Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/5765
標題: 空氣懸浮微粒有機萃取物對雌性激素於人類乳癌細胞所誘發細胞毒性、核酸損害、與基因表現失衡之影響
Effects of particulate matter (PM) on the induction of cytotoxic, DNA damage and altered gene expression by 17β-estradiol in human breast cancer cells
作者: 陳姿婷
Chen, Tzu-Ting
關鍵字: particulate matter;空氣懸浮微粒;DNA damage;estradiol;breast cancer cells;核酸損害;雌性激素;乳癌細胞
出版社: 環境工程學系所
引用: 方茹萍(2004),雌性激素於人類乳癌細胞株誘發基因表現失衡及核酸氧化損害作用之研究,國立中興大學環境工程研究所碩士論文,台灣台中 行政院環境保護署,96年台灣地區空氣污染防制總檢討 行政院環境保護署,97年台灣地區空氣污染防制總檢討 行政院環境保護署,97年台灣地區空氣品質監測年報 行政院環境保護署,98年台灣地區空氣品質監測年報 行政院環境保護署,空氣污染防制法規 林淵淙(2000),餐廳廚房排放廢氣及周圍大氣中多環芳香烴之特徵,國立成功大學環境工程研究所碩士論文,台灣台南 林欣儀(2005),多環芳香烴和微粒共同暴露對細胞毒性之研究,國立陽明大學環境衛生研究所碩士論文,台灣台北 林家琦(2007),懸浮微粒脂溶性萃取物誘發人類乳癌細胞及肺纖維母細胞之毒性和DNA損害,國立中興大學環境工程研究所碩士論文,台灣台中 洪珮慈(2009),探討雌性激素受體與芳香族碳氫化物受體間訊息傳遞之交互作用,國立中興大學環境工程研究所碩士論文,台灣台中 莊秉潔(2006),台灣火力電廠環境空氣品質平行監測期末報告 莊凱任(2006),大氣次微米微粒對人體心血管系統影響之研究,國立台灣大學醫學院毒理學研究所碩士論文,台灣台北 莊明傑(2008),戴奧辛與多氯聯苯所調控之基因表現改變對雌性激素於人類乳癌細胞誘發核酸損壞及修補作用之影響,國立中興大學環境工程研究所碩士論文,台灣台中 許美華(2008),應用CMB受體模式解析中台灣沿海與都會區空氣懸浮微粒污染來源,國立中興大學環境工程研究所碩士論文,台灣台中 郭育良等人(2007),職業病概論,華杏出版股份有限公司 陳沛蓉(2004),拜香、香菸、稻草燃燒產生微粒之細胞毒性研究,國立陽明大學環境衛生研究所碩士論文,台灣台北 陳建翰(2009),機車廢氣對大鼠心臟及生殖發育毒性之探討,國立台灣大學醫學院毒理學研究所碩士論文,台灣台北 彭麗珠(2010),台灣中部地區大氣中粒狀污染物之多環芳香烴化合物分佈特性之研究,國立中興大學環境工程研究所碩士論文,台灣台中 黃于芳(2007),微粒空氣污染物對心臟功能不全大鼠之心血管研究,國立台灣大學醫學院毒理學研究所碩士論文,台灣台北 黃群真(2006),戴奧辛誘發人類乳癌細胞株(MCF-7及MDA-MB-231 cells)細胞毒性及核酸氧化損壞作用研究,國立中興大學環境工程研究所碩士論文,台灣台中 劉懿賢(2008),台灣中部地區空氣懸浮微粒之水溶性及脂溶性萃取物誘發人類乳癌細胞之細胞毒性和DNA氧化損害,國立中興大學環境工程研究所碩士論文,台灣台中 饒佳文(2010),Benzo[a]pyrene於人類乳腺腫瘤細胞株誘發氧化壓力及核酸損壞作用之研究,國立中興大學環境工程研究所碩士論文,台灣台中 Andrews, W.C. 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摘要: 
空氣懸浮微粒(Particulate matter, PM)是一種混和複雜的粒子,不僅大小和型態上不同,甚至化學、物理和生物特性都有所不同;流行病學研究指出,懸浮微粒被認為對人類健康會造成危害,包括其具有潛在的雌性激素活性,擾亂人體內分泌功能,進而影響生殖系統和增加罹患乳癌之風險。然而,懸浮微粒之暴露與特定基因表現失序、核酸損壞與細胞死亡之相關性仍未完全確立,且其作用機制仍屬未知。本研究主要目的是探討人類乳腺細胞暴露於空氣懸浮微粒之有機溶劑萃取液,對雌性激素(17β-estradiol, E2)於人類乳癌細胞誘發基因表現失衡,進而造成細胞胞內氧化壓力、DNA損害以及細胞死亡之影響。
研究結果顯示,當MCF-7和MDA-MB-231細胞經懸浮微粒之有機溶劑萃取液預處理後再暴露於E2 之下,各組暴露時間與不同濃度E2之細胞毒性及氧化壓力生成結果均無顯著之差異;但由彗星法(comet assay)分析結果顯示,單獨E2 (10 nM)即可誘發MDA-MB-231細胞核酸損壞之效應,但經懸浮微粒之有機溶劑萃取液(5×10-3 72 h)預處理後,此一效應將完全被抑制;相反地,在MCF-7細胞中懸浮微粒之有機溶劑萃取液預處理條件下能促進E2所誘發核酸損壞效應。此外,添加芳香族碳氫化合物受體蛋白(AhR)抑制劑(α-NF),探討AhR受體蛋白是否也是誘發核酸損害與修補效應因素之一,研究結果顯示,在MCF-7細胞中添加AhR抑制劑,會使得效應消失,由此可知,AhR受體蛋白在此研究中也扮演一重要角色。
進一步由西方墨點(western blotting)分析,結果顯示,MCF-7細胞經懸浮微粒之有機溶劑萃取液預處理後再暴露於E2 (10 nM),會誘發CYP1A1基因表現量與些微CYP1B1基因表現量上升,MDA-MB-231細胞則有相反之結果;研究證實懸浮微粒之有機溶劑萃取液預處理條件,能透過改變細胞色素CYP 1A1與CYP 1B1表現,進而影響E2於MCF-7與MDA-MB-231細胞之核酸損害效應。
透過上述結果,證實懸浮微粒之有機溶劑萃取液於MCF-7與MDA-MB-231細胞,能藉由調控與E2相關代謝活化酵素表現失序,進而導致E2代謝失衡及核酸損壞效應之啟動。此外在乳癌細胞中,AhR和ERα於E2所誘發之核酸損害效應上,扮演一個重要角色。

