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Antiestrogenic potentials of ortho-PCB congeners by single or complex exposure

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Abstract

Di-ortho PCB congeners 52, 138, 153 and 180, and the mono-ortho coplanar congener 118 have been detected as a complex mixture in human tissue in Korea. This study examined the antiestrogenic effects of samples exposed to single or combination treatment of the ortho-PCB congeners. In order to determined the combined toxicity, a sample mixture (M1, M2, M3, M4, and M5) was designed based on the ortho-PCB congeners found in Korean human tissue. With the exception of PCB 52, the ortho-PCB congeners (PCB 118, 138, 153, and 180) showed weak antiestrogenic activity. The antiestrogenic activity of di-ortho PCB congeners (PCB 138, 153, and 180) was induced by the depletion of endogenous E2 as well as through the ER-dependent pathway, whereas the antiestrogenic activity of mono-ortho PCB 118 was only induced through the depletion of endogenous E2. When the MCF7-BUS cells were treated with mixtures containing the no effective concentration (10-6 M) of the PCB congeners, M3 (PCB 118 + PCB 138 + PCB 180) and M4 (PCB 118 + PCB 138) had an antiestrogenic effect but the other mixtures (M1; PCB 52 + PCB 118 + PCB 138 + PCB 180, M2; PCB 118 + PCB 138 + PCB 153 + PCB 180, M5; PCB 118 + PCB 180) did not. Although the mechanism for the interaction between the PCB congeners is not completely understood, it was presumed that exposure to a mixture of the PCB congeners might have synergistic effects on their antiestrogenicity through the ER-independent pathway.

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References

  • Arcaro, K. F, O’Keefe, P. W., Yang, Y, Clayton, W., and Gierthy, J. F., Antiestrogenicity of environmental polycyclic aromatic hydrocarbons in human breast cancer cells.Toxicology, 133, 115–127(1999).

    Article  PubMed  CAS  Google Scholar 

  • Arnold, S. F., Klotz, D. M., Collins, B. M., Vonier, P. M., Gillette, L. J., and MaLachlan, J. A., Synergistic activation of estrogen receptor with combinations of environmental chemicals.Science, 272, 1489–1492 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Bates, M. N., Hannah, D. J., Buckland, S. J., Taucher, J. A., and van Maanen, T., Chlorinated organic contaminants in breast milk of New Zealand women.Environ. Health Perspect., 102(Suppl 1), 211–217 (1994).

    PubMed  CAS  Google Scholar 

  • Bonefeld-Jorgensen, E. C, Andersen, H. R., Rasmussen, T. H., and Vinggaard, A. M., Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity.Toxicology, 158,141–153(2001).

    Article  PubMed  CAS  Google Scholar 

  • Bosveld, A. T., Kennedy, S. W., Scinen, W., and van den Berg, M., Ethoxyresorufin-O-deethylase (EROD) inducing potencies of planar chlorinated aromatic hydrocarbons in primary cultures of hepatocytes from different developmental stage of the chicken,Arch. Toxicoi, 71, 746–750 (1997).

    Article  CAS  Google Scholar 

  • Bradford, M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal. Biochem., 72, 248–254 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Bradlow, H. L, Telang, N. T., Sepkovic, D. W., and Osborne, M. P., 2-Hydroxyestrone: the ‘good’ estrogen,J. Endocr, 150, s529-s265(1996).

    Google Scholar 

  • Buchanan, D. L, Ohsako, S., Tohyama, C, Cooke, P. S., and Iguchi, T., Dioxin inhibition of estrogen-induced mouse uterine epithelial mitogenesis involves changes in cyclin and transforming growth factor-beta expression.Toxicol. Sci., 66, 62–68 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Buchanan, D. L, Sato, T., Peterson, R. E., and Cooke, P. S., Antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse uterus: critical role of the aryl hydrocarbon receptor in stromal tissue.Toxicoi. Sci., 57, 302–311. (2000)

    Article  CAS  Google Scholar 

  • Bulger, W. H. and Kupfer, D., Estrogenic activity of pesticides and other xenobiotics on the uterus and male reproductive tract. In: Korach, M., McLachlan, J. A. (eds) Endocrine toxicology. Raven Press, New York, pp 1–33. (1985).

    Google Scholar 

  • Chu, I., Villeneuve, D. C, Yagminas, A., Lecavalier, P., Hakansson, H., Ahlborg, U. G, Valli, V. E., Kennedy, S. W., Bergman, A., Seegal, R. F, and Feeley, M., Toxicity of PCB 77 (3,3’,4,4’- Tetrachlorobiphenyl) and PCB 118 (2,3’,4,4’,5-Pentachlorobi-phenyl) in the rat following subchronic dietary exposure,Fund. Appl. Toxicoi., 26, 282–292 (1995).

