This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coumoul, X. Articles by Barouki, R. Search for Related Content PubMed PubMed Citation Articles by Coumoul, X. Articles by Barouki, R.

Differential Regulation of Cytochrome P450 1A1 and 1B1 by a Combination of Dioxin and Pesticides in the Breast Tumor Cell Line MCF-7¹

Institut National de la Santé et de la Recherche Médicale U490, Université René Descartes, 75270 Paris Cedex 06 [X. C., M. D., R. B.], and Laboratoire Environnement et Chimie Analytique CNRS ERS 657, Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris, 75231 Paris Cedex 05 [C. R.], France

Dioxin and pesticides with xenoestrogenic activity are environmental contaminants that are suspected of promoting human diseases such as cancers. However, few studies have addressed the molecular consequences of a combination of these contaminants, a situation that is likely to occur in the environment. We investigated the effects of natural and xenoestrogens on basal and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 (CYP) 1A1 and 1B1. The CYP1B1/1A1 ratio is a critical determinant of the metabolism and toxicity of estradiol in mammary cells. Here we show that in MCF-7 cells, 17ß-estradiol and -endosulfan can repress whole cell ethoxyresorufin-O-deethylase activity, lowering CYP1A1 mRNA levels as well as promoter activity as assessed by transient transfection assays. These negative effects are observed at both the basal and tetrachlorodibenzo-p-dioxin-induced levels. Under the same conditions, CYP1B1 mRNA levels and promoter activity are not affected. The effects on mRNA-induced levels are also observed in another mammary cell line, T47D, but not in mammary cell lines that do not express aryl hydrocarbon receptor and estrogen receptor (ER). Moreover, the use of ER antagonists shows that these effects are ER dependent in MCF-7 cells. In human hepatoma HepG2 cells, which lack functional ER, -endosulfan, but not 17ß-estradiol, displays a repressive effect on CYP1A1 through a different mechanism. These results show that xenoestrogens, by altering the ratio of CYP1B1/CYP1A1, could redirect estradiol metabolism in a more toxic pathway in the breast cell line MCF-7.

This article has been cited by other articles:

				S. Hirakawa, H. Iwata, Y. Takeshita, E.-Y. Kim, T. Sakamoto, Y. Okajima, M. Amano, N. Miyazaki, E. A. Petrov, and S. Tanabe Molecular Characterization of Cytochrome P450 1A1, 1A2, and 1B1, and Effects of Polychlorinated Dibenzo-p-dioxin, Dibenzofuran, and Biphenyl Congeners on Their Hepatic Expression in Baikal Seal (Pusa sibirica) Toxicol. Sci., June 1, 2007; 97(2): 318 - 335. [Abstract] [Full Text] [PDF]

				C. Gouedard, R. Barouki, and Y. Morel Induction of the Paraoxonase-1 Gene Expression by Resveratrol Arterioscler. Thromb. Vasc. Biol., December 1, 2004; 24(12): 2378 - 2383. [Abstract] [Full Text] [PDF]

				M. Yoshida, S. Katashima, J. Ando, T. Tanaka, F. Uematsu, D. Nakae, and A. Maekawa Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats initiated with N-ethyl-N'-nitro-N-nitrosoguanidine, with induction of cytochrome P450s in the liver and consequent modulation of estrogen metabolism Carcinogenesis, November 1, 2004; 25(11): 2257 - 2264. [Abstract] [Full Text] [PDF]

				Z.-H. Chen, Y.-J. Hurh, H.-K. Na, J.-H. Kim, Y.-J. Chun, D.-H. Kim, K.-S. Kang, M.-H. Cho, and Y.-J. Surh Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells Carcinogenesis, October 1, 2004; 25(10): 2005 - 2013. [Abstract] [Full Text] [PDF]

				J. Listgarten, S. Damaraju, B. Poulin, L. Cook, J. Dufour, A. Driga, J. Mackey, D. Wishart, R. Greiner, and B. Zanke Predictive Models for Breast Cancer Susceptibility from Multiple Single Nucleotide Polymorphisms Clin. Cancer Res., April 15, 2004; 10(8): 2725 - 2737. [Abstract] [Full Text] [PDF]

				W. G. Foster, E. V. Younglai, O. Boutross-Tadross, C. L. Hughes, and M. G. Wade Mammary Gland Morphology in Sprague-Dawley Rats following Treatment with an Organochlorine Mixture in Utero and Neonatal Genistein Toxicol. Sci., January 1, 2004; 77(1): 91 - 100. [Abstract] [Full Text] [PDF]

				D. C. Spink, B. H. Katz, M. M. Hussain, B. T. Pentecost, Z. Cao, and B. C. Spink Estrogen regulates Ah responsiveness in MCF-7 breast cancer cells Carcinogenesis, December 1, 2003; 24(12): 1941 - 1950. [Abstract] [Full Text] [PDF]

				T. K. H. Chang, J. Chen, V. Pillay, J.-Y. Ho, and S. M. Bandiera Real-Time Polymerase Chain Reaction Analysis of CYP1B1 Gene Expression in Human Liver Toxicol. Sci., January 1, 2003; 71(1): 11 - 19. [Abstract] [Full Text] [PDF]