Metabolism of 3‑Chlorobiphenyl (PCB 2) in a Human-Relevant Cell Line: Evidence of Dechlorinated Metabolites

Chun-Yun Zhang; Xueshu Li; Susanne Flor; Patricia Ruiz; Anneli Kruve; Gabriele Ludewig; Hans-Joachim Lehmler

doi:10.1021/acs.est.2c03687

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Metabolism of 3‑Chlorobiphenyl (PCB 2) in a Human-Relevant Cell Line: Evidence of Dechlorinated Metabolites

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Metabolism of 3‑Chlorobiphenyl (PCB 2) in a Human-Relevant Cell Line: Evidence of Dechlorinated Metabolites

Chun-Yun Zhang, Xueshu Li, Susanne Flor, Patricia Ruiz, Anneli Kruve, Gabriele Ludewig and Hans-Joachim Lehmler

Environmental science & technology, Vol.56(17), pp.12460-12472

08/22/2022

DOI: 10.1021/acs.est.2c03687

PMCID: PMC9573771

PMID: 35994059

Appears in UI Libraries Support Open Access

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Abstract

Lower chlorinated polychlorinated biphenyls (LC-PCBs) and their metabolites make up a class of environmental pollutants implicated in a range of adverse outcomes in humans; however, the metabolism of LC-PCBs in human models has received little attention. Here we characterize the metabolism of PCB 2 (3-chlorobiphenyl), an environmentally relevant LC-PCB congener, in HepG2 cells with in silico prediction and nontarget high-resolution mass spectrometry. Twenty PCB 2 metabolites belonging to 13 metabolite classes, including five dechlorinated metabolite classes, were identified in the cell culture media from HepG2 cells exposed for 24 h to 10 μM or 3.6 nM PCB 2. The PCB 2 metabolite profiles differed from the monochlorinated metabolite profiles identified in samples from an earlier study with PCB 11 (3,3′-dichlorobiphenyl) under identical experimental conditions. A dechlorinated dihydroxylated metabolite was also detected in human liver microsomal incubations with monohydroxylated PCB 2 metabolites but not PCB 2. These findings demonstrate that the metabolism of LC-PCBs in human-relevant models involves the formation of dechlorination products. In addition, untargeted metabolomic analyses revealed an altered bile acid biosynthesis in HepG2 cells. Our results indicate the need to study the disposition and toxicity of complex PCB 2 metabolites, including novel dechlorinated metabolites, in human-relevant models.

ADMET predictor

PCB 2 metabolites

HepG2 cells

MetaDrug

Nt-HRMS

dechlorination

untargeted metabolomics

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Details

Title: Subtitle: Metabolism of 3‑Chlorobiphenyl (PCB 2) in a Human-Relevant Cell Line: Evidence of Dechlorinated Metabolites
Creators: Chun-Yun Zhang - University of Iowa
Xueshu Li - University of Iowa
Susanne Flor - University of Iowa
Patricia Ruiz - Agency for Toxic Substances and Disease Registry
Anneli Kruve - Stockholm University
Gabriele Ludewig - University of Iowa
Hans-Joachim Lehmler - University of Iowa
Resource Type: Journal article
Publication Details: Environmental science & technology, Vol.56(17), pp.12460-12472
DOI: 10.1021/acs.est.2c03687
PMID: 35994059
PMCID: PMC9573771
NLM abbreviation: Environ Sci Technol
ISSN: 0013-936X
eISSN: 1520-5851
Publisher: American Chemical Society
Grant note: DOI: 10.13039/100000066, name: National Institute of Environmental Health Sciences, award: ES005605, ES013661, ES014901, ES027169, ES031098
Language: English
Date published: 08/22/2022
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Radiation Oncology; Iowa Superfund Research Program
Record Identifier: 9984294941102771

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