PUBLICATION
BDE-99, but not BDE-47, is a Transient Aryl Hydrocarbon Receptor Agonist in Zebrafish Liver Cells
- Authors
- Yang, J., Zhu, J., Chan, K.M.
- ID
- ZDB-PUB-160628-13
- Date
- 2016
- Source
- Toxicology and applied pharmacology 305: 203-15 (Journal)
- Registered Authors
- Chan, King-Ming
- Keywords
- Ahr activation, BDE-99, CYP1A, reporter-gene assay, zebrafish
- MeSH Terms
-
- Animals
- Cell Line
- Cytochrome P-450 CYP1A1/genetics*
- Cytochrome P-450 CYP1A1/metabolism
- Flame Retardants/pharmacology*
- Gene Expression/drug effects
- Genes, Reporter
- Glucuronosyltransferase/genetics*
- Halogenated Diphenyl Ethers/pharmacology*
- Liver/cytology*
- Luciferases/genetics
- Protein Domains/genetics
- Receptors, Aryl Hydrocarbon/agonists*
- Receptors, Aryl Hydrocarbon/genetics
- Receptors, Steroid/genetics
- Zebrafish
- Zebrafish Proteins/genetics
- PubMed
- 27343407 Full text @ Tox. App. Pharmacol.
- CTD
- 27343407
Citation
Yang, J., Zhu, J., Chan, K.M. (2016) BDE-99, but not BDE-47, is a Transient Aryl Hydrocarbon Receptor Agonist in Zebrafish Liver Cells. Toxicology and applied pharmacology. 305:203-15.
Abstract
Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting chemicals that affect the environment and the health of humans and wildlife. In this study, the zebrafish liver (ZFL) cell line was used in vitro to investigate two major PBDE contaminants: 2, 2', 4, 4', 5-pentabromodiphenyl ether (BDE-99) and 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47). BDE-99 was found to significantly induce cytochrome P450 (CYP1A), uridine diphosphate glucuronosyl transferase 1 family a, b (ugt1ab), 7-ethoxyresorufin-O-deethylase activity and an aryl hydrocarbon receptor (Ahr) dependent xenobiotic response element luciferase reporter system, confirming the Ahr-mediated activation of CYP1A by BDE-99. The time-course effect indicated that the role of BDE-99 in Ahr-mediated signaling is likely to be transient and highly dependent on the ability of BDE-99 to induce CYP1A and ugt1ab, and presumably its metabolism. BDE-99 also exhibited a significant dose-response effect on a developed zebrafish pregnane X receptor luciferase reporter gene system. However, the other abundant contaminant under study, BDE-47, did not exhibit the above effects. Together, these results indicated that the molecular mechanism of PBDEs induced in ZFL cells is a chemically specific process that differs between members of the PBDE family. CYP1A induction derived by BDE-99 warrants further risk assessment as the humans, wildlife and environment are exposed to a complex mixture including dioxin-like compounds and carcinogenic compounds.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping