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Distinct susceptibility of induction of methylation of p16(ink4a) and p19(arf) CpG islands by X-radiation and chemical carcinogen in mice
Yang, Chen1,2; Gu, Liankun1; Deng, Dajun1
关键词DNA methylation H. felis Ink4a/Arf Susceptibility N-nitrosomethylurea X-radiation
刊名MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
2014-07-01
DOI10.1016/j.mrgentox.2014.04.012
768页:42-50
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
研究领域[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
关键词[WOS]ABERRANT DNA METHYLATION ; HELICOBACTER-PYLORI INFECTION ; TUMOR-SUPPRESSOR GENE ; HUMAN CANCERS ; RAY-IRRADIATION ; P16 ; CELLS ; HYPERMETHYLATION ; PROGRESSION ; DYSPLASIA
英文摘要

Inactivation of the tumor suppressor genes p16(ink4a) and p19(arf)/p14(arf) by hypermethylation of promoter CpG islands occurs frequently in various tumors. The aim of this study is to investigate the difference of susceptibility of methylation induced by carcinogens between p16(ink4a) and p19(arf). The methylation status of both genes was analyzed by denaturing high performance liquid chromatography (DHPLC) and bisulfite-sequencing, respectively. The expression level of P16 protein was analyzed by immunohistochemistry. Results showed that p16(ink4a) methylation was detected in the glandular stomach, small intestine and other organs of mice following X-radiation and subsequent bone marrow transplantation (BMT), but not in mock control mice. We found that the intestinal tract was the most sensitive organ for X-ray induced p16(ink4a) methylation. Loss of P16 protein expression was observed in the intestinal tissues of X-irradiated mice, but not in the mock control mice. Interestingly, p19(arf) methylation was not observed in the gastrointestinal tissues of the negative control mice following X-radiation/BMT. However, administration of N-nitrosomethylurea and/or Helicobacter fells infection promoted methylation of p(19arf) CpG islands in the gastrointestinal tracts, but did not promote p16(ink4a) methylation. In addition, p16(ink4a) methylation was detected not only in the X-irradiated GFP-negative tissue cells, but also in the GFP-positive bone marrow-derived cells that were transplanted into the BMT mice after X-radiation. In conclusion, the methylation susceptibility of p16(ink4a) and p19(arf) to carcinogen treatments was remarkably different: X-radiation indirectly induces systemic p16(ink4a) methylation, especially in the intestine; whereas N-nitrosomethylurea and/or H. felis infection induce p19(arf) methylation in their target organs. (C) 2014 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000337883400006
项目编号90919015 ; 30921140311 ; IRT13003 ; 2010CB529303
资助机构National NSFC funds ; Education Ministry Innovative Research Team Program ; National Basic Research Program of China (973 Program)
引用统计
被引频次:1[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60098
专题北京大学临床肿瘤学院_病因研究室
北京大学临床肿瘤学院_病因学研究室
作者单位1.Peking Univ, Canc Hosp & Inst, Dept Etiol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China
2.King Med Diagnost Ctr, Dept Med, Guangzhou 510330, Guangdong, Peoples R China
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Yang, Chen,Gu, Liankun,Deng, Dajun. Distinct susceptibility of induction of methylation of p16(ink4a) and p19(arf) CpG islands by X-radiation and chemical carcinogen in mice[J]. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS,2014,768:42-50.
APA Yang, Chen,Gu, Liankun,&Deng, Dajun.(2014).Distinct susceptibility of induction of methylation of p16(ink4a) and p19(arf) CpG islands by X-radiation and chemical carcinogen in mice.MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS,768,42-50.
MLA Yang, Chen,et al."Distinct susceptibility of induction of methylation of p16(ink4a) and p19(arf) CpG islands by X-radiation and chemical carcinogen in mice".MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 768(2014):42-50.
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