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氯乙烯致大鼠DNA损伤与肝代谢酶活性动态变化的研究 被引量:3

DNA Damages and Activities of Vinyl Chloride Metabolizing Enzymes with Time in Rats Exposed to Vinyl Chloride
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摘要 [目的 ]研究氯乙烯 (VC)对大鼠肝细胞和外周血淋巴细胞DNA的损伤作用 ,及对VC代谢酶 [谷胱甘肽硫转移酶 (GST)、细胞色素P45 0 2E1(CYP2E1)、乙醇脱氢酶 (ADH)和乙醛脱氢酶 (ALDH) ]活性的影响 ;探索VC所致损伤的早期敏感检测指标。 [方法 ]大鼠染毒 12周 ,分别在第 3、6、9和 12周处死动物 ,DNA损伤采用单细胞凝胶电泳 (彗星试验 )法 ,代谢酶活性测定采用分光光度法。 [结果 ]彗星细胞数目随染毒剂量和染毒时间的增加而增加 ,肝细胞DNA损伤细胞百分率第 12周中剂量组和高剂量组分别为 12 .3 8%和 17.88% ,外周血淋巴细胞DNA损伤细胞百分率第 3周高剂量组为 7.3 3 % ,第 12周中剂量组和高剂量组分别为 16.2 5 %和 2 8.2 5 % ,均显著高于相应对照组 ,彗星细胞发生率与VC染毒剂量间存在显著相关关系。ALDH和CYP2E1活性随染毒时间和染毒剂量的增加发生改变 ,差异具显著性。肝细胞DNA损伤与CYP2E1活性相关。 [结论 ]VC可导致肝细胞和外周血淋巴细胞DNA发生损伤 ,且存在剂量 反应和时间 效应关系 ;VC致肝细胞DNA损伤与CYP2E1代谢酶活性相关。彗星细胞率可作为VC所致肝脏损伤的早期检测指标。 To investigate DNA damage of liver cells and lymphocytes of rats exposed to vinyl chloride (VC),to examine the activities of VC metabolizing enzymes including GST,CYP2E1,ADH,and ALDH, and to explore early sensitive indexes to detect damage induced by VC. VC was given to rats by in injection 3 times a week for 12 weeks,and rats were killed at the 3rd,6th,9th and 12th week. DNA damage was detected by single cell gel electrophoresis(comet assay). The activities of metabolizing enzymes were measured by spectrophotometer. The numbers of comet cells in the experimental groups were significantly different from that of the control group. The ratios of comet cells had correlation with the doses of VC and the time. The activities of CYP2E1 and ALDH changed with time and doses of VC, there was a significant difference between the experimental and control groups. The DNA damage of liver cells had correlation with the activities of CYP2E1 in this study. [Conclusion] VC can cause DNA damage of liver cells and lymphocytes,a dose-response and time-effect relationships were observed between doses of VC and DNA damage. There was correlation between DNA damage of liver cells and the activity of CYP2E1. The ratio of comet cells is an early and sensitive indicator of damage induced by VC.
出处 《劳动医学》 北大核心 2004年第2期98-100,113,共4页
基金 国家自然科学资金资助项目 (编号 :30 0 70 650 )
关键词 氯乙烯 大鼠 DNA损伤 肝代谢酶 动态变化 彗星实验 VC DNA damage metabolizing enzyme comet assay
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