Particular matters(PM)is a complex mixture of particles differences in size and morphology as well as in their physiochemical and biological characteristics. Epidemiological studies indicates that PM are known to induce a broad spectrum of adverse health effect in human, including disruption of endocrine function and the subsequent induction of dysfunction of reproduction and increased risk of developing breast cancer. The mechanisms by which PM exert their actions in human remain elusive. The link between PM exposure and deregulation of specific gene expression involving DNA damage and cell death is not conclusive, and any mechanism responsible remains unknown. The objective of this research is to investigate whether exposure to the organic solvent extracts of PM modulate the induction of imbalances in gene expression and oxidative stress, DNA lesions, and cell death by 17β-estradiol (E2) in human breast cancer cell lines.
Results indicated that pretreatment of PM did not modulate the extent of the cytotoxic response and oxidative stress induced by estrogen in MCF-7 cells and MDA-MB-231 cells. Further investigation indicated that E2 (10 nM) alone induced DNA strand breaks in MDA-MB-231 cells as measured by the Comet assay. The DNA-damaging effects induced by E2 in MDA-MB-231 cells were completely blocked by pretreatment of PM (5×10-3 for 72 h). In contrast, with PM pretreatment, significant increases in DNA strand breaks were detected in MCF-7 cells exposed to E2. Furthermore, the induction of DNA damage by 17β-estradiol(E2) in human MCF-7 breast cancer cells were completely blocked with co-treatment with AhR antagonist(α-NF). This evidence suggests that AhR receptor plays an important role in PM-induced modulation of the induction of DNA damage by 17β-estradiol(E2) in human MCF-7 breast cancer cells. The PM-induced modulation of the differential induction of DNA damage by estrogen in MDA-MB-231 and MCF-7 cells was primarily mediated through alteration of the expression of CYP1A1 and CYP1B1 as determined by western blotting assay.
Overall, this evidence suggests that organic solvent extracts of PM is capable of inducing imbalances in the expression of enzymes responsible for the bioactivation of estrogen leading to the subsequent accumulation of DNA damage in MDA-MB-231 and MCF-7 cells. Furthermore we confirmed that AhR and ER α play a role in modulating the induction of DNA damage by E2 in human breast cancer cells.
URI: http://hdl.handle.net/11455/5765
其他識別: U0005-2301201119015400
Appears in Collections:環境工程學系所

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