Abstract
Ionizing radiation induces genomic instability in the progeny of irradiated cells that have divided several to a few dozen times. Previous studies suggest that DNA double-strand breaks (DSBs) are involved in the induction of genomic instability. Since it seems unlikely that DSBs persist through several cycles of cell division, we hypothesize that some DNA lesions, but not DSBs per se, are involved in inducing genomic instability. In this study, we examine whether non-DSB types of damage, particularly oxidative base lesions, induce genomic instability. Chromosomes were irradiated with UVA because it generates mainly oxidative base damage and only a small amount of DSBs. We transferred an UVA-irradiated human chromosome 21 into unirradiated immortalized mouse cells derived from fibroblasts using a microcell-mediated chromosome transfer. UVA-irradiated chromosomes were analyzed by the Whole Chromosome Painting Fluorescence in situ Hybridization (WCP-FISH) with specific probes for human chromosome 21. Most of the cells that were transferred with unirradiated human chromosome 21 remained diploid. However, we found that cells that were transferred with a UVA (4000kJ/m2) irradiated human chromosomes became polyploid and that structural aberrations occurred not only in the UVA-irradiated human chromosomes but also in the unirradiated mouse chromosomes. These results suggest that non-DSBs type of DNA damage induced by UVA irradiation induces genomic instability.
