PNNL

Abstract

Radiation induced genomic instability has been described in a host of normal and transformed cells in vitro (Morgan 2003a). This instability can manifest as cell killing, micronuclei formation, transformation induction, di- and tri- nucleotide repeat instability, gene amplifications and mutations, and chromosomal rearrangements. Cytogenetic alterations are perhaps the best described of these endpoints following radiation exposures and will be the focus of this chapter. Chromosomal instability is characterized as either multiple sub populations of chromosomally rearranged metaphase chromosomes, or as newly arising chromatid and/or chromosomal aberrations occurring in the clonally expanded decedents of an irradiated cell. Some chromosomal changes appear to entail recombination events involving DNA repeat sequences within the genome, e.g., interstitial telomere-repeat like sequences (Day et al. 1998) and may be manifestations of telomere dysfunction in unstable clones of cells (Murnane and Sabatier 2004). Others, including the appearance of chromatid aberrations, indicate that DNA lesions can manifest in the preceding cell cycle multiple cell generations after the initial insult.