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Journal ArticleDOI

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.

AbstractOne 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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Journal ArticleDOI
TL;DR: Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin‐layer chromatography and this should open the way technically for more detailed information to be obtained on body burdens of paraben and in particular whether body burdens are different in cancer from those in normal tissues.
Abstract: Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term, low-dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin-layer chromatography. More detailed studies enabled identification and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 +/- 4.2 ng x g(-1) tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 +/- 2.2 ng x g(-1) tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues.

647 citations


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

  • ...They have been shown to regulate oestrogen-responsive reporter gene expression in yeast cells (Routledge et al., 1998; Jin-Sung et al., 2000; Nishihara et al., 2000) and in human breast cancer cells (Byford et al., 2002; Darbre et al., 2002, 2003), and expression of the endogenous…...

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Journal ArticleDOI
TL;DR: Removal of EDCs from three aspects is reviewed, that is, physical means, biodegradation, and chemical advanced oxidation (CAO).
Abstract: Endocrine disrupting compounds (EDCs) are pollutants with estrogenic or androgenic activity at very low concentrations and are emerging as a major concern for water quality. Within the past few decades, more and more target chemicals were monitored as the source of estrogenic or androgenic activity in wastewater, and great endeavors have been done on the removal of EDCs in wastewater. This article reviewed removal of EDCs from three aspects, that is, physical means, biodegradation, and chemical advanced oxidation (CAO).

607 citations


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

  • ...(USEPA, 1997) This broad class of chemicals includes natural estrogens, such as estrone (E1),17β-estradiol (E2), and estriol (E3) (Blair et al., 2000; Nishihara et al., 2000; Folmar et al., 2002; Zhu et al., 2006); natural androgens such as testosterone (T), dihydrotestosterone (DHT), and…...

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Journal ArticleDOI
TL;DR: The results suggest that the 4-hydroxyl group of the A- phenyl ring and the B-phenyl ring of BPA derivatives are required for these hormonal activities, and substituents at the 3,5-positions of the phenyl rings and the bridging alkyl moiety markedly influence the activities.
Abstract: The endocrine-disrupting activities of bisphenol A (BPA) and 19 related compounds were comparatively examined by means of different in vitro and in vivo reporter assays. BPA and some related compounds exhibited estrogenic activity in human breast cancer cell line MCF-7, but there were remarkable differences in activity. Tetrachlorobisphenol A (TCBPA) showed the highest activity, followed by bisphenol B, BPA, and tetramethylbisphenol A (TMBPA); 2,2-bis(4-hydroxyphenyl)-1-propanol, 1,1bis(4-hydroxyphenyl)propionic acid and 2,2-diphenylpropane showed little or no activity. Anti-estrogenic activity against 17bestradiol was observed with TMBPA and tetrabromobisphenol A (TBBPA). TCBPA, TBBPA, and BPA gave positive responses in the in vivo uterotrophic assay using ovariectomized mice. In contrast, BPA and some related compounds showed significant inhibitory effects on the androgenic activity of 5a-dihydrotestosterone in mouse fibroblast cell line NIH3T3. TMBPA showed the highest antagonistic activity, followed by bisphenol AF, bisphenol AD, bisphenol B, and BPA. However, TBBPA, TCBPA, and 2,2diphenylpropane were inactive. TBBPA, TCBPA, TMBPA, and 3,3#-dimethylbisphenol A exhibited significant thyroid hormonal activity towards rat pituitary cell line GH3, which releases growth hormone in a thyroid hormone-dependent manner. However, BPA and other derivatives did not show such activity. The results suggest that the 4-hydroxyl group of the A-phenyl ring and the B-phenyl ring of BPA derivatives are required for these hormonal activities, and substituents at the 3,5-positions of the phenyl rings and the bridging alkyl moiety markedly influence the activities.

580 citations


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

  • ...For estrogen receptor ligand activity, xenobiotics require an unhindered hydroxyl group on an aryl ring and a hydrophobic group attached para to the hydroxyl group (Blair et al., 2000; Elsby et al., 2000; Fang et al., 2000; Hong et al., 2002; Nishihara et al., 2000)....

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  • ...For estrogen receptor ligand activity, xenobiotics require an unhindered hydroxyl group on an aryl ring and a hydrophobic group attached para to the hydroxyl group (Blair et al., 2000; Elsby et al., 2000; Fang et al., 2000; Hong et al., 2002; Nishihara et al., 2000)....

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Journal ArticleDOI
TL;DR: There is a need to carry out detailed evaluation of the potential for parabens, together with other oestrogenic and genotoxic co‐formulants of bodycare cosmetics, to increase female breast cancer incidence, to interfere with male reproductive functions and to influence development of malignant melanoma.
Abstract: This toxicology update reviews research over the past four years since publication in 2004 of the first measurement of intact esters of p-hydroxybenzoic acid (parabens) in human breast cancer tissues, and the suggestion that their presence in the human body might originate from topical application of bodycare cosmetics. The presence of intact paraben esters in human body tissues has now been confirmed by independent measurements in human urine, and the ability of parabens to penetrate human skin intact without breakdown by esterases and to be absorbed systemically has been demonstrated through studies not only in vitro but also in vivo using healthy human subjects. Using a wide variety of assay systems in vitro and in vivo, the oestrogen agonist properties of parabens together with their common metabolite (p-hydroxybenzoic acid) have been extensively documented, and, in addition, the parabens have now also been shown to possess androgen antagonist activity, to act as inhibitors of sulfotransferase enzymes and to possess genotoxic activity. With the continued use of parabens in the majority of bodycare cosmetics, there is a need to carry out detailed evaluation of the potential for parabens, together with other oestrogenic and genotoxic co-formulants of bodycare cosmetics, to increase female breast cancer incidence, to interfere with male reproductive functions and to influence development of malignant melanoma which has also recently been shown to be influenced by oestrogenic stimulation.

512 citations


Journal ArticleDOI
TL;DR: This research presents a meta-analyses of the immune system’s response to exposure to radiation and shows clear patterns of decline in the immune systems of men and women aged 65 and over.
Abstract: Robert E. Chapin, Jane Adams, Kim Boekelheide, L. Earl Gray Jr, Simon W. Hayward, Peter S.J. Lees, Barry S. McIntyre, Kenneth M. Portier, Teresa M. Schnorr, Sherry G. Selevan, John G. Vandenbergh, and Susan R. Woskie Pfizer, Inc., Groton, CT University of Massachusetts, Boston, MA Brown University, Providence, RI U.S. Environmental Protection Agency, Research Triangle Park, NC Vanderbilt University Medical Center, Nashville, TN Johns Hopkins University, Baltimore, MD Schering Plough Research Institute, Summit, NJ American Cancer Society, Atlanta, GA National Institute for Occupational Safety and Health, Cincinnati, OH U.S. Public Health Service (Ret), Silver Spring, MD North Carolina State University, Raleigh, NC University of Massachusetts, Lowell, MA

469 citations


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.

912 citations