    Article  CAS  Google Scholar 

  • Cogliano, V. J., Assessing the cancer risk from environmental PCBs.Environ. Health Perspect, 106, 317–323 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Dannan, G. A., Porubek, D. J., Netson, S. D., Waxman, D. J., and Guengerish, F P., 17β-Estradiol 2-and 4-hydroxylation catalyzed by rat hepatic cytochrome P450: roles of individual forms, inductive effects, developmental patterns, and alterations by gonadectomy and hormone replacement,Endocrinology, 118, 1952–1960 (1986).

    PubMed  CAS  Google Scholar 

  • Dewailly, E., Ryan, J. J., Lailberte, C, Bruneau, S., Weber, J. P., Gingras, S., and Carrier, G, Exposure of remote martime populations to coplanar PCBs.Environ. Health Perspect., 102(Suppl 1), 205–209(1994).

    PubMed  CAS  Google Scholar 

  • Drenth, H. J., Bouwman, C. A., Scinen, W., and Van den Berg, M., Effects of some persistent halogenated environmental contaminants on aromatase (CYP19) activity in the human choriocarcinoma cell line JEG-3.Toxicoi. Appl. Pharmacol., 148,50–55(1998).

    Article  CAS  Google Scholar 

  • Ecobichon, D. J. and MacKenzie, D. O., The uterotrophic activity of commercial and isomerically-pure chlorobiphenyls in the rat,Res. Commun. Chem. Path. Pharmacol., 9, 85–95, (1974).

    CAS  Google Scholar 

  • Environmental Health in Europe No. 3. Level of PCBs, PCDDs and PCDFs in human milk. Second round of WHO-coordinated exposure study (1996).

  • Furst, P. C. and Wilmers, K., Human milk as a bioindicator for body burden of PCDDs, PCDFs, organochlorine pesticides, and PCBs.Environ. Health Perspect, 102(Suppl. 1), 187–193(1994).

    PubMed  CAS  Google Scholar 

  • Gillette, J. S., Hansen, L. G, and Rose, R. L, Metabolic effects of episodic polychlorinated biphenyl (PCB) congeners,Rev. Toxicoi. Environ. Toxicoi., 4,129–159 (2002).

    Google Scholar 

  • Graumann, K., Breithofer, A., and Jungbauer, A., Monitoring of estrogen mimics by a recombinant yeast assay: synergy between natural and synthetic compounds?The science of the total environment, 225, 69–79 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Hestermann, E. V, Stegeman, J. J., and Hahn, M. E., Relative contributions of affinity and intrinsic efficacy to aryl hydrocarbon receptor ligand potency,Toxicoi. Appl. Pharmacol., 168,160–172(2000).

    Article  CAS  Google Scholar 

  • Kimbrough, R. D., Polychlorinated biphenyls (PCBs) and human health: an update.Crit. Rev. Toxicol., 25,133–163 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Korach, K. S., Sarver, P., Chae, K., McLachlan, J. A., and McKinney, J. D., Estrogen receptor-binding activity of polychlorinated hydroxybiphenyls: Conformationally restricted structural probes,Mol. Pharmacol., 33,120–126 (1988).

    PubMed  CAS  Google Scholar 

  • Korach, K. S. Davis, V. L, Curtis, S. W., and Bcchinfuso, W. P., Xenoestrogens and estrogen receptor action, In Thomas, J. A., and Colby, H. D. (Eds.).Endcrine Toxicology, Taylor & Francis, pp. 181–205, (1997).

    Google Scholar 

  • Leece, B., Denomme, M. A., Towner, R., Li, A., Landers, J., and Safe, S., Nonadditive interactive effects of polychlorinated biphenyl congeners in rats: role of the 2,3,7,8-tetrachlorodi-benzo-p-dioxin receptor.Canadian Journal of Physiology and Pharmacology, 65,1908–1912 (1987).

    PubMed  CAS  Google Scholar 

  • Machala, M. and Vondracek, J., Estrogenic activity of xenobiotics.Vet. Med., 43, 311–317 (1998).

    CAS  Google Scholar 

  • MaFarland, V. A. and Clarke, J. U., Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener-specific analysis.Environ. Health Perspect, 81, 225–239 (1989).

    Article  Google Scholar 

  • Navas, J. M. and Segner, H., Antiestrogenic activity of anthropogenic and natural chemicals.Environ. Sci. Pollut. Res., 5, 75–82(1998).

