Hydralazine induces Z-DNA conformation in a polynucleotide and elicits anti(Z-DNA) antibodies in treated patients.
We studied the effect of hydralazine, an antihypertensive drug with lupus-inducing side effects, on the conformation of poly(dG-m5dC).poly(dG-m5dC) and a plasmid with a 23 bp insert of (dG-dC)n.(dG-dC)n sequences. Using an e.l.i.s.a. with a monoclonal anti-(Z-DNA) antibody Z22, we found that hydralazine provoked the Z-DNA conformation in poly(dG-m5dC).poly(dG-m5dC) at 250-500 microM concentration. The supercoiled form of hydralazine-treated plasmid bound to Z22 in a gel-retardation assay. To examine further whether Z-DNA could act as an inciting agent in anti-nuclear antibody production in patients, we analysed 65 sera from 25 hypertensive patients taking hydralazine and found anti-(Z-DNA) antibodies in 82% of these sera. Sera from age-matched normal controls showed no binding to Z-DNA. Data on sera drawn sequentially from four hypertensive patients showed that antibodies were present after the drug treatment. These data demonstrate the presence of a high incidence of anti-(Z-DNA) antibodies in patients treated with hydralazine and suggest that a possible mechanism for the production of autoantibodies in drug-related lupus might involve the induction and stabilization of Z-DNA by drugs.
Thomas
T J
TJ
Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.
Seibold
J R
JR
Adams
L E
LE
Hess
E V
EV
D000107:Acetylation; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood*; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006830:Hydralazine / Q000009:adverse effects* / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009690:Nucleic Acid Conformation; D011089:Polydeoxyribonucleotides / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D011089:Polydeoxyribonucleotides; C016681:poly(dG).poly(dC); D006830:Hydralazine; D004247:DNA