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The emerging contaminant 3,3 '-dichlorobiphenyl (PCB-11) impedes Ahr activation and Cyp1a activity to modify embryotoxicity of Ahr ligands in the zebrafish embryo model (Danio rerio)
Journal article   Peer reviewed

The emerging contaminant 3,3 '-dichlorobiphenyl (PCB-11) impedes Ahr activation and Cyp1a activity to modify embryotoxicity of Ahr ligands in the zebrafish embryo model (Danio rerio)

Monika A Roy, Karilyn E Sant, Olivia L Venezia, Alix B Shipman, Stephen D McCormick, Panithi Saktrakulkla, Keri C Hornbuckle and Alicia R Timme-Laragy
ENVIRONMENTAL POLLUTION, Vol.254 Part A, 113027
2019
DOI: 10.1016/j.envpol.2019.113027
PMCID: PMC7027435
PMID: 31421573

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Abstract

3,3'-dichlorobiphenyl (PCB-11) is an emerging PCB congener widely detected in environmental samples and human serum, but its toxicity potential is poorly understood. We assessed the effects of three concentrations of PCB-11 on embryotoxicity and Aryl hydrocarbon receptor (Ahr) pathway interactions in zebrafish embryos (Danio rerio). Wildtype AB or transgenic Tg(gut:GFP) strain zebrafish embryos were exposed to static concentrations of PCB-11 (0, 0.2, 2, or 20 mu M) from 24 to 96 h post fertilization (hpf), and gross morphology, Cytochrome P4501a (Cypl a) activity, and liver development were assessed via microscopy. Ahr interactions were probed via co-exposures with PCB-126 or beta-naphthoflavone (BNF). Embryos exposed to 20 mu M PCB-11 were also collected for PCB-11 body burden, qRT-PCR, RNAseq, and histology. Zebrafish exposed to 20 mu M PCB-11 absorbed 0.18% PCB-11 per embryo at 28 hpf and 0.61% by 96 hpf, and their media retained 136% PCB-11 at 28 hpf and 0.84% at 96 hpf. This concentration did not affect gross morphology, but altered the transcription of xenobiotic metabolism and liver development genes, impeded liver development, and increased hepatocyte vacuole formation. In co-exposures, 20 mu M PCB-11 prevented deformities caused by PCB-126 but exacerbated deformities in co-exposures with BNF. This study suggests that PCB-11 can affect liver development, act as a partial agonist/antagonist of the Ahr pathway, and act as an antagonist of Cypl a activity to modify the toxicity of compounds that interact with the Ahr pathway. (C) 2019 Elsevier Ltd. All rights reserved.
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