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Endocrinic Effects of Toxaphene and Chlordane in Human Hepatoma Cell (HepG2 Cell) Transfected with Estrogen Receptor and Luciferase Reporter Gene  

Kim Kyeong-Bae (서울대학교 수의과대학)
Jung Ji-Won (서울대학교 수의과대학)
Yang Se-Ran (서울대학교 수의과대학)
Kang Kyung-Sun (서울대학교 수의과대학)
Lee Yong-Soon (서울대학교 수의과대학)
Publication Information
Toxicological Research / v.20, no.3, 2004 , pp. 205-211 More about this Journal
Abstract
Concern that some chemicals in our environment may affect human health by disrupt-ing normal endocrine function has prompted a research on interactions of environmental contaminants with steroid hormone receptor. Toxaphene and chlordane are among the 12 persistent organic pollutants identified by the United Nations Environment Programme as requiring urgent attention. We compared the estrogenic activity of two organochlorine pesticides, toxaphene and chlordane, at estrogen receptor a (ER$\alpha$) and estrogen receptor $\beta$ (ER$\beta$). Human hepatoma cells (HepG2) were transiently transfected with rat ER$\alpha$ or ER$\beta$ plus an estrogen-responsive complement C3-luciferase (C3-Luc) reporter gene. After transfection, cells were treated with various concentrations of toxaphene and chlordane to investigate agonism or antagonism of these chemicals. Both toxaphene and chlordane were potent agonists in HepG2 cells for ER$\alpha$. In contrast, these chemicals had a minimal agonist activity with ER$\beta$ and almost abolished 17$\beta$-estradiol-induced ER$\beta$-mediated activity. Therefore, toxaphene and chlordane behaved as an ER$\alpha$ agonist and an ER$\beta$ antagonist with estrogen-responsive reporter plasmid C3-Luc, and exposure to these organochlorine pesticides could have a crictical effect on normal endocrine function.
Keywords
Endocrine disruptor; Toxaphene; Chlordane; Estrogen receptors; ER${\alpha}$; ER${\beta}$; agonist; antagonist;
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1 Breithofer, A., Graumann, K., Scicchtano, M.S., Karathanasis, S.K., Butt, T.R. and Jungbauer, A. (1998): Regulation of human estrogen receptor by phytoestrogens in yeast and human cells. J. Steroid. Biochem. Mol. Biol., 67, 421-429   DOI   ScienceOn
2 Collins, B.M., McLachlan, J. and Arnold, S.F. (1997): The estrogenic and antiestrogenic activities of phytochernicals with the human estrogen receptor expressed in yeast. Steroids, 62, 365-372   DOI   ScienceOn
3 Gaido, K.W., Leonard L.S., Lovell S., Gould J.C., Babal D., Portier C.J. and McDonnell D.P. (1997): Evalution of chemicals with endocrine modulating activity in yeastbased steroid hormone receptor gene transcription assay. Toxicol. Appl. Pharmacal., 143, 205-212
4 Kuiper, G., Enmark, E., Peltohuikko, M., Nilsson, S. and Gustafsson, J.A. (1996): Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. USA, 93, 5925-5930
5 Mosselman, S., Polman, J. and Dijkema, R. (1996): ERbeta: identification and characterization of a novel human estrogen receptor. FEBS Lett., 392, 49-53
6 Paech, K., Webb, P., Kuiper, G., Nilsson, S., Gustafsson, J.A., Kushner, P.J. and Scanlan, T.S. (1997): Differential ligand activation of estrogen receptors ER$\alpha$ and ER$\beta$ at AP1 sites. Science, 277, 1508-1510   DOI   PUBMED   ScienceOn
7 Bonefeld Jorgensen E.C., Autrup H. and Hansen J.C. (1997): Effect of toxaphene on estrogen receptor functions in human breast cancer cells. Carcinogenesis, 18, 1651-1654   DOI   ScienceOn
8 Kuiper, G., Lemmen, J.G., Carlsson, B., Corton, J.C., Safe, S.H., van der Saag, P.T., van der Burg, B. and Gustafsson J.A. (1998): Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology, 139, 4252-4263   DOI   ScienceOn
9 Chen, C.W., Hurd, C., Vorojeikina, D.P, Arnold, S.F. and Notides, A.C. (1997): Transcriptional activation of the human estrogen receptor by DDT isomers and methbolites in yeast and MCF-7 cells. Biochem. Pharmacol., 53, 1161-1172
10 Ogawa, S., Inoue, S., Watanabe, T., Hiroi, H., Orimo, A., Hosoi, T., Ouchi, Y. and Muramatsu, M. (1998): The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro. Biochem. Biophys. Res. Commun., 243, 122-126
11 Arnold, S.F., Robinson, M.K., Notides, A.C., Guillette, L.J. Jr. and McLachlan, J.A. (1996): A yeast estrogen screen for examining the relative exposure of cells to natural and xenoestrogens. Environ. Health Perspect., 104, 544-548
12 lng, N.H. and O'Malley, B.W. (1995): The steroid hormone receptor superfamily-Molecular mechanisms of action. In Molecular Endocrinology: Basic Concepts and Clinical Correlations, Raven Press, New York, pp. 195-215
13 Tremblay, G.B., Tremblay, A., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Labrie, F. and Giguere, V. (1997): Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. Mol. Endocrinol., 11, 353-365
14 Kuiper, G. and Gustafsson, J.A. (1997): The novel estrogen receptor-beta subtype: Potential role in the cell- and promoter-specific actions of estrogens and antiestrogens. FEBS Lett., 410, 87-90
15 Chun, Y. and Shiuan, C. (1999): Two organochlorine pesticides, toxaphene and chlordane, are antagonists for estrogen-related receptor alpha-1 orphan receptor. Cancer Res., 59, 4519-4524
16 Fisher, B. E. (1999): Most unwanted: persistent organic pollutants. Environ. Health Perspect., 107, A18-A23
17 Petit, F., Le Goff, P., Cravedi J.P., Valotaire, Y. and Pakdel, F. (1997): Two complementary bioassays for screening the estrogenic potency of xenobiotics: recombinant yeast for trout estrogen receptor and trout hepatocyte cultures. J. Mol. Endocrinol., 19, 321-335   DOI   ScienceOn
18 Darimont, B.D., Wagner, R.L., Apriletti, J.W., Stallcup, M.R., Kushner, P.J., Baxter, J.D., Fletterick, R.J. and Yamamoto, K.R. (1998): Structure and specificity of nuclear receptor-coactivator interactions. Genes Dev., 12, 3343-3356
19 Maness, S.C., Mcdonnell, D.P. and Gaido, K.W. (1998): Inhibition of androgen receptor-dependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells. Toxicol. Appl. Pharmacal., 151, 135-142
20 Muramatsu, M. and Inoue, S. (2000): Estrogen receptors: How do they control reproductive and nonreproductive functions? Biochem. Biophys. Res. Commun., 270,110
21 Pike, A.C.W., Brzozowski, A.M., Hubbard, R.E., Bonn, T., Thorsell, A.G., Engstrom, O., Ljunggren, J., Gustafsson, J.K. and Carlquist, M. (1999): Structure of the ligandbinding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist. EMBO J., 18, 4608-4618