GENOMIC INSTABILITY INDUCED BY IONIZING-RADIATION

Genomic instability is characterized by the increased rate of acquisit ion of alterations in the mammalian genome. These changes encompass a diverse set of biological end points including karyotypic abnormalitie s, gene mutation and amplification, cellular transformation, clonal he terogeneity and delayed reproductive cell death, The loss of stability of the genome is becoming accepted as one of the most important aspec ts of carcinogenesis, and the numerous genetic changes associated with the cancer cell implicate genomic stability as contributing to the ne oplastic phenotype, Multiple metabolic pathways govern the accurate du plication and distribution of DNA to progeny cells; other pathways mai ntain the integrity of the information encoded by DNA and regulate the expression of genes during growth and development. For each of these functions, there is a normal baseline frequency at which errors occur, leading to spontaneous mutations and other genomic anomalies. This re view summarizes the current status of knowledge about radiation-induce d genomic instability. Those events and processes likely to be involve d in the initiation and perpetuation of the unstable phenotype, the po tential role of epigenetic factors in influencing the onset of genomic instability, and the delayed effects of cellular exposure to ionizing radiation are discussed. (C) 1996 by Radiation Research Society