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標題: 尼古丁衍生之亞硝胺及戴奧辛對雌性激素於人類MCF-7乳腺癌細胞誘發核酸損壞作用之研究
Investigation of the effects of Nicotine-derived nitrosamine ketone and Dioxins on estrogen-induced DNA damage in human MCF-7 breast cancer cells
關鍵字: 戴奧辛
comet Assay
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摘要: 本研究主要目的為探討TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) 和NNK (Nicotine-derived nitrosamine ketone) 對雌性激素誘發人類乳腺癌細胞核酸損害作用之研究。本研究利用單細胞凝膠電泳 (Comet Assay) 的方法、將人類乳癌腺細胞分別暴露於TCDD 和NNK對雌性激素雌二醇(17β-estradiol, E2)所誘發之細胞毒性以及DNA損傷之影響。研究結果顯示,人類乳腺癌細胞 (MCF-7) 單獨暴露於E2 (1 nM)、 NNK (1-10 nM) 、或TCDD (1 nM) 並無明顯之DNA 單股斷裂現象,當同時添加E2 (1 nM) 及TCDD (1 nM),DNA單股斷裂則有明顯上升(2.5倍)。類似之結果亦可發現於同時添加E2 (1 nM)與 NNK (10 nM),控制組相比DNA單股斷裂上升4倍。此一證據顯示證明TCDD 和NNK可促進雌性激素所誘發之DNA損傷作用。進一步之研究結果顯示,同時暴露於E2 (1 nM)、NNK (10 nM)、及TCDD (10 nM), DNA單股斷裂有2.5倍,由此結果證實,人類乳腺癌細胞同時暴露於E2、TCDD及NNK三者之間可能有拮抗作用之現象,但作用機制不清楚還需進一步研究。
The objectives of this research were to investigate the effects of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Nicotine-derived nitrosamine ketone (NNK) on the estrogen-induced DNA damage in human MCF-7 breast cancer cells. In this study, we applied the single cell electrophoresis assay (COMET) to explore the impact of TCDD and NNK on the extent of DNA damage induced by estrogen (17β-estradiol, E2) in MCF-7 cells. Results from COMET assay confirmed that E2 (1 nM), NNK (1-10 nM) , or TCDD (1 nM) alone did not induce significant increases in the number of DNA strand breaks in MCF-7 cells whereas significant increases in the number of DNA strand breaks were detected in cells treated with TCDD (10 nM) when compared to control (~4 fold). Co-treatment of E2 (1 nM) and TCDD (1-10 nM) further enhance the induction of DNA damage in cells (~2.5-12.5 fold). Similarly, in the presence of NNK (10 nM), induced significant increases in the number of DNA strand breaks (~4 fold) were detected in cells exposed to E2 (1 nM). This finding indicates that both TCDD and NNK are capable of enhancing estrogen-induced DNA damage in human cultured cells. By contrast, the extent of DNA lesions were dramatically reduced in cells co-treated with NNK (10 nM), TCDD (10 nM), and E2 (1 nM) when compared to control (~2.5 fold). Overall, this evidence strongly suggests the presence of antagonistic effect of among these three compounds on the formation of DNA lesions in MCF-7 cells. Further studies are needed to uncover the underlying mechanism of this event.
文章公開時間: 2018-08-25
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