    CAS  Google Scholar 

  • Oenga, G N., Spink, D. C, Carpenter, D. O., TCDD and PCBs inhibit breast cancer cell proliferation.Toxicol. in Vitro, 18, 811–819(2004).

    Article  PubMed  CAS  Google Scholar 

  • Olea, N., Pulgar, R., Perez, P., Olea-Serrano, F., Rivas, A., Novillo-Fertrell, A., Pedraza, V, Soto, A. M., and Sonnenschein, C, Estrogenicity of resin-based composites and sealants used in dentistry.Environ. Health Perspect., 104,198–305 (1996).

    Article  Google Scholar 

  • Parkinson, A., Robertson, L., and Safe, S., Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: structure-activity rules,Chem. Biol. Interact, 30, 271–285 (1981).

    Article  Google Scholar 

  • Perez, P., Pulgar, R., Olea-Serrano, F., Villalobos, M., Rivas, A., Metzler, M., Pedraza, V, and Olea, N., The estrogenicity of bisphenol A-related diphenylalkanes with various substituents at the central carbon and the hydroxy groups.Environ. Health Perspect, 106,198–305(1998).

    Article  Google Scholar 

  • Plišková, M., Vondráèek, J., Canton, R. F, Nera, J., Koèan, A., Petrik, J., Tronvec, T., Sanderson, T, van den Berg, M., and Machala, M., Impact of polychlorinated biphenyls contamination on estrogenic activity in human male serum.Environ. Health Perspect, 113,1277–1284(2005).

    Article  PubMed  CAS  Google Scholar 

  • Porter, W. and Safe, S. H., Estrogenic and antiestrogenic compounds, In Puga, A., and Wallace, K.B. (Eds). Molecular biology of the toxic response. Talylor & Francis, pp. 269–279, (1999).

    Google Scholar 

  • Safe, S., Astroff, B., Harris, M., Zacharewski, T., Dickerson, R., Romkes, M., and Biegel, L. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds as antioestrogens: characterization and mechanisms of action.Pharmacol. Toxicol., 69, 400–409 (1991).

    PubMed  CAS  Google Scholar 

  • Safe, S., Polychlorinated biphenyls (PCBs): Environmental impact, biological and toxic responses, and implications for risk assessment.Critical Reviews in Toxicology, 24, 87–149 (1994a).

    Article  PubMed  CAS  Google Scholar 

  • Safe, S. Dietary and environmental estrogens and antiestrogens and their possible role in human disease.Environ. Sci. Pollut. Res., 1,29–33 (1994b).

    Article  CAS  Google Scholar 

  • Safe, S., Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.Pharmacology and Therapeutics, 67, 247–281 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Safe, S., Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds,Teratog. Carcinog. Mutagen., 17, 285–304(1997).

    Article  PubMed  CAS  Google Scholar 

  • Safe, S., Interactions between hormone and chemicals in breast cancer.Annu. Rev. Pharmacol. Toxicol., 38, 121–158 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Safe, S. and Wörmke, M., Inhibitory arylhydrocarbon receptorestrogen receptor a cross-talk and mechanisms of action.Chemical Research in toxicology, 16, 807–816 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Schmitz, H.-J., Hagenmaier, A., Hagenmaier, H.-P, Bock, K. W., and Schrenk, D., Potency of mixtures of polychlorinated biphenyls as inducers of dioxin receptor-regulated CYP1A activity in rat hepatocytes and H4IIE cells.Toxicology, 99, 47–54(1995).

    Article  PubMed  CAS  Google Scholar 

  • Schneider, J., Huh, M. M., Bradlow, H. L., and Fishman J., Antiestrogenic action of 2-hydroxyestrone on MCF-7 human breast cancer cells,Journal of Biological Chemistry, 259, 4840–4845 (1984).

    PubMed  CAS  Google Scholar 

  • Shou, M., Korzekwa, K. R., Brooks, E. N., Krausz, K. W., Gonzalez, F. J., and Gelboin, H. V, Role of human hepatic cytochrome P450 1A2 and 3A4 in the metabolic activation of estrone,Carcinogenesis, 18, 207–214 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Simpson, E. R., Mahendroo, M. S., Means, G D., Kilgore, M. W., Hinshelwood, M. M., Graham-Lorence, S., Amarneh, B., Ito, Y, Fischer, C. R., Michael, M. D., Mendelson, C. R., and Bulun, S. E., Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis.Endocrine Reviews, 15,342–355(1994).

    Article  PubMed  CAS  Google Scholar 

  • Skehan, P., Storeng, R., Scudiero, D., Monk, A., McMahon, J., Vistica, D., Warren, J. T, Bokesch, H., Kenny, S., and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening.Journal of the National Cancer Institute, 82, 1107–1112(1990).

    Article  PubMed  CAS  Google Scholar 

  • Smeets, J. M. W., van Holsteijn, I., Giesy, J. P., and van den Berg, M., The anti-estrogenicity of Ah receptor agonists in Carp(Cyprinus carpio) hepatocytes.Toxicological Sciences, 52,178–188(1999).

    Article  PubMed  CAS  Google Scholar 

  • Soto, A. M., Sonnenschein, C, Chung, K. L, Fernandez, M. F, Olea, N., and Serrano, F. O., The E-SCREEN assay as a tool to identify estrogens: An update on estrogenic environmental pollutants.Environmental Health Perspectives, 103(suppl 71), 113–122(1995).

    Article  PubMed  CAS  Google Scholar 

  • Spink, D. C, Eugster, H. P., Lincoln, D. W. 2nd, Schuetz, J. D., Schuetz, E. G., Johnson, J. A., Kaminsky, L. S., and Gierthy, J. F., 17 Beta-estradiol hydroxylation catalyzed by human cytochrome P450 1A1: a comparison of the activities induced by 2,3,7,8-tetrachlorodibenz-p-dioxin in MCF-7 cells with those from heterologous expression of the cDNA,Arch. Biochem. Biophys., 293, 342–348 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Stancel, G M., Boettger-Tong, H., Chiappetta, C, Hyder, S. M., Kirkland, J. L, Murthy, L., and Loose-Mitchell, D. S., Toxicology of estrogens and environmental estrogens: what is the role of elemental interactions.Environ, Health Perspect, 103(Suppl 7), 29–33(1995).

    Article  CAS  Google Scholar 

  • Suchar, L. A., Chang, R. L., Rosen, R. T, Lech, J., and Conney, A. H., High performance liquid chromatography separation of hydroxylated estradiol metabolites: formation of estradiol metabolites by liver microsomes from male and female rats.Journal of Pharmacology and Experimental Therapeutics, 272,197–206(1995).

    PubMed  CAS  Google Scholar 

  • Suh, J., Kang, J. S., Yang, K. H., and Kaminski, N. E., Antagonism of aryl hydrocarbon receptor-dependent induction of CYP 1A1 and inhibition of IgM expression by di-ortho-substituted polychlorinated biphenyls.Toxicol. Appl. Pharmacol., 187, 11–21 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Tsuchiya, Y, Nakajima, M., and Yokoi, T., Cytochrome P450-mediated metabolism of estrogens and its regulation in human,Cancer Lett., 227,115–124 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Vakharia, D. D. and Gierthy, J. F., Use of a combined human liver microsome-estrogen receptor binding assay to assess potential estrogen modulating activity of PCB metabolites.Toxicology Lett., 114, 55–65 (2000).

    Article  CAS  Google Scholar 

  • Woodhouse, A. and Cooke, G M., Suppression of aromatase activityin vitro by PCBs 28 and 105 and Arochlor 1221,Toxicology Lett., 152, 91–100 (2004).

    Article  CAS  Google Scholar 

  • Yamazaki, H., Shaw, P. W., Guengerich, F. P., and Shimada T., Roles of cytochromes P450 1A2 and 3A4 in the oxidation of estradiol and estrone in human liver microsomes,Chem. Res. Toxicol., 11,659–665(1998).

    Article  PubMed  CAS  Google Scholar 

  • Yoo, Y C, Lee, S. K., Lee, S. Y, Yang, J. Y, In, S. W., Kim, K. W., and Chung, K. H., Distribution of organochlorines pesticides in Korean human tissue.Yakhak Hoeji, 45, 366–377 (2002).

    Google Scholar 

  • Zacharewski, T, Harris, M., and Safe, S., Evidence for the mechanism of action of the 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated decrease of nuclear estrogen receptor levels in wild-type and mutant mouse heap 1c1c7 cells.Biochem. Pharmacol., 41,1931–1939 (1991).

    Article  PubMed  CAS  Google Scholar 

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  1. National Institute of Scientific Investigation, 158-707, Seoul, Korea

    Sang Ki Lee

  2. College of Pharmacy, Sungkyunkwan University, 440-746, Suwon, Korea

    Seung Min Oh, Byung Taek Ryu & Kyu Hyuck Chung

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Oh, S.M., Ryu, B.T., Lee, S.K. et al. Antiestrogenic potentials of ortho-PCB congeners by single or complex exposure. Arch Pharm Res 30, 199–209 (2007). https://doi.org/10.1007/BF02977695

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