Induction of putative new cytochrome P450 isozyme in rat liver by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Abstract

Changes in hepatic enzymes responsible for mutagenic activation of food mutagens-carcinogens by treatment with 2-amino-1-methyl-6-phenylimidazo [4, 5-b]pyridine (PhIP) in male F344 rats were examined using the Salmonella mutation test, with 3 heterocyclic aromatic amines as substrates, and further characterized by Western blot analysis with anti-P450 monoclonal antibodies (MoAbs) against rat P450IA1 and P450IA2. Enzymatical and immunochemical analyses indicated that PhIP could induce a putative new P450 isozyme, mol. wt., 51,000, together with P450IA1 and P450IA2 in rat liver microsomes. The profiles of induced P450 molecular species varied dramatically, depending on the time after PhIP administration.