Effects of lupus-inducing drugs on the B to Z transition of synthetic DNA.
Five drugs associated with systemic lupus erythematosus were studied for their effect on the salt-induced right-handed (B) to left-handed (Z) transition of poly(dG-me5dC) X poly(dG-me5dC). Using circular dichroism spectroscopy, procainamide and hydralazine were found to reduce the midpoint of B to Z transition from 0.8M NaCl to 0.5M NaCl and to increase the rate of this transition at 1M NaCl. Isoniazid and D-penicillamine had less effect on the midpoint of transition and practically no effect on the kinetics. N-acetyl procainamide (a structurally related control for procainamide) and L-canavanine had no effect. Procainamide caused slight reduction in the helix-coil transition (melting) temperature of calf thymus DNA. At a concentration of 1:1 (DNA phosphate:drug ratio), procainamide and hydralazine also caused the aggregation of calf thymus DNA. Since altered DNA conformations, such as Z-DNA, are more immunogenic, these results suggest that the induction or stabilization of Z-DNA by these drugs might be important in the pathogenesis of at least some cases of systemic lupus erythematosus.
D002172:Canavanine / Q000494:pharmacology; D002942:Circular Dichroism; D004247:DNA; D006830:Hydralazine / Q000494:pharmacology; D007538:Isoniazid / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced*; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D010396:Penicillamine / Q000494:pharmacology; D011089:Polydeoxyribonucleotides; D011342:Procainamide / Q000494:pharmacology
D011089:Polydeoxyribonucleotides; D006830:Hydralazine; D002172:Canavanine; C029988:poly(dG-m(5)dC).poly(dG-m(5)dC); D004247:DNA; D010396:Penicillamine; D011342:Procainamide; D007538:Isoniazid