苯急性暴露对Sprague-Dawley大鼠全基因组DNA甲基化的影响

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。

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

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.