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

Abstract

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.

• Authors: T J Thomas, R P Messner
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 29 Issue 5 Pg. 638-45 (May 1986) ISSN: 0004-3591 [Print] United States
• PMID: 3718555 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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