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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01 Oct 2017
TL;DR: In this article, the authors identify and summarize human, animal, and mechanistic toxicity data for 24 BPA analogues of emerging interest to research and regulatory communities, and analyze data available from the high throughput screening programs Tox21/ToxCast.
Abstract: Background Recent studies report widespread usage or exposure to a variety of chemicals with structural or functional similarity to bisphenol A (BPA), referred to as BPA analogues or derivatives. These have been detected in foodstuffs, house dust, environmental samples, human urine or blood, and thermal paper. Compared to BPA relatively little is known about potential toxicity of these compounds. Objective To identify and summarize human, animal, and mechanistic toxicity data for 24 BPA analogues of emerging interest to research and regulatory communities. Methods The objective was addressed by two efforts: 1) a systematic review of the available research; and 2) analysis of data available from the high throughput screening programs Tox21/ToxCast. We used systematic review methods to identify relevant studies from the published literature. Over 5,100 literature studies were screened for relevance and 166 were considered relevant. Analyses of the high throughput screening data focused on assessing structural and biological similarity among the BPA analogues and between BPA or estradiol (E2). Results Reports on 16 of the 24 analogues were found in the published literature. There were no studies of human health effects, animal toxicity or mechanistic studies for 8 of the 24 compounds. The only human health effect that was reported was dermal sensitization to 4,4-BPF, 2,2-BPF or BPS. The majority of the available research was conducted in vitro. Analysis of the Tox21/ToxCast data showed that in general, BPA analogues and derivatives are more structurally and biologically similar to BPA, and to each other, than to E2. Taken together, the published literature and the data available in Tox21/ToxCast demonstrate that many of the BPA analogues that are potential replacements for BPA have biological activity within the range of activity observed for BPA. Conclusion The results of these analyses suggest that many of these chemicals may have endocrine activity in vivo. Given that these chemicals have potential widespread use, they should be pursued in further testing and reconsidered as appropriate replacements for BPA in consumer products.
16 citations
01 Jan 2006
TL;DR: The putative endocrine-disrupting effect of OPs and CMs in wildlife is largely a prediction based on data obtained from laboratory animals, and the significant structural differences between anti androgenic and nonantiandrogenic OP insecticides are difficult to understand.
Abstract: Publisher Summary Many organochlorine insecticides can interact with estrogen, androgen, and progesterone receptors. Many results from in vitro screening tests indicate that tested organophosphates (OPs) are not estrogenic. Estrogenic and/or antiandrogenic activities are exhibited by a number of pesticides, especially organochlorine pesticides. However, some organophosphate (OP) and carbamate (CM) pesticides are also reported to be positive in, in vitro assay systems. Antiandrogenic compounds so far reported include metabolites of vinclozolin, linuron, iprodione, chlozolinate, procymidone, flutamide, p,p'-DDE, a metabolite of p,p'-DDT, and ketoconazole. Many pesticides, including OPs and CMs, have been found to bind to androgen receptor (AR) and to act as antagonists of AR. Pesticides such as DDT and methoxychlor are well known to act as endocrine disruptors. Investigations of incidents involving misuse of OP and CM pesticides have revealed virtually no endocrine-disrupting activity of these chemicals. The putative endocrine-disrupting effect of OPs and CMs in wildlife is largely a prediction based on data obtained from laboratory animals. The influence of these pesticides on human health is also discussed, based on observed endocrine-disrupting actions of OPs and CMs, in vitro and in laboratory animals in vivo. Currently, the significant structural differences between antiandrogenic and nonantiandrogenic OP insecticides are difficult to understand. Further study of the structural requirements for estrogenic and antiandrogenic activities, and of the mechanisms of action of OP insecticides is needed.
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TL;DR: There was an association between the EEQ and the E2 in environmental water, suggesting a high estrogen risk in Japan coastal waters, and results indicated that abnormal VTG synthesis was induced by environmental estrogen (EE) pollution in Nagasaki Port and Tokyo Bay.
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17 Mar 2005
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TL;DR: Results of the yeast estrogen screen (YES) assay demonstrated that the reaction products of HRP-catalyzed 4-nonylphenol conversion lacked estrogenic activity.
Abstract: The xenoestrogen alkylphenols 4-nonylphenol (3.4 mg/L) and octylphenol (6.0 mg/L) were oxidized by hydrogen peroxide using horseradish peroxidase (HRP) as a biocatalyst. Substrate transformation required about one mole of peroxide per mole of phenolic compound. A high degree of conversion of alkylphenol was achieved within a 3-h reaction time. In the case of 4-nonylphenol, HRP treatment led to complete disappearance of Microtox toxicity. Results of the yeast estrogen screen (YES) assay demonstrated that the reaction products of HRP-catalyzed 4-nonylphenol conversion lacked estrogenic activity. A new approach to the YES assay has been suggested based on observations made during this study.
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Cites background from "Estrogenic Activities of 517 Chemic..."
...The aromatic structure of most estrogenic compounds (Tabira et al. 1999; Nishihara et al. 2000), including alkylphenols, indicates that they have the potential to be substrates of a group of oxidative enzymes, including various polyphenol oxidases (e....
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...The aromatic structure of most estrogenic compounds (Tabira et al. 1999; Nishihara et al. 2000), including alkylphenols, indicates that they have the potential to be substrates of a group of oxidative enzymes, including various polyphenol oxidases (e.g., laccases or tyrosinase) and peroxidases…...
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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