大鼠肺鳞癌癌变过程中基因组甲基化水平动态研究

doi:10.3969/j.issn.1004-616x.2009.01.007

癌变·畸变·突变 ›› 2009, Vol. 21 ›› Issue (1): 27-029.doi: 10.3969/j.issn.1004-616x.2009.01.007

大鼠肺鳞癌癌变过程中基因组甲基化水平动态研究

刘文斌,刘晋祎，周紫垣，周燕虹，敖　琳，崔志鸿，曹　佳

第三军医大学军事预防医学院军事毒理学教研室，重庆　400038

收稿日期:2008-08-27 修回日期:2008-10-24 出版日期:2009-01-30 发布日期:2009-01-30

Genomic Methylation During Carcinogenesis of Lung Squamous Cell Carcinoma in Wistar Rats

LIU Wen-bin, LIU Jin-yi, ZHOU Zi-yuan, ZHOU Yan-hong, AO Lin, CUI Zhi-hong, CAO Jia

Department of Hygienic Toxicology, Preventive Medicine College, Third Military Medical University, Chongqing 400038，China

Received:2008-08-27 Revised:2008-10-24 Online:2009-01-30 Published:2009-01-30

摘要/Abstract

摘要： 背景与目的：研究大鼠肺鳞癌癌变各阶段基因组DNA甲基化水平动态变化趋势。材料与方法：支气管灌注3-甲基胆蒽(MCA)及二乙基亚硝胺(DEN)碘油溶液诱发Wistar大鼠肺鳞癌模型。采用免疫组化法检测大鼠肺鳞癌癌变各阶段基因组DNA甲基化水平，利用图像分析系统测量其平均光密度值和积分光密度值。结果: 经支气管灌注MCA及DEN碘油溶液，诱发Wistar大鼠肺鳞癌模型，共获取癌变各阶段标本154例，其中增生25例，鳞状化生组织27例，不典型增生组织37例，原位癌组织30例，浸润癌组织25例。大鼠肺鳞癌癌变各阶段基因组DNA甲基化水平按上述顺序呈递减的趋势，癌变各阶段甲基化水平与正常对照组比较，差异具有统计学意义(P<0.01)，正常和癌变支气管上皮基底层甲基化水平高于腔细胞层，差异亦具有统计学意义(P<0.01)。结论: 大鼠肺鳞癌癌变过程中基因组DNA甲基化水平的降低，可能是介导其癌变的重要表遗传学机制。

关键词: 肺肿瘤, DNA甲基化, 抗5-甲基化胞嘧啶抗体, 癌变

Abstract: BACKGROUND AND AIM: To investigate thel changes of genomic methylation during lung carcinogenesis in Wistar rats. MATERIALS AND METHODS: Squamous cell carcinoma of lung was induced with 3-methylcholanthrene (MCA) and diethyinitrosamine (DEN) in iodized oil by left intra-bronchial instillation in 80 Wistar rats. The status of genomic methylation was evaluated by immunohistochemistry with anti 5-mc antibody, and the mean optical density and integrated optical density were measured by image analysis system. RESULTS: A total of 154 specimens of various phases during carcinogenesis were obtained: 25 hyperplasia, 27 squamous metaplasia, 33 dysplasia, 30 carcinoma in situ and 25 infiltrating carcinoma. The immunohistochemical scores of 5-mc were significantly decreased in hyperplasia, squamous metaplasia, dysplasia, carcinoma in situ and infiltrating carcinoma (P<0.01). 5-mc immunostaining was significantly higher in the basal cells than in the luminal cells in normal and carcinogenesis phase (P<0.01). CONCLUSION: The decrease of genomic methylation level suggested that it may be an important epigenetic mechanism during carcinogenesis of lung squamous cell carcinoma in rats.

Key words: lung cancer, DNA methylation, anti 5-mc antibody, carcinogenesis

刘文斌, 刘晋祎, 周紫垣, 周燕虹, 敖　琳, 崔志鸿, 曹　佳. 大鼠肺鳞癌癌变过程中基因组甲基化水平动态研究[J]. 癌变·畸变·突变, 2009, 21(1): 27-029.

LIU Wen-bin, LIU Jin-yi, ZHOU Zi-yuan, ZHOU Yan-hong, AO Lin, CUI Zhi-hong, CAO Jia. Genomic Methylation During Carcinogenesis of Lung Squamous Cell Carcinoma in Wistar Rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2009, 21(1): 27-029.

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大鼠肺鳞癌癌变过程中基因组甲基化水平动态研究

Genomic Methylation During Carcinogenesis of Lung Squamous Cell Carcinoma in Wistar Rats

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