高福,蔡建明,崔建国,杨平,黄越承,李百龙,闵锐,倪瑾,孙顶.INK4A基因及P16蛋白在辐射诱导小鼠白血病模型中的变化[J].中华放射医学与防护杂志,2008,28(5):475-478
INK4A基因及P16蛋白在辐射诱导小鼠白血病模型中的变化
Alterations of INK4A gene and P16 protein in leukemia mice model induced by 60Co γ-ray irradiation
投稿时间:2007-09-17  
DOI:
中文关键词:  INK4A  白血病模型  辐射  P16蛋白
英文关键词:INK4A  Leukemia model  Irradiation  P16 protein
基金项目:
作者单位E-mail
高福 200433 上海, 第二军医大学放射医学教研室  
蔡建明 200433 上海, 第二军医大学放射医学教研室 cjm882003@yahoo.com.cn 
崔建国 200433 上海, 第二军医大学放射医学教研室  
杨平 200433 上海, 第二军医大学放射医学教研室  
黄越承 200433 上海, 第二军医大学放射医学教研室  
李百龙 200433 上海, 第二军医大学放射医学教研室  
闵锐 200433 上海, 第二军医大学放射医学教研室  
倪瑾 200433 上海, 第二军医大学放射医学教研室  
孙顶 200433 上海, 第二军医大学放射医学教研室  
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中文摘要:
      目的 研究INK4A基因及编码的P16蛋白在辐射诱导的小鼠白血病模型中的改变。方法 7.0 Gy 60Co γ射线分4次照射BALB/c小鼠建立辐射诱导的小鼠白血病模型; PCR扩增INK4A 基因第1、第2 外显子,检测等位基因纯合性缺失,甲基化敏感酶切PCR 法检测INK4A基因的甲基化发生情况,并应用PCR单链构象多态性分析方法检测碱基突变的发生;Western blot检测P16蛋白含量改变。结果 在21例白血病模型组织中,外显子2缺失5例,4例发生甲基化,有11例蛋白表达明显下降。结论 辐射诱导的小鼠白血病模型发生过程中伴有P16蛋白表达下降, INK4A基因改变以纯合性缺失和甲基化为主。
英文摘要:
      Objective To investigate the alterations of INK4A gene and protein in the leukemia model of mice induced by 60Co γ-ray irradiation. Methods BALB/c mice were irradiated 4 times weekly with 60Co γ-ray irradiation to establish the animal model of lymphocyte leukemia, and the total absorbed dose was 7.0 Gy. PCR was used to amplify exons 1 and 2 of INK4A gene and to detect the homozygous deletion. The occurrence of methylation in the 5'CpG island was studied with methylation sensitive enzyme PCR. PCR-SSCP-silver staining technique was used to detect the mutation. The expression of P16 protein was detected with Western blot. Results In 21 cases of leukemia model tissues, there were 5 cases of depletion of the exon 2 of INK4A gene, and 4 cases of methylation in the priming domain of the exon 1, 11 cases of protein expression decreased. Conclusions The decrease in p16 expression might participate in the radiation- induced tumorigenesis. The homozygous deletion and methylation are the main causes of inactivation of INK4A gene in mice.
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