사람 MCF-7 세포에서 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)에 의한 소핵형성과 타목시펜에 의한 TCDD유도 소핵형성 억제효과
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
김종원, 한의식, 전혜승, 엄미옥, 박미선, 정해권, 심웅섭, 오혜영,
소속 상세정보
김종원 ( Kim Jong-Won )
식품의약품안전청 국립독성연구소 유전독성과
한의식 ( Han Eui-Sik )
식품의약품안전청 국립독성연구소 유전독성과
전혜승 ( Jun Hye-Seung )
식품의약품안전청 국립독성연구소 유전독성과
엄미옥 ( Eom Mi-Ok )
식품의약품안전청 국립독성연구소 유전독성과
박미선 ( Park Mi-Sun )
식품의약품안전청 국립독성연구소 유전독성과
정해권 ( Jung Hai-Kwan )
식품의약품안전청 국립독성연구소 유전독성과
심웅섭 ( Shim Woong-Seop )
고려대학교 생물학과
오혜영 ( Oh Hye-Young )
식품의약품안전청 국립독성연구소 유전독성과
KMID : 0603520010060010010
Abstract
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.
키워드
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); in vitro micronucleus assay; Estrogen receptor; MCF-7 cells
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