,et al.Protective effects of EGCG against methylation changes induced by low dose radiation[J].Chinese Journal of Radiological Medicine and Protection,2014,34(9):647-651
Protective effects of EGCG against methylation changes induced by low dose radiation
Received:March 09, 2014  
DOI:10.3760/cma.j.issn.0254-5098.2014.09.002
KeyWords:Epigallocatechin gallate  Radiation damage  Methylation  Rad23b  Ddit3
FundProject:南京军区医药卫生科研基金(11MA092)
Author NameAffiliationE-mail
徐凯 Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China  
王静子 Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China  
杨丹 Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China  
张有为 Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China  
薛利军 Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China  
耿建 Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China  
陈亚楠 Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China  
郁红菊 Department of Medical Oncology, Nanjing Clinical School, Nanjing General Hospital of Nanjing Military Command, PLA, Southern Medical University, Nanjing 210002, China  
褚晓源 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 investigate the role of epigallocatechin gallate (EGCG) in reversing the CpG island methylation of Rad23b and Ddit3 gene promoter and its mRNA expression induced by 0.5 Gy X-rays.Methods Thirty BALB/c male mice were randomly divided into 6 groups: control group, irradiation group, low/high dose of EGCG group, low/high dose of EGCG with irradiation group. For the irradiation group, mice were fractionally exposed with 6 MV X-rays for 10 d (0.05 Gy/d×10 d). 2 hours after the final irradiation, all mice were killed and such tissues as blood, kidney, liver, spleen, brain, and lung were collected. Methylation and expression levels of Rad23b and Ddit3 were measured by bisulfate sequencing primers (BSP) and Real-time PCR, respectively.Results Compare to the control group, Rad23b was hypermethylated in PBMC, liver, spleen, brain and lung (t=-20.19, -14.80, -12.05, -28.42, -12.58, P<0.05) in the irradiation group. Meanwhile, its mRNA expression level was down-regulated in PBMC, liver, brain and lung (t=25.25, 17.43, 11.53, 22.85, P<0.05). Similarly, a significant hypermethylation change of Ddit3 was observed in PBMC, liver and lung after irradiation (t=-52.89, -20.31, -3.85, P<0.05) so that the mRNA expression of Ddit3 decreased in PBMC and liver (t=11.89, 16.52, P<0.05). Compared to the irradiation group, EGCG with different concentrations of 10, 20 mg/kg significantly reduced the methylation level of Rad23b and Ddit3 (t=-13.39-7.99, P<0.05), and induced re-expression of mRNA (t=-34.02--2.89, P<0.05). This change was more notable in the irradiation group with the high dose of EGCG. Conclusions As a natural drug, EGCG may play an important role in affecting DNA methylation and hence protects DNA from radiation damage.
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