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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 莊曜宇(Eric Yao-Yu Chuang) | |
| dc.contributor.author | Sufeng Chiang | en |
| dc.contributor.author | 江蘇峰 | zh_TW |
| dc.date.accessioned | 2021-06-08T06:14:15Z | - |
| dc.date.copyright | 2007-02-27 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-02-12 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/25458 | - |
| dc.description.abstract | 隨著奈米科技的快速發展，奈米材料已廣泛應用於各個層面。其中以二氧化鈦奈米粒子 (titanium dioxide nanoparticles) 用途最普遍也最為常見。因為其尺寸大小為奈米等級，奈米材料具有和塊材 (bulk material) 截然不同的物理與化學性質。這些特質使奈米材料有很好的發展與應用，卻也可能因此對人體健康造成不良影響。根據過去文獻，已知二氧化鈦奈米粒子可造成細胞損壞，導致細胞凋亡 (apoptosis)，並引起發炎反應。本研究以人類淋巴球母細胞 (TK6) 與人類肺部上皮細胞 (A549) 針對最廣為使用的二氧化鈦奈米粒子，探討其所可能引起的細胞毒性 (cytotoxicity) 與基因毒性 (genotoxicity)。希望在奈米科技發展的同時，能提供奈米材料在生物毒性方面的相關資訊，使奈米科技得以更安全地發展。本研究採用40 nm的銳鈦礦 (anatase) 二氧化鈦奈米粒子處理人類細胞株，經過24小時後，利用Colony formation assay與MTT assay觀察奈米粒子暴露所造成細胞毒性。基因晶片 (DNA microarray) 主要應用在觀察大量基因之表現，為找出特定基因調控極為方便、快速與可靠的方法。本研究同時利用基因晶片觀察二氧化鈦奈米粒子所造成基因毒性。希望能找出奈米粒子所誘發之特定基因，以建立二氧化鈦奈米粒子造成基因毒性之生物指標 (biomarker)，並進而研究二氧化鈦奈米粒子對人體細胞的生理機制之影響。實驗結果顯示，二氧化鈦奈米粒子暴露所造成人類淋巴球母細胞與人類肺部上皮細胞之細胞毒性，需要較長時間才會表現，在短期內並無法觀察到任何細胞毒性。二氧化鈦奈米粒子暴露所造成人類淋巴球母細胞與人類肺部上皮細胞之基因毒性經過基因晶片分析發現，二氧化鈦奈米粒子引發細胞表現大量細胞修復基因與細胞凋亡相關基因，同時亦觀察到細胞內調控氧化壓力 (oxidative stress) 平衡與發炎反應 (inflammatory response) 相關基因的表現。此結果顯示二氧化鈦奈米粒子造成細胞氧化壓力增加，並進而造成細胞傷害，最後還可能引起發炎反應。本研究所得結果，仍有待進一步的研究與探討。另一方面，經過觀察二氧化鈦奈米粒子粒徑與外觀型態，本研究發現二氧化鈦奈米粒子在水溶液中會以極快速度聚結 (aggregate) 成較大粒徑粒子。此特性導致傳統的活體與細胞實驗方法難以觀察到奈米粒子所可能引發的毒性影響，因此對於傳統實驗方法，仍需經過檢討與修正，才能實際應用於奈米粒子的毒性測試。 | zh_TW |
| dc.description.abstract | Along with rapid development of nanotechnology, extensive applications of nanomaterials have been carried out in diverse aspects. Among them, titanium dioxide nanoparticles provide most widespread applications and they are the most common nanomaterials. Because of the nano scale, nanomaterials are substantially different in specific physical and chemical properties from those bulk materials of the same composition. These characteristics allow excellent development and application of nanomaterials; yet the adverse effects on human health may also be generated possibly. According to past literatures, it has been known that titanium dioxide nanoparticles could cause cell damage, apoptosis and inflammatory response. In this study, a human lymphoblastoid cell line (TK6), and a human pulmonary epithelial cell line (A549) were used to determine possible cytotoxicity and genotoxicity induced by titanium dioxide nanoparticles, which have been used most extensively. It was expected to provide relevant information about biohazard of nanomaterials and to facilitate safer development of nanotechnology. In this study, human cell lines were exposed to titanium dioxide nanoparticles of 40 nm in anatase. After 24 hours, Colony formation assay and MTT assay were used to assess cytotoxicity derived from exposure of