Possible mechanisms of ionizing radiation-induced genomic instability

Mammalian cells exposed to ionizing radiation can show an increased rate of changes in their genome even after any generations. These changes can involve point mutations, chromosome rearrangements and variability in the number of short tandem repeats. The large proportion of cells in the irradiated population that demonstrate these changes suggests that this induced genomic instability is not brought about by mutations in specific genes. Instead, it has been suggested that ionizing radiation may cause genomic instability through its ability to generate epigenetic changes or chain reactions of chromosome rearrangements. Radiation-induced epigenetic changes could involve increased expression of genes through various signal transduction pathways or suppression of genes by changes in DNA methylation. Similar to the genomic instability observed in cancer cells and some human genetic diseases, altered expression of a variety of genes could be responsible, including genes involves in DNA repair, DNA replication, cell cycle regulation, telomere maintenance, or genes influencing the level of spontaneous DAN damage. Chain reactions of chromosome rearrangements could also contribute to genomic instability through the generation of breakage/fusion/bridge cycles and the creation of recombination hotspots. The variety of the delayed changes seen in irradiated cells suggests that more than one mechanism may be involved. The exact mechanisms responsible for radiation-induced genomic instability may depend on the cell type and the nature of the ionizing radiation. A complete understanding of the effects of ionizing radiation on mammalian cells therefore requires further studies on the nature of the genomic instability involved and the mechanisms by which ionizing radiation promotes this process. (author)