Species difference among experimental rodents in induction of P450IA family enzymes by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Rats, mice, hamsters and guinea pigs were given an i.p. injection of 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), a protein-derived pyrolysate component present in cooked foods, and inductions of cytochrome P450 (P450) in the liver and kidney of these animals were examined. The activity and amount of P450s corresponding to the rat P450IA1 and P450IA2 were assessed by means of a bacterial mutation test using 3 carcinogenic heterocyclic aromatic amines including PhIP as substrates and by Western blotting with a monoclonal antibody reactive with both P450IA1 and P450IA2. In rats, PhIP induced P450IA1, P450IA2 and a new but unspecified P450 isozyme in the liver, and induced P450IA1 in the kidney. However, PhIP induced none of these P450 isozymes in mice, hamsters and guinea pigs.