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: It is demonstrated that plastic teethers can be a source of infant exposure to well‐established and unknown EDCs, and manufacturers should critically revisit the use of parabens in plastic Teethers and further toys.
Abstract: Concerns have been raised regarding the human health effects of endocrine disrupting chemicals (EDCs), many of which are associated with and leaching from plastics. As infants are particularly vulnerable to EDCs, we have investigated whether plastic teethers for babies represent a relevant source of exposure. Applying effect-directed analysis, we use bioassays to screen teethers, toys used to soothe a baby's teething ache, for endocrine activity and chemical analysis to identify the causative compounds. We detected significant endocrine activity in two of 10 plastic teethers. Those samples leached estrogenic and/or antiandrogenic activity as detected in the Yeast Estrogen Screen and Yeast Antiandrogen Screen. After sample fractionation, gas chromatography-mass spectrometry non-target screening revealed that methyl-, ethyl- and propylparaben were responsible for the observed estrogenic and antiandrogenic activity in one product. The second product is likely to contain at least six different antiandrogenic compounds that remain so far unidentified. This study demonstrates that plastic teethers can be a source of infant exposure to well-established and unknown EDCs. Because of their limited value to the product, but potential toxicity, manufacturers should critically revisit the use of parabens in plastic teethers and further toys. Moreover, plastic teethers might leach EDCs that escape routine analysis and, thus, toxicological evaluation. The resulting uncertainty in product safety poses a problem to consumers, producers and regulators that remain to be resolved.
23 citations
TL;DR: In this paper, the biological activities of the isoprenylated-flavonoids from the root barks and/or barks of moraceous plants and from Glycyrrhiza species were reviewed.
Abstract: Among a large number of phenolic compounds isolated from natural source, various isoprenoid-substituted phenolic compounds have often been found in plants. Moraceous plants and licorice ( Glycyrrhiza species) are rich sources of the isoprenoid-substituted phenolic compounds, including flavonoids. Some of the Morus flavonoids, such as kuwanons G and H, have been regarded as optically active Diels-Alder type adducts. Furthermore, some of the isoprenylated-flavonoids from the moraceous plants and licorice showed the interesting biological activities. This article reviews the biological activities of the isoprenylated-flavonoids from the root barks and/or barks of moraceous plants and from Glycyrrhiza species by our group. The chemical studies concerning the biological activities of these compounds are also described briefly.
23 citations
24 Feb 2018
TL;DR: A systems biology approach to advancing adverse outcome pathways for risk assessment, and a systems Biology approach to advances in adverse outcome pathway recognition and prediction.
Abstract: A systems biology approach to advancing adverse outcome pathways for risk assessment , A systems biology approach to advancing adverse outcome pathways for risk assessment , کتابخانههای دانشگاه کردستان
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TL;DR: Results implied that the transcription activation mediated by hormone receptors was the potential endocrine‐disrupting mechanism of the test chemicals.
Abstract: The present study intended to develop receptor-mediated luciferase reporter gene assays to evaluate and compare the estrogen receptor (ER), androgen receptor (AR) and thyroid hormone receptor (TR) activities of target chemicals. Di-2-ethylhexyl-phthalate (DEHP), chlorpyrifos (CPF), 2,4-dichlorophenoxyacetic acid (2,4-D) and bisphenol A (BPA) are some of the most common contaminants in drinking water and are frequently detected in China and worldwide. The chemicals were tested at concentrations of 0.1, 1, 10 and 100 times their maximum contaminant level in drinking water. The results showed that BPA possessed various activities on ER, AR and TR. DEHP and CPF could suppress 17β-estradiol or testosterone activity with different potencies, and DEHP possessed weaker anti-thyroid hormone activity. 2,4-D showed no agonist or antagonist activity against these hormone receptors, but it significantly enhanced the activity of testosterone through AR. Furthermore, the mixture of DEHP and CPF exhibited stronger ER and AR antagonist activities than each single component alone, but their combined effects were less than the expected effects based on the additive model. These results implied that the transcription activation mediated by hormone receptors was the potential endocrine-disrupting mechanism of the test chemicals. Our study also provided useful tools for evaluation of their endocrine disrupting activity.
22 citations
Cites background from "Estrogenic Activities of 517 Chemic..."
...D (Nishihara et al., 2000; Kojima et al., 2004)....
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...D (0.01–1000mM) showed no anti-estrogenic activity (Nishihara et al., 2000)....
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...01–1000mM) showed no anti-estrogenic activity (Nishihara et al., 2000)....
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..., 2008), and there have been many reports of negative results for the estrogen-like activity of 2,4-D (Nishihara et al., 2000; Kojima et al., 2004)....
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TL;DR: The toxicological data for chloroxylenol indicate lack of genotoxicity, no evidence of carcinogenicity, and minimal systemic toxicity, and negligibly small potential for harm related to consumer or health-care worker exposure to chloroxolenol in liquid soaps used in dish washing and hand washing.
22 citations
References
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Book•
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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