title: Dose validation of PhIP hair level as a biomarker of heterocyclic aromatic amines exposure: a feeding study.
abstract: Hair measurement of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a promising biomarker of exposure to this carcinogen formed in cooked meats. However, the dose relationship between normal range intake and hair levels and the modulating effects of CYP1A2 metabolism and hair melanin need to be evaluated. We conducted a randomized, cross-over feeding study among 41 non-smokers using ground beef cooked to two different levels of doneness, 5 days a week for 1 month. PhIP was measured by liquid chromatography/mass spectrometry in food (mean low dose = 0.72 µg/serving; mean high dose = 2.99 µg/serving), and change in PhIP hair level was evaluated. CYP1A2 activity was assessed in urine with the caffeine challenge test and head hair melanin was estimated by UV spectrophotometry. We observed a strong dose-dependent increase in hair PhIP levels. This increase was highly correlated with dose received (ρ = 0.68, P < 0.0001). CYP1A2 activity and normalizing for hair melanin did not modify the response to the intervention. Consumption of PhIP at doses similar to those in the American diet results in a marked dose-dependent accumulation of PhIP in hair. Hair PhIP levels may be used as a biomarker of dietary exposure in studies investigating disease risk.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Kim
authors.initials: K
authors.lastname: Yonemori
authors.forename: Kami K
authors.initials: KK
authors.lastname: White
authors.affiliation: Analytical Biochemistry Shared Resource, University of Hawaii Cancer Center, Honolulu, HI 96813, USA and.
authors.forename: Adrian A
authors.initials: AA
authors.lastname: Franke
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.affiliation: Masonic Cancer Center and Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 2231 6th St SE, Minneapolis, MN 55455, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Turesky
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000302:isolation & purification / Q000378:metabolism*; D002273:Carcinogens / Q000302:isolation & purification / Q000633:toxicity*; D002417:Cattle; D002853:Chromatography, Liquid; D003296:Cooking; D019388:Cytochrome P-450 CYP1A2 / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D005504:Food Analysis; D006197:Hair / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000302:isolation & purification / Q000633:toxicity*; D013058:Mass Spectrometry; D008460:Meat / Q000009:adverse effects; D008543:Melanins / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D007093:Imidazoles; D008543:Melanins; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019388:Cytochrome P-450 CYP1A2