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研究生:李姵儀
研究生(外文):Pei-Yi
論文名稱:鹼基切除修補抑制核苷酸切除修補路徑的再接合
論文名稱(外文):A subsequent induction of base excision repair inhibits rejoining of nucleotide excision repair
指導教授:劉銀樟曾博修曾博修引用關係
指導教授(外文):Yin-Chang LiuBor-Show Tzang
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:生化暨生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:英文
論文頁數:52
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曝露外在環境或細胞代謝過程所產生的過氧化自由基及烷基化分子都會導致去氧核醣核酸的受損,此時受損的細胞就會使細胞走向死亡、突變、細胞周期停滯或使腫瘤轉移及活化去氧核醣核酸的修補機致。最近在人類細胞的研究有指出藥物與去氧核醣核酸或導致去氧核醣核酸損傷上具有相互作用。阿摩西林(amoxicillin)是一種常見於治療細菌感染的抗生素,在本篇的研究上對於阿摩西林造成細胞去氧核醣核酸所造成的損傷是感到興趣的,我們將阿摩西林利用培養的方式加到人類細胞內,再使用comet-NE方法偵測此藥物對去氧核醣核酸所造成的損傷。我們發現阿摩西林處理後會產生細胞內過氧化物,所以我們建議在哺乳細胞所造成的氧化去氧核醣核酸損傷可能是透過過氧化自由基。除此之外我們也注意到秋水仙素或阿摩西林,當此二者藥物在紫外燈照射後存在於細胞內可以發現NER在gap-rejoining被阻礙的,這相同的情形在處理以紫三醇(Taxol)或甲磺酸甲酯(MMS)的細胞中都有被發現的。我們建議在紫外燈照射後會引起氧化去氧核醣核酸受損會抑制核苷酸切除修補路徑的再接合。

DNA damage can be caused by exposure to environmental agents or by normal cellular metabolic processes that can cause cell killing, mutation, tumorigenesis, cell cycle arrest, neoplasm transformation, and activation of DNA repair. Recent study indicates that the drug may have potential to interact with DNA and cause DNA damage in human cells. Amoxicillin is a commonly prescribed drug for anti- bacterial infection. In this study, we are interested in the effect of the drug on the cellular DNA integrity. Amoxicillin was added to the human cells in culture, and the DNA adducts induced by the drug were accessed by a comet-NE assay. The results show the intracellular reactive oxygen species (ROS) were increased after amoxicillin treatment. Thus, we suggest that amoxicillin causes oxidative DNA damage in mammalian cells via ROS. Otherwise, we have noted that colcemid or amoxicillin, when they were present in cells recovering from UV irradiation, the gap-rejoining during the NER was perturbed. The similar effect on rejoining were also found when cells treatment with taxol or MMS. We suspected that an induction oxidative DNA damages immediately following UV irradiation would perturb the rejoining of NER as the result of competition between NER and BER for rejoining the gaps produced during the repair process. Thus, we hypothesize that an induction subsequent to NER could jeopardize the completion of NER.

Abstract...................................................................................................................2

摘要.........................................................................................................................3

Abbreviations............................................................................................................4

Introduction...............................................................................................................6

Materials and Methods..............................................................................................11
Results....................................................................................................................20
Discussion...............................................................................................................25
References...............................................................................................................29
Figures and Legends...................................................................................................................32
Appendixes..............................................................................................................48


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