Estrogenic Activities of 517 Chemicals by Yeast Two-Hybrid Assay.

Abstract

One of the urgent tasks in understanding endocrine disruptors (EDs) is to compile a list of suspected substances among the huge number of chemicals by using the screening test method. We developed a simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators. To date, we have tested the estrogenic activity of more than 500 chemicals including natural substances, medicines, pesticides, and industrial chemicals. 64 compounds were evaluated as positive, and most of these demonstrated a common structure; phenol with a hydrophobic moiety at the para-position without bulky groups at the ortho-position. These results are expected to facilitate further risk assessment of chemicals.

Emerging contaminants in surface waters and their relevance for the production of drinking water in Europe

“…Laboratory research has shown that a large number of different chemicals can exert estrogenic effects (Blair et al 2000;Legler et al 2000;Nishihara et al 2000;Houtman et al 2004b), including the natural estrogenic hormones 17b-estradiol, estriol and estrone, the synthetic estrogenic hormone and contraceptive pill ingredient 17a-ethynylestradiol, and phytoestrogens like isoflavonoides and coumestrol. Furthermore, various pesticides and industrial compounds, such as alkylphenols, alkylphenolethoxylates, and bisphenol A, which are applied as surfactants, plasticizers, and raw materials for the production of polycarbonate plastic, are estrogenic.…”

Phthalate Esters Detected in Various Water Samples and Biodegradation of the Phthalates by Microbes Isolated from River Water.

“…[1][2][3][4][5][6] Recently, di-n-butyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) have in particular been attracting attention as being suspects in disrupting the endocrine system. [7][8][9][10] PEs are considered to be biodegradable and having low bioaccumulation. However, they have been constantly detected in air, water and fish since the 1970's, although they have been decreasing since 1980.…”

Yeast Two-Hybrid Detection Systems That Are Highly Sensitive to a Certain Kind of Endocrine Disruptors

“…These systems showed higher sensitivity to the above synthetic chemicals than the former two-hybrid systems. 1,16) The use of the entire hER in combination with the co-activator NRBD resulted in higher response to estrogens than did the use of Gal4 DBD-hER LBD or Gal4 DBD-hER (reference 1 and our unpublished results). This is in part brought about by the synergistic action of AF-1 and AF-2 of hER , which cooperatively mediates recruitment of co-activator SRC-1.…”

“…17) A liganddependent direct interaction between the B domain in AF-1 and the C-terminal domains of ER has also been reported and is supposed to stabilize this cooperative interaction between hER and SRC-1. 17) E2 is known to be equally effective in binding to the two ER subtypes, hER and hER , but generally induces higher transcriptional activation by hER than by hER in cultured 16) is the concentration of a tested chemical showing 10% of the highest estrogenic activity of E2 in a given system. N, negative; nt, not tested.…”