Impact of age on N-methyl-N-nitrosourea induced microsatellite instability in young and old C57BL/6J mice.

ABSTRACT

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.