Persistent genomic instability in the yeast Saccharomyces cerevisiae induced by ionizing radiation and DNA-damaging agents

A "hypermutable" genome is a common characteristic of cancer cells, and it may contribute to the progressive accumulation of mutations required for th e development of cancer. It has been reported that mammalian cells survivin g exposure to gamma radiation display several highly persistent genomic ins tability phenotypes which may reflect a hypermutability similar to that see n in cancer, These phenotypes include an increased mutation frequency and a decreased plating efficiency, and they continue to be observed many genera tions after the radiation exposure. The underlying causes of this genomic i nstability have not been fully determined, We show here that exposure to ga mma radiation and other DNA-damaging treatments induces a similar genomic i nstability in the yeast Saccharomyces cerevisiae. A dose-dependent increase in intrachromosomal recombination was observed in cultures derived from ce lls surviving gamma irradiation as many as 50 generations after the exposur e. Increased forward mutation frequencies and low colony-forming efficienci es were also observed. Persistently elevated recombination frequencies in h aploid cells were dominant after these cells were mated to nonirradiated pa rtners, and the elevated recombination phenotype was also observed after tr eatment with the DNA-damaging agents ultraviolet light, hydrogen peroxide, and ethyl methanesulfonate, Radiation-induced genomic instability in yeast may represent a convenient model for the hypermutability observed in cancer cells. (C) 2001 by Radiation Research Society.