Mixture effects of estrogenic compounds on proliferation and pS2 expression of MCF-7 human breast cancer cells.
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.
van Meeuwen
J A
JA
Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80177, 3508 TD Utrecht, The Netherlands. J.A.vanMeeuwen@iras.uu.nl
Ter Burg
W
W
Piersma
A H
AH
van den Berg
M
M
Sanderson
J T
JT
D000230:Adenocarcinoma / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D004967:Estrogens; D010936:Plant Extracts; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins