PUBLICATION
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)
- Authors
- Roy, M.A., Sant, K.E., Venezia, O.L., Shipman, A.B., McCormick, S.D., Saktrakulkla, P., Hornbuckle, K.C., Timme-Laragy, A.R.
- ID
- ZDB-PUB-190820-4
- Date
- 2019
- Source
- Environmental pollution (Barking, Essex : 1987) 254: 113027 (Journal)
- Registered Authors
- Keywords
- 3,3?-dichlorobiphenyl, Aryl hydrocarbon receptor (Ahr) pathway, Danio rerio, Developmental toxicity, Mixtures, PCB-11
- Datasets
- GEO:GSE118955
- MeSH Terms
-
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/physiology
- Water Pollutants, Chemical/toxicity*
- Receptors, Aryl Hydrocarbon/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Ligands
- Toxicity Tests
- Animals
- Animals, Genetically Modified
- Polychlorinated Biphenyls/toxicity*
- Zebrafish/embryology
- Zebrafish/metabolism
- Cytochrome P-450 CYP1A1/metabolism*
- PubMed
- 31421573 Full text @ Environ. Pollut.
Citation
Roy, M.A., Sant, K.E., Venezia, O.L., Shipman, A.B., McCormick, S.D., Saktrakulkla, P., Hornbuckle, K.C., Timme-Laragy, A.R. (2019) 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 (Barking, Essex : 1987). 254:113027.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping