RADIATION-INDUCED GENOMIC INSTABILITY

Quantitative assessment of the heritable somatic effects of ionizing r adiation exposures has relied upon the assumption that radiation-induc ed lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial rou nd of DNA replication or as a consequence of error-prone enzymatic pro cessing of lesions. The standard experimental protocols for the assess ment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations ) evaluate these various endpoints at a single snapshot in time. In co ntrast with the aforementioned approaches, some studies have specifica lly assessed radiation effects as a function of time following exposur e. Evidence has accumulated in support of the hypothesis that radiatio n exposure induces a persistent destabilization of the genome. This in stability has been observed as a delayed expression of lethal mutation s, as an enhanced rate of accumulation of non-lethal heritable alterat ions, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induc ed genomic instability have not yet been delineated. The aim is to int egrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.