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系統識別號 U0026-0808201721430200
論文名稱(中文) 雙酚類化合物及其降解產物之雄激素受體、鹽皮質激素受體及甲狀腺激素受體干擾活性變化探討
論文名稱(英文) Investigating the variation of androgen receptor, mineralocorticoid receptor, and thyroid hormone receptor disrupting activities of bisphenols and their degradation derivatives
校院名稱 成功大學
系所名稱(中) 環境工程學系
系所名稱(英) Department of Environmental Engineering
學年度 105
學期 2
出版年 106
研究生(中文) 徐悅芝
研究生(英文) Yueh-Chih Hsu
學號 P56044013
學位類別 碩士
語文別 中文
論文頁數 118頁
口試委員 指導教授-周佩欣
口試委員-徐駿森
口試委員-侯文哲
中文關鍵字 內分泌干擾物質  雙酚類化合物  光降解  酵素降解  報導基因試驗法  液相層析串聯式質譜儀 
英文關鍵字 Endocrine disrupting chemicals  Bisphenols  Degradation  Yeast-based reporter bioassays  High performance liquid chromatography tandem mass spectrometry 
學科別分類
中文摘要 雖然科技進步為人類帶來便利性,但也隨之排放了不同種類的污染物至環境中。內分泌干擾物質 (Endocrine disrupting chemicals, EDCs)正是近幾年受到大眾所關注的污染物之一,其會干擾生物體內分泌系統的正常作用,導致病變的產生。EDCs包括各種類(抗)激素物質,其中雙酚A (Bisphenol A, BPA)廣泛用於製造日常生活用品,且已被證實具有各種類(抗)激素活性,因此科學家們嘗試使用其他與BPA結構類似之雙酚類物質 (Bisphenols, BPs)來取代BPA在產品上的應用。為了評估BPs於環境中降解或在生物體中代謝後是否仍具有內分泌干擾活性,本研究選定五種BPs,包括BPA、BPS、BPF、四氯BPA、四溴BPA進行光降解、水解及酵素代謝批次實驗。研究中使用報導基因酵母菌生物試驗法檢測BPs降解前後之抗雄激素、抗鹽皮質激素及類甲狀腺激素活性變化,並搭配高效液相層析儀及液相層析串聯式質譜儀偵測BPs的濃度變化及可能降解產物。
光降解實驗中,BPS、四氯BPA及四溴BPA於光照72小時後之去除率分別為33.0、88.2及98.9%。四氯BPA及四溴BPA經光降解後之抗鹽皮質激素活性及類甲狀腺激素活性皆降低,而抗雄激素活性則是與降解前差異不大。四氯BPA及四溴BPA之濃度於S9酵素代謝實驗中有明顯降低,且其抗雄激素活性及類甲狀腺激素活性有些微降低。BPS、BPF及BPA之濃度於多酚氧化酵素代謝實驗中有顯著降低。BPF經多酚氧化酵素代謝後之抗雄激素活性及類甲狀腺激素活性降低。由以上降解實驗可得知,BPs於光降解或酵素代謝過程中可能會產生仍具類(抗)激素活性的降解產物,其於環境中的流布與宿命值得進一步探討。
英文摘要 SUMMARY
Endocrine disrupting chemicals (EDCs) are substances which can interfere with the normal function of endocrine system of animals. Because bisphenol A (BPA) has polluted the environment for decades, scientists try to replace BPA in products by other bisphenols (BPs). Unfortunately, some BPs also have endocrine disrupting activities. Thus, it is necessary to elucidate the endocrine disrupting activity and the fate of BPs. In the present study, batch degradation experiments of five BPs were carried out, including photodegradation, hydrolysis and enzymatic activation. Samples were analyzed using bioassays, high performance liquid chromatography diode array detector and tandem mass spectrometry to investigate the variations in endocrine disrupting activities, BPs concentrations, and potential degradation products. The results revealed that BPA, bisphenol F (BPF), tetrachlorobisphenol A (TeCBPA) and tetrabromobisphenol A (TBBPA) exhibited androgen receptor (AR) antagonist, mineralocorticoid receptor (MR) antagonist, and thyroid hormone receptor (TR) agonist activities. The concentrations of TeCBPA and TBBPA dropped and transformed to degradation products in photodegradation experiments. MR antagonist activities and TR agonist activities of TeCBPA and TBBPA decreased after 72 hours of photolysis, but AR antagonist activities did not change significantly. TeCBPA and TBBPA were metabolized after incubation with rat liver S9 fraction. AR antagonist activities of TeCBPA and TR agonist activities of TBBPA and BPA decreased. Also, the concentrations of BPA, BPF, and BPS decreased when being incubated with tyrosinase. After reaction, AR antagonist and TR agonist activities of BPF decreased. It is worthwhile to pay attention to the occurrence and fate of degradation products of BPs since some of them still showed endocrine disrupting activities.

Key word: Endocrine disrupting chemicals, Bisphenols, Degradation, Yeast-based reporter bioassays, High performance liquid chromatography tandem mass spectrometry
論文目次 摘要 I
Abstract III
誌謝 VI
目錄 VII
表目錄 XI
圖目錄 XIII
第一章 前言 1
1-1研究動機 1
1-2研究目的 2
第二章 文獻回顧 3
2-1內分泌干擾物質 3
2-1-1抗雄激素物質 3
2-1-2抗鹽皮質激素物質 5
2-1-3類甲狀腺激素物質 7
2-2 雙酚類化合物 8
2-2-1雙酚A 12
2-2-2雙酚S 13
2-2-3雙酚F 15
2-2-4氯化雙酚A 16
2-2-5四溴雙酚A 18
2-3雙酚類化合物之降解研究 20
2-3-1光降解 20
2-3-2水解或微生物降解 20
2-3-3酵素代謝 21
2-4生物試驗法 25
2-4-1活體內生物試驗法 25
2-4-2活體外生物試驗法 25
2-5儀器分析方法 27
2-5-1層析儀 27
2-5-2偵測儀器 28
第三章 實驗步驟與方法 31
3-1實驗架構 31
3-2實驗材料及設備 32
3-2-1實驗藥品與材料 32
3-2-2實驗設備 33
3-3儲備溶液及樣本配製方法 34
3-4降解實驗設置 35
3-4-1光降解實驗 35
3-4-2水解實驗 36
3-4-3大鼠肝臟S9酵素代謝實驗 36
3-4-4氧化及開環酵素測試實驗 37
3-5樣本前處理 39
3-5-1樣本前處理 39
3-5-2管柱層析法分離及樣本收集 39
3-6報導基因重組酵母菌試驗法 40
3-6-1活性試驗機制 40
3-6-2抗雄激素、抗鹽皮質激素與類甲狀腺激素活性試驗 41
3-6-3活性試驗結果計算 43
3-7儀器分析 45
3-7-1逆相高效液相層析儀 (RP-HPLC) 45
3-7-2高效液相層析串聯式質譜儀 46
第四章 結果與討論 49
4-1 BPs之內分泌干擾活性 49
4-2光降解 54
4-2-1 BPs光降解趨勢 54
4-2-2光降解產物定性/定量分析 63
4-2-3 TeCBPA經光降解之類(抗)激素活性變化 67
4-2-4 TBBPA經光降解之類(抗)激素活性變化 73
4-3水解 79
4-3-1 BPs水解趨勢 79
4-4大鼠肝臟S9酵素代謝 80
4-4-1降解成效 80
4-4-2抗雄激素活性變化 81
4-4-3抗鹽皮質激素活性變化 83
4-4-4類甲狀腺激素活性變化 84
4-5氧化及開環酵素代謝測試實驗 86
4-5-1降解成效 86
4-5-2抗雄激素活性變化 87
4-5-3抗鹽皮質激素活性變化 89
4-5-4類甲狀腺激素活性變化 90
第五章 結論與建議 92
5-1結論 92
5-2建議 94
參考文獻 95
附錄 107
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