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Journal ArticleDOI

Estrogenic Activities of 517 Chemicals by Yeast Two-Hybrid Assay

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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Citations
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Journal ArticleDOI
TL;DR: To assess the endocrine disrupting effect of styrene oligomers, one styrene monomer, three styrene dimers and seven styrene trimers, newly isolated from optical isomers, tested concluded that these substances have no estrogenic activity.

26 citations

Journal ArticleDOI
TL;DR: Among 66 food additives, 17 compounds stimulated the proliferation of MCF-7 cells, but their concentrations giving maximal cell yield were higher than that of 17β-estradiol and their estrogenic activities were weak.
Abstract: Estrogenic activities of more than 90 chemicals including food additives, foodstuffs of plant origin, and some chemicals, which could be orally ingested, were examined by assaying estrogen receptor (ER)-dependent proliferation of MCF-7 cells. Among 66 food additives, 17 compounds stimulated the proliferation, but their concentrations giving maximal cell yield were higher than that of 17β-estradiol and their estrogenic activities were weak. Flavonoids had relatively strong estrogenic activities. In the assay of ER competitive binding to human ERα and ERβ in vitro, the antioxidant t-butylhydroxyanisole (BHA) had the capacity to compete with 17β-estradiol, while the capacity of o-phenyl phenol (OPP) was too small to calculate. Both BHA and OPP induced a decrease in gene expression of ERα and an increase in that of progesterone receptor in a time-dependent manner. These effects were similar to that of 17β-estradiol, a though much higher concentrations were required for these compounds than 17β-estradiol. These results may suggest that we should be careful not to ingest excessive food additives.

26 citations

Journal ArticleDOI
TL;DR: The findings were to detect the estrogenic activity of etocrylene and octocrylene in vitro, in addition to confirming the activities of some ultraviolet absorbers as previously reported.
Abstract: The estrogenic activities of ultraviolet absorbers and their related compounds were investigated using MCF-7 cell proliferation assay. Nine of 33 chemicals (benzophenone, 2,4-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 4-hydroxybenzophenone, 3-(4-methylbenzylidene) camphor, ethyl 2-cyano-3,3-diphenylacrylate (etocrylene) and 2-ethylhexyl-2-cyano-3,3-diphenylacrylate (octocrylene)) were positive compared with the vehicle control. Benzhydrol, ethyl cinnamate and 2,2'-dihydroxy-4-methoxybenzophenone were weakly active. When each xenoestrogen was added to the cells along with ICI 182780, an estrogen receptor (ER) antagonist, the cell growth was reduced according to its doses. Therefore, the cell proliferation was suggested to generate through ER. Most of these chemicals were also positive using CHOOSER assay, a new method of testing estrogenic activity of xenoestrogen. Each xenoestrogen was also confirmed to bind to ERalpha and ERbeta using a human ER competitive binding assay against 17beta-estradiol. The concentration order of the strength of its inhibitory effect using both ERalpha and ERbeta was similar to that of MCF-7 cell proliferation assay, except for benzyl 4-hydroxybenzoate (B4HB). B4HB showed a stronger activity on CHOOSER assay and the competitive binding assay using both ERalpha and ERbeta, although there was no activity observed on MCF-7 cell proliferation assay. Our findings were to detect the estrogenic activity of etocrylene and octocrylene in vitro, in addition to confirming the activities of some ultraviolet absorbers as previously reported.

26 citations

Journal ArticleDOI
TL;DR: The structural assignment of two water soluble isoflavone analogs of Daidzein and Genistein was initially assumed to be the corresponding sulfates on the basis of the facts that these analogs were hydrolyzed by sulfatase as mentioned in this paper.

26 citations

Journal ArticleDOI
TL;DR: Uterine weights of weanlings increased significantly in these groups, suggesting that the sensitivity of this parameter for predicting estrogenic ability of the test compound is comparable to that of the uterotrophic assay.
Abstract: A two-generation reproduction toxicity study was conducted in rats with a reference estrogenic pesticide, methoxychlor, to validate the sensitivity and competency of current guidelines recommended by the United States Environmental Protection Agency; Japanese Ministry of Agriculture, Forestry and Fisheries; and Organisation for Economic Co-operation and Development for predicting reproductive toxicity of the test compound based on estrogenic endocrine disrupting effects. Both sexes of SD rats were exposed to methoxychlor in the diet at concentrations of 0, 10, 500 and 1500 ppm for two successive generations. The present study has successfully detected estrogenic activities and reproductive toxicities of methoxychlor, as well as its systemic toxicity. Body weights, body weight gains and food consumption of both sexes of animals were suppressed significantly in the 500 and 1500 ppm groups. Typical reproductive toxicities observed in females of these groups included, but were not limited to, prolonged estrous cycle, reduced fertility, decreased numbers of implantation sites and newborns, decreased ovary weights and/or increased incidences of cystic ovary. Uterine weights of weanlings increased significantly in these groups, suggesting that the sensitivity of this parameter for predicting estrogenic ability of the test compound is comparable to that of the uterotrophic assay. Reproductive toxicities of methoxychlor seemed less potent in males than in females. Methoxychlor delayed preputial separation and significantly reduced sperm counts and reproductive organ weights of males of the 500 and/or 1500 ppm groups; however, most males that failed to impregnate females in the same group showed normal fertility when they were re-mated with untreated females. Neither systemic nor reproductive toxicities appeared in the 10 ppm group.

25 citations


Cites background from "Estrogenic Activities of 517 Chemic..."

  • ...…estrogenicity was undetectable or at least very weak in a variety of in vitro assays (Jobling et al. 1995; Jones et al. 1998; Korner et al. 1998; Nishihara et al. 2000), did exert such estrogen-like effects as an increase in uterine weights of female weanlings and decreases in numbers of…...

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  • ...In contrast, 2,4-dichlorophenol, whose estrogenicity was undetectable or at least very weak in a variety of in vitro assays (Jobling et al. 1995; Jones et al. 1998; Korner et al. 1998; Nishihara et al. 2000), did exert such estrogen-like effects as an increase in uterine weights of female weanlings and decreases in numbers of implants and newborns (Aoyama et al....

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References
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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.

917 citations