Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/52029
標題: An in vivo study on one carbon metabolism during tumor progression
葉酸單碳代謝與腫瘤生長之相關研究
作者: 謝上智
Hsieh, Shang-Chih
關鍵字: Folate;葉酸
出版社: 食品暨應用生物科技學系所
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摘要: 
Folate plays a crucial role in the one-carbon metabolism that maintains cellular DNA synthesis and methylation reactions. Previous clinical studies indicated that some cancer patients had low plasma folate concentration. In the present study, we investigated folate metabolism in tumor bearing mice. In separate experiments the nude mice were inoculated subcutaneously with different type of tumor cells and plasma folate concentrations were monitored periodically. The impacts of different tumor xenografts on folate status and the one-carbon metabolic fluxes in different tissues were investigated using stable isotopic tracers and gas chromatography/mass spectrometry. There was a trend of reduction in folate concentration in tissues of tumor bearing mice. Folate dependent homocysteine remethylation reactions were down-regulated in multiple tissues in the tumor group in comparison with the non-tumor group. Further studies on the mechanism by which tumor xenograft alters folate and one carbon metabolism are warranted.

葉酸是單碳代謝中一個重要的甲基提供者維持一些生理功能,包括脫氧核糖核酸的合成與修復。臨床研究報告顯示部分癌症病人有葉酸下降的現象,但其機制尚未闡明。在本研究中我們建立動物腫瘤模式來評估葉酸在動物血液及肝臟中代謝的情況。並且探討癌症腫瘤對單碳代謝中與葉酸的利用相關酵素的影響。
本研究以不同種人類癌細胞注射到裸鼠皮下後,飼養在病源 (specific pathogen-free) 環境下,定時追蹤葉酸狀態,並利用氣相層析質譜儀追蹤分析各組織單碳代謝路徑分布情形。本研究發現,腫瘤小鼠肝臟以及腎臟中依賴葉酸的同半胱胺酸再甲基化途徑明顯著低於正常小鼠。在動物模式中,腫瘤的生長造成肝臟中依靠葉酸的同半胱胺酸再甲基化途徑下降以及肝臟中特定葉酸代謝基因表現改變。未來我們要去進一步探討以上現象是透過何種機制影響葉酸及單碳代謝循環。
URI: http://hdl.handle.net/11455/52029
Appears in Collections:食品暨應用生物科技學系

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