Acquired immunogenicity of human DNA damaged by N-hydroxy-N-acetyl-4-aminobiphenyl

4-Aminobiphenyl, a known carcinogen, has many environmental sources like cigarette smoke, industrial waste, and so forth. It can be metabolized to form a potent mutagen, N-hydroxy-N-acetyl-4-aminobiphenyl (N-OH-AABP) that undergoes further processing to form electrophilic nitrenium ions which interact with DNA-forming covalent adducts, thereby exerting genotoxic effects. While the mutagenicity of N-OH-AABP has been amply reported, no extensive studies have been performed to assess the immunogenicity of N-OH-AABP-modified DNA. In this study, human placental DNA was modified with N-OH-AABP, and the structural perturbations in the DNA molecule were evaluated by ultraviolet spectroscopy and nuclease S1 digestion. Native and N-OH-AABP-modified DNA were used as antigens for immunizing female rabbits. The modified DNA was found to be highly immunogenic, eliciting high titer immunogen-specific antibodies, while the native form was almost nonimmunogenic. The induced antibodies exhibited wide range of heterogeneity in recognizing various nucleic acid conformers and DNA bases. We also detected deposits of immune complex in glomerular basement membrane in rabbits immunized with N-OH-AABP-DNA. Possible role of N-OH-AABP-DNA in the induction of antibodies in cancer patients and the related consequences have been discussed.