苯急性暴露对Sprague-Dawley大鼠全基因组DNA甲基化的影响  

Effects of an acute exposure of benzene on DNA methylation in Sprague-Dawley rats

作　　者：胡俊杰[1,2] 马慧敏[1] 张文兵[1] 李林朋[1,2] 于志强[1] 盛国英[1] 傅家谟[1] 

机构地区：[1]中国科学院广州地球化学研究所//有机地球化学国家重点实验室,广东广州510640 [2]中国科学院研究生院,北京100049

出　　处：《生态环境学报》2010年第12期2902-2905,共4页Ecology and Environmental Sciences

基　　金：国家自然科学基金(NSFC-21007072);中国科学院知识创新工程重要方向项目(KZCX2-YW-GJ02);中国科学院知识创新工程基金(KZCX2-YW-403);中国科学院广州地球化学研究所知识创新领域前沿项目(GIGCX-09-01)

摘　　要：现有文献表明,DNA甲基化异常与肿瘤的发生密切相关,其中全基因组DNA甲基化水平的改变已经被认为是癌症发生的生物标志物;同时,大量遗传毒理学实验证明苯可以引起DNA突变和断裂,然而苯暴露引起全基因组DNA甲基化异常的现象,目前鲜有文献报道。为了揭示苯引起全基因组DNA甲基化变化的致毒机制,本实验中,Sprague-Dawley(SD)雄性大鼠经口灌胃急性暴露于以500 mg.kg-1(以体质量计)的苯中,在暴露6、12、24、30 h后采集SD雄性大鼠体内血液、肝脏、肾脏和肺,利用高效液相色谱分析方法检测全基因组DNA甲基化水平。结果表明,SD雄性大鼠血液和肝脏的全基因组DNA甲基化水平显著下降,而在肾脏和肺中没有显著地变化,表现出组织特异性。本实验率先报道了苯的暴露可以引起全基因组DNA甲基化水平的异常,从表观遗传学的角度解释了苯影响人体健康的机制。Recently,many reports showed that alterations of DNA methylation are closely associated with cancer development,and the abrrent global DNA methyaltion level has been considered as a biomarker of carcinogenesis.Meanwhile,numerous genetic toxicology data showed that benzene could cause DNA mutaiton and break.However,there was no research report about the direct realtionship between benzene exposure and abrrent global DNA methylation level.In an effort to elucidate the possible mechanism of tumor-inducing potential of benzene,the experiment was designed to investigate the changes of global DNA methylation level in Sprague-Dawley rats after benzene exposure.The blood,kidney,liver and lung of rats were collected at 6,12,24,30 hours after an acute dose（500 mg·kg-1 bodyweight） of benzene exposure,and the DNA methylation status was analyzed by high performance liquid chromatography.Our results showed significant global methylation level changes in blood and liver,but not found in kidney and lung tissues.These results firstly confirmed that benzene could tissue-specifically modulate the DNA methylation pattern,which could help to elucidate the toxicological mechanism of benzene at the epigenetic perspectives.

关 键 词：苯 DNA甲基化 表观遗传学 DNA去甲基化 

分 类 号：X171.5[环境科学与工程—环境科学]