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© 1989 Oxford University Press

research-article

Hepatocarcinogenic heterocyclic aromatic amines that induce cytochrome P-448 isozymes, mainly cytochrome P-448H (P-450IA2), responsible for mutagenic activation of the carcinogens in rat liver

Masakuni Degawa, Seishiro Tanimura, Toshinori Agatsuma and Yoshiyuki Hashimoto

Department of Hygienic Chemistry, Pharmaceutical Institute, Tohoku University Aobayama, Sendai 980, Japan

Male F344 rats were treated with hepatocarcinogenic heterocydic aromatic amines such as amino acid-and protein-pyrolysate components (Trp P-1, Trp P-2, Glu P-1, Glu P-2, A{alpha}C, MeA{alpha}C, IQ and MeIQx) and changes in microsomal cytochrome P-450 isozymes in the livers were examined by means of immuno-Western blotting using anti-rat cytochrome P-450 monoclonal antibodies. The results suggested that all chemicals tested induce cytochrome P-448 isozymes, particularly cytochrome P-448H (P-450IA2), which efficiently mediate mutagenic activation of the carcinogens. This was substantiated by the enzymatic analyses with the substrates showing different characters to rat cytochrome P-450 isozyme-mediated mutagenesis.


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