Inducible genomic instability: new insights into the biological effects of ionizing radiation

The biological consequences of exposure to ionizing radiation include gene mutation, chromosome aberrations, malignant transformation and cell death. These effects are attributed to the production of irreversible damage at the time of the irradiation. However, there is now considerable evidence that cells that have survived irradiation may produce descendants in which a high frequency of de novo chromosome aberrations and gene mutations arise or in which there is an enhanced death rate. These delayed effects are manifestations of an induced genomic instability. All the various delayed effects are induced at very high frequency and are unlikely to be due to conventional mutational changes. At present little is understood of the processes involved in the initiation of inducible instabilities and in the maintenance and transmission of the phenotype over many generations of cell replication. However, it is becoming evident that the expression of inducible instability has a strong dependence on the type of radiation exposure, the cell type irradiated and the 'genetic predisposition' of the irradiated cell. Radiation-induced genomic instability presents a major challenge to conventional radiobiology concepts and has important implications for mechanistic studies of radiation action particularly in the context of radiogenic malignancy.