title: Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans.
abstract: Consumption of red meat is associated with an increased risk of colorectal cancer, whereas cruciferous vegetable consumption reduces cancer risk. While the mechanisms remain to be determined, cruciferous vegetables may act by altering the metabolism of carcinogens present in cooked food, such as the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The aim of this study was to evaluate the effect of cruciferous vegetable consumption on the metabolism of PhIP in 20 non-smoking Caucasian male subjects. The study consisted of three 12-day phases, namely two periods of avoidance of cruciferous vegetables (phases 1 and 3) and a high cruciferous vegetable diet period (phase 2), when subjects ingested 250 g each of Brussels sprouts and broccoli per day. At the end of each study phase, the subjects consumed a cooked meat meal containing 4.90 microg PhIP and urine samples were collected for up to 48 h. Cruciferous vegetable consumption significantly increased hepatic CYP1A2, as demonstrated by changes in saliva caffeine kinetics. Samples of N(2)-hydroxy-PhIP-N(2)-glucuronide (the major urinary metabolite of PhIP in humans), N(2)-hydroxy-PhIP-N(3)-glucuronide and their trideuterated derivatives (to serve as internal standards) were synthesized and a liquid chromatography-mass spectrometry-mass spectrometry method developed for their analysis. In phases 1 and 3, the excretion of N(2)-hydroxy-N(2)-PhIP-glucuronide in 0-48 h urine samples was six times that of N(2)-hydroxy-PhIP-N(3)-glucuronide. Cruciferous vegetable consumption significantly increased the urinary excretion of N(2)-hydroxy-PhIP-N(2)-glucuronide in 0-48 h urine samples to 127 and 136% of levels observed in phases 1 and 3, respectively. In contrast, the urinary excretion of N(2)-hydroxy-PhIP-N(3)-glucuronide was unchanged. While the urinary excretion of both PhIP metabolites accounted for approximately 39% of the PhIP dose in phases 1 and 3, they accounted for approximately 49% of the dose in phase 2. This study demonstrates that cruciferous vegetable consumption can induce both the phase I and II metabolism of PhIP in humans.
authors.affiliation: BIBRA International Ltd, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK.
authors.forename: David G
authors.initials: DG
authors.lastname: Walters
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Young
authors.forename: Cynthia
authors.initials: C
authors.lastname: Agus
authors.forename: Mark G
authors.initials: MG
authors.lastname: Knize
authors.forename: Alan R
authors.initials: AR
authors.lastname: Boobis
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Gooderham
authors.forename: Brian G
authors.initials: BG
authors.lastname: Lake
mesh_terms: D015415:Biomarkers / Q000652:urine*; D001937:Brassica / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D002853:Chromatography, Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004032:Diet; D020719:Glucuronides / Q000652:urine; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D013058:Mass Spectrometry; D014675:Vegetables; D044465:White People
chemical_list: D015415:Biomarkers; D002273:Carcinogens; D020719:Glucuronides; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019388:Cytochrome P-450 CYP1A2; D014453:Glucuronosyltransferase