Interspecies differences in metabolism of heterocyclic aromatic amines by rat and human P450 1A2

The catalytic efficiences of cytochrome P450 (P450)-mediated N-oxidation of the 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-me thyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by recombinant human P450 1A2 we re 10-19-fold higher than rat P450 1A2, while methoxyresorufin O-demethylat ion activity was comparable for both P450s. Similar findings were observed with rat and human liver microsomal samples. Interspecies differences in P4 50 enzyme expression and catalytic activities may be significant and must b e considered when assessing human health risk. (C) 1999 Elsevier Science Ir eland Ltd. All rights reserved.