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Title: Development of a recombinant human ovarian (BG1) cell line containing estrogen receptor α and β for improved detection of estrogenic/antiestrogenic chemicals.

Authors: Brennan, Jennifer C; Bassal, Arzoo; He, Guochun; Denison, Michael S

Published In Environ Toxicol Chem, (2016 Jan)

Abstract: Estrogenic endocrine-disrupting chemicals are found in environmental and biological samples, commercial and consumer products, food, and numerous other sources. Given their ubiquitous nature and potential for adverse effects, a critical need exists for rapidly detecting these chemicals. The authors developed an estrogen-responsive recombinant human ovarian (BG1Luc4E2) cell line recently accepted by the US Environmental Protection Agency (USEPA) and Organisation for Economic Co-operation and Development (OECD) as a bioanalytical method to detect estrogen receptor (ER) agonists/antagonists. Unfortunately, these cells appear to contain only 1 of the 2 known ER isoforms, ERα but not ERβ, and the differential ligand selectivity of these ERs indicates that the currently accepted screening method only detects a subset of total estrogenic chemicals. To improve the estrogen screening bioassay, BG1Luc4E2 cells were stably transfected with an ERβ expression plasmid and positive clones identified using ERβ-selective ligands (genistein and Br-ERβ-041). A highly responsive clone (BG1LucERβc9) was identified that exhibited greater sensitivity and responsiveness to ERβ-selective ligands than BG1Luc4E2 cells, and quantitative reverse-transcription polymerase chain reaction confirmed the presence of ERβ expression in these cells. Screening of pesticides and industrial chemicals identified chemicals that preferentially stimulated ERβ-dependent reporter gene expression. Together, these results not only demonstrate the utility of this dual-ER recombinant cell line for detecting a broader range of estrogenic chemicals than the current BG1Luc4E2 cell line, but screening with both cell lines allows identification of ERα- and ERβ-selective chemicals.

PubMed ID: 26139245 Exiting the NIEHS site

MeSH Terms: Biological Assay; Cell Line; Endocrine Disruptors/toxicity*; Environmental Pollutants/toxicity*; Estrogen Antagonists/toxicity*; Estrogen Receptor alpha/drug effects*; Estrogen Receptor alpha/genetics; Estrogen Receptor alpha/metabolism*; Estrogen Receptor beta/drug effects*; Estrogen Receptor beta/genetics; Estrogen Receptor beta/metabolism*; Estrogens, Non-Steroidal/toxicity*; Female; Gene Expression/drug effects; Genistein/pharmacology; Humans; Ovary/cytology; Ovary/metabolism*; Pesticides/toxicity; Plasmids/genetics; Polymerase Chain Reaction; Transfection

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