Carcinogen-DNA Adduct Formation as a Predictor of Metabolic Activation Pathways and Reactive Intermediates in Benzidine Carcinogenesis
Benzidine (BZ) is a strong hepatocarcinogen in rats, mice and hamsters and induces mammary tumors in female rats (1–4). However, BZ has been primarily implicated as a human urinary bladder carcinogen as a result of occupational exposure in the dye and rubber industries (5). Limited carcinogenicity experiments in dogs confirm BZ’s ability to induce bladder carcinomas, although its potency in this species appears to be less than that of 4-aminobiphenyl and 2-naphthylamine (6,7). Over the last few years, we have examined carcinogen-DNA adduct formation from BZ in relation to specific metabolic activation pathways and have suggested the involvement of different biologically reactive intermediates leading to liver and urinary bladder carcinogenesis (8–15). In this paper, we will review the findings which resulted in these conclusions. In addition, we will present data on the mechanisms of BZ peroxidation and on the ability of human bladder and colon to catalyze the peroxidative activation of BZ to DNA-bound adducts.
KeywordsAcetylator Phenotype Hepatic Cytosol Carcinogenic Aromatic Amine Metabolic Activation Pathway Urinary Bladder Carcinogenesis
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