Simulation of exon deletion mutations induced by low-LET radiation at the HPRT locus

The induction of HPRT mutants with exon deletions after irradiation with ph otons was simulated using the biophysical radiation track structure model P ARTRAC. The exon-intron structure of the human HPRT gene was incorporated i nto the chromatin fiber model in PARTRAC. After gamma and X irradiation, si mulated double-stranded DNA fragments that overlapped with exons were assum ed to result in exon deletion mutations with a probability that depended on the genomic or the geometric distance between the breakpoints, The consequ ences of different assumptions about this probability of deletion formation were evaluated on the basis of the resulting fractions of total, terminal and intragenic deletions. Agreement with corresponding measurements was obt ained assuming a constant probability of deletion formation for fragments s maller than about 0.1 Mbp, and a probability of deletion formation decreasi ng with increasing geometric or genomic distance between the end points for larger fragments. For these two assumptions, yields of mutants with exon d eletions, size distributions of deletions, patterns of deleted exons. and p atterns of deleted STS marker sites surrounding the gene were calculated an d compared with experimental data. The yields, size distributions and exon deletion patterns were grossly consistent, whereas larger deviations were f ound for the STS marker deletion patterns in this comparison. (C) 2001 by R adiation Research Society.