3-氯-4-二氯甲基-5-羟基-2(5氢)-呋喃酮对L-02细胞DNA损伤与ras基因表达的影响  

Effect of 3-chloro-4-(dicholoromethyl)-5-hydroxy-2(5H)-furanone on DNA damage and expression of ras gene in L-02 cells

作　　者：刘爱林[1] 吴建军[1] 邹亚玲[1] 鲁文清[1] 

机构地区：[1]华中科技大学同济医学院公共卫生学院劳动卫生与环境卫生学系,武汉430030

出　　处：《卫生毒理学杂志》2004年第4期207-209,共3页Journal of Health Toxicology

基　　金：国家自然科学基金资助 (30 1 70 794)

摘　　要：目的　研究饮水氯化消毒副产物 3 氯 4 二氯甲基 5 羟基 2 (5氢 ) 呋喃酮 (MX)对人胚肝细胞 (L 0 2 )DNA损伤与ras基因表达的诱导 ,初步探讨MX致癌的分子机制。方法　以L 0 2细胞作为靶细胞 ,应用彗星试验 (SCGE)和原位杂交试验 (ISH)研究MX诱导L 0 2细胞DNA损伤与ras基因表达。MX设 10、3 0、10 0和 3 0 0 μmol L 4个剂量 ,二甲基亚砜 (DMSO ,10mL L)为溶剂对照 ,H2 O2 (3 0 0 μmol L)和B(a)P(2 0 0 μmol L)分别为SCGE和ISH的阳性对照。 结果　与溶剂对照相比 ,3 0、10 0和 3 0 0 μmol L的MX能明显增加L 0 2细胞的DNA迁移度 (P <0 0 5 ,P <0 0 1,P <0 0 0 1) ;同时也明显增加ras基因表达水平 (P <0 0 0 1,P <0 0 0 1,P <0 0 1)。MX在 10～ 10 0 μmol L的浓度范围内 ,诱导的ras基因表达水平和DNA迁移度呈正相关 (r =0 79)。结论　饮水氯化消毒副产物MX可诱导L 0 2细胞DNA损伤与ras基因表达 ,ras基因表达水平可能与DNA损伤程度有关。Objective To study of DNA damage and expression of ras gene induced by 3-chloro-4-(dicholoromethyl)-5-hydroxy-2(5H)-furanone (MX) in L-02 cells,and to explore the possible mechanism of cancer caused by MX.Methods L-02 cells were exposed to MX at the concentration of 10,30,100 and 300 μmol/L.Single cell gel electrophoresis(SCGE) and in situ hybridization (ISH) assay were used to detect DNA damage and the expression of ras gene in L-02 cells. DMSO(10 mL/L) was used as solvent control. H 2O 2 (300 μmol/L) and B(a)P (200 μmol/L)were selected as positive control for SCGE assay and ISH assay respectively.Results (1)DNA migration and ras gene expression were significantly increased in L-02 cells exposed to MX at the concentration of 30,100 and 300 μmol/L in comparison with solvent control. (2) There was striking association between ras gene expression and DNA migration in L-02 cells when the MX concentration was between 10 and 100 μmol/L (r=0.79).Conclusion MX could induce obvious DNA damage and ras gene expression in L-02 cells, and ras gene expression might be affected by DNA damage.

关 键 词：RAS基因 表达水平 诱导 DNA损伤 细胞DNA SCGE 对照 呋喃酮 氯甲基 溶剂 

分 类 号：R735[医药卫生—肿瘤] R734.204[医药卫生—临床医学]