A comprehensive investigation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) metabolism in the mouse using a multivariate data analysis approach.

ABSTRACT: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a potent rodent carcinogen and a potential human carcinogen because of its existence in the normal human diet. N2-OH-PhIP, a major PhIP metabolite, has been identified as a precursor of genotoxic species. In vitro data supported the view that CYP1A2 is the major enzyme responsible for the formation of N2-OH-PhIP. However, disruption of the CYP1A2 gene in mouse failed to inhibit PhIP-induced carcinogenesis. To investigate the mechanism underlying this observation, the metabolism of PhIP in wild-type, Cyp1a2-null, and CYP1A2-humanized mice was examined in detail using a metabolomic approach. Following data acquisition in a high-resolution LC-MS system, urinary metabolomes of the control and PhIP-treated mice were characterized in a pr

SUBMITTER: Chen C 

PROVIDER: S-EPMC1850849 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature