Low Dose/Low Dose Rate Radiation-Induced Genomic Instability:
W.F. Morgan (University of Maryland, Baltimore)
Cellular exposure to DNA damaging agents like ionizing radiation can result in mutations, gene amplifications, chromosomal rearrangements, carcinogenesis, and even cell death. The paradigm for understanding how induced damage results in these cellular endpoints dictates that cellular responses to the induced damage, e.g., DNA repair, and cell cycle arrest "fix" the damage and thereby seal the fate of the irradiated cell. This presentation will focus on delayed genetic effects occurring in the progeny of cells after exposure to low dose/ low dose rate ionizing radiation, including delayed chromosomal rearrangements, and recombination events as determined by a plasmid based assay system for homologous recombination. We will present new data on how changes in gene expression as measured by differential display and DNA microarray analysis provides a mechanism by which cells display a memory of irradiation, and introduce candidate genes that may play a role in initiating and perpetuation the unstable phenotype. In addition, we will describe how the cellular micro-environment can perpetuate instability in clonally expanded populations of cells surviving irradiation. These results will be discussed in terms of non-targeted "bystander" like effects where by cells that themselves were not irradiated exhibit many of the same detrimental effects as irradiated cells and what implication these effects may have for radiation therapy. This work was supported by the Biological and Environmental Research Program (BER), U.S. Department of Energy, Grant No. DE-FG02- 01ER63230, and National Institute of Health Awards CA73924 and CA 83872.
