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 the early stages of steroidogenesis, DES and E2 directly induced a reduction in P450scc mRNA expression in inverse proportion to their doses, and treatment with cAMP restored the decreased P 450scc RNA expression.
28 citations
Cites background or methods from "Estrogenic Activities of 517 Chemic..."
...To determine thedifferences in theeffects of synthetic andnatural estrogens on the steroidogenic genes, we treated the cells with 17β-estradiol (E2; Wako Pure Chemical, Osaka, Japan), which is an endogenous estrogen withapotencyequivalent to that ofDES (Nishihara et al. 2000), under the same conditions as those used for the DES exposure experiment....
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...…andnatural estrogens on the steroidogenic genes, we treated the cells with 17β-estradiol (E2; Wako Pure Chemical, Osaka, Japan), which is an endogenous estrogen withapotencyequivalent to that ofDES (Nishihara et al. 2000), under the same conditions as those used for the DES exposure experiment....
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...Interestingly, treatment of TTE1 cells with E2, which has a potency equivalent to that of DES (Nishihara et al. 2000), did not cause histone deacetylation in the P450sccpromoter region....
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01 Aug 2006
TL;DR: This edition supersedes any previously released draft or final profile and is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced.
Abstract: DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. A Toxicological Profile for dichlorobenzenes, Draft for Public Comment was released in September 2004. This edition supersedes any previously released draft or final profile. Toxicological profiles are revised and republished as necessary. For information regarding the update status of previously released profiles, contact ATSDR at: iv DICHLOROBENZENES This page is intentionally blank. v DICHLOROBENZENES FOREWORD This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary. The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for the hazardous substance described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a hazardous substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile begins with a public health statement that describes, in nontechnical language, a substance's relevant toxicological properties. Following the public health statement is information concerning levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine a substance's health effects is described in a health effects summary. Data needs that are of significance to protection of public health are identified by ATSDR and EPA. Each profile includes the following: (A) The examination, summary, and interpretation of available toxicologic information and epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects; (B) A determination of whether adequate information on the health effects of each substance is available or in the process of development to determine levels of exposure that present a significant risk to human health of acute, subacute, and chronic health effects; and (C) Where appropriate, identification of toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans. The principal audiences for the …
28 citations
Cites result from "Estrogenic Activities of 517 Chemic..."
...The negative results for 1,2-DCB in this system are consistent with a lack of estrogenic activity of 1,2-DCB in in vitro yeast two-hybrid assays (Eguchi et al. 2003; Nishihara et al. 2000)....
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TL;DR: These studies are indispensable for demonstrating the health effects of PAH derivatives, since they would contribute to the comprehensive toxicity prediction of many kinds ofPAH derivatives.
Abstract: Polycyclic aromatic hydrocarbons (PAHs) are included in various environmental pollutants such as airborne particles and have been reported to induce a variety of toxic effects. On the other hand, PAH derivatives are generated from PAHs both through chemical reaction in the atmosphere and metabolism in the body.PAH derivatives have become known for their specific toxicities such as estrogenic/antiestrogenic activities and oxidative stress, and correlations between the toxicities and structures of PAH derivatives have been shown in recent studies. These studies are indispensable for demonstrating the health effects of PAH derivatives, since they would contribute to the comprehensive toxicity prediction of many kinds of PAH derivatives.
27 citations
TL;DR: Assessment of the accuracy of the binding assay system and tested SDs and STs by three types of ER binding assay, finding that styrene oligomers showed no estrogenic activity.
27 citations
TL;DR: While estrogen signaling is initiated by the enterolignans/precursors examined, their signals are differentially and directionally modulated later in the pathways, resulting in the differences at the cell function level.
Abstract: Mammalian lignans or enterolignans are metabolites of plant lignans, an important category of phytochemicals. Although they are known to be associated with estrogenic activity, cell signaling pathways leading to specific cell functions, and especially the differences among lignans, have not been explored. We examined the estrogenic activity of enterolignans and their precursor plant lignans and cell signaling pathways for some cell functions, cell cycle and chemokine secretion. We used DNA microarray-based gene expression profiling in human breast cancer MCF-7 cells to examine the similarities, as well as the differences, among enterolignans, enterolactone and enterodiol, and their precursors, matairesinol, pinoresinol and sesamin. The profiles showed moderate to high levels of correlation (R values: 0.44 to 0.81) with that of estrogen (17β-estradiol or E2). Significant correlations were observed among lignans (R values: 0.77 to 0.97), and the correlations were higher for cell functions related to enzymes, signaling, proliferation and transport. All the enterolignans/precursors examined showed activation of the Erk1/2 and PI3K/Akt pathways, indicating the involvement of rapid signaling through the non-genomic estrogen signaling pathway. However, when their effects on specific cell functions, cell cycle progression and chemokine (MCP-1) secretion were examined, positive effects were observed only for enterolactone, suggesting that signals are given in certain directions at a position closer to cell functions. We hypothesized that, while estrogen signaling is initiated by the enterolignans/precursors examined, their signals are differentially and directionally modulated later in the pathways, resulting in the differences at the cell function level.
27 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