Effects of lupus-inducing drugs on the B to Z transition of synthetic DNA

Arthritis Rheum. 1986 May;29(5):638-45. doi: 10.1002/art.1780290508.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Canavanine / pharmacology
  • Circular Dichroism
  • DNA*
  • Hydralazine / pharmacology
  • Isoniazid / pharmacology
  • Lupus Erythematosus, Systemic / chemically induced*
  • Nucleic Acid Conformation / drug effects*
  • Penicillamine / pharmacology
  • Polydeoxyribonucleotides
  • Procainamide / pharmacology


  • Polydeoxyribonucleotides
  • Hydralazine
  • Canavanine
  • poly(dG-m(5)dC).poly(dG-m(5)dC)
  • DNA
  • Penicillamine
  • Procainamide
  • Isoniazid