Induction of genetic instability by ionizing radiation.
Evidence is presented to support the hypothesis that radiation may induce a heritable, genome-wide process of instability that leads to an enhanced frequency of genetic changes occurring among the progeny of the original irradiated cell. This instability is transmissible over many generations of cell replication. Mutational instability is induced in a relatively large fraction (approximately 10%) of the cell population, and may be modulated by factors acting in vivo. Thus, it cannot be a targeted event involving a specific gene or set of genes. There is no dose-response relationship in the range 2-12 Gy, suggesting that the instability phenotype may be induced by quite low radiation doses. The molecular mechanisms associated with the genesis of mutations in unstable populations differ from those for direct X-ray-induced mutations. These results suggest that it may not be possible to predict the nature of the dose-response relationship for the ultimate genetic effects of radiation based on a qualitative or quantitative analysis of the original DNA lesions.
Little
J B
JB
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115, USA. jlittle@hsph.harvard.edu
D000512:Alpha Particles; D000818:Animals; D016466:CHO Cells; D002455:Cell Division / Q000528:radiation effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D004249:DNA Damage; D015321:Gene Rearrangement; D016678:Genome; D009154:Mutation; D011833:Radiation Injuries, Experimental