title: Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity.
abstract: Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings--sunset yellow and tartrazine--were identified as novel human ERα activators, activating the human ER with an EC(50%) concentration of 220 and 160 nM, respectively.
authors.affiliation: Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Axon
authors.forename: Felicity E B
authors.initials: FE
authors.lastname: May
authors.forename: Luke E
authors.initials: LE
authors.lastname: Gaughan
authors.forename: Faith M
authors.initials: FM
authors.lastname: Williams
authors.forename: Peter G
authors.initials: PG
authors.lastname: Blain
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wright
mesh_terms: D001391:Azo Compounds / Q000633:toxicity*; D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism*; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000139:chemically induced / Q000378:metabolism; D013645:Tartrazine / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000502:physiology; D015262:Xenobiotics / Q000633:toxicity
chemical_list: D001391:Azo Compounds; D004396:Coloring Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D015262:Xenobiotics; C005842:6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt; D013645:Tartrazine