Hydroxylated polychlorinated biphenyls as inhibitors of the sulfation and glucuronidation of 3-hydroxy-benzo[a]pyrene

Peter van den Hurk; Gerhard A Kubiczak; Hans-Joachim Lehmler; Margaret O James

doi:10.1289/ehp.02110343

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Hydroxylated polychlorinated biphenyls as inhibitors of the sulfation and glucuronidation of 3-hydroxy-benzo[a]pyrene

Journal article

Open access

Peer reviewed

Hydroxylated polychlorinated biphenyls as inhibitors of the sulfation and glucuronidation of 3-hydroxy-benzo[a]pyrene

Peter van den Hurk, Gerhard A Kubiczak, Hans-Joachim Lehmler and Margaret O James

Environmental health perspectives, Vol.110(4), pp.343-348

04/2002

DOI: 10.1289/ehp.02110343

PMCID: PMC1240796

PMID: 11940451

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Abstract

Polychlorinated biphenyls (PCBs) can be metabolized by cytochromes P450 to hydroxylated biotransformation products. In mammalian studies, some of the hydroxylated products have been shown to be strong inhibitors of steroid sulfotransferases. As a part of ongoing research into the bioavailability of environmental pollutants in catfish intestine, we investigated the effects of a series of hydroxylated PCBs (OH-PCBs) on two conjugating enzymes, phenol-type sulfotransferase and glucuronosyltransferase. We incubated cytosolic and microsomal samples prepared from intestinal mucosa with 3-hydroxy-benzo[a]pyrene and appropriate cosubstrates and measured the effect of OH-PCBs on the formation of BaP-3-glucuronide and BaP-3-sulfate. We used PCBs with 4, 5, and 6 chlorine substitutions and the phenolic group in the ortho, meta, and para positions. OH-PCBs with the phenolic group in the ortho position were weak inhibitors of sulfotransferase; the median inhibitory concentration (IC50) ranged from 330 to 526 microM. When the phenol group was in the meta or para position, the IC50 was much lower (17.8-44.3 microM). The OH-PCBs were more potent inhibitors of glucuronosyltransferase, with IC50s ranging from 1.2 to 36.4 microM. The position of the phenolic group was not related to the inhibitory potency: the two weakest inhibitors of sulfotransferase, with the phenolic group in the ortho position, were 100 times more potent as inhibitors of glucuronosyltransferase. Inhibition of glucuronosyltransferase by low concentrations of OH-PCBs has not been reported before and may have important consequences for the bioavailability, bioaccumulation, and toxicity of other phenolic environmental contaminants.

Environmental Pollutants - adverse effects

Glucuronosyltransferase - drug effects

Hydroxylation

Arylsulfotransferase - drug effects

Environmental Pollutants - pharmacokinetics

Biological Availability

Male

Dose-Response Relationship, Drug

Animals

Polychlorinated Biphenyls - adverse effects

Glucuronosyltransferase - metabolism

Digestive System - enzymology

Biotransformation

Benzopyrenes - metabolism

Catfishes - physiology

Female

Polychlorinated Biphenyls - pharmacokinetics

Arylsulfotransferase - metabolism

Details

Title: Subtitle: Hydroxylated polychlorinated biphenyls as inhibitors of the sulfation and glucuronidation of 3-hydroxy-benzo[a]pyrene
Creators: Peter van den Hurk - Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA. pvdhurk@clemson.edu
Gerhard A Kubiczak
Hans-Joachim Lehmler
Margaret O James
Resource Type: Journal article
Publication Details: Environmental health perspectives, Vol.110(4), pp.343-348
DOI: 10.1289/ehp.02110343
PMID: 11940451
PMCID: PMC1240796
NLM abbreviation: Environ Health Perspect
ISSN: 0091-6765
eISSN: 1552-9924
Publisher: United States
Grant note: ES 07375 / NIEHS NIH HHS ES 05781 / NIEHS NIH HHS ES 07380 / NIEHS NIH HHS
Language: English
Date published: 04/2002
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute
Record Identifier: 9984000922902771

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