title: BDE-99, but not BDE-47, is a transient aryl hydrocarbon receptor agonist in zebrafish liver cells.
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.
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong Special Administrative Region.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong Special Administrative Region.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong Special Administrative Region. Electronic address: kingchan@cuhk.edu.hk.
authors.forename: King Ming
authors.initials: KM
authors.lastname: Chan
mesh_terms: D000818:Animals; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D005411:Flame Retardants / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D014453:Glucuronosyltransferase / Q000235:genetics*; D055768:Halogenated Diphenyl Ethers / Q000494:pharmacology*; D008099:Liver / Q000166:cytology*; D008156:Luciferases / Q000235:genetics; D000077297:Pregnane X Receptor; D000072417:Protein Domains / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D019363:Cytochrome P-450 CYP1A1; D005411:Flame Retardants; D014453:Glucuronosyltransferase; D055768:Halogenated Diphenyl Ethers; D008156:Luciferases; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon; D011987:Receptors, Steroid; D029961:Zebrafish Proteins; D000099148:UGT1A1 Enzyme; C477694:2,2',4,4',5-brominated diphenyl ether; C511295:2,2',4,4'-tetrabromodiphenyl ether
keywords: Ahr activation; BDE-99; CYP1A; Reporter-gene assay; Zebrafish