生化学と分析生化学

概要

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

Md. Asad Khan, Kiran Dixit, Moinuddin and Khursheed Alam

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-NO- modified DNA presents unique epitopes which may be one of the factors for the autoantibody induction in bladder cancer patients. The results suggest that 4-ABP-NO-modification of self-antigen(s) can generate neoepitopes capable of inducing bladder cancer characteristic autoantibodies. The preferential binding of 4-ABP-NO-modified DNA bladder cancer anti- DNA antibodies points out the likely role of oxidatively modified in the initiation/progression of bladder cancer. Moreover, oxidatively modified genomic DNA antigen, appear to be more suitable as a trigger for bladder cancer. The aim of this study was to evaluate whether biomarkers of environmental tobacco smoke exposure [i.e., 4-aminobiphenylDNA (4-ABP-DNA) adducts] were common pathway for the predictive of the risk of cancers.