title: In vivo human metabolism of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
abstract: 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 microg [2-14C] PhIP (17.5 [microCi 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.
authors.affiliation: Surgery Service, Little Rock VA Hospital, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, 72205, USA.
authors.forename: N P
authors.initials: NP
authors.lastname: Lang
authors.forename: S
authors.initials: S
authors.lastname: Nowell
authors.forename: M A
authors.initials: MA
authors.lastname: Malfatti
authors.forename: K S
authors.initials: KS
authors.lastname: Kulp
authors.forename: M G
authors.initials: MG
authors.lastname: Knize
authors.forename: C
authors.initials: C
authors.lastname: Davis
authors.forename: J
authors.initials: J
authors.lastname: Massengill
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: S
authors.initials: S
authors.lastname: MacLeod
authors.forename: K H
authors.initials: KH
authors.lastname: Dingley
authors.forename: J S
authors.initials: JS
authors.lastname: Felton
authors.forename: K W
authors.initials: KW
authors.lastname: Turteltaub
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood* / Q000633:toxicity / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry; D009153:Mutagens / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity
chemical_list: D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine