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)

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.