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研究生:簡志軒
研究生(外文):Zhi-Xuan Jian
論文名稱:分析國內高溫烹調肉品中常見的異環胺
論文名稱(外文):Analysis of heterocyclic amines in Taiwanese high- temperature processed meats and fish
指導教授:吳焜裕吳焜裕引用關係
口試委員:鄭尊仁陳家揚施偉仲
口試日期:2016-07-11
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:129
中文關鍵詞:大腸直腸癌異環胺高溫烹調肉品液相層析串聯質譜儀
外文關鍵詞:Colorectal cancerHeterocyclic aminesHigh-temperature processed meats and fishLiquid chromatography-tandem mass spectrometry
相關次數:
  • 被引用被引用:1
  • 點閱點閱:331
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
大腸直腸癌(Colorectal cancer, CRC)是全世界目前癌症發病和死亡的主要項目之一。亞洲部分國家的生活方式和飲食習慣,如台灣、韓國、新加坡和日本之發病率已有快速增加之趨勢。根據台灣的全國癌症登記資料顯示,過去六年來每年大腸直腸癌發生率已躍居全國癌症發生率的第一名,每年超過14000 例,已然成為當今國內最具挑戰性的臨床和公共衛生問題之一。
近年來國內食品安全事件頻傳,許多人開始懷疑食品中所含的有害物質可能與大腸直腸癌的發生有關。根據國際文獻顯示肉類及其加工產品均可能產生大腸直腸癌的致癌因子,其中異環胺(Heterocyclic amines, HCAs)目前已被認定為重要的大腸直腸癌致癌物之一。高溫燒烤紅肉、白肉、魚肉及肉類加工製品,肉類中胺基酸、肌酸酐、醣類會相互作用產生異環胺,而這些異環胺物質可能會導致乳癌、肝癌、攝護腺癌、大腸癌等癌症。但目前國內不僅缺乏食品當中異環胺的資料,更無異環胺暴露評估的相關研究。
因此本研究的目的擬分析國內高溫烹調肉品中常見的四個異環胺物質即
IQ(2-Amino-3-methyl-imidazo(4,5-f)-quinoline),
MeIQ(2-Amino-3,4-dimethylimidazo[4,5-f]quinolone),
MeIQx(2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline),
PhIP(2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine)等可能致癌物在國內高溫烹調肉品中的濃度,探討在這些高溫烹調肉品當中異環胺的濃度情形。
本研究將建立肉類食品當中異環胺的前處理方法以及液相層析串聯質譜儀(Liquid chromatography-tandem mass Spectrometry, LC-MS/MS)分析方法,分析國內高溫烹調肉品當中異環胺的含量。
本研究分析的食品樣本是自2016 年2 月開始收集自台北市傳統市場、便當、連鎖速食店、夜市等,樣本經過樣品均質、鹼水解、過濾、液液萃取等過程後,再離心取上清液進行分析。分析管柱是使用C18 管柱,並以同位素內標準品定量,有良好的線性(r2>0.995),同日(Intra-day)和異日(Inter-day)的精密度(Precision)和準確度(Accuracy)之變異皆落在15 %的誤差範圍之內。IQ 的LOD(Limit of
detection)和LOQ(Limit of quantitation)分別為0.05 ng/g 和0.1 ng/g,MeIQ 的LOD和LOQ 分別為0.05 ng/g 和0.1 ng/g,MeIQx 的LOD 和LOQ 分別為0.05 ng/g 和0.1 ng/g,PhIP 的LOD 和LOQ 分別為0.01 ng/g 和0.1 ng/g。在本研究收集到的肉類食品樣本當中,所分析到的四個異環胺物質濃度範圍落在小於LOD到13.94 ng/g之間。
暴露評估的部分是使用貝氏統計馬可夫鏈蒙地卡羅(Bayesian Statistic Markov chain Monte Carlo, BSMCMC)的抽樣方法作模擬,並利用國家攝食資料數之攝食量數據估算終生平均每日暴露劑量(Life average daily dose, LADD)。結果顯示,依本研究所分析到的異環胺濃度值,對台灣19 至65 歲成人的暴露量落在我們可以接受的風險值以下。

