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KMID : 0603520010060010010
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Journal of Korean Association of Cancer Prevention
2001 Volume.6 No. 1 p.10 ~ p.18
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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) Induced Micronuclei Formation and Inhibition Effect of Tamoxifen Against TCDD-induced Micronuclei Formation in Human Breast Estrogen Receptor Positive MCF-7 Cells
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Kim Jong-Won
Han Eui-Sik
Jun Hye-Seung
Eom Mi-Ok
Park Mi-Sun
Jung Hai-Kwan
Shim Woong-Seop
Oh Hye-Young
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Abstract
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To identify mutagenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) which are not identified by ICH (Internation Harmonization of Technological Requirements for Registration of Pharmaceuticals for Human Use) guideline-recommended standard genotoxicity test battery; Ames test, chromosome aberration assay, mouse Iymphoma tk+/- assay, in vivo micronucleus assay. The in vitro micronucleus assay (MN) was chosen. The in vitro MN using MCF-7 cells was useful to identify mutagenicity of bisphenol A and di (2-ethyhexyl) phthalate (DEHP). In this study, we found that TCDD induced MN formation significantly. Further to investigate the relationship between MN formation and estrogen receptor (ER), we comparatively assessed MN formation of TCDD in different human breast cells; MCF-7 cells (ER positive) and in MCF-10A cells (ER negative), MDA-MB-231 cells (ER negative). TCDD induced MN formation in MCF-7 cells (ER positive) but not or little induced MN formation in MCF-10A cells (ER negative) and MDA-MB-231 (ER negative). We also have examined the effect of estrogen inhibitor, tamoxifen, against TCDD induced MN formation. Tamoxifen inhibited TCDD-induced MN formation up to 47.3% in MCF-7 cells. We concluded the in vitro MN using MCF-7 cells is a good test method for detecting nongenotoxic carcinogen and identifying the genotoxicity of endocrine distruptors which are not identified by standard genetic toxicology test battery and additive endpoints should be included.
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KEYWORD
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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in vitro micronucleus assay, Estrogen receptor, MCF-7 cells
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