Age is an important factor in the evaluation of chemical toxicology. Chemical carcinogenic compounds can induce genomic mutations. However, few studies have been conducted on the association between genomic mutation frequency, such as microsatellite instability (MSI), and the age of mice treated with a nitrosourea mutagen. In the current work, we treated young (6 weeks) and old (10 months) mice with N-methyl-N-nitrosourea (MNU) for 4 months; the MSI frequency was then measured using polymerase chain reaction (PCR) and short tandem repeat (STR) scanning. The percentage of animals with MSI in the old group was significantly higher than that in the young group (100% and 75%). The frequency of MSI events was significantly different between the two groups as well (15.8% for old and 9.4% for young). The ratio of MSI loci displayed no obvious difference between the two groups. In addition, a few loci, including D15Mit5 and D8Mit14 exhibited the highest frequency of MSI events. Since specific loci showed increased MSI in the present study and a higher frequency in previous studies, these loci could be regarded as “hot spot”. These results suggested that old mice would be more susceptible to this mutagen, and prone to accrue MSI. The hot spot microsatellite loci are potentially useful markers for genomic instability analysis.

年龄是评价化学毒理学的重要因素。化学致癌化合物可诱发基因组突变。然而，关于基因组突变频率（例如微卫星不稳定性 (MSI)）与接受亚硝基脲诱变剂治疗的小鼠年龄之间的关联的研究很少。在目前的工作中，我们用N-甲基-N治疗年轻（6 周）和年老（10 个月）小鼠-亚硝基脲 (MNU) 4 个月；然后使用聚合酶链反应 (PCR) 和短串联重复 (STR) 扫描测量 MSI 频率。老年组MSI动物比例明显高于青年组（100%和75%）。MSI 事件的频率在两组之间也有显着差异（老年人为 15.8%，年轻人为 9.4%）。MSI 基因座的比率显示两组之间没有明显差异。此外，包括 D15Mit5 和 D8Mit14 在内的一些基因座表现出最高频率的 MSI 事件。由于特定位点在本研究中显示出增加的 MSI，而在以前的研究中显示出更高的频率，因此这些位点可以被视为“热点”。这些结果表明老年小鼠更容易受到这种诱变剂的影响，并且容易产生 MSI。