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-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by recombinant human P450 1A2 were 10-19-fold higher than rat P450 1A2, while methoxyresorufin O-demethylation activity was comparable for both P450s. Similar findings were observed with rat and human liver microsomal samples. Interspecies differences in P450 enzyme expression and catalytic activities may be significant and must be considered when assessing human health risk.
Turesky
R J
RJ
Nestle Research Center, Nestec Ltd., Vers-chez-les-Blanc, Lausanne, Switzerland. robert.turesky@rdls.nestle.com
Constable
A
A
Fay
L B
LB
Guengerich
F P
FP
D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D011804:Quinolines / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013045:Species Specificity; D013379:Substrate Specificity
D007093:Imidazoles; D011804:Quinolines; D011994:Recombinant Proteins; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019388:Cytochrome P-450 CYP1A2; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline