Browse > Article
http://dx.doi.org/10.3746/jkfn.2004.33.9.1486

Assessing Heavy Metals for Estrogenicity Using a Combination of In vitro and In vivo Assays  

Park, Chul (Dept. of Food Science and Nutrition, University of Ulsan)
Kim, So-Jung (Dept. of Food Science and Nutrition, University of Ulsan)
Shin, Wan-Chul (Dept. of Food Science and Nutrition, University of Ulsan)
Kim, Hae-Gyoung (Dept. of Food Science and Nutrition, University of Ulsan)
Choe, Suck-Young (Dept. of Food Science and Nutrition, University of Ulsan)
Publication Information
Journal of the Korean Society of Food Science and Nutrition / v.33, no.9, 2004 , pp. 1486-1491 More about this Journal
Abstract
The estrogenicities of six heavy metal compounds, which contaminate frequently in foods, were assayed using a combination of in vitro and in vivo assays. The assays were 1) estrogen receptor dependent transcriptional expression assay, 2) E-screen assay and, 3) the uterotropic assay in mice. The chemicals studied were 17$\beta$ -estradiol, diethylstilbestrol (DES), arsenic oxide, bis(tri-n-butyltin), cadmium chloride, chromium chloride, lead acetate, and mercuric chloride. Using the estrogen receptor dependent transcriptional expression assay, the following estrogenicity ranking was measured: bis(tri-n-butyltin) > cadmium chloride > chromium chloride >> mercuric chloride >lead acetate = arsenic oxide. Using E-screen test, the following estrogenicity ranking was measured: bis(tri-n-butyltin) > cadmium chloride > chromium chloride >> mercuric chloride > lead acetate = arsenic oxide. Results from the uterotropic assay showed that bis(tri-n-butyltin), cadmium chloride, chromium chloride caused an increase in uterine wet weight, while lead acetate, mercuric chloride, and arsenic oxide failed to do so. Bis(tri-n-butyltin), cadmium chloride and chromium chloride showed the highest estrogenicity in three assay systems. Recent studies suggesting that bis(tri-n-butyltin), cadmium chloride have estrogenicities are compatible with the present finding. Furthermore, our study is suggesting that chromium chloride may be estrogenic. The results demonstrate that this three level-assay combination (transcriptional activation, cell proliferation, and an in vivo effect in an estrogen-responsive tissue) could serve as a useful method to assess the estrogenicity of heavy metals.
Keywords
heavy metals; estrogenicity; estrogen receptor dependent transcriptional expression assay; E-screen assay;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Hui R, Cornish AL, McClelland RA, Robertson JFR, Blamey RW, Musgrove EA, Nicholson RI, Sutherland RL. 1996. Cyclin D1 and estrogen receptor messenger RNA levels are positively correlated in primary breast cancer. Clin Cancer Res 2: 923-928
2 Jacobson JL, Jacobson SW. 1996. Dose-response in perinatal exposure to polychlorinated biphenyls (PCBs): The Michigan and North Carolina cohort studies. Toxicol Ind Health 12: 435-445   DOI
3 Koopman-Esseboom C, Weisglas-Kuperus N, de Ridder MAJ, Van der Paauw CG, Tuinstra LGMT, Sauer PJJ. 1996. Effects of polychlorinated biphenyls/dioxin exposure and feeding type on infants' mental and psychomotor development. Pediatrics 97: 700-706
4 Bern HA. 1992. The fragile fetus. In Chemically-induced alterations in sexual and functional development: the wildlife/human connection. Colborn T, Clement C, eds. Princeton Scientific Publishing, Princeton, NJ. p 9-15
5 Jobling S, Sumpter JP. 1993. Detergent components in sewage effluent are weakly estrogenic to fish: An in vitro study using rainbow trout hepatocytes. Aquat Toxicol 27: 361-372   DOI   ScienceOn
6 Newbold R. 1995. Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmental estrogens. Environ Health Perspect 103(Suppl.): 83-87   DOI   ScienceOn
7 White R, Jobling S, Hoarse SA, Sumpter JP, Parker MG. 1994. Environmentally persistent alkylphenolic compounds are estrogenic. Endocrinology 135: 175-182   DOI   ScienceOn
8 Kelce WR, Gray LE, Wilson EM. 1998. Antiandrogens as environmental endocrine disrupters. Reprod Fertil Dev 10: 105-111   DOI   ScienceOn
9 Colborn T, vom Saal FS, Soto AM. 1993. Developmental effect of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect 101: 378-384   DOI   ScienceOn
10 ATSDR. 1998. Toxicological Profile for Mercury. Agency for Toxic Substances and Disease Registry, Atlanta, GA
11 Reel JR, Lamb V, Neal BH. 1996. Survey and assessment of mammalian estrogen biological assays for hazard characterization. Fundan Appl Toxicol 34: 288-305   DOI   ScienceOn
12 Lapcic KO, Hampl R, Hill M, Whi K, Maharik NA, Adlercreutz H. 1998. Radioimmunoassay of free genistein in human serum. J Steroid Biochem Molec Biol 64: 261-268   DOI   ScienceOn
13 Miksicek RJ. 1993. Commonly occurring plant flavonoids have estrogenic activity. Mol Pharmacol 44: 37-43
14 Kim SJ, Park C, Kim HG, Shin WC, Choe SY. 2004. A study on the estrogenecity of Korean arrowroot (Pueraria thunbergiana). J Korean Soc Food Sci Nutr 33: 16-21   DOI   ScienceOn
15 Kramer V, Helferich WG, Bergman A, Klasson-Wehler E, Giesy JP. 1997. Hydroxylated polychlorinated biphenyl metabolites are anti-estrogenic in a stably transfected human breast adenocarcinoma (MCF7) cell line. Toxicol Appl Pharmacol 144: 363-376   DOI   ScienceOn
16 Ernst M, Parker MG, Rodan GA. 1991. Functional estrogen receptors in osteoblastic cells demonstrated by transfection with a reporter gene containing an estrogen element. Mol Endocrinol 5: 1597-1606   DOI   ScienceOn
17 Lee SJ, Kim CM, Lee SD, Park JG, Ryi SH, Suh PG. 1995. Overexpression of phospholipase C-1 in colorectal carcinomas is associated with overexpression of factors that bind its promoter. J Biol Chem 270: 16378-16384   DOI   ScienceOn
18 Lee SK, Choi HS, Song MR, Lee MO, Lee JW. 1998. Estrogen receptor, a common interaction partner for subset of nuclear receptors. Mol Endocrinol 12: 1184-1192   DOI   ScienceOn
19 Soto AM, Chung KL, Sonnennschein C. 1994. The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells. Environ Health Perspect 102: 380-383   DOI   ScienceOn
20 Soto AM, Sonnennschein C, Chung KL, Fernandez MF, Olea N, Serrano FO. 1995. The E-screen assay as a tool to identify estrogens: An update on estrogenic environmental pollutants. Environ Health Perspect 103(Suppl. 7): 113- 122   DOI
21 Kuiper GGJM, Lemmen JG, Carsson B, Corton JV, Safe SH, van der Saag PT, van der Burg B, Gustafsson J-$\AA$. 1998. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor $\beta$. Endocrinology 139: 4252-4263   DOI   ScienceOn
22 Daston GP, Gooch JW, Breslin WJ, Shuey DL, Nikiforov AI, Fico TA, Gorsuch JW. 1997. Environmental estrogens and reproductive health: A discussion on the human and environmental data. Reprod Toxicol 11: 465-481   DOI   ScienceOn
23 Zahid ZR, Al-Hakkak ZS, Kadhim AHH. 1990. Comparative effects of trivalent and hexavalentchromium on spermatogenesis of the mouse. Toxicol Environ Chem 25: 131-136   DOI
24 Martin MB, Reiter R, Pham T, Avellanet YR, Camara J, Lahm M, Pentecost E, Pratap K, Gilmore BA, Divekar S, Dagata RS, Bull JL, Stoica A. 2003. Estrogen-like activity of metals in MCF-7 breast cancer cells. Endocrinology 144: 2425-2436   DOI   ScienceOn
25 Johnson MD, Kenney N, Stoica A, Hilakivi-Clarke L, Singh B, Chepko G, Clarke R, Sholler PF, Lirio AA, Foss C, Reiter R, Trock B, Paik S, Martin MB. 2003. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med 9: 1081-1084   DOI   ScienceOn
26 Gotz R. 2004. Cadmium is a metalloestrogen. Pharm Unserer Zeit 33: 83-87   DOI   ScienceOn
27 Henson MC, Chedrese PJ. 2004. Endocrine disruption by cadmium, a common environmental toxicant with paradoxical effects on reproduction. Exp Biol Med (Maywood) 229: 383-392   DOI
28 Golub M, Doherty J. 2004. Triphenyltin as a potential human endocrine disruptor. J Toxicol Environ Health B Crit Rev 7: 281-295   DOI   ScienceOn
29 Song TT, Hendrich S, Murphy PA. 1999. Estrogenic activity of glycitein, a soy isoflavone. J Agric Food Chem 47: 1607- 1610   DOI   ScienceOn
30 Reeves PG, Rossow KL, Lindlauf J. 1993. Development and testing of the AIN-93 purified diets for rodents: Result on growth, kidney calcification and bone mineralization in rats and mice. J Nutr 123: 1923-1931
31 Breithofer A, Graumann K, Scicchitano MS, Karathanasis SK, Butt TR, Jungbauer A. 1998. Regulation of human estrogen receptor by phytoestrogens in yeast and human cells. J Steroid Biochem Molec Biol 67: 421-429   DOI   ScienceOn