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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.

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  • Authors+Show Affiliations

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    BIBRA International Ltd, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK.

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    Source

    Carcinogenesis 25:9 2004 Sep pg 1659-69

    MeSH

    Biomarkers
    Brassica
    Carcinogens
    Chromatography, Liquid
    Cytochrome P-450 CYP1A2
    Diet
    European Continental Ancestry Group
    Glucuronides
    Glucuronosyltransferase
    Humans
    Imidazoles
    Liver
    Male
    Mass Spectrometry
    Vegetables

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15073045

    Citation

    Walters, David G., et al. "Cruciferous Vegetable Consumption Alters the Metabolism of the Dietary Carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Humans." Carcinogenesis, vol. 25, no. 9, 2004, pp. 1659-69.
    Walters DG, Young PJ, Agus C, et al. Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans. Carcinogenesis. 2004;25(9):1659-69.
    Walters, D. G., Young, P. J., Agus, C., Knize, M. G., Boobis, A. R., Gooderham, N. J., & Lake, B. G. (2004). Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans. Carcinogenesis, 25(9), pp. 1659-69.
    Walters DG, et al. Cruciferous Vegetable Consumption Alters the Metabolism of the Dietary Carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Humans. Carcinogenesis. 2004;25(9):1659-69. PubMed PMID: 15073045.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans. AU - Walters,David G, AU - Young,Philip J, AU - Agus,Cynthia, AU - Knize,Mark G, AU - Boobis,Alan R, AU - Gooderham,Nigel J, AU - Lake,Brian G, Y1 - 2004/04/08/ PY - 2004/4/10/pubmed PY - 2004/10/6/medline PY - 2004/4/10/entrez SP - 1659 EP - 69 JF - Carcinogenesis JO - Carcinogenesis VL - 25 IS - 9 N2 - 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. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/15073045/full_citation L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgh164 DB - PRIME DP - Unbound Medicine ER -