鄭尊仁2006-07-252018-06-292006-07-252018-06-292002-07-31http://ntur.lib.ntu.edu.tw//handle/246246/4955氯乙烯是人類致癌物質（IARC, 1987 ），許多流行病學研究都指出氯乙烯 暴露和肝癌之間的相關性，而DNA 產 生傷害是癌症發生一個很關鍵性的步 驟，所以過去有許多氯乙烯暴露和DNA 傷害的研究，除了DNA 鍵結物外，細 胞遺傳學方面也發現氯乙烯會造成染色 體變異、姊妹染色體交換、微核和DNA 股斷裂的產生，最近又發現8-OHdG 可 作為評估DNA 氧化壓力傷害的指標。 這些DNA 傷害指標除了與暴露的相 關，代謝與基因修補多形性也可能與氯 乙烯DNA 傷害有關。所以本研究探討 姊姊染色分體交換、8-OHdG 以及DNA 單股斷裂與氯乙烯暴露之相關。並評估 易感性基因CYP2E1 ，ALDH2 ，GSTT1 ， GSTM1 及XRCC1 基因多形性與氯乙烯 引起之DNA 傷害的相關性。 本研究分三部分，姊姊染色分體部 分有90 名男性員工，其中高暴露（˜ 1 ppm ）32 人，低暴露29 人，非暴露組 29 人。非暴露組是同一公司，其他製造 廠工人沒有致突變物的暴露。氧化壓力 指標8-OHdG 部分包括五家氯乙烯聚合 工廠共205 名男性員工，採集尿液及血 液樣本。彗星分析法部分研究對象為三 家氯乙烯聚合工廠的男性作業員工，共 33 人，採集氯乙烯暴露當天下午的血液 和氯乙烯暴露隔天早晨的尿液樣本。所 有工人皆以問卷訪視的資料獲得氯乙烯 聚合工人的個人基本資料、生活習慣、 疾病史及工作概況等。 研究結果顯示，高暴露組比對照 組，姊姊染色分體顯著升高（8.0 vs 7.2, p<0.05 ），低暴露組也比對照組高，但未 達統計顯著。年齡大於45 歲及抽煙皆與 姊姊染色分體顯著相關。至於基因多形 性，XRCC1 （exon10 ）Gln-Gln 比 Gln-Arg/Arg-Arg, CYP2E1 C2C2 比 C1C1/C1C2 ，ALDH2 1-2/2-2 比1-1 皆顯 著升高。當我們把易感性基因型合起 來，在高暴露組具有2 個以上易感形基 因的比具一個或沒有易感形基因的姊姊 染色分體交換頻率高，但未達顯著，但 在低暴露組，具2 個以上易感性基因 者，比一個或沒有著顯著升高，並有明 顯趨勢，而在對照組易感形基因則與姊 姊染色分體無關。在氧化壓力DNA 傷 害方面，B 型C 型肝炎與8-OHdG 明顯 相關，喝酒也有明顯相關，但氯乙烯暴 露、抽煙，及年齡與8-OHdG 則無關。 有趣的是，血漿中Vitamin A 上升與8-OHdG 增加也有關。彗星分析法部 分，結果發現氯乙烯尿中代謝產物 TdGA 的濃度與空氣中氯乙烯濃度有相 關，但是與彗星分析評估DNA 單股斷 裂沒有顯著相關。而抽煙、年齡和飲食 習慣等潛在干擾因子在本研究中對彗星 分析的結果也沒有產生影響。 研究顯示姊姊染色分體比尿中 8-OHdG 及彗星試驗對氯乙烯基因毒性 偵測比較敏感。此外，代謝及基因修補 多形性對氯乙烯基因毒性可能有修飾作 用。Vinyl chloride monomer (VCM) has been recognized as a human carcinogen. A large number of epidemiology studies have suggested an association between VCM exposure and liver cancer. DNA damage is a critical step in the carcinogenesis. DNA adducts and cytogenetic methods including chromosome aberrations, sister chromatid exchange frequency and micronuclei have been used to assess DNA damage in VCM exposure workers. However, the dose-response relationship between the low dose exposure to VCM and DNA damage remains unclear. In this study, we used sister chromatid exchange （SCE ） Comet assay and urinary 8-OHdG to assess the VCM-induced DNA damage, and to evaluate the association between gene polymorphism and VCM-related damage. Analysis showed that SCE was higher in high exposure group than in control group ( 8.0 vs 7.2, p<0.05). Low exposure group also had higher SCE than control, but this did not reach a significance. SCE also increased with age and smoking. Further, XRCC1 Gln-Gln, CYP2E1 C2C2 and ALDH2 1-2/2-2 had higher SCE than their counterpart. When susceptible genotypes were considered together, those with at least 2 susceptible genotypes had higher SCE in low exposure group. Similar trend was also observed in high exposure group, although not significant. There is no association between genotypes and SCE in controls. Urinary 8-OHdG was not associated with VCM exposure, age and smoking. However, 8-OHdG was significantly associated with Hepatitis B and C injection, and alcohol drinking. Interesting, plasma vitamin A levels were inversely associated with urinary 8-OHdg. Urinary TdGA was found to be associated with air VCM levels. However, there was no relationship between the urinary TdGA levels and DNA SSB. Our results indicated that SCE is more sensitive than urinary 8-OHdG and comet assay in detecting VCM-induced genotoxicity.Furthermore, metabolic and DNA repair genotypes may modify DNA damage caused by VCM.application/pdf108566 bytesapplication/pdfzh-TW國立臺灣大學公共衛生學院職業醫學與工業衛生研究所聚氯乙烯基因多形性姊姊染色分體8-OHdG彗星分析DNA 單股斷裂Thiodiglycolic acidPolyvinyl chloridecomet assayDNA single-strand breaksthiodiglycolic acid (TdGA)[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/4955/1/902320B002125.pdf