title: Comparison of in vitro hormone activities of novel flame retardants TBB, TBPH and their metabolites TBBA and TBMEPH using reporter gene assays.
abstract: The anti-androgenic and anti-thyroid hormonal activities of the two novel brominated flame retardants, TBB and TBPH and of their metabolites TBBA and TBMEPH have been compared using the luciferase reporter gene assays. Only the parent compounds TBB and TBPH exhibited anti-glucocorticoid activity with IC50 values of 1.9 μM and 0.3 μM. Furthermore, mode of action for these two compounds is by direct competing to the glucocorticoid receptor (GR) with IC50 values of 0.03 μM and 0.002 μM. All four tested compounds possess anti-androgenic and anti-thyroid hormonal activities, without agonist activities on the respective receptors. Anti-androgenic activities with IC50 values of 43.5 μM, 0.1 μM, 47.5 μM and 1.3 μM were found for TBB, TBPH, TBBA and TBMEPH. The anti-thyroid hormonal IC50 values of 37.5 μM, 0.1 μM, 22.8 μM and 32.3 μM for TBB, TBPH, TBBA and TBMEPH, together with the above quoted results, indicate that metabolism can modify anti-androgenic, anti-glucocorticoid and anti-thyroid hormonal effects of these novel brominated flame retardants. Furthermore, the parent flame retardants are shown to be able to disrupt the function of the GR as antagonists by direct competition to the receptor.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Klopčič
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Darja Gramec
authors.initials: DG
authors.lastname: Skledar
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Lucija Peterlin
authors.initials: LP
authors.lastname: Mašič
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia. Electronic address: marija.sollner@ffa.uni-lj.si.
authors.forename: Marija Sollner
authors.initials: MS
authors.lastname: Dolenc
mesh_terms: D001681:Biological Assay; D001970:Bromobenzoates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005411:Flame Retardants / Q000494:pharmacology*; D017930:Genes, Reporter; D055768:Halogenated Diphenyl Ethers / Q000494:pharmacology*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D010795:Phthalic Acids / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism
chemical_list: C000612045:2,3,4,5-tetrabromo benzoic acid; C544268:2-ethylhexyltetrabromobenzoate; D001970:Bromobenzoates; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D010795:Phthalic Acids; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011988:Receptors, Thyroid Hormone; C585475:bis(2-ethylhexyl)-2,3,4,5-tetrabromophtalate; C016132:tetrabromophthalic acid
keywords: Brominated flame retardants; Endocrine active compounds; Hormone activity; Metabolites; Reporter gene assay