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: In this paper, the effect of polycyclic aromatic hydrocarbons (PAHs) on estrogenic and antiestrogenic activity was evaluated by yeast two-hybrid assay expressing human estrogen receptor α.
Abstract: Estrogenic/antiestrogenic activities of 14 polycyclic aromatic hydrocarbons (PAHs) and 63 monohydroxylated PAHs (OHPAHs) having 2 to 6 rings were evaluated by yeast two-hybrid assay expressing human estrogen receptor α .R elative effective potencies of estrogenic and antiestrogenic activities were calculated as the inverse values of the relative concentration of the test compound that gave the same activities of E2 and 4-hydroxytamoxifen, respectively. PAHs did not show any estrogenic/antiestrogenic activity, but several OHPAHs having 3 to 5 rings showed activities. Especially, OHPAHs having 4 rings such as 3-, 4- and 10-hydroxybenz[a]anthracenes (3-, 4- and 10OHBaAs) and 2-hydroxychrysene (2-OHCh) showed strongly estrogenic activity. Several other OHPAHs having 4 rings such as 2- and 3-hydroxybenzo[c]phenanthrenes (2-, 3- OHBcPhs), 2-OHBaA and 3-OHCh showed strongly antiestrogenic activity. The length-to-breadth (L/B) ratios of the rectangular van der Walls planes surrounding the ring molecules of estrogenic OHPAHs were in the narro wr angefrom 1.599 to 1.734. The distances between the oxygen atom of the phenol group and farthest hydrogen atom (O-H distance) of the estrogenic OHPAHs ranged from 10.825 A to 11.738 A. The L/B ratios and O-H distances of antiestrogenic OHPAHs were in the wider ranges from 1.277 to 1.734 and from 8.47 A to 11.681 A, respectively. The partial charges (atomic unit) of the phenol group of both estrogenic and antiestrogenic OHPAHs were in the range from −0.250 atmic unit (au) to −0.253 au. The similarity of these values to those of E2 and diethylstilbestrol suggested that the compositions of estrogenic OHPAHs were similar to them and that the compositional conditions of estrogenic OHPAHs were much smaller than those of antiestrogenic OHPAHs. These results raise the possibility of predicting the estrogenic/antiestrogenic activities of OHPAHs from their structural characteristics, although using only the abov et hree parameters might not be enough for accurate estimations.
89 citations
TL;DR: Results indicate that, in contrast to other EDs, 4‐nonylphenol may exhibit a potent cytotoxicity through apoptosis via the caspase cascade and cell cycle arrest at the G2/M phase, and suggest that 4‐ nonyl phenol may affect neurogenesis in the CNS.
Abstract: Endocrine disruptors (EDs) are a great concern throughout the world, because they have adverse effects on human health and wildlife. In the present study, we investigated the effects of EDs on the proliferation and survival of murine neural stem cells (NSCs). In contrast to bisphenol A, phthalic acid benzyl n-butyl ester, phthalic acid di-n-butyl ester and phthalic acid di(2-ethylhexyl) ester, the treatment of NSCs with 4-nonylphenol for 24 h inhibited cell growth in a concentration-dependent manner. In addition, treatment with 4-nonylphenol resulted in nuclear condensation and DNA fragmentation (morphological changes due to apoptosis) in NSCs after 12 h of exposure, and activated caspase-3 after 6 h and 9 h of exposure. Furthermore, an exposure to 4-nonylphenol led to the accumulation of cells at the G2/M phase interface and down-regulated the protein levels of cyclin A and B1, which are the major regulatory proteins at the G2 to M transition of the cell cycle. Together, these results indicate that, in contrast to other EDs, 4-nonylphenol may exhibit a potent cytotoxicity through apoptosis via the caspase cascade and cell cycle arrest at the G2/M phase, and suggest that 4-nonylphenol may affect neurogenesis in the CNS.
85 citations
Cites background from "Estrogenic Activities of 517 Chemic..."
...The results of this study indicate that 4-NP inhibited the growth of NSCs at a lower concentration when compared with BPA, BBP, DBP and DEHP....
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...The estrogenic activity of 4-NP has been reported to be more potent than that of BPA, BBP, DBP and DEHP (Nishihara et al. 2000)....
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TL;DR: An approach to a multi-organic risk assessment for these substances was made by measuring the gene-expression of the four mentioned receptors in the pituitary, the uterus and the thyroid after a five-day treatment in comparison to estradiol.
85 citations
TL;DR: Thermodynamic analysis revealed that the adsorption behaviors of E1, E2, E3 and EE2 could be considered as an exothermic, physical and reversible process, resulting in their higher adsorptive capacities at lower temperature.
84 citations
TL;DR: A need for an endocrine-centric component for overall health assessments is described and information supporting the idea that using such a component will help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs is provided.
Abstract: BackgroundHydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessibl
84 citations
Cites methods from "Estrogenic Activities of 517 Chemic..."
...Statistical modeling (Orton et al. 2012), in vitro and in vivo assays (Silva et al. 2002), quantitative structure analysis (Nishihara et al. 2000), gene expression (Richter et al. 2014), and other tools have been used to assess a number of laboratory-defined mixtures that interact with single…...
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...2002), quantitative structure analysis (Nishihara et al. 2000), gene expression (Richter et al....
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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