|本期目录/Table of Contents|

[1]续志斌,马文彦,张林,等.氯乙烯对大鼠肝细胞MGMT 基因甲基化的影响[J].慢性病学杂志,2016,(09):952-955.
　XU Zhi-bin,MA Wen-yan,ZHANG Lin,et al.Effect of vinyl chloride on DNA methylation of MGMT in rats[J].,2016,(09):952-955.
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氯乙烯对大鼠肝细胞MGMT 基因甲基化的影响(PDF)

《慢性病学杂志》[ISSN:1674-8166/CN:11-5900/R]

卷:
期数:
2016年09期
页码:
952-955
栏目:
论著
出版日期:
2016-10-27

文章信息/Info

Title:
Effect of vinyl chloride on DNA methylation of MGMT in rats
作者:
续志斌;  马文彦;  张林;  高怡;  田凤?;  吕懿;  仇玉兰
山西医科大学公共卫生学院卫生毒理教研室，太原030001
Author(s):
XU Zhi-bin;  MA Wen-yan;  ZHANG Lin;  GAO Yi;  TIAN Feng-jie;  LYU Yi;  QIU Yu-lan
Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China Corresponding author: QIU Yu-Lan, E-mail:ylqiu@sina.com
关键词:
氯乙烯; MGMT 基因; DNA 甲基化; mRNA 表达
Keywords:
Vinyl chloride;  MGMT gene;  DNA methylation;  mRNA expression
分类号:
R114
DOI:
-
摘要:
目的通过检测氯乙烯染毒大鼠肝细胞MGMT 基因启动子区甲基化的水平及mRNA 的表达，探讨MGMT 基因在氯乙烯致癌过程中的表观遗传机制。方法选取96只健康雄性SD 大鼠，随机分为四组：阴性对照组 和低剂量(5 mg/kg)、中剂量(25 mg/kg)、高剂量(125 mg/kg)三个氯乙烯染毒组。采用腹腔注射染毒，每周3 次。每组分别于染毒第6、8、12 周末随机处死8 只，取其肝脏。采用甲基化特异性实时荧光定量（qMSP） 检测 大鼠肝细胞MGMT 基因启动子区甲基化的水平，采取实时荧光定量（qPCR） 测定MGMT mRNA 表达量。结 果染毒6周时，各氯乙烯染毒组MGMT 基因启动子区甲基化水平均高于阴性对照组，随着染毒剂量的增加而 下降，低剂量组和中剂量组与对照组相比，差异有统计学意义（P＜0.05）；MGMT mRNA 表达量随着染毒剂量 的增加而上升，且高剂量组与低剂量组和中剂量组相比，差异有统计学意义（P＜0.05）。染毒8周时，MGMT 基 因启动子区甲基化水平和mRNA 表达量在各组间差异无统计学意义（P＞0.05）。染毒12周时，MGMT 基因启动 子区甲基化水平随着染毒剂量的增加而升高，且高剂量组与对照组相比，差异有统计学意义（P＜0.05）；但 MGMT mRNA 表达量在各组间差异无统计学意义（P＞0.05）。结论氯乙烯可致大鼠肝细胞MGMT 基因启 动子区甲基化水平升高，可能参与氯乙烯致癌的表观遗传机制。
Abstract:
Objective To detect aberrant methylation in the promoter and mRNA expression of MGMT in rats′ liver and to discuss the epigenetic mechanism of vinyl chloride (VC). Methods Ninety-six healthy SD male rats were randomly divided into a negative control group and three VC exposed groups (5 mg/kg, 25 mg/kg, 125 mg/kg). There were 24 rats in each group. Different dose of VC was given to SD rats by intraperitoneal injection every other day, totally three times a week. Eight rats in each group were killed at the end of 6, 8 and 12 weeks respectively. The methylation status of the 5′ region of MGMT were detected by Quantitative Real- time methylation specific PCR (qMSP). The mRNA expression of MGMT were examined by Real- time PCR (qPCR). Results At the end of 6 weeks, the methylation levels of MGMT in three VC exposed groups were higher than the control group, and the levels decreased with the increase of the exposure dose; The differences between 5 mg/kg, 25 mg/kg groups and the control group were significant (P<0.05). The mRNA expression in 125 mg/kg group decreased in comparison with 25 mg/kg, 5 mg/kg groups in 6 weeks (P＜0.05). After 8 weeks, there was no singificant differences of methylation level and mRNA expression between different groups (P＜0.05). At the end of 12 weeks, the methylation levels of MGMT increased with the increase of the exposure dose, and the level of 125 mg/kg group was higher than that of the control group (P＜0.05). However, the differences of mRNA expres-sions of MGMT in the groups weren′t significant (P＞0.05). Conclusion Hypermethylation of 5′ region of MGMT can be induced by VC. It may be helpful to illuminate the epigenetic mechanism of VC.

参考文献/References:

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备注/Memo

备注/Memo:
基金项目：山西省基础研究计划项目（2013011059-1）；山西省回国留学人员科研资助项目（2016-056） 作者简介：续志斌，硕士在读，研究方向：职业毒理学 通信作者：仇玉兰，E-mail：ylqiu@sina.com
更新日期/Last Update: 2016-10-27