WANG Jing-zi,ZHANG You-wei,MAO Xiao-bei,et al.Genome-wide DNA methylation changes induced by low dose radiation in mouse[J].Chinese Journal of Radiological Medicine and Protection,2013,33(4):341-345 |
Genome-wide DNA methylation changes induced by low dose radiation in mouse |
Received:December 04, 2012 |
DOI:10.3760/cma.j.issn.0254-5098.2013.04.002 |
KeyWords:Low dose radiation Methylation DNMT1 MBD2 |
FundProject:南京军区医药卫生科研基金课题(No.11MA092) |
Author Name | Affiliation | E-mail | WANG Jing-zi | Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China | | ZHANG You-wei | Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China | | MAO Xiao-bei | Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China | | LIU Xiao-bei | Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China | | REN Li-li | Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China | | CHU Xiao-yuan | Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China | chuxiaoyuan6906@gmail.com |
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Abstract:: |
Objective To study the whole genome DNA methylation changes induced by low dose radiation (LDR) in mouse, and mRNA expression profiles of DNMT1 and MBD2 in peripheral blood mononuclear cell (PBMC) and tissues.Methods Thirty male BALB/c mice were randomly divided into 3 groups: control, single exposure (0.5 Gy), and fractionated exposure of 6 MV X-rays for 10 d (0.05 Gy/d×10 d). Control mice were sham-treated. To determine the immediate (early) effect of irradiation, 15 mice (5/group) were sacrificed 2 h after the last irradiation. The other 15 mice were sacrificed 1 month after the last irradiation (delayed effect). Before sacrifice, blood was sampled immediately. Kidney, liver, spleen, brain and lung tissues were collected. A global DNA methylation quantification Kit and high-performance liquid chromatography (HPLC) were used to investigate the methylation level in blood DNA. The expressions of DNMT1 and MBD2 were determined by RT-PCR. Results For the early effects of irradiation, as compared with controls, fractionated exposure to X-ray irradiation led to the significant depression of global DNA methylation level in blood (t =10.19 and 8.93, P <0.05). DNMT1 and MBD2 mRNA were down-regulated in PBMC, kidney and liver (t =5.06, 3.01, 3.97, 12.25, 3.50 and 3.73, P <0.05), and MBD2 was also down-regulated in spleen (t =3.03, P<0.05). However, no changes were observed in single exposed group. As for the delayed effects, the methylation levels of blood were not changed in the single or fractionated exposed groups, and only MBD2 mRNA was down-regulated in PBMC and brain of fractionated exposed group(t =3.52 and 2.85, P <0.05). Conclusions Fractionated LDR exposure can induce genome DNA hypomethylation, which is tissue-specific, and may be related with down-regulation of DNMT1 and MBD2. |
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