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    CMUR > College of Medicine > School of Medicine > Research reports >  Item 310903500/25249
    Please use this identifier to cite or link to this item: http://ir.cmu.edu.tw/ir/handle/310903500/25249


    Title: 4-Methoxylestradiol在肺細胞的生物活性
    The Bioactivity of 4-Methoxylestradiol in Lung Cells
    Authors: 鄭雅興;林嬪嬪
    Contributors: 中國醫藥大學醫學系
    Keywords: TCDD;E2 metabolite;4-methoxyestradiol;Oxidative stress;Lung cell
    Date: 2007-07
    Issue Date: 2010-07-16 10:22:01 (UTC+8)
    Abstract: 本計畫為兩年計畫之第二年。長期目標是建立動情素代謝物4-Methoxyestradiol 在肺細胞的生物活性及與女性肺腺癌的相關性。4-Methoxyestradiol 是TCDD 與動情素在肺細胞交互作用引發的主要動情素代謝產物,但其生物活性所知有限。因此,本計劃擬於兩年內將完成:1. 探討4-Methoxyestradiol 在肺細胞與肺腺癌細胞模式引發的氧化傷害; 2.探討4-Methoxyestradiol 抑制細胞生長的分子機制; 3. 鑑別4-Methoxyestradiol 對肺細胞可能造成的氧化基因傷害與抗氧化劑的應用。前置實驗已證實,4-Methoxyestradiol 不僅抑制肺癌細胞生長同時刺激氧化自由基 (reactive oxygen species)的形成。因此,第一年(2006-2007)在與國家衛生研究院環境衛生與職業醫學組林嬪嬪副研究員的合作下,我們發現4-Methoxyestradiol 對肺細胞產生的氧化壓力(oxidative stress)造成細胞防禦機制GSH/GSSG ratio 的顯著下降及基因的氧化性傷害(oxidative DNA damages)。甚且,4-Methoxyestradiol 對肺細胞生長抑制的機制經由免疫螢光偵測(Immunohistochemistry) 發現與 mitotic arrest 相關。計畫的第二年(2007-2008) , 我們將進一步研究 4-Methoxyestradiol 引起mitotic arrest 的分子機制及對細胞內抗氧化酵素 Superoxide dismutase 與Catalase 的影響,鑑別自由基的種類與基因受損的相關性,並測試不同抗氧化劑的作用,提供4-Methoxyestradiol 引發自由基對細胞與基因傷害的可能預防方向,進而提供戴奧辛與動情素交互作用和女性肺癌的相關機制探討和動物實驗模式的建立。

    Epidemiological studies indicated that people exposed to dioxins were prone to the development of lung diseases including lung cancer. Animal studies demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased liver tumors and promoted lung metaplasia in females. Metabolic changes in 17beta-estradiol (E2) resulted from an interaction between TCDD and E2 could be associated with gender difference. Previously, we reported that methoxylestradiols (MeOE2), especially 4MeOE2, accumulated in human lung cells (BEAS-2B) co-treated with TCDD and E2. In the present study, we demonstrate unique accumulation of 4MeOE2, as a result of TCDD╱E2 interaction, and revealed its bioactivity in human lung epithelial cell line (H1355). 4-Methoxyestradiol treatment significantly decreased cell growth and increased mitotic index. Elevation of ROS and SOD activity, with a concomitant decrease in the intracellular GSH╱GSSG ratio were also detected in 4MeOE2- treated cells. Quantitative Comet assay showed increased oxidative DNA damage in the 4MeOE2-treated H1355 cells, which could be significantly reduced by the antioxidant Nacetylcysteine (NAC). However, inhibition of cell growth and increase in mitotic arrest induced by 4MeOE2 was unaffected by NAC. We concluded that 4MeOE2 accumulation resulting from TCDD and E2 interaction would contribute to the higher vulnerability on lung pathogenesis in females when exposed to TCDD.
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