Details

Autor(en) / Beteiligte

• Roy, Monika A.
• Sant, Karilyn E.
• Venezia, Olivia L.
• Shipman, Alix B.
• McCormick, Stephen D.
• Saktrakulkla, Panithi
• Hornbuckle, Keri C.
• Timme-Laragy, Alicia R.

Titel

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)

Ist Teil von

• Environmental pollution (1987), 2019-11, Vol.254 (Pt A), p.113027-113027, Article 113027

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 μM) from 24 to 96 h post fertilization (hpf), and gross morphology, Cytochrome P4501a (Cyp1a) 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 μM PCB-11 were also collected for PCB-11 body burden, qRT-PCR, RNAseq, and histology. Zebrafish exposed to 20 μM PCB-11 absorbed 0.18% PCB-11 per embryo at 28 hpf and 0.61% by 96 hpf, and their media retained 1.36% 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 μM 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 Cyp1a activity to modify the toxicity of compounds that interact with the Ahr pathway. [Display omitted] •Less than 1% of 20 μM PCB-11 administered to zebrafish embryos is absorbed into tissue.•20 μM PCB-11 alone does not affect gross morphology but alters liver-related gene expression and stunts liver development.•Co-exposures of 20 μM PCB-11 with Ahr agonists either rescues or exacerbates toxicity, depending on the co-exposure. Exposure to PCB-11 can impede liver development, modify aryl hydrocarbon receptor activation, and inhibit Cytochrome P4501a (Cyp1a) enzyme activity.