環境致癌因子中抽煙佔很重要的部分。香煙中含有多種致癌物質，其中環氧乙烷的含量約為5μg/cig.，目前環氧乙烷已被歸類為人體致癌物，因此由於抽煙而暴露於環氧乙烷所造成人體之致癌風險是值得探討。 本研究的目的係建立modified Edman degradation方法來測量環氧乙烷與血紅素形成之共價鍵結物(N-hydroxyethylvaline；HEV)，以探討抽煙習慣與體內蛋白質鍵結物濃度的相關性，並由HEV濃度推估暴露到環氧乙烷之劑量及致癌風險。本研究對象係來自台中捐血站之162位自願者，並針對研究對象進行問卷調查收集基本資料，及血液收集，事前分離紅血球並萃取血紅素，再經處理後，利用GC/MS-NCI分析，以質荷比348與352之訊號比值來計算HEV之濃度。結果顯示非抽煙組體內之HEV濃度為58.3±45.6 pmol/g Hb，抽煙組HEV濃度為205.9±151.4 pmol/g Hb，國人HEV含量與文獻值一致，且抽煙與否與HEV濃度值達統計上顯著相關(p<0.0001)，而每天抽煙支數及抽煙年數皆與體內HEV濃度達統計上顯著相關(p<0.0001)，針對非抽煙族群而言，二手煙暴露與體內HEV值沒有明顯相關(p=0.9374)，但抽煙族群中，其二手煙暴露與否則與體內HEV值達統計上顯著相關(p=0.0131)。另外將HEV濃度值進行複迴歸分析，發覺抽煙與否、每天抽煙支數與體內HEV值有顯著相關。而非抽煙族群與抽煙族群之暴露劑量平均分別為259.2及915.1 ppm?h，而致癌風險值平均分別為4.15×10-5及1.463×10-4，兩者皆與抽煙達統計上顯著差異(p<0.0001)。 本研究結果證實體內HEV可作為評估長期因抽煙暴露到環氧乙烷之生物指標，且驗證長期抽煙會使癌症發生之危險性增加。; Tobacco smoke is considered as the most important factor in environmental carcinogenesis and contains numerous carcinogens. Among them, ethylene oxide is classified as a known human carcinogen, and there is about 5μg per cigarette. It has been of interest to study the potential cancer risk caused by ethylene oxide exposures during smoking. The objective of the study was to establish the modified Edman degradation methods to analyze ethylene oxide-induced hemoglobin adducts (N-hydroxyethylvaline, HEV), and then to investigate the factors that affect the formation of HEV in smokers and non-smokers. Results from this study would be used to estimate the accumulated internal doses and external exposures of ethylene oxide and finally to assess cancer risk. Ten ml of blood samples was collected from 162 volunteers which background informations were collected by questionnaires. Red blood cells were immediately harvested from each fresh blood sample and stored at -80oC until used for purification of hemoglobin. Approximate 100 mg of globin was dissolved in formamide and derivatized with pentafluorophenyl isothiocyanate. After cleanup, samples were analyzed using gas chromatograph / negative chemical ionization-mass spectrometer (GC/NCI-MS). The amounts of HEV are 58.3±45.6 pmol/g Hb in non-smokers and 205.9±151.4 pmol/g Hb in smokers which are significantly different (p<0.0001). Our results show that the amounts of HEV are linearly correlated with number of cigarettes smoked per day (r = 0.53), years of smoking (r = 0.28), and bags of cigarettes smoked per day (r = 0.44). Cumulative external exposures are estimated to be 259.2 and 915.1 ppm×h of ethylene oxide in non-smokers and smokers, respectively. The corresponding cancer risk are 4.15×10-5 and 1.46×10-4. This study validates that HEV is a sensitive and specific biomarker to assess ethylene oxide exposures from tobacco smoke. These results also confirm that smokers will have higher cancer risk than nonsmokers due to the exposures to ethylene oxide.
