title: Assessment of thyroid hormone activity of halogenated bisphenol A using a yeast two-hybrid assay.
abstract: The thyroid hormone agonist/antagonist activities of halogenated derivatives of bisphenol A (BPA) were assessed using a yeast two-hybrid assay incorporating the human thyroid hormone α (TRα), both with and without possible metabolic activation by rat liver S9 preparation. In the absence of the rat liver S9 preparation, 3,3',5,5'-tetrabromobisphenol A (TBBPA), 3,3',5,5'-tetrachlorobisphenol A (TCBPA), and 3,3',5-trichlorobisphenol A (3,3',5-triClBPA) exhibited agonist activity, whereas 3-chlorobisphenol A (3-ClBPA), 3,5-dichlorobisphenol A (3,5-diClBPA), 3,3'-dichlorobisphenol A (3,3'-diClBPA), and BPA did not. The activities of TBBPA and TCBPA increased markedly (7.6-fold and 3.1-fold, respectively) after their metabolic activation with the rat liver S9 preparation. TBBPA, TCBPA, and 3,3',5-triClBPA inhibited the binding of triiodothyronine (T3) to TRα at 2×10(-5) M without rat liver S9 treatment and 4×10(-6) M with rat liver S9 treatment, demonstrating their T3 antagonist activity. These results revealed that metabolic activation by rat liver S9 significantly increased the agonist/antagonist potential of some halogenated BPAs.
authors.affiliation: Institute for Environmental Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. terasaki@u-shizuoka-ken.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Terasaki
authors.forename: Koji
authors.initials: K
authors.lastname: Kosaka
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kunikane
authors.forename: Masakazu
authors.initials: M
authors.lastname: Makino
authors.forename: Fujio
authors.initials: F
authors.lastname: Shiraishi
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D001681:Biological Assay / Q000379:methods*; D052244:Endocrine Disruptors / Q000633:toxicity*; D054879:Halogenation; D006801:Humans; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D013963:Thyroid Hormones / Q000378:metabolism*; D018675:Toxicity Tests / Q000379:methods*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; D013963:Thyroid Hormones; C006780:bisphenol A; D000098826:Bisphenol A Compounds