The effect of hydroxyl radical on the antigenicity of native DNA

Abstract

Hydroxyl free-radical mediated in vitro modification of native calf thymus DNA showed single-strand breaks, decrease in melting temperature and structural alteration of purine and pyrimidine bases. Experimentally induced antibodies against modified DNA exhibited polyspecificity. Native DNA, RNA and synthetic polynucleotides in B-conformation were found to be an effective inhibitor of induced antibody-immunogen interaction. Naturally occurring human anti-DNA autoantibodies showed enhanced recognition of modified DNA as compared to native polymer. IgG isolated from anti-DNA antibody-positive SLE sera by Protein A-Sepharose 4B chromatography were affinity purified on nDNA-(polylysyl-Sepharose 4B) matrix. In competitive binding experiments, the affinity-isolated IgG showed almost equal recognition of both native DNA and hydroxyl radical modified DNA. The possible role of hydroxyl radicals in the etiopathogenesis of SLE has been discussed.