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Journal ArticleDOI

Estrogenic Activities of 517 Chemicals by Yeast Two-Hybrid Assay

TL;DR: 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 test the estrogenic activity of chemicals.
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.

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Journal ArticleDOI
22 Mar 2018
TL;DR: An indirect quantitation method based on liquid chromatography tandem-mass spectrometry (LC/MS/MS) has been developed for the analysis of glucuronic acid and sulfuric acid conjugates of ethylparaben, for which standard reference reagents are not available as mentioned in this paper.
Abstract: An indirect quantitation method based on liquid chromatography tandem-mass spectrometry (LC/MS/MS) has been developed for the analysis of glucuronic acid and sulfuric acid conjugates of ethylparaben, for which standard reference reagents are not available. This method was then used for determining both the ethylparaben conjugates in human urine. The decay of these two conjugates in urine samples containing β-glucuronidase/arylsulfatase appeared to follow the first-order-like reaction kinetics; 4-hydroxybenzoic acid was not produced in the reaction. In addition, a multiple regression (MR) equation was obtained (Radj=0.99, P<0.01) for the increase in ethylparaben concentration and decrease in the peak areas of its glucuronic acid and sulfuric acid conjugates. In the case of methylparaben and its glucuronic acid and sulfuric acid conjugates, a higher P-value was obtained in the MR equation for the glucuronic acid conjugate, owing to the low urinary concentration of methylparaben. Furthermore, this method was applied to determine the concentration of ethylparaben and its two conjugates in urine samples. Following the ingestion of an ethylparaben-containing supplement drink, ~16% of ethylparaben was excreted as a mixture of ethylparaben and its glucuronic acid and sulfuric acid conjugates in the first morning urine of the subject on the following day.
Journal ArticleDOI
TL;DR: In this paper , the antiestrogenicity of 4,4′-(9-Fluorenylidene)dianiline (BAFL) was assessed using a variety of methods and looked into its impacts on the development of females in CD-1 mice.
Journal ArticleDOI
16 Dec 2005
TL;DR: In this article, the authors measured the estrogen agonist activity of four phenolic compounds, 3-methyl-4nitrophenol, 3 methylthiomoiety, 2-isopropyl-6-methyl4-pyrimidinol, 4(methythio)phenol, which have been formed by hydrolysis of organophosphorus compounds commercialized as insecticides in Japan by using yeast two-hybrid assay system.
Abstract: We measured the estrogen agonist activity of four phenolic chemicals, 3-methyl-4nitrophenol, 3-methyl-4-(methylthio)phenol, 2-isopropyl-6-methyl-4-pyrimidinol, 4(methythio)phenol which have been formed by hydrolysis of organophosphorus compounds commercialized as insecticides in Japan by using yeast two-hybrid assay system. It was found that both phenolic compounds substituted at 4-position with the methylthiomoiety exhibited human estrogen receptor ƒ¿, hERƒ¿, agonist activity judging from the values of ECx10 and that the activity was about a half or one-third compared with that of BisphenolA(BPA). On the other hand, the others expressed cytotoxicity for the yeast cells rather than the activity. In order to estimate the possibility of incorporation into the yeast cells, the common logarithm of n-octanol/water partition coefficient, logKow, and aqueous solubility, Sw, were used as indexes. In addition, to reveal the relationships between the activity and the molecular structure of the phenolic chemicals, 17ƒÀ-estradiol (E2), and BPA, the atom charge and the dipole moment (ƒÊ) were calculated by using Gaussian R 98W program package in terms of B3LYP and 6-311G basis set, and correlation analysis on the charge distribution among the chemicals was carried out. It was found that the low estrogenic activity was explained on the basis of the low ability of the incorporation into the yeast cells in terms of logKow and Sw, and that there was significant correlation between the estrogenic activity and ƒÊ, in the range from 2 to 3 Debye, rather than the charge distribution at the aromatic ring including hydroxyl group in the
References
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Book
01 Jan 1996
TL;DR: The cause of disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure, is traced to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system.
Abstract: For years, scientists have noticed disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure. Humans are not immune either, with sperm counts dropping by as much as 50% in recent decades and with women seeing a rise in hormone-related cancers, endometriosis and other disorders. This book traces the cause of these aberrations and diseases to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system. The conclusions are as obvious as they are inescapable - unless we make vital changes in the way we manufacture and employ the artefacts of our "good life", there will be no life at all.

917 citations