title: Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.
abstract: BACKGROUND
  The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP) and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions. Although several studies have reported the formation of 4-ABP-DNA adducts, no extensive work has been done to investigate the immunogenicity of 4-ABP-modified DNA and its possible involvement in the generation of antibodies in bladder cancer patients.
  
  
  RESULTS
  Human DNA was modified by N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), a reactive metabolite of 4-ABP. Structural perturbations in the N-OH-AABP modified DNA were assessed by ultraviolet, fluorescence, and circular dichroic spectroscopy as well as by agarose gel electrophoresis. Genotoxicity of N-OH-AABP modified DNA was ascertained by comet assay. High performance liquid chromatography (HPLC) analysis of native and modified DNA samples confirmed the formation of N-(deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-4ABP) in the N-OH-AABP damaged DNA. The experimentally induced antibodies against N-OH-AABP-modified DNA exhibited much better recognition of the DNA isolated from bladder cancer patients as compared to the DNA obtained from healthy individuals in competitive binding ELISA.
  
  
  CONCLUSIONS
  This work shows epitope sharing between the DNA isolated from bladder cancer patients and the N-OH-AABP-modified DNA implicating the role of 4-ABP metabolites in the DNA damage and neo-antigenic epitope generation that could lead to the induction of antibodies in bladder cancer patients.
authors: Department of Biochemistry, J N Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh, India.
authors: Uzma
authors: U
authors: Shahab
authors: Moinuddin
authors: Saheem
authors: S
authors: Ahmad
authors: Kiran
authors: K
authors: Dixit
authors: Safia
authors: S
authors: Habib
authors: Khursheed
authors: K
authors: Alam
authors: Asif
authors: A
authors: Ali
mesh_terms: D000611:Aminobiphenyl Compounds / Q000633:toxicity*; D000974:Antibodies, Antinuclear / Q000737:chemistry / Q000276:immunology; D002273:Carcinogens / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D018736:DNA Adducts / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D009690:Nucleic Acid Conformation / Q000187:drug effects; D010920:Placenta / Q000737:chemistry / Q000187:drug effects; D011247:Pregnancy; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*
chemical_list: D000611:Aminobiphenyl Compounds; D000974:Antibodies, Antinuclear; D002273:Carcinogens; D018736:DNA Adducts; C001365:N-hydroxy-4-acetylaminobiphenyl; D004247:DNA
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