Genomic instability induced by ionizing radiation.
Genomic instability is characterized by the increased rate of acquisition of alterations in the mammalian genome. These changes encompass a diverse set of biological end points including karyotypic abnormalities, gene mutation and amplification, cellular transformation, clonal heterogeneity and delayed reproductive cell death. The loss of stability of the genome is becoming accepted as one of the most important aspects of carcinogenesis, and the numerous genetic changes associated with the cancer cell implicate genomic stability as contributing to the neoplastic phenotype. Multiple metabolic pathways govern the accurate duplication and distribution of DNA to progeny cells; other pathways maintain 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 review summarizes the current status of knowledge about radiation-induced genomic instability. Those events and processes likely to be involved in the initiation and perpetuation of the unstable phenotype, the potential role of epigenetic factors in influencing the onset of genomic instability, and the delayed effects of cellular exposure to ionizing radiation are discussed.
Morgan
W F
WF
Laboratory of Radiobiology and Environmental Health, University of California, San Francisco, 94143-0750, USA.
Day
J P
JP
Kaplan
M I
MI
McGhee
E M
EM
Limoli
C L
CL
D000818:Animals; D002453:Cell Cycle; D016923:Cell Death; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002875:Chromosomes / Q000528:radiation effects; D002877:Chromosomes, Human / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects*; D005784:Gene Amplification / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D005796:Genes / Q000528:radiation effects*; D016678:Genome; D006801:Humans; D008322:Mammals; D016296:Mutagenesis; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000528:radiation effects
D004247:DNA