4-Aminobiphenyl and Nitric Oxide Synergistically Modified Human DNA: It’s Implication in Bladder Cancer

Bladder cancer is a disease of continuing public health significance. Some known risk factors for bladder cancer development include smoking, occupational exposure, genetic susceptibility, infectious diseases and radiation therapy. Smoking and occupational exposure have strongly implicated aromatic amines as being carcinogenic for the bladder, with 4-aminobiphenyl (4-ABP) being one of the most potent. 4-ABP is a major etiological agent of human bladder cancer, and its metabolites are able to form DNA adducts that may induce mutation and initiate bladder carcinogenesis. Binding characteristics and specificity of bladder cancer anti-DNA antibodies were analyzed by direct binding and inhibition enzyme-linked immunosorbent assay. The data show preferential binding of bladder cancer antibodies to 4-ABP-NOmodified DNA in comparison with native native DNA. A band shift assay further substantiated the enhanced recognition of 4-ABP-NO-modified DNA by anti-DNA antibodies. Cancer antibodies exhibited enhanced binding with the modified human DNA as compared to the native form. Lymphocyte DNA from cancer patients showed appreciable recognition of anti-4-ABP–NO-DNA IgG as compared to the DNA from healthy subjects. The 4-ABP-NOmodified DNA presents unique epitopes which may be one of the factors for the autoantibody induction in bladder cancer patients.