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研究生: 陳怡靜
Chen, yi-ching
論文名稱: 波羅蜜與quinolone對真核細胞topoisomerase I活性抑制分析及誘導腫瘤
Inhibitory effects of Artocarpus heterophyllus and Quinolone on
指導教授: 林榮耀
Lin, Jung-Yaw
簡秋源
Chien, Chiu-Yuan
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
畢業學年度: 84
語文別: 中文
論文頁數: 74
中文關鍵詞: 拓樸脢
英文關鍵詞: topoisomerase, apoptosis
論文種類: 學術論文
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  • 細胞內DNA的拓樸狀態(topology).受topoisoerase所主宰 .
    Topoisomerase 參與複製(replication)轉錄(transcription)重組(
    recombination)及修復(repair)等DNA代謝中重要反應 . 喜樹精(
    camptothecin)因為它能穩定topoisomerase與DNA所形成的共價化合物 ,
    使DNA的缺口無法補齊 , 而造成細胞毒性(cytotoxicity), 所以被拿來作
    為藉由有有效抑制topoisomerase I的抗癌藥物 . 本論文證實了兩大類有
    地效topoisomerase I活性的抑制物 , 分別來自中藥波羅蜜的單離成分及
    quinolone類的化學合成藥物 . 這些化和物對topoisomerase I佸性抑制
    與否 , 是藉由檢測藥物是否會抑制真核細胞topoisomerase I調節DNA的
    超螺旋狀態 , 這方法稱為topoisomerase I relaxation assay . 由於藥
    物作用到DNA與topoisomerase 共價化何物上 , 使細胞堆積許多有缺口的
    DNA與蛋白的化合物 ,這時候topoisomerase的存在反而造成細胞的毒性物
    . 因DNA的斷裂 , 接著許多代謝也被迫庭止 , 最後造成細胞死亡(
    apoptosis) . 已有報告指出camptothecin 會造成人類血癌細胞株HL-60
    進行計畫性死亡 , 本論文篩選出的兩類藥物 , 也希望藉由一些細胞進行
    有計畫性死亡的特徵 , 來觀察這些藥物對HL-60細胞株的毒性 ; 這些特
    徵在本論文主要分成兩大類 , 分別是 : (1)當細胞進行有計畫性死亡時
    由於活化細胞內endonuclaese , 而造成DNA小片段的斷裂 ,經藥物處理後
    的細胞 , `可將萃取出來的DNA交由凝膠電泳分析出小片段的DNA .

    In the cells , the topology of DNA is orchestrated by enzyme
    known as topoisomerase Topoisomerases are involved in many
    aspects of DNA metabolism such as replication ,transcription ,
    recombination , and repair reactions . Camptothecin , which
    stabolizes the covalent intermediate of topoisomerase I and DNA
    is effective , by cytotoxicity , drug for cancer therapy . In
    this study , two new kinds oftopoisomerase I inhibitor purified
    from the Chinese herbs (Artocarpus heterophyllus ) and synthetic
    quinolone derivatives have been demonstrated to be strong
    topoisomerase inhibitors by using topoisomerase I relaxation
    assay .Increasing the steady-state concentration of their
    covalent DNA cleavage complex will convert topoisomerase into
    physiological toxins that introducehigh levels of transient
    protein-associated breaks in the genome of treatedcells .
    Collision of DNA relication forks with cleavable complexes has
    been proposed as a mechanism inducing cell death . We have known
    that the topoisomerase I inhibitor camptothecin induced
    apoptosis ( programmedcell death ) of cells of human
    promyelogenous leukemia HL-60 cells .The two new kinds of
    topoisomerase I inhibitors that we have identified in this study
    , also can induce apoptosis of cell of human promyelogenous
    leukemia HL-60 through the following cell features were focused
    to characterize the mode cell : [a] Activation of an
    endonuclease in apoptoticcells resulted in the formation of low
    molecular weight DNA fragmentswhich were confirmed by agarose
    gel electrophoresis . [b] Changes in cellular morphology of
    apoptotic cells resulted in the early appearanceof shrunken
    cells with vacuolated cytoplasma and regions of intensechromatin
    staining around the nuclear periphery . By this study , we
    hopeto identify the gene products which couple the stimulus of
    programmed cancer cell death , and to determine intrinsic
    cellular sensitivity( or resistance ) which will be important
    targets for new types ofantitumor drugs .
    In the cells , the topology of DNA is orchestrated by enzyme

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