Polycyclic aromatic hydrocarbons in food--efflux of the conjugated biomarker 1-hydroxypyrene is mediated by Breast Cancer Resistance Protein (ABCG2) in human intestinal Caco-2 cells.

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are well-known food contaminants comprising compounds with carcinogenic properties. Pyrene (PYR) is an important non-carcinogenic PAH because its metabolites are frequently used as biomarkers to assess human PAH exposure. This study investigated for the first time the formation and transport of PYR metabolites in the human small intestinal Caco-2 cell model using HPLC technique. The intermediate phase I metabolite 1-hydroxypyrene formed by cytochrome P450 monooxygenases is subsequently conjugated by phase II enzymes to the water-soluble PYR 1-glucuronide as minor and PYR 1-sulfate as major metabolites. The formation of the latter is mediated by human sulfotransferases 1A1*Arg, 1A2*1, 1A3, and 1B1. Caco-2 monolayer experiments revealed a predominantly apical transport of both conjugates mediated by the breast cancer resistance protein (BCRP/ABCG2). Additional treatment with several aryl hydrocarbon receptor (AhR) agonists indicate an AhR-driven induction of PYR-metabolizing enzymes and/or ABCG2. Overall, this study provides advanced mechanistic insights into the bioavailability of PYR and underlines a key role of the human small intestinal epithelium for the first pass metabolism of contaminants in food.

• Authors: Stefanie Hessel, Alfonso Lampen, Albrecht Seidel
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 62 Pg. 797-804 (Dec 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 24140465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Biomarkers
• Neoplasm Proteins
• Polycyclic Aromatic Hydrocarbons
• Pyrenes
• Cytochrome P-450 Enzyme System
• pyrene
• Sulfotransferases
• iodothyronine sulfotransferase
• Arylsulfotransferase
• SULT1A1 protein, human
• SULT1A2 protein, human
• monoamine-sulfating phenol sulfotransferase
• 1-hydroxypyrene

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (metabolism)
• Arylsulfotransferase (metabolism)
• Biological Availability
• Biological Transport
• Biomarkers (metabolism)
• Caco-2 Cells (drug effects)
• Cytochrome P-450 Enzyme System (metabolism)
• Food Contamination
• Humans
• Neoplasm Proteins (metabolism)
• Polycyclic Aromatic Hydrocarbons (pharmacokinetics)
• Pyrenes (metabolism, pharmacokinetics)
• Sulfotransferases (metabolism)