The major goal of this project is to: Determine the metabolic capabilities of the human uroepithelial cells, for activation of 4-aminobiphenyl and its N-hydroxy metabolites. Identify which of the proximate metabolites are converted to reactive electrophilic species. Identify the DNA-adducts that are generated by interaction of the ultimate electrophile with the DNA. Evaluate the biological effects of interaction of 4-aminobiphenyl derivatives with urothelial DNA - at the level of (A) mutation and (B) neoplastic transformation.
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