title: Evaluation of the toxic effects of brominated compounds (BDE-47, 99, 209, TBBPA) and bisphenol A (BPA) using a zebrafish liver cell line, ZFL.
abstract: The toxic effects of three polybrominated diphenyl ether (PBDE) congeners (BDE-47, -99, and -209), tetrabromobisphenol A (TBBPA) and bisphenol A (BPA), were evaluated by determining their 24h and 96 h median lethal concentrations using a zebrafish liver cell line, ZFL. It was found that BDE-47, BDE-99 and TBBPA showed comparative cytotoxicity within the range of 1.2-4.2 μM, and were more toxic than BPA (367.1 μM at 24 h and 357.6 μM at 96 h). However, BDE-209 induced only 15% lethality with exposures up to 25 μM. The molecular stresses of BDE-47, -99, TBBPA and BPA involved in thyroid hormone (TH) homeostasis and hepatic metabolism were also investigated. Using a reporter gene system to detect zebrafish thyroid hormone receptor β (zfTRβ) transcriptional activity, the median effective concentration of triiodothyronine (T3) was determined to be 9.2×10(-11) M. BDE-47, BDE-99, TBBPA and BPA alone, however, did not exhibit zfTRβ agonistic activity. BPA displayed T3 (0.1 nM) induced zfTRβ antagonistic activity with a median inhibitory concentration of 19.3 μM. BDE-47, BDE-99 and TBBPA displayed no antagonistic effects of T3-induced zfTRβ activity. Target gene expressions were also examined under acute exposures. The significant inhibition of different types of deiodinases by all of the test chemicals indicated TH circulation disruption. All four chemicals, especially BPA, were able to affect transcripts of phase II hepatic metabolizing enzymes (UGT2A1, SULT1) in vitro. In conclusion, the zfTRβ reporter gene system developed here helps delineate an in vitro model to enable the analysis of the TH disruption effects of environmental pollutants in fish. BPA and the brominated compounds tested were able to disrupt the TH system at the gene expression level, probably through the deiodination pathways.
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. Electronic address: kingchan@cuhk.edu.hk.
authors.forename: King Ming
authors.initials: KM
authors.lastname: Chan
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D010636:Phenols / Q000633:toxicity; D011075:Polybrominated Biphenyls / Q000633:toxicity; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism; D013963:Thyroid Hormones / Q000032:analysis; D014284:Triiodothyronine / Q000032:analysis; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D055768:Halogenated Diphenyl Ethers; D010636:Phenols; D011075:Polybrominated Biphenyls; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D014284:Triiodothyronine; D014874:Water Pollutants, Chemical; C477694:2,2',4,4',5-brominated diphenyl ether; C511295:2,2',4,4'-tetrabromodiphenyl ether; C020806:tetrabromobisphenol A; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C010902:decabromobiphenyl ether
keywords: Endocrine disruption; Reporter gene system; Thyroid hormone receptor