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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16 Jun 2006
TL;DR: LASとLASの生分解生成物SPCの汚染状況を調べるために, LASとSPCの分析方法が十分に環境試料に適用可能であることを確認し, 環
Abstract: LASとLASの生分解生成物SPCの汚染状況を調べるために, 本研究で開発したLASとSPCの分析方法が十分に環境試料に適用可能であることを確認し, 環境中濃度分布を求めた。さらに, 両物質のエストロゲン・アゴニスト作用及びアンタゴニスト作用を改良酵母エストロゲンアッセイ系試験: 法により検討し, 併せて酵母毒性試験法を用いて微生物毒性を求めた。本研究で調査した河川流域では, LAS濃度及びSPC濃度は水生生物に影響を及ぼさない程度であったが, LASがSPCより高い濃度で検出されたことから, 下水道普及率は十分ではなく, 生活排水の寄与が高い河川流域であったと考えられる。一方, 河川及び干潟底質中からはLAS及びSPCは殆ど検出されなかったが, LASとSPCの環境中挙動について鉛直分布調査を含めた十分なデータの蓄積が必要であろう。酵母Two-hybrid及びYTOX試験を用いた環境毒性評価において, LASとSPCのエストロゲン・アゴニスト作用及びアンタゴニスト作用は認められなかった。酵母毒性試験: より, LASの微生物毒性は非常に高いことが再確認されたが, SPCの微生物毒性はLASより低く, 水環境に影響を及ぼすレベルではない結果を得た。
Dissertation•
01 Dec 2011
TL;DR: In this article , the chronic toxic effects of cresols on reproduction and gene expression using D. magna was investigated. And the bioconcentration behavior of Cresol isomers was also investigated.
TL;DR: In this article , the structure-related transformation of various plastic additives by the gastric and intestinal (GI) microbiota from crucian carp, with the degradation ratio of bisphenols and triphenyl phosphate faster than those of brominated compounds.
Abstract: Ingestion is a major exposure route for hydrophobic organic pollutants in fish, but the microbial transformation and estrogenic modification of the novel plastic additives by the gut microbiota of fish remain obscure. Using an in vitro approach, we provide evidence that structure-related transformation of various plastic additives by the gastric and intestinal (GI) microbiota from crucian carp, with the degradation ratio of bisphenols and triphenyl phosphate faster than those of brominated compounds. The degradation kinetics for these pollutants could be limited by oxygen and cometabolic substrates (i.e., glucose). The fish GI microbiota could utilize the vast majority of carbon sources in a Biolog EcoPlate, suggesting their high metabolic potential and ability to transform various organic compounds. Unique microorganisms associated with transformation of the plastic additives including genera of Citrobacter, Klebsiella, and some unclassified genera in Enterobacteriaceae were identified by combining high-throughput genetic analyses and metagenomic analyses. Through identification of anaerobic transformation products by high-resolution mass spectrometry, alkyl-cleavage was found the common transformation mechanism, and hydrolysis was the major pathway for ester-containing pollutants. After anaerobic incubation, the estrogenic activities of triphenyl phosphate and bisphenols A, F, and AF declined, whereas that of bisphenol AP increased.
01 Jan 2005
TL;DR: In this article, the yeast two-hybrid method was used to demonstrate ligand binding, dose responses, and consequences of ligand-binding that are critical for NR function.
Abstract: Objectives. Nuclear receptors (NRs) are ligand-activated transcription factors that regulate development and cellular differentiation, endocrine functions, and metabolism and transport of nutrients and drugs. Understanding of NR action is therefore essential for students of pharmacy and biology. Currently, there are no convenient laboratory exercises that clearly demonstrate the components and mechanisms of NR action. Design. Employing the yeast two-hybrid method, we developed a simple hands-on exercise that demonstrated ligand binding, dose responses, and consequences of ligand binding that are critical for NR function. Assessment. The exercise uses inexpensive, non-radioactive reagents and standard laboratory equipment. The results are directly visible, easy to interpret, and reproducible. The whole exercise can be conducted in a single day. In a real life test, a majority of the students who participated reported that their understanding of NR action had increased. Conclusions. This simple exercise can be applied to other NRs and modified to demonstrate pharmacological concepts including competitive antagonism, partial agonism, and structure-activity relationship.
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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.
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