inhibitor of PADPRP activity. Little or no increase in [³H]-NAD incorporation was observed with equivalent concentrations of phenylalanine, phenylalaninamide or tryptophan. However, a 1.29-fold increase was noted with 0.5 µM tryptophanamide, a 1.26-fold increase with 0.5 µM prolinamide and a 1.4-fold increase with 50 µM proline. PA increased PADPRP activity in B- and T-cell lines but not in promyelocytic leukemia or epithelial cell lines. Since poly (ADP-ribosylation) is important in the cellular response to various agents, the increased ADP-ribosylation of intracellular molecules may be a key event in the induction of autoantibodies.

Key Words: Drug-induced lupus • Poly (ADP-ribosylation) • Procainamide • Hydralazine

Lupus, Vol. 2, No. 3, 167-172 (1993)
DOI: 10.1177/096120339300200307


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