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)

Environmental Pollution
By: , and 

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Abstract

Background: 3,3’-Dichlorobiphenyl (PCB-11) is a non-legacy PCB congener widely detected in environmental samples and has been detected in human serum, but its toxicity potential is poorly understood. Objectives: We measured PCB-11 in wild caught fish and assessed its embryotoxicity and interactions with the aryl hydrocarbon receptor (Ahr) pathway in developing zebrafish (Danio rerio). Methods: PCB-11 was measured in wild freshwater fish from a river in Western Massachusetts. In the laboratory, zebrafish embryos were exposed to 45 µg/L, 450 µg/L, or 4,500 µg/L PCB-11 from 24-96 hours post fertilization (hpf), when they were assessed for gross morphology and Cyp1a activity using the in vivo EROD bioassay. Ahr pathway interactions were probed by co-exposing zebrafish to the Ahr agonists PCB-126 and the model PAH beta-naphthoflavone (BNF). Liver development was assessed using the Tg(gut:GFP) zebrafish line. Zebrafish exposed to 4,500 µg/L PCB-11 were also collected at 96 hpf for qRT-PCR, RNAseq, and histology. Results: Environmental concentrations of PCB-11 ranged from 103.0-136.0 ng/kg wet weight in wild fish tissue. Exposure to PCB-11 alone mildly affected EROD activity but did not affect gross morphology. However, 4,500 µg/L PCB-11 alone altered the expression of xenobiotic metabolism and liver development genes, impeded liver development, and increased vacuole formation in histology sections. In co-exposures, 4,500 µg/L PCB-11 prevented deformities caused by PCB-126 but exacerbated deformities in co-exposures with BNF. Discussion: PCB-11 is present in wild fish caught near a paper recycling facility in Western Massachusetts. Higher concentrations that may be present elsewhere such as the 4,500 µg/L PCB-11 concentration tested in zebrafish, can affect liver development, act as both a partial agonist/antagonist of the Ahr pathway, and act as an antagonist of Cyp1a activity to modify the toxicity of compounds that interact with the Ahr pathway.

Additional publication details

Publication type Article
Publication Subtype Journal Article
Title 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)
Series title Environmental Pollution
DOI 10.1016/j.envpol.2019.113027
Volume 254
Issue Part A
Year Published 2019
Language English
Publisher Elsevier
Contributing office(s) Leetown Science Center
Description 113027
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