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Coexposure to Phytoestrogens and Bisphenol a Mimics Estrogenic Effects in an Additive Manner



Anne Katchy, Caroline Pinto, Philip Jonsson, Trang Nguyen-Vu, Marchela Pandelova, Anne Riu, Karl-Werner Schramm, Daniel Samarov, Jan-Ake Gustafsson, Maria Bondesson, Cecilia Williams


Endocrine-disrupting chemicals (EDC) are abundant in our environment. A number of EDCs, including bisphenol A (BPA) can bind to the estrogen receptors, ERα and ERβ, and may contribute to estrogen-linked diseases such as breast cancer. Early-exposure is of particular concern; many EDCs can cross the placenta and infants have measurable levels of e.g. BPA. In addition, infants are frequently fed soy-based formula that contains phytoestrogens. Effects of combined exposure to xeno- and phytoestrogens are poorly studied. Here, we extensively compared to what extent BPA, genistein and an infant soy formula extract mimic estrogen-induced gene transcription and cell proliferation. We investigated ligand-specific effects on ER activation in HeLa-ERα and ERβ reporter cells, and on proliferation, genome-wide endogenous gene expression and non-ER mediated effects in MCF7 breast cancer cells and whether co-exposure results in additive effects. The biological relevance was explored using enrichment analyses of Gene Ontology biological processes and clustering with clinical breast cancer profiles. We demonstrate that the co-exposure to BPA and genistein, or soy formula extract, results in functional and transcriptional additive effects. The proliferative and transcriptional effects of the tested compounds mimic those of 17β-estradiol, and are abolished by co-treatment with an ER antagonist. Gene expression profiles induced by each compound clustered with poor-prognosis breast cancer, indicating that exposure may adversely affect breast cancer prognosis. This study accentuates that co-exposure to BPA and soy-based phytoestrogens results in cooperative effects that mimics estrogen, and may contribute to estrogen-linked diseases, including breast cancer.
Toxicological Sciences


Bisphenol A, Genistein, Soy formula extract, Estrogen receptor, Transcriptional activation, Proliferation, Concentration addition


Katchy, A. , Pinto, C. , Jonsson, P. , Nguyen-Vu, T. , Pandelova, M. , Riu, A. , Schramm, K. , Samarov, D. , Gustafsson, J. , Bondesson, M. and Williams, C. (2013), Coexposure to Phytoestrogens and Bisphenol a Mimics Estrogenic Effects in an Additive Manner, Toxicological Sciences (Accessed April 24, 2024)
Created November 26, 2013, Updated October 12, 2021