期刊
TOXICOLOGY LETTERS
卷 159, 期 3, 页码 272-283出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2005.05.017
关键词
zearalenones; MCF-7; MDA-MB-231; E-screen assay; MTT test; estrogens
类别
Many man-made chemicals (pesticides) and naturally occurring compounds (mycotoxins and phytoestrogens) can enter the food chain and bind to estrogen receptors (ERs). Mycotoxins, including zearalenone (ZEA) and its derivatives, can occur worldwide in cereals and cause several health disorders. In order to characterize the estrogenic activity of zearalenone and its derivatives (alpha-zearalenol (alpha-ZEA), beta-zearalenol (beta-ZEA), alpha-zearalanol (alpha-ZAL) and beta-zearalanol (beta-ZAL)), the proliferation of ER-positive (MCF-7) and ER-negative (MDA-MB-231) human breast cancer cell lines was measured. After exposure at levels ranging from 0.1 pM to 0.1 mu M, cell proliferation (E-screen assay) was evaluated by MTT test through estrogenic parameters. On the MCF-7 cell line, estrogenic concentration that induced 50% cellular proliferation (EC50) of beta-zearalenol was statistically higher (5.2 x 10(-3) mu M) than those of other zearalenone-related compounds, in agreement with other authors. All mycotoxins showed similar estrogenic parameters, with the exception of a-zearalenol that induced a higher proliferative effect (PE = 2.6) and relative proliferative potency (RPP = 7). Since MCF-7 contains both ER alpha and ER beta-positive cells, at the mRNA and protein level, the estrogenic activity induced by mycotoxins may be ER-mediated, particularly through ER alpha that was the predominant ER subtype in these cells. A partial antagonism of mycotoxin-related estrogenic proliferation was seen when tamoxifen was used, confirming a receptor-dependent estrogenic response. MDA-MB-231 cells did not show ERs and after exposure to mycotoxins or 17 beta-estradiol marginal PE values related to growth variability of MDA-MB-231 were found. Further studies are needed to understand in human tissues the mechanisms of action of ZEA and its derivatives that may be found as contaminants in the human diet. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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