Promoted Instability in an X-ray Irradiated Chromosome Transferred into Werner Syndrome Cells

Copyright © 2015 by Hirosaki University. All rights reserved. Ionizing radiation is a potent genotoxic agent that can induce delayed biological effects referred to as genomic instability. Delayed chromosomal instability has been studied as a typical phenotype of genomic instability in the progeny of irradiated cells, but the mechanisms by which it arises remain obscure. The previous chromosome transfer study revealed that chromosomal instability could be transmitted to the progeny of unirradiated recipient cells by a chromosome exposed to ionizing radiation1). To determine whether the transmitted chromosomal instability is promoted in cells with compromised genomic integrity, we examined chromosome transfer to the cells which have defect of DNA repair genes, such as ataxia telangiectasia mutated gene (ATM), Nijmegen breakage syndrome protein 1 gene (NBS1) and Werner syndrome (WRN) gene. Unfortunately, we could not get clone of ATM or NBS1 deficient cells but we could get Werner syndrome cell line (WS780: WRNmut) which carries transferred chromosome 9. The results indicated that both unirradiated and irradiated chromosomes 9 were stable after chromosome transfer in microcell hybrids derived from non-WS control cells (GM638: WRNwt). In contrast, although all six WRNmutderived microcell hybrids had no rearrangements in the transferred-unirradiated chromosome 9, 11-28% of cells showed the rearranged chromosome 9 in three out of seven WRNmut-derived microcell hybrids transferred with the 6 Gy-irradiated chromosome 9. Thus, the present study demonstrates the possibility that chromosome instability mediated by an irradiated chromosome is promoted in WS cells that harbor multiple defects of genomic integrity.