In vivo human metabolism of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

To better understand the interactions of the pathways of activation and detoxification on the metabolism of the putative carcinogen, PhIP, we administered a dose of 70–84 μg [2-14C] PhIP (17.5 μCi 14C) 48–72 h before scheduled colon surgery. Blood and urine collected for the next 48–72 h was evaluated by linear accelerator mass spectroscopy (AMS) and scintillation counting LC-MS to identify specific PhIP metabolites. The thermostable phenol sulfotransferase (SULT1A1) phenotype was correlated with the 4′-PhIP-SO4 levels in the urine at 0–4 h (R=0.86, P=0.059). The CYP1A2 activity had a negative correlation with PhIP serum levels at 1 h (R=0.94, P=0.06) and a positive correlation with urine N-OH-PhIP levels at 0–4 h (R=0.85, P=0.15). This low level radioisotope method of determining the influence of phenotype on metabolism will significantly improve our understanding of the interrelationships of these pathways and provide a critical foundation for the development of individual risk assessment.