急性低剂量辐射对小鼠肝脏及骨髓DNA甲基化的影响  

Effects of acute low dose radiation on DNA methylation in liver and bone marrow of mice

作　　者：陈凤鸣[1] 吴宏[1] 张梦[2] 关雪晶[1] 何晓莉[1] 蒋林[1] 

机构地区：[1]重庆医科大学基础医学院组织胚胎学教研室 干细胞与组织工程研究室,重庆400016 [2]重庆医科大学药学院,重庆400016

出　　处：《基础医学与临床》2014年第7期933-938,共6页Basic and Clinical Medicine

基　　金：重庆市渝中区科技计划(20110321)

摘　　要：目的观察低剂量辐射(LDR)对小鼠肝脏及骨髓单个核细胞(BMNC)DNA甲基化及甲基化转移酶的影响。方法直线加速器一次性全身X射线1.0 Gy均匀照射C57BL/6小鼠,建立辐射损伤模型。并于照射后1、3、7和14 d取眼球血进行外周血细胞计数,处死小鼠提取肝脏及BMNC,高效液相色谱法检测全基因组DNA甲基化的水平,Western blot检测DNA甲基化转移酶1(DNMT1)、DNMT3A及DNMT3B的水平。结果与正常组相比,辐射组白细胞及血小板计数均明显降低(P<0.05),白细胞在1 d时降至最低,而血小板在3 d时降至最低,14 d仍未恢复正常。辐射组肝及BMNC全基因组DNA甲基化水平下降(P<0.05),其后均逐渐恢复正常。与正常组相比,辐射组肝脏及BMNC DNMT1及DNMT3A表达显著升高(P<0.05),14 d时仍未恢复至正常,DNMT3B的表达也显著升高(P<0.05),但在7 d时已恢复至正常。结论低剂量辐射可导致小鼠肝脏及骨髓DNA甲基化水平的降低及DNMTs表达的升高。Objective To study the effect of acute low dose radiation on DNA methylation and DNA methyltransferase（DNMT） in liver and bone marrow of mice.Methods The C57BL/6 mice were irradiated by linear accelerator with X ray.the peripheral blood cells were examined in 1,3,7,14 days after radiation,Then these mice were killed,liver and BMNC were examined.The DNA methylation level of whole gene was detected by HPLC,the expression of DNMT1,DNMT3A and DNMT3B were detected by Western blot（WB）.Results Compared with those in the normal group,the numbers of peripheral leukocyte and platelet significantly decreased in the radiation group,the peripheral leukocyte in the first day dropped to the lowest and platelet fell to lowest in the third day,they all failed to returne to normal at the 14rd.The DNA methylation level of radiation group was decreased significantly,but with the increase of time,the methylation level returned to normal.the expression of DNMT1 and DNMT3A were increased significantly in the radiation group and not returned to normal in the 14rd,the expression of DNMT3B were increased significantly,but returned to normal at day 7.Conclusions Acute low dose radiation can decrease the methylation level of DNA and the expression of DNMTs.

关 键 词：低剂量辐射 DNA甲基化 DNA甲基化转移酶 表观遗传学 

分 类 号：R144[医药卫生—公共卫生与预防医学]