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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 潘敏雄(Min-Hsiung Pan) | |
dc.contributor.author | Yu-Hsuan Lin | en |
dc.contributor.author | 林宇軒 | zh_TW |
dc.date.accessioned | 2021-06-08T03:32:07Z | - |
dc.date.copyright | 2019-08-19 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-08-12 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/21364 | - |
dc.description.abstract | 多環芳香烴 (Polycyclic aromatic hydrocarbons, PAHs) 為已知存在於環境中的一類汙染物,主要由有機物之不完全燃燒所產生,其存在的環境包含空氣、土壤、水等。目前已有許多研究證實部分多環芳香烴對於人體具有致突變性與致癌性,由於食安意識的抬頭,隨飲食途徑攝入之多環芳香烴逐漸受到重視,而其中又以苯駢芘 (Benzo[a]pyrene, BaP) 最具代表性。苯駢芘進入人體後會藉由生物體中外生性物質代謝 (Xenobiotic metabolism) 的一期反應酵素如細胞色素1A1 (Cytochrome P450 1A1, CYP1A1) 與細胞色素1B1 (Cytochrome P450 1B1, CYP1B1) 來進行生物轉換作用,形成反應性較高的苯駢芘二醇環氧化物 (Benzo[a]pyrene diol epoxide, BPDE),其具有與DNA結合成BPDE-DNA加合物並造成基因突變的能力。轉換後之苯駢芘代謝物可再經由二期反應酵素作用,進行去毒性的程序並將去毒後之代謝物排出體外。許多研究發現柑橘類果皮當中含有的多甲氧基黃酮具有抗氧化、抗發炎、抗癌的能力,而5-去甲基川陳皮素 (5-demethylnobiletin, 5-DMNB) 亦為其中之一,5-去甲基川陳皮素主要是柑橘果皮中的川陳皮素經過自然水解而形成,於長期儲存之果皮含量通常會較新鮮果皮多,有文獻指出其具有抗發炎、抗癌等生物活性。本實驗想藉由動物模式與細胞模式去了解5-去甲基川陳皮素對於飲食途徑攝入之苯駢芘代謝是否造成影響。結果顯示給予了5-去甲基川陳皮素後能夠抑制因苯駢芘所誘導而活化之芳香烴受體訊號傳遞路徑,進而改變一期反應酵素中細胞色素1B1之生成,另外也能夠增加二期反應酵素裡Glutathione S-transferases與UDP-glucuronosyltransferase之基因表現,使生物體具有更佳的去毒性能力。綜合以上原因,5-去甲基川陳皮素能夠讓BPDE與DNA結合產生之BPDE-DNA加合物減少,降低因BaP代謝而產生之致突變性或致癌性,達到預防癌症起始階段之功效。 | zh_TW |
dc.description.abstract | Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants and formed by incomplete combustion of organic matter or charred food. Many studies indicated that PAHs have gene-mutated activity and carcinogenic properties. Among these PAHs, benzo[a]pyrene (BaP) is the most well-known PAHs, and it is classified to group I carcinogen by IARC. Dietary BaP could be metabolized by phase I enzymes, cytochrome P450s (CYPs) such as CYP1A1 and CYP1B1. After metabolization, it could transform the BaP to benzo[a]pyrene diol epoxide (BPDE), and then combine with DNA to form BPDE-DNA adducts, which cause the initiation of cancer. Glutathione S-transferase (GST) and UDP-glucuronosyltransferase (UGT) are phase II enzymes that can conjugate with BaP metabolites and excrete them from body. 5-demethylnobiletin (5-DMNB) is a phytochemical which found in citrus peels, especially in long-storage citrus peels. Researches indicated that 5-DMNB had anti-inflammatory and anti-cancer ability. This study will show that 5-DMNB can change the metabolism of BaP by decreased CYP1B1 level and upregulated the GST and UGT expression, and then decrease BPDE-DNA adducts levels. In conclusion, 5-DMNB can decrease the toxicity of BaP and it maybe have the prevention effect of cancer caused by BaP. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T03:32:07Z (GMT). No. of bitstreams: 1 ntu-108-R05641027-1.pdf: 2818439 bytes, checksum: 374a4d1170606f9e2a4d8def54e74e27 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 誌謝 I
中文摘要 II Abstract III Abstract graph IV 目錄 V 附圖目錄 VIII 附表目錄 IX 表目錄 X 圖目錄 XI 縮寫表 XII 第壹章、文獻回顧 1 第一節 多環芳香烴 1 (一) 多環芳香烴之簡介 1 (二) 多環芳香烴之生成 2 (三) 多環芳香烴之暴露途徑 2 (四) 多環芳香烴之毒理特性 6 (五) 苯駢芘之簡介 7 (六) 苯駢芘之代謝 7 (七) Phase I & II 代謝酵素與表觀遺傳學之調控 9 (八) 肝癌細胞HepG2於AhR訊號傳遞路徑之細胞模式 12 第二節 柑橘類果皮中之多甲氧基黃酮 12 (一) 多甲氧基黃酮類 12 (二) 5-去甲基川陳皮素 13 第貳章、 實驗目的與實驗架構 15 第一節 研究目的 15 第二節 實驗架構 16 (一) 動物模式 16 (二) 細胞模式 17 第參章、材料與方法 18 第一節 實驗材料 18 (一) 儀器設備與耗材 18 (二) 試劑與藥品 19 第二節 細胞試驗 20 (一) 細胞培養 20 (二) 細胞存活率分析 (MTT試驗) 20 第三節 動物試驗 22 (一) 動物來源與飼養環境 22 (二) 飼養步驟 22 (三) 動物犧牲 22 第四節 實驗分析方法 23 (一) 動物組織均質與蛋白質萃取 23 (二) RNA抽取 24 (三) 合成cDNA 25 (四) 即時聚合酶鏈鎖反應 26 (五) 細胞蛋白質萃取 27 (六) 蛋白質定量 28 (七) 西方墨點法 29 (八) DNA抽取 32 (九) BPDE-DNA 加合物之測定 33 (十) 小鼠糞便收集與萃取 33 (十一) 糞便中BaP代謝物之測定 34 第五節 數據統計分析 36 第肆章、結果與討論 37 第一節 處理BaP及5-DMNB對於HepG2細胞存活率之影響 37 第二節 給予BaP及5-DMNB對於ICR小鼠體重之影響 37 第三節 給予BaP及5-DMNB對於ICR小鼠肝、腎、脾之影響 38 第四節 給予BaP及5-DMNB對於血清生化數值之影響 39 第五節 給予BaP及5-DMNB對於phase I 代謝酵素之影響 40 第六節 給予BaP及5-DMNB對於AhR訊號傳遞路徑之影響 42 第七節 給予BaP及5-DMNB對於phase II代謝酵素之影響 42 第八節 給予BaP及5-DMNB對於BPDE-DNA加合物生成之影響 43 第九節 給予BaP及5-DMNB對於ICR小鼠糞便中BaP與BaP 代謝物之影響 44 第伍章、結論 46 第陸章、圖表 47 第柒章、參考文獻 57 | |
dc.language.iso | zh-TW | |
dc.title | 探討5-去甲基川陳皮素對於苯駢芘代謝之影響 | zh_TW |
dc.title | The effects of 5-demethylnobiletin on benzo[a]pyrene metabolism | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 王應然(Ying-jang Wang),黃步敏(Bu-Miin Huang),何元順(Yuan-Soon Ho),廖秀娟(Hsiu-Chuan Liao) | |
dc.subject.keyword | 多環芳香烴,苯駢芘,外生性物質代謝,BPDE-DNA加合物,5-去甲基川陳皮素, | zh_TW |
dc.subject.keyword | Polycyclic aromatic hydrocarbons,benzy[a]pyrene,cyrochroms P450s,BPDE-DNA adducts,5-demethylnobiletin, | en |
dc.relation.page | 66 | |
dc.identifier.doi | 10.6342/NTU201902231 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2019-08-12 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 食品科技研究所 | zh_TW |
顯示於系所單位: | 食品科技研究所 |
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