溴二氯甲烷暴露對大鼠大腸上皮細胞影響之研究

The effect of bromodichloromethane exposure on colonic epithelial cell in rat

廖皓安(Hao-An Liao)

指導教授 ： 楊俊毓

高雄醫學大學/健康科學院/公共衛生學研究所/碩士(2012年)

摘要

為減少因水體汙染造成的疾病，現行有許多消毒方法可使用在自來水殺菌上，其中加氯消毒是目前最普遍的消毒方法。消毒附產物中三鹵甲烷(THMS)占了60％為最主要常見的汙染物。自來水中常見的THMS有四種，即CHCl3、CHBr3、CHBr2Cl、CHBrCl2，台灣目前自來水中THMs以CHCl3及CHBrCl2占最多。目前有許研究證實三鹵甲烷的暴露和癌症的發生間有相關性，像膀胱癌、大腸直腸癌、胰臟癌。大腸直腸癌占台灣癌症死因的第三名，而大腸癌是由息肉型腺體瘤發展而成，因此本研究利用rat F344/N進行十三週的CHBrCl2暴露，研究PCNA、Met、p-Met、Survivin在大腸上皮細胞的表達。結果顯示暴露於CHBrCl2會使腸道息肉增加(p=0.017)，PCNA、Met、p-Met、Survivin在組織切片上表達的比率在低劑量(50mg/kg)分別為33.3％、16.7％、16.7％、16.7％，在高劑量(100mg/kg)為42.9％。p-Met與Survivin被發現在上皮細胞增生處有表達。另外分析comet assay所做的THMs劑量效應與對正常膀胱上皮細胞的DNA損傷評估，比起CHCl3和CHBr3，CHBr2Cl和CHBrCl2對DNA的損傷更為顯著。總之暴露於CHBrCl2會造成大腸增生性細胞上p-Met與Survivin的異常表達。三鹵甲烷，特別是CHBrCl2，在正常膀胱細胞株會誘導DNA損傷。這些結果表明，長期暴露於CHBrCl2可能會導致正常結腸上皮細胞的惡性轉化。

關鍵字

三鹵甲烷 ； 溴二氯甲烷 ； 大腸癌

並列摘要

In order to reduce the diseases by water pollution, there are many disinfection methods can be used .The most commonly used method is chlorination. Trihalomethanes (THMS) accounted for more than 60% of the disinfection by products, and are the most important pollutants. There are four kinds of trihalomethanes: that are CHCl3, CHBr3, CHBr2Cl and CHBrCl2. In Taiwan, CHCl3 and CHBrCl2 are often found. Studies have demonstrated the correlation between trihalomethanes exposure and the occurrence of cancers, such as bladder cancer, colorectal cancer, pancreatic cancer. Colorectal cancer is the third cause of cancer death in Taiwan. In this study, F344 / N rats were exposed to CHBrCl2 for 13 weeks. The immunohistochemistry (IHC) was used to examine the expression of PCNA, Met, p-Met, Survivin in colon epithelial cells. The results showed that exposure of CHBrCl2 increased the occurrence of colon polyps (p = 0.017). The percentage of tissue sections with increased expressions of PCNA, Met, p-Met and Survivin were 33.3, 16.7, 16.7 1nd 16.7%, respectively, for low dose (50 mg/kg) group, and 42.9% for each protein in high dose (100 mg/kg) group. The increased expression of p-Met and Survivin were found in hyperplastic colon epithelial cells. In addition, exposure to THMs caused dose-dependent increases in DNA damages, as assessed by Comet assay, in normal bladder epithelial cells. CHBrCl2 and CHBr2Cl caused significantly more DNA damages, compared with CHCl3 and CHBr3, CHBr3and CHBr2Cl caused DNA damages in a dose-dependent manner. In summary, exposure to CHBrCl2 caused aberrant expressions of p-Met and Survivin in hyperplastic colonic cells. THMs, in particular CHBrCl2, induced DNA damages in normal bladder cell line. These results suggest that long-term exposure to CHBrCl2 may cause malignant transformation of normal colon epithelial cells.

並列關鍵字

THMs ； colon cancer

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