Colorectal cancer (CRC) is a major cause of cancer associated morbidity and
mortality worldwide. The epidemiology of CRC varies remarkably among different population. Incidence rates are highest in the developed countries of North America, Australia, and New Zealand; intermediate in Europe and low in Asia, South America and Africa. However, the incidence rate grows rapidly in some Asian countries with westernization of life style and diet habits, such as Taiwan, South Korea, Singapore and Japan.
CRC has nowadays become the most common newly diagnosed cancer among both men and women since 2007 and leads to a huge burden in public health in Taiwan. According to the national census of Taiwan, there are more than 5000 subjects died of CRC and more than 14000 incident cases annually in our country thus CRC nowadays become one of the most challenging clinical and public health problems. Inter-regional difference in the incidence of CRC, including differences among population living in geographic proximity but with different life styles, strongly suggests that environment contributes the pathogenesis of CRC.
The environmental factors might lead to this disease through altering the risk of genetic changes. Strong evidence exists for a link between diet/life style and CRC. High-fat/low-fiber consumption, red meat consumption, and environmental carcinogens and mutagens were considered probably related to risk of CRC. Regarding dietary factors, though earlier studies indicated that low dietary fiber intake and high animal fat/red meat are closely correlated with increased risk of CRC. A group of compounds known as heterocyclic amines (HCAs) have been proposed as carcinogens. HCAs are formed in meats cooked at high temperature, and are potent mutagens and animal carcinogens; however, the carcinogenic potential in humans has not been established.
Surprisingly, systematically studies regarding the relationship between meat consumption containing HCAs and CRC were few in Taiwan. We intend to analyze HCAs in high-temperature processed meats and fishes, exposures to HCAs, and potential risk associated with HCAs exposures. The HCAs of interests in this study are mainly the frequently detected, such as IQ, MeIQ, MeIQx, and PhIP in cooked meat. We will development a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to analyze the levels of HCAs in high-temperature processed meats and fishes.
Food samples were collected from supermarkets, chain supermarkets, lunch, fast food and night markets. Samples were analyzed with C18 column after homogenization, addition of internal standards, base hydrolysis, absorption of lipid and filtration. This method provide good accuracy, precision and linearity. In 50 samples, total HCAs contents of the samples ranged between nd and 13.94 ng/g.
By using residues and intake rates collected from National food consumption database, life average daily dose (LADD) was simulated by Bayesian Statistic Markov chain Monte Carlo (BSMCMC). As the result, we can know that the exposure of HCAs in adults in Taiwan is acceptable HCAs intake level.

中文摘要...............................................................................................................i Abstract .............................................................................................................. iii 表目錄..................................................................................................................xi
圖目錄................................................................................................................ xv
第一章 簡介.........................................................................................................1
1.1 前言............................................................................................................ 1
1.2 大腸直腸癌(Colorectal cancer, CRC).......................................................2
1.3 異環胺(Heterocyclic amines, HCAs)與大腸直腸癌的關係....................3
1.4 食品中的異環胺........................................................................................ 5
1.5 本研究所選擇的異環胺............................................................................ 6
1.6 異環胺代謝途徑........................................................................................ 8
1.7 分析方法回顧.......................................................................................... 10
1.8 暴露劑量評估.......................................................................................... 14
1.9 貝氏統計馬可夫鏈蒙地卡羅模擬法...................................................... 14
1.10 攝食資料庫.............................................................................................. 15
第二章 研究目的..............................................................................................17
第三章 材料與方法...........................................................................................19
3.1 化學標準品與溶劑.................................................................................. 19
3.2 儀器設備及耗材...................................................................................... 21
3.3 樣本收集及前處理方法.......................................................................... 22
3.4 儀器分析.................................................................................................. 24
3.4.1 標準溶液配製.............................................................................. 27
3.4.2 分析方法開發.............................................................................. 27
3.5 質譜條件最佳化...................................................................................... 28
3.6 分析方法確效.......................................................................................... 34
3.6.1 檢量線的配製及結果.................................................................. 34
3.6.2 偵測極限與定量極限.................................................................. 35
3.6.3 同日及異日之精密度與準確度.................................................. 35
3.6.4 基質效應、回收率、過程效率.................................................. 36
3.7 QC 樣本,定量與資料分析 ................................................................... 36
3.8 暴露評估.................................................................................................. 36
3.9 暴露劑量推估.......................................................................................... 37
3.10 攝食資料庫.............................................................................................. 37
3.11 BSMCMC 模式建立 ............................................................................... 37
3.12 致癌斜率因子(Cancer slope factor)........................................................38
3.13 應用軟體.................................................................................................. 38
第四章 結果與討論............................................................................................39
4.1 液相層析串聯質譜儀層析圖.................................................................. 39
4.2 LOD、LOQ、校正曲線、基質效應、回收率、過程效率 ................. 42
4.3 同日及異日之精密度與準確度.............................................................. 56
4.4 食品樣本分析結果.................................................................................. 73
4.5 分析結果討論.......................................................................................... 79
4.5.1 牛肉樣品分析結果...................................................................... 79
4.5.2 豬肉樣品分析結果...................................................................... 83
4.5.3 雞肉樣品分析結果...................................................................... 87
4.5.4 魚肉樣品分析結果...................................................................... 91
4.5.5 四種肉品分析結果比較-燒烤 .................................................... 94
4.5.6 三種肉品分析結果比較-炸 ........................................................ 96
4.5.7 三種肉品分析結果比較-滷 ........................................................ 98
4.5.8 兩種肉品分析結果比較-油煎 .................................................. 100
4.5.9 四種肉品分析結果比較............................................................ 102
4.6 風險評估................................................................................................ 104
第五章 結論與建議.........................................................................................109
附錄............................................................................................................. 113
參考文獻...................................................................................................... 125

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