titanium dioxide nanoparticles. DNA microarray is mainly applied as a high-throughput analysis for expression levels of a large quantity of genes, which allocates a very convenient, fast and reliable method to find out the mechanism of specific genes. At the same time, DNA microarray was used to analyze the genotoxicity induced by titanium dioxide nanoparticles. It was expected to determine specific genes induced by nanoparticles, so as to find out detectable biomarkers of the genotoxicity induced by titanium dioxide nanoparticles, and to further study on influence of titanium dioxide nanoparticles towards physiological mechanism of human cells. The results showed that the cytotoxicity of human lymphoblastoid cell line and human pulmonary epithelial cell line derived from exposure of titanium dioxide nanoparticles took longer period of time to appear, and none of the cytotoxicity was shown within short period of time. As for the genotoxicity of human lymphoblastoid cell line and human pulmonary epithelial cell line induced by titanium dioxide nanoparticles, after analysis with DNA microarray, it was found out that titanium dioxide nanoparticles triggered expression of massive amount of cell repair genes and apoptosis-related genes. The expression of some genes related to balance of oxidative stress and inflammatory response in cells were also observed at the same time. The results showed that exposure of titanium dioxide nanoparticles resulted in increase of oxidative stress of cells and further damage to cells, which may even induced inflammatory response at the end. The results obtained from this study still need to be further researched and discussed. On the other hand, after observation on size and appearance of titanium dioxide nanoparticles, it was discovered that the titanium dioxide nanoparticles would aggregate into larger particles in an extremely rapid manner. Such characteristics are obstacles for traditional method of animal and cell experiments on assessing possible toxic influence induced by nanoparticles. Therefore, the traditional methods of experiments still need to be reviewed and modified, so they can be actually applicable to toxicity test of nanoparticles. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T06:14:15Z (GMT). No. of bitstreams: 1 ntu-96-R93921134-1.pdf: 2992826 bytes, checksum: 02e7a5b3fce28e3baf33f5c415cac6c1 (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | 口試委員審定書 i
誌謝 ii 中文摘要 iii 英文摘要 v 目錄 vii 圖目錄 ix 表目錄 x 第一章 研究概述 1 第一節 本文概觀 1 第二節 前言 2 第三節 研究目的 3 第二章 研究介紹 5 第一節 奈米粒子的特性 5 第二節 二氧化鈦奈米粒子 6 第三節 奈米粒子的生物毒性探討 8 第四節 奈米粒子的生物動力性途徑 9 第五節 奈米粒子在呼吸系統的沈降分布與毒性 10 第六節 奈米粒子在呼吸道的清理機制 11 第七節 奈米粒子進入血液循環系統與神經系統 11 第八節 奈米粒子造成生物毒性的分子機制 12 第九節 奈米粒子的生物毒性與氧化壓力 14 第十節 奈米粒子造成生物毒性的其他方式 16 第十一節 二氧化鈦奈米粒子所造成的生物毒性 16 第三章 研究設計與架構 19 第一節 二氧化鈦奈米粒子觀察 19 第二節 細胞模型的建構 20 第三節 人類細胞株暴露二氧化鈦粒子 20 第四節 二氧化鈦奈米粒子所產生細胞毒性的觀察 22 第五節 二氧化鈦奈米粒子所產生基因毒性的觀察 23 