Biomonitoring an Albumin Adduct of the Cooked Meat Carcinogen 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine in Humans.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is formed in cooked meats and may be linked to dietary associated colorectal, prostate, and mammary cancers. Genotoxic N-oxidized metabolites of PhIP react with the Cys 34 of albumin (Alb) to form a sulfinamide adduct, a biomarker of the biologically effective dose. We examined the kinetics of PhIP-Alb adduct formation in plasma of volunteers on a 4-week semi-controlled diet of cooked meat containing known quantities of PhIP. The adduct was below the limit of detection (LOD) (10 femtograms PhIP/mg Alb) in most subjects before the meat feeding, but increased by up to 560-fold at week four in subjects who ate meat containing 8.0 to 11.7 μg of PhIP per 150 - 200 g serving. In contrast, the adduct remained below the LOD in subjects who ingested 1.2 or 3.0 μg PhIP per serving. Correlations were not seen between PhIP-Alb adduct levels and PhIP intake levels (P = 0.76), the amount of PhIP accrued in hair (P = 0.13), the amounts of N-oxidized urinary metabolites of PhIP (P = 0.66), or caffeine CYP1A2 activity (P = 0.55), a key enzyme involved in the bioactivation of PhIP. The half-life of the PhIP-Alb adduct was less than 2 weeks, signifying that the adduct was not stable. PhIP-Alb adduct formation is direct evidence of bioactivation of PhIP in vivo. However, the PhIP hair biomarker is a longer-lived and more sensitive biomarker to assess exposure to this potential human carcinogen.