研究生: |
杜姿慧 Tu, Tzu-Hui |
---|---|
論文名稱: |
鎝99m鄂惹電子造成DNA斷裂之研究 Strand Breaking of Plasmid DNA by Auger electrons from intercalated 99mTc |
指導教授: |
許志楧
Hsu, Ian C. 羅建苗 Lo, Jem-Mau |
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
原子科學院 - 生醫工程與環境科學系 Department of Biomedical Engineering and Environmental Sciences |
論文出版年: | 2009 |
畢業學年度: | 97 |
語文別: | 中文 |
論文頁數: | 90 |
中文關鍵詞: | 鄂惹電子 、DNA斷裂 |
相關次數: | 點閱:2 下載:0 |
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鄂惹電子 (Auger electrons) 具高線性能量轉移 (linear energy transfer, LET 4-26 keV/μm)引起DNA單股及雙股斷裂,是一具潛力及前瞻性的癌症基因治療方法。過去已有許多鄂惹電子斷裂DNA的研究,但大多以碘-125射源為主,關於鎝-99m的研究卻不多。本研究以鎝-99m為射源,提供另一鄂惹電子發射體的劑量關係與斷裂DNA資訊。實驗條件為在不同時間、以99mTc-APMED插入pIRES plasmid DNA、鎝-99m劑量、及不同濃度二甲基亞碸 (dimethyl sulfoxide, DMSO)的變因下,利用瓊脂膠電泳與Image J軟體分析、定量DNA斷裂片段。實驗結果顯示:使用supercoiled form DNA與99mTc反應時,衰變數量為5×1010/cm3、時間由3 h、6 h、12 h至24 h,DNA損害產生的open circular form、linear form分別由15 %增加至28%、46%、65 %及2 %增加至3%、5%、8 %。但若使用linear form DNA與99mTc反應時,衰變數量為1011/cm3,反應時間由3 h、6 h至24 h,消失的linear form DNA百分比由80%減少至45%、24%。DMSO為氫氧自由基的清除者,在含DMSO的反應結果中,確實會抑制因DNA損害的open form與Linear form形成。另外,DMSO與鎝-99m的比例與抑制DNA損害效果成正比,甚至當DMSO濃度達2M時,DNA 損害的現象幾乎觀察不到。利用鎝-99m進行鄂惹電子打斷DNA的研究,依其衰變次數所造成的DNA單股斷裂及雙股斷裂,在本研究中,首次作有系統化的評估。
Auger electrons are impression as a potential and prospective gene therapy becaused of its high energy transfer (LET 4-26 keV/μm). There were many studies on DNA breakage induced by Auger electrons, and most of them applied 125I to the experiment rarely with 99mTc. In this study, we developed a new application of 99mTc radionuclide as the Auger electron emitter to obtain more information about the correlation between the dose of 99mTc and DNA breakage with various conditions of time, dose of 99mTc, and proportion of Dimethyl sulfoxide (DMSO). Quantification of DNA damage was analyzed by electrophoresis and Image J. The results shown, in supercoiled form DNA model from 3 hr to 24 hr, the open form DNA and linear form DNA produced by Auger electrons respectively arose from 15% to 65% and 2% to 8% under exposed to 5□1011 decays/cm3 99mTc amount. But in linear form DNA model from 3 hr to 24 hr, the disappearance of linear form DNA percentage, decreased from 80 % to 24 % under exposed approximately to 1011 decays/cm3. DMSO is a scavenger for hydroxyl radical. In DMSO condition, the inhibition of open form and linear form formation from DNA damage were observed. Additionally, the ratio of DMSO/99mTc and inhibition of DNA damage are in direct proportion. DNA damage has been observed decreased extremely, when excess amount of DMSO was present in experiment procedure.
Based on the results in this study, DNA damage fit in with decays of 99mTc and DMSO condition. Thereby, 99mTc with low energy and suitable half time could be an ideal radionuclide for Auger electron study.
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