The role of cytochromes P-450 and N-acetyl transferase in the carcinogenicity of aromatic amines and amides.

Abstract

1. Epidemiological studies have clearly identified the aromatic amines 2-naphthylamine, benzidine and 4-aminobiphenyl as human carcinogens. Many other compounds of this class are suspected to be human carcinogens. 2. At least 12 heterocyclic aromatic amines have been isolated from cooked food, nine of which have been shown to be carcinogenic in vivo. The significance of these compounds in the aetiology of human cancer is yet to be established. 3. Specific forms of cytochrome P-450 have been shown to be involved in the initial step in the activation (N-hydroxylation) of aromatic amines and amides. A possible polymorphism exists for the N-hydroxylation of 2-acetylaminofluorene in human liver microsomes. 4. N-Acetyltransferase is involved in the further activation of arylhydroxamic acids and N-hydroxyarylamines to reactive intermediates. Polymorphisms in the expression of this enzyme activity have been associated with certain types of human cancer. 5. Polymorphisms in both cytochrome P-450 and N-acetyltransferase expression may be critical determinants in the susceptibility of individuals to the toxicity and carcinogenicity of aromatic amines and amides.