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

To better understand the interactions of the pathways of activation and det oxification on the metabolism of the putative carcinogen, PhIP, we administ ered a dose of 70-84 mu g [2-C-14] PhIP (17.5 mu Ci C-14) 48-72 h before sc heduled colon surgery. Blood and urine collected for the next 48-72 h was e valuated by linear accelerator mass spectroscopy (AMS) and scintillation co unting LC-MS to identify specific PhIP metabolites. The thermostable phenol sulfotransferase (SULT1A1) phenotype was correlated with the 4'-PhIP-SO4 l evels 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) a nd 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 o f phenotype on metabolism will significantly improve our understanding of t he interrelationships of these pathways and provide a critical foundation f or the development of individual risk assessment. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.