Endocrine disrupting potentials of Bisphenol A, Bisphenol A dimethacrylate, 4-n-Nonyl-phenol and 4-Octylphenol assessed in cell model systems for effects on the estrogen-, androgen-, aryl hydrocarbon-receptor and aromatase activity
An array of plastic components is known to possess endocrine disruption (ED) potentials. Bisphenol A (BPA) and BPA-Dimethacrylate (BPA-DM) are monomers used to high extent in the plastic industry and as dental sealants. Alkylphenols such as 4-n-nonylphenol (NP) and 4-octylphenol (OP) are widely used as surfactants. We have investigated the effect in vitro of these four plasticizers in four cell culture model systems.The estrogenic potencies were analyzed using the stable ERE-luciferase transfected cell line MVLN measuring the relative estrogen receptor (ER) transactivated luciferase units (RLU). Effects on the Androgen receptor (AR) trans-activation were investigated by co-transfection of the CHO-K1 hamster cells using the reporter vector MMTV-LUC and the AR expression vector pSVAR0. Effects on the CYP19 aromatase, an important enzyme in the steroid synthesis pathway involved in the conversion of androgens to estrogens in an array of cells, were assessed in the human choriocarcinoma JEG-3 cells using the classical [3H]2O assay. Trans-activation of the Aryl hydrocarbon receptor (AhR) was determined in the mouse hepatoma Hepa1.12cR cell line, stable transfected by an AhR-CALUX construct determining RLU. All four compounds elicited a response in each of the four bioassays. Thus, our in vitro data clearly indicates that the four tested plasticizers have ED potentials and that such effects can be mediated via several cellular pathway systems including the estrogen- and the androgen hormones, and activity of aromatase and AhR transactivation.Acknowledgement. The authors contributed equally to this work. We thank technical assistants Anne Keblovszki and Inger Sørensen for their excellent skills in the laboratory work. The data is a part of the European Union project ENDOMET: Dysregulation of endogenous steroid metabolism potentially alters neuronal and reproductive system development: effects of environmental plasticizers. Program "Quality of Life and Management of Living Resources". (Contract no. QLK4-CT-2002-02637). http://endomet.bham.ac.uk .
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EU-CREDO Conference in PRAG: Endocrine Disrupters, 2005