Estrogenic Activities of 517 Chemicals by Yeast Two-Hybrid Assay
01 Aug 2000-Journal of Health Science (The Pharmaceutical Society of Japan)-Vol. 46, Iss: 4, pp 282-298
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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TL;DR: This study provides a cost-effective and robust technology with the capability of treating secondary effluents for reuse applications and remarkable removal efficiencies of micropollutants by the pilot system is attributed to synergistic effects of combining ozonation, ceramic membrane filTration and BAC filtration.
36 citations
TL;DR: It is suggested that BP can be converted into ring-hydroxylated derivatives that have estrogenic activity after exposure to light and BP-4OH was more potent than BP-3OH for promoting estrogen receptor (ER)-mediated transcription and uterotrophic activity.
36 citations
TL;DR: Chronic exposure to higher than normal levels of IF induces alterations in the reproductive development of female mice through an estrogenic effect, suggesting that too much phytoestrogen can have adverse effects on offspring.
Abstract: Isoflavone (IF), a type of phytoestrogen, has multiple beneficial effects, but too much phytoestrogen can have adverse effects on offspring. To examine whether chronic exposure to high IF has adverse effects on reproductive development, mice offspring were exposed to IF through dietary administration to dams during pregnancy and lactation and to the offspring directly after weaning until sacrifice. In male offspring, there was no difference between the IF group and controls; however, in female offspring in the IF group, remarkably earlier puberty and induction of multioocyte follicles on postnatal day (PND) 21 were observed. Gene expression levels of estrogen receptor β decreased in the ovary and vagina on PND 21. These results suggest that chronic exposure to higher than normal levels of IF induces alterations in the reproductive development of female mice through an estrogenic effect.
35 citations
01 Jan 2003
TL;DR: Findings demonstrate that results of the reporter gene assay for ER-alpha agonists correlated well with those of the uterotrophic assay, but antagonistic change of 9 of 10 chemicals in the uterOTrophic assay was not detected by the reporterGene assay forER-alpha antagonists.
Abstract: We performed a reporter gene assay for estrogen receptor (ER)-alpha agonists and antagonists of 10 chemicals that showed both estrogen agonistic and reduced the estrogenic effect of ethinyl estradiol in a rat uterotrophic assay. The chemicals tested by the immature uterotrophic assay were p -(tert -pentyl)phenol, 4,4?-thiobis-phenol, 4,4?-(hexafluoroisopropylidene)diphenol, 2,2-bis(4-hydroxyphenyl)-4-methyl-n-pentane, 4,4?-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol, 4-(phenylmethyl)phenol, 4,4?-dihydroxybenzophenone, 2,2?,4,4?-tetrahydroxybenzophenone, 4hydroxybenzophenone and 2,4,4?-trihydroxybenzophenone. Although all chemicals examined in this study were positive in the reporter gene assay for ER-alpha agonists, 4,4?-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol was only positive in the reporter gene assay for ER-alpha antagonists. These findings demonstrate that results of the reporter gene assay for ER-alpha agonists correlated well with those of the uterotrophic assay, but antagonistic change of 9 of 10 chemicals in the uterotrophic assay was not detected by the reporter gene assay for ER-alpha antagonists. # 2003 Published by Elsevier Science Ireland Ltd.
35 citations
TL;DR: The model predicts the presence or absence of estrogenic activity according to a pre-defined cut-off in activity as determined in a recombinant yeast assay and was shown to meet the OECD Principles for (Q)SAR Validation, making it potentially useful for regulatory purposes.
Abstract: (Q)SAR models can be used to reduce animal testing as well as to minimise the testing costs. In particular, classification models have been widely used for estimating endpoints with binary activity. The aim of the present study was to develop and validate a classification-based quantitative structure-activity relationship (QSAR) model for endocrine disruption, based on interpretable mechanistic descriptors related to estrogenic gene activation. The model predicts the presence or absence of estrogenic activity according to a pre-defined cut-off in activity as determined in a recombinant yeast assay. The experimental data was obtained from the literature. A two-descriptor classification model was developed that has the form of a decision tree. The predictivity of the model was evaluated by using an external test set and by taking into account the limitations associated with the applicability domain (AD) of the model. The AD was determined as coverage of the model descriptor space. After removing the compoun...
34 citations
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