REACTIVE OXYGEN SPECIES MODIFIED THYMINE AND POLY(DT) PRESENT UNIQUE EPITOPE FOR HUMAN ANTI-DNA AUTOANTIBODIES

Hydroxyl radical, one of the most potent of all reactive oxygen specie s has been implicated in many human degenerative diseases and is known to modify adenine and thymine in cellular DNA. In the present studies , adenine, thymine and their synthetic homopolymers poly(dA), poly(dT) were ROS-modified and subsequently used as inhibitors of native DNA b inding to human anti-DNA autoantibodies. Besides nDNA, modified thymin e and poly(dT) were effective inhibitors of DNA-anti-DNA antibody inte raction. The relative affinity of ROS-modified poly(dT) was better tha n that of native DNA. Visual detection of modified thymine and poly(dT ) binding to affinity purified anti-DNA IgG by an indirect band shift assay support competition inhibition data. The enhanced recognition of ROS-DNA by anti-DNA autoantibodies, as reported earlier, could be due to the ROS-induced modification of thymine. (C) 1997 Elsevier Science B.V.