Analysis of the relationship between microsatellite instability and thymic lymphoma induced by N-methyl-N-nitrosourea in C57BL/6J mice
Analysis of the relationship between microsatellite instability and thymic lymphoma induced by N-methyl-N-nitrosourea in C57BL/6J mice
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微卫星不稳定性与N-甲基-N-亚硝基脲诱导C57BL/6J小鼠胸腺淋巴瘤的关系分析
DOI：
10.1016/j.mrfmmm.2014.11.007
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发表时间：
2015-01-01
影响因子：
2.3
通讯作者：
Chen, Zhenwen
中科院分区：
文献类型：
--
作者：
Huo, Xueyun;Zhang, Shuangyue;Chen, Zhenwen
微卫星不稳定性（MSI）与多种肿瘤的发生密切相关，且常与肿瘤的特异性表现密切相关。然而，MSI与肿瘤的关系尚不清楚。本研究旨在探讨N-甲基-N-亚硝基脲（MNU）致突变作用下MSI与肿瘤形成的关系。在实验的第1周开始时，向小鼠施用MNU（90 mg/kg）或PBS和DMSO（对照）。在整个实验时间过程中存活的31只小鼠中，19只（61.3%）小鼠发生胸腺淋巴瘤。此外，52.6%（10/19）的肿瘤已转移到肝脏。我们使用一组42个突变敏感位点检测MNU处理小鼠的MSI。在6个器官中有19个位点（45.2%）发生了70个MSI事件。D8 Mit 14位点的MSI较其他位点高。胸腺MSI发生率高于其他器官。有趣的是，在转移性和非转移性肝脏之间没有观察到显著差异。未发生肿瘤的MNU处理胸腺中的MSI频率（4.6%，23/（42 x 12））显著高于发生淋巴瘤的胸腺中的MSI频率（0.5%，4/（42 x 19））（p < 0.0001）。这些结果表明，尽管胸腺肿瘤发生与MSI相关，但在MNU治疗后未发生肿瘤的患者中发生频率更高。我们的研究为MSI发生与肿瘤发生之间的关系提供了额外的见解。(C)2014爱思唯尔有限公司版权所有。
Microsatellite instability (MSI) has been found to be closely associated with many types of human tumors and often shows strong correlations with specific tumor features. However, the relationship between MSI and tumors are still unclear. The aim of the present study is to explore the relationships between MSI, tumor formation under the mutagenic effects of N-methyl-N-nitrosourea (MNU). Mice were administered with either MNU (90 mg/kg) or PBS and DMSO (control) at the beginning of the 1st week of the experiment. Of the 31 mice that survived the entire experimental time course, 19(61.3%) mice developed thymic lymphomas. In addition, 52.6% (10/19) of the tumors had metastasized to the liver. We detected MSI in MNU-treated mice using a panel of 42 mutation-sensitive loci. Nineteen loci (45.2%) in six organs showed 70 MSI events. Locus D8Mit14 showed enhanced MSI compared with the other examined loci. MSI frequency in thymus was higher than in other organs. Interestingly, there was no significant difference observed between the metastatic and non-metastatic livers. The MSI frequency (4.6%, 23/(42 x 12)) in the MNU-treated thymus that had never developed tumor was significantly higher than this in the thymus that had developed lymphoma (0.5%, 4/(42 x 19)) (p < 0.0001). These results indicate that, although thymic tumorigenesis is associated with MSI, it occurs with higher frequency in these that have not developed tumors upon the MNU-treatment. Our study provides additional insights into the relationship between MSI occurrence and tumorigenesis. (C) 2014 Elsevier B.V. All rights reserved.