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研究生:周佩儀
研究生(外文):Chou Pei-Yi
論文名稱:二氯乙烷及氯乙烯暴露工人之基因毒性研究
論文名稱(外文):The genetic toxicity from VCM and EDC exposure in workers
指導教授:鄭尊仁鄭尊仁引用關係
指導教授(外文):Tsun-Jen Cheng
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
論文出版年:1999
畢業學年度:87
語文別:英文
論文頁數:107
中文關鍵詞:二氯乙烷氯乙烯姊妹染色分體交換頻率麩胺基硫轉移脢酒精脫氫脢細胞氧化酵素 CYP2E1
外文關鍵詞:12-dichloride ethylene (EDC)Vinyl chloride monomer (VCM)sister chromatid exchange (SCEs)glutathione S-transferase (GST)aldehyde dehydrogenase (ALDH2)cytochrome P450 2E1 (CYP 2E1)
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二氯乙烷為合成氯乙烯之原料,故氯乙烯製造工人會同時暴露在二氯乙烷及氯乙烯單體中。氯乙烯或二氯乙烷可能經由CYP 2E1活化成親電子的中間代謝產物如chloroethene oxide (CEO)和chloroacetaldhyde (CAA),再經由GSTs和ALDH2代謝排出體外,其中間代謝產物CEO及CAA可能與DNA、RNA及蛋白質等大分子產生鍵結物,引發基因突變。過去曾有研究報告指出,氯乙烯製造工人其姊妹染色分體交換頻率有上升的趨勢,但這些研究對象可能同時具有二氯乙烷暴露,故無法釐清二氯乙烷對基因毒性的影響。故本研究欲探討二氯乙烷及氯乙烯暴露對於工人姊妹染色分體交換頻率之影響。此外,我們同時也探討CYP 2E1、GST T1、GST M1以及ALDH2等基因多型性對於姊妹染色分體交換頻率之影響。
本研究對象為台灣某兩家氯乙烯製造廠的77名男性現職員工,進行姊妹染色分體交換(SCEs)實驗,並以環境偵測及個人採樣濃度配合工人目前的工作職務及工作所在區域作為暴露分組之依據。另外,所有受訪員工均接受詳細的問卷調查,包括基本資料、生活習慣(抽煙及喝酒情形等)、詳細工作史及醫療史,基因多型性係利用聚合脢鍊鎖反應(PCR)分析。
結果顯示,抽煙者之SCEs頻率明顯高於非抽煙者( p<0.01),而隨著氯乙烯及二氯乙烷暴露之增加,SCEs頻率亦隨之上升,且在二氯乙烷暴露濃度大於0.5 ppm時,達到統計上的顯著差異( p<0.01)。另以二氯乙烷及氯乙烯混合暴露分組之方式表示,發現混合暴露指標(hygienic effect)大於0.5以上者,SCEs頻率即有明顯的增加。而GST T1 、GST M1、CYP 2E1及ALDH2等基因多型性與姊妹染色分體交換(SCEs)頻率均未能達到統計上的顯著相關。
綜言之,具有抽煙習慣者之姊妹染色分體交換(SCEs)頻率顯著地高於非抽煙者,且達到統計上的顯著。此外,除氯乙烯以外,二氯乙烷之暴露亦會造成姊妹染色分體交換頻率之增加,而GST T1、GST M1、CYP 2E1及ALDH2等基因多型性對於姊妹染色分體交換頻率之增加並無顯著之影響。

Vinyl chloride monomer (VCM), an important material for plastic industry, is genotoxic in human. Previous studies focused on the genotoxicity of workers engaged in vinyl chloride polymerization. However, workers from VCM manufacturing plant may be exposed to VCM or 1,2-ethylene dichloride (EDC). VCM or EDC is metabolized by cytochrome CYP2E1 or glutathione S-transferase (GST) to form chloroethylene (CEO) and chloroactetaldehyde (CAA), which may either cause genetic toxicity or are further detoxified by GST and aldehyde dehydrogenase (ALDH2). The study was designed to investigate the genetic toxicity from VCM and EDC exposure in workers.
A total of 77 male workers from two vinyl chloride production plants were included in this study. Personal and area sampling were conducted to determine EDC and VCM exposure levels. Standardized cytogenetic method was used to determine the frequency of sister chromatid exchanges (SCEs) in peripheral blood lymphocytes. The questionnaire included detailed occupational history, cigarette smoking, alcohol consumption, and medications. CYP 2E1, GST T1, GST M1, and ALDH2 genotypes will be further determined using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to investigate if these genotypes will affect VCM/EDC induced-SCE.
In analysis, smoking was significantly associated with an increase SCE frequency ( p<0.01). As exposure to VCM and EDC increase, SCE frequency for both smokers and non-smokers increase as well. In addition, SCE frequency was significantly greater when exposure to EDC was more than 0.5 ppm. In combination exposure of both VCM and EDC, SCE frequency appear to be higher in those with hygienic effect greater than 0.5. However, GST T1、GST M1、CYP 2E1 and ALDH2 genotypes were not associated with SCEs.
The results suggest that smoking status and exposure to relative the low level of EDC were significantly associated with an increase SCE frequency in VCM manufacturing workers.
Key Words: Vinyl chloride monomer (VCM)、1,2-dichloride
ethylene (EDC)、sister chromatid exchange (SCEs)、
glutathione S-transferase (GSTs)、cytochrome P450
2E1 (CYP 2E1)、aldehyde dehydrogenase (ALDH2)

頁次
中文摘要……………………………………………………………………i
英文摘要……………………………………………………………………iii
目錄…………………………………………………………………………v
圖目錄………………………………………………………………………vii
表目錄………………………………………………………………………viii
第一章 前言…………………………………………………………………1
第二章 研究目的及假說……………………………………………………3
第三章 文獻探討……………………………………………………………4
第一節 氯乙烯單體製造過程…………………………………………4
第二節 二氯乙烷簡介及其相關研究…………………………………8
1.二氯乙烷的特性…………………………………………………8
2.生物轉化…………………………………………………………8
3.健康危害…………………………………………………………10
4.致癌性……………………………………………………………11
5.基因毒性…………………………………………………………12
6.作業環境空氣中有害物質暴露標準……………………………13
第三節 氯乙烯簡介及其相關研究……………………………………13
1. 二氯乙烷的特性………………………………………………13
2.生物轉化…………………………………………………………14
3.健康危害…………………………………………………………15
4.致癌性……………………………………………………………16
5.基因毒性…………………………………………………………17
6.作業環境空氣中有害物質暴露標準……………………………18
第四節 姊妹染色分體交換(SCEs)頻率…………………………19
第五節 易感性標記…………………………………………………23
1.CYP 2E1基因多型性……………………………………………23
2.GST T1 及 GST M1 基因多型性………………………………26
3. ALDH2 基因多型性……………………………………………28
第四章 材料與方法………………………………………………………31
第一節 研究對象及暴露分組………………………………………31
第二節 流行病學資料………………………………………………35
第三節 姊妹染色分體交換(SCEs)頻率…………………………36
第四節 基因多型性分析……………………………………………37
第五節 統計分析……………………………………………………43
第五章 結果………………………………………………………………44
第六章 討論………………………………………………………………50
第七章 結論………………………………………………………………55
參考文獻…………………………………………………………………56
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