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 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.
Lang
N P
NP
Surgery Service, Little Rock VA Hospital, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, 72205, USA.
Nowell
S
S
Malfatti
M A
MA
Kulp
K S
KS
Knize
M G
MG
Davis
C
C
Massengill
J
J
Williams
S
S
MacLeod
S
S
Dingley
K H
KH
Felton
J S
JS
Turteltaub
K W
KW
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
D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine