Document Detail

Mixture effects of estrogenic compounds on proliferation and pS2 expression of MCF-7 human breast cancer cells.
MedLine Citation:
PMID:  17651883     Owner:  NLM     Status:  MEDLINE    
Humans are exposed to a variety of food-borne phytochemicals (PC) as well as synthetic chemicals (SC). Some of these compounds have been reported to have estrogenic or anti-estrogenic properties and are therefore suspected endocrine disruptors. Until now it remains unclear if non-additive effects occur in combinations with endogenous estrogens, such as 17beta-estradiol (E(2)). To investigate such interactions, several PC and SC were tested individually, in mixtures and as combinations of mixtures with E(2) for effects on ERalpha receptor mediated cell proliferation and estrogen regulated pS2 expression level in MCF-7(bus) cells. PCs (coumestrol, genistein, naringenin, catechin, epicatechin, quercetin) or SCs (4-nonylphenol, octylphenol, beta-hexachlorocyclohexane, bisphenol A, methoxychlor, dibutyl phthalate) were mixed (PCmix and SCmix) either in concentrations reflecting human serum concentrations or at equipotent concentrations for estrogenicity. EC(50) values were applied in two approaches of the concentration-addition model (the method of isoboles and the cumulative estrogen equivalency method) to assess mixture effects. In both models PCmix and SCmix or combinations of the mixtures with E(2) showed no departure from additivity. In conclusion, the tested PCs and SCs appeared to act as (full) agonists for the estrogen receptor and interacted in mixtures and with estradiol in an additive way. In addition, it is concluded that the possible contribution of food-borne PCs to the estrogenic effect of xenobiotics is likely to be more significant than that caused by food-borne SCs.
J A van Meeuwen; W Ter Burg; A H Piersma; M van den Berg; J T Sanderson
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Publication Detail:
Type:  Journal Article     Date:  2007-06-15
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  45     ISSN:  0278-6915     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-01     Completed Date:  2007-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2319-30     Citation Subset:  IM    
Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80177, 3508 TD Utrecht, The Netherlands.
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MeSH Terms
Adenocarcinoma / genetics
Breast Neoplasms / genetics,  metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects*
Dose-Response Relationship, Drug
Environmental Exposure
Estrogen Receptor alpha / metabolism
Estrogens / pharmacology*
Gene Expression Regulation, Neoplastic
Plant Extracts / chemistry,  pharmacology
Tumor Suppressor Proteins / genetics,  metabolism*
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Estrogens; 0/Plant Extracts; 0/TFF1 protein, human; 0/Tumor Suppressor Proteins

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