Radiation specific patterns of loss of heterozygosity on chromosome 17q

We and others have previously reported that the percentage of ionizing radiation-induced TK(-) mutants exhibiting loss of heterozygosity (LOH) is not significantly different from those occurring spontaneously. In order to search further for a distinguishing feature of the X-ray-induced spectrum, and to characterize mechanisms of chromosomal scale mutagenesis, we used detailed mapping information to analyze the extent of LOH along chromosome 17q. Significant differences were observed when the extent of LOH tracts was considered. The representation of very long LOH tracts (>/=41 cM) was significantly (p=0.004) more common among spontaneous mutants, while relatively local LOH events, involving only markers in a 1-10 cM region surrounding the tk locus, are significantly (p=0.018) more prevalent among X-ray-induced mutants. Our data suggests that, although large deletions are recoverable, X-ray-induced autosomal deletions are not evenly distributed over the available size range. This indicates a mechanistic rather than biological restriction to the size of radiation-induced deletions, and demonstrates that the pattern of LOH may also be useful as a distinguishing component of the mutational spectrum.