Journal Article

Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-<i>b</i>]pyridine (PhIP) in humans

David G. Walters, Philip J. Young, Cynthia Agus, Mark G. Knize, Alan R. Boobis, Nigel J. Gooderham and Brian G. Lake

in Carcinogenesis

Volume 25, issue 9, pages 1659-1669
Published in print September 2004 | ISSN: 0143-3334
Published online September 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh164
Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans

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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 μg 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 N2-hydroxy-PhIP-N2-glucuronide (the major urinary metabolite of PhIP in humans), N2-hydroxy-PhIP-N3-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 N2-hydroxy-N2-PhIP-glucuronide in 0–48 h urine samples was six times that of N2-hydroxy-PhIP-N3-glucuronide. Cruciferous vegetable consumption significantly increased the urinary excretion of N2-hydroxy-PhIP-N2-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 N2-hydroxy-PhIP-N3-glucuronide was unchanged. While the urinary excretion of both PhIP metabolites accounted for ∼39% of the PhIP dose in phases 1 and 3, they accounted for ∼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.

Keywords: AUC0–∞, area under the salivary concentration/time curve; CYP, cytochrome P450; HPLC, high performance liquid chromatography; LC-MS-MS, liquid chromatography-mass-spectrometry-mass spectrometry; MeIQx, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline; MRM, multiple reaction monitoring; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; UGT, UDPglucuronosyltransferase

Journal Article.  5848 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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