title: Cell-transforming activity and estrogenicity of bisphenol-A and 4 of its analogs in mammalian cells.
abstract: Estrogenicity is an important mechanism in hormonal carcinogenesis but not sufficient to explain the carcinogenic activity of all estrogens. Additional mechanisms, related to genetic alterations, in conjunction with estrogenicity mediated through the estrogen receptor, have been suggested. An environmental estrogen bisphenol-A (BP-A) and its analogs are widespread in our living environment. Because of the potential for human exposure, the possible relationship between carcinogenicity and estrogenicity of these bisphenols was studied using mammalian cells. We quantitatively compared the cell-transforming activity of BP-A and 4 of its analogs (BP-2, BP-3, BP-4 and BP-5) in Syrian hamster embryo (SHE) cells lacking estrogen-receptor expression. The transforming activity determined by the morphological transformation frequencies in SHE cells treated with the bisphenols ranked: BP-4 > BP-5 > BP-3 > BP-A > BP-2. We also compared the estrogenicity of the 5 bisphenols in MCF7 human breast cancer cells as determined by cell proliferation or progesterone receptor (PgR) expression assayed by RT-PCR. When MCF7 cells were treated with the bisphenols, the proliferative potency ranked: BP-A > BP-5 > BP-4 > BP-3 = BP-2. The level of mRNA for PgR in cells treated with the bisphenols was BP-A > BP-5 > BP-4 > BP-3 > BP-2. These indicate that the transforming activity does not correlate with the estrogenicity of the bisphenols, except for BP-2 that has the weakest activity at the both endpoints. In addition, our results suggest that bisphenols with few, if any, transforming and estrogenic activities could be altered by a modification of the chemical structure. Published 2001 Wiley-Liss, Inc.
authors.affiliation: Department of Pharmacology, The Nippon Dental University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kanai
authors.forename: J C
authors.initials: JC
authors.lastname: Barrett
authors.forename: M
authors.initials: M
authors.lastname: Metzler
authors.forename: T
authors.initials: T
authors.lastname: Tsutsui
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004054:Diethylstilbestrol / Q000737:chemistry / Q000633:toxicity; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005333:Fetus; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D017312:Toremifene / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004054:Diethylstilbestrol; D004958:Estradiol; D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D000077267:Fulvestrant; D010636:Phenols; D011980:Receptors, Progesterone; D017312:Toremifene; C006780:bisphenol A; D000098826:Bisphenol A Compounds