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Lookup NU author(s): Andrew Axon, Dr Felicity May, Dr Luke GaughanORCiD, Professor Faith Williams, Professor Peter Blain, Professor Matthew Wright
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
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 ER alpha and ER beta, 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 ER alpha-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 ERa activators, activating the human ER with an EC50% concentration of 220 and 160 nM, respectively. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
Author(s): Axon A, May FEB, Gaughan LE, Williams FM, Blain PG, Wright MC
Publication type: Article
Publication status: Published
Journal: Toxicology
Year: 2012
Volume: 298
Issue: 1-3
Pages: 40-51
Print publication date: 16/08/2012
Online publication date: 03/05/2012
Date deposited: 26/06/2017
ISSN (print): 0300-483X
ISSN (electronic): 1879-3185
Publisher: Elsevier Ireland Ltd
URL: http://dx.doi.org/10.1016/j.tox.2012.04.014
DOI: 10.1016/j.tox.2012.04.014
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