第四章 實驗材料與方法 27 第一節 二氧化鈦粒子之來源 27 第二節 二氧化鈦奈米粒子粒徑測量 28 第三節 以電子顯微鏡觀察二氧化鈦奈米粒子 28 第四節 人類細胞株培養 29 第五節 二氧化鈦奈米粒子的暴露 30 第六節 Colony formation assay 30 第七節 MTT assay 31 第八節 人類細胞total RNA的萃取與純化 32 第九節 基因晶片 33 第五章 實驗結果 37 第一節 二氧化鈦奈米粒子粒徑測量結果 37 第二節 電子顯微鏡觀察二氧化鈦奈米粒子結果 38 第三節 Colony formation assay之結果 41 第四節 MTT assay之結果 42 第五節 人類細胞total RNA的萃取與純化 44 第六節 基因晶片分析結果 47 第六章 討論與展望 51 第一節 二氧化鈦粒子粒徑大小 51 第二節 二氧化鈦奈米粒子於水溶液中之行為模式 53 第三節 二氧化鈦奈米粒子暴露所引起之細胞毒性 55 第四節 二氧化鈦奈米粒子暴露所誘發之基因毒性 60 第五節 結語 69 參考文獻 73 附錄一 各組基因晶片實驗於正規化前後的二維平面分布圖 83 附錄二 具明顯變化基因列表 87 圖 1 表面原子比例與粒徑關係 6 圖 2 奈米粒子在人體內完整的生物動力性途徑 9 圖 3 奈米粒子粒徑大小與其在呼吸道的沈降分布關係圖 10 圖 4 奈米粒子造成生物毒性的分子機制 13 圖 5 階層式氧化壓力模型 14 圖 6 奈米粒子造成氧化壓力昇高，並引起發炎反應 15 圖 7 雙色基因晶片系統實驗原理 24 圖 8 基因晶片的完整實驗流程 33 圖 9 微米級二氧化鈦粒子之外觀 38 圖 10 25 NM銳鈦礦二氧化鈦粒子 (東成昌) 之外觀 39 圖 11 25 NM金紅石二氧化鈦粒子 (東成昌) 之外觀 39 圖 12 TINANO 40之外觀 40 圖 13 二氧化鈦奈米粒子暴露濃度與TK6細胞株存活率關係 41 圖 14 二氧化鈦奈米粒子暴露濃度與A549細胞株存活率關係 42 圖 15 二氧化鈦奈米粒子暴露濃度與TK6細胞株細胞存活率關係 43 圖 16 二氧化鈦奈米粒子暴露濃度與A549細胞株細胞存活率關係 43 圖 17 第一套TK6細胞株所純化TOTAL RNA經過1%洋菜膠電泳分析 46 圖 18 第二套TK6細胞株所純化TOTAL RNA經過1%洋菜膠電泳分析 46 圖 19 A549細胞株所純化TOTAL RNA經過1%洋菜膠電泳分析 47 圖 20 重量濃度與表面積表示之差異 58 圖 21 兩套基因晶片實驗表現相同基因 67 表 1 原子分子與生物細胞粒徑之比較 5 表 2 三種二氧化鈦之密度 7 表 3 二氧化鈦奈米粒子粒徑測量結果 37 表 4 超音波震盪與加入表面分散劑前後二氧化鈦奈米粒子粒徑測量結果比較 37 表 5 人類細胞所純化TOTAL RNA利用分光光度計之濃度估計與品質分析 45 表 6 第一套與第二套TK6 細胞株所進行基因晶片實驗相關係數 47 表 7 各組基因晶片實驗結果螢光點訊噪比大於1.5倍之螢光點數 48 表 8 不同粒徑奈米粒子的聚結常數與半衰期 54 表 9 第一套TK6細胞株具有1.5倍以上變化基因分群 63 表 10 第二套TK6細胞株具有1.5倍以上變化基因分群 64 表 11 A549細胞株具有2倍以上變化基因分群 65 表 12 共同基因被向下調控基因列表 66 表 13 共同基因被向上調控基因列表 68 | |
| dc.language.iso | zh-TW | |
| dc.subject | 基因晶片 | zh_TW |
| dc.subject | 發炎反應 | zh_TW |
| dc.subject | 二氧化鈦奈米粒子 | zh_TW |
| dc.subject | 基因毒性 | zh_TW |
| dc.subject | 氧化壓力 | zh_TW |
| dc.subject | 細胞毒性 | zh_TW |
| dc.subject | 生物指標 | zh_TW |
| dc.subject | titanium dioxide nanoparticle | en |
| dc.subject | biomarker | en |
| dc.subject | oxidative stress | en |
| dc.subject | inflammatory response | en |
| dc.subject | genotoxicity | en |
| dc.subject | cytotoxicity | en |
| dc.subject | DNA microarray | en |
| dc.title | 二氧化鈦奈米粒子所造成人類細胞毒性與基因毒性之探討 | zh_TW |
| dc.title | Study the Cytotoxicity and Genotoxicity of TiO2 Nanoparticles in Human Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鄭尊仁(Tsun-Jen Cheng),蔡孟勳(Mong-Hsun Tsai) | |
| dc.subject.keyword | 二氧化鈦奈米粒子,細胞毒性,基因毒性,基因晶片,生物指標,氧化壓力,發炎反應, | zh_TW |
| dc.subject.keyword | titanium dioxide nanoparticle,cytotoxicity,genotoxicity,DNA microarray,biomarker,oxidative stress,inflammatory response, | en |
| dc.relation.page | 118 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2007-02-14 | |
| dc.contributor.author-college | 電機資訊學院 | zh_TW |
| dc.contributor.author-dept | 電機工程學研究所 | zh_TW |
| Appears in Collections: | 電機工程學系 | |
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| File | Size | Format | |
|---|---|---|---|
| ntu-96-1.pdf Restricted Access | 2.92 MB | Adobe PDF |
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