The Maintenance of Genome Integrity is Tissue-Specific

抄録

In order to understand how mutagens behave and act in vivo, it is important to understand how the integrity of the genome is maintained and protected in each specific tissue. Although several lines of evidence suggest that the systems used to protect and maintain the genome can change or are modified during cellular differentiation processes, and when cells alter their status from a proliferating to a non-proliferating state, data on individual tissues is very limited. Recent studies on the age-dependent accumulation of spontaneous mutations in transgenic mice clearly indicate that there is tissue-specificity when examining genome maintenance and protection. The genome is most unstable in epithelial tissues of the small and large intestine when compared to 13 other organs and tissues. The genome is highly protected in brain, skin and testis. Studies of the molecular nature of specific mutations suggest the presence of unique tissue-specific mechanisms leading to the formation of mutations in specific tissues. Studies of mutations in DNA repair gene deficient mice have shown that some of the genes involved in mismatch repair are indispensable in many tissues for the maintenance of the genome. The Xpa and Xpc genes involved in nucleotide excision repair have also been shown to be important in some tissues. However, the studies reported to date are only a beginning, and a complete comprehensive picture of the maintenance and repair of the genomic integrity in individual tissues remains to be developed.