title: Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds.
abstract: The endocrine-disrupting activities of bisphenol A (BPA) and 19 related compounds were comparatively examined by means of different in vitro and in vivo reporter assays. BPA and some related compounds exhibited estrogenic activity in human breast cancer cell line MCF-7, but there were remarkable differences in activity. Tetrachlorobisphenol A (TCBPA) showed the highest activity, followed by bisphenol B, BPA, and tetramethylbisphenol A (TMBPA); 2,2-bis(4-hydroxyphenyl)-1-propanol, 1,1-bis(4-hydroxyphenyl)propionic acid and 2,2-diphenylpropane showed little or no activity. Anti-estrogenic activity against 17beta-estradiol was observed with TMBPA and tetrabromobisphenol A (TBBPA). TCBPA, TBBPA, and BPA gave positive responses in the in vivo uterotrophic assay using ovariectomized mice. In contrast, BPA and some related compounds showed significant inhibitory effects on the androgenic activity of 5alpha-dihydrotestosterone in mouse fibroblast cell line NIH3T3. TMBPA showed the highest antagonistic activity, followed by bisphenol AF, bisphenol AD, bisphenol B, and BPA. However, TBBPA, TCBPA, and 2,2-diphenylpropane were inactive. TBBPA, TCBPA, TMBPA, and 3,3'-dimethylbisphenol A exhibited significant thyroid hormonal activity towards rat pituitary cell line GH3, which releases growth hormone in a thyroid hormone-dependent manner. However, BPA and other derivatives did not show such activity. The results suggest that the 4-hydroxyl group of the A-phenyl ring and the B-phenyl ring of BPA derivatives are required for these hormonal activities, and substituents at the 3,5-positions of the phenyl rings and the bridging alkyl moiety markedly influence the activities.
authors.affiliation: Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan. skitamu@hiroshima-u.ac.jp
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kitamura
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Seigo
authors.initials: S
authors.lastname: Sanoh
authors.forename: Ryuki
authors.initials: R
authors.lastname: Kohta
authors.forename: Norimasa
authors.initials: N
authors.lastname: Jinno
authors.forename: Kazumi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Nariaki
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Watanabe
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001559:Benzhydryl Compounds; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D006727:Hormone Antagonists / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D013006:Growth Hormone; D006727:Hormone Antagonists; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds