CELLULAR AND MOLECULAR ANALYSIS OF MUTAGENESIS INDUCED BY CHARGED-PARTICLES OF DEFINED LINEAR-ENERGY-TRANSFER

Mutation induction by charged particles of defined linear energy trans fer (LET) and gamma rays was scored using human-hamster hybrid A(L) ce lls. The LET values for charged particles accelerated at the Radiologi cal Research Accelerator Facility ranged from 10 keV/mu m protons to 1 50 keV/mu m He-4 ions. The induced mutant fractions at both the S1 and HGPRT loci were dependent on the dose and LET. In addition, for each dose examined, the mutant yield at the S1 locus was 30-60-fold higher than at the corresponding HGPRT locus. To determine whether the mutati on spectrum was comparably dependent on dose and LET, independent S1(- ) and HGPRT(-) mutants induced by 150 keV/mu m He-4 ions and gamma ray s were isolated, and their DNA was analyzed by both Southern blotting and multiplex PCR methods. While the majority of radiation-induced mut ants showed deletions of varying sizes, the relative percentage of lar ge deletions was found to be related to both the dose and LET of the r adiation examined. Using a mutation system that can detect multilocus changes, results of the present study show that radiation-induced chro mosomal loss can be in the millions of base pairs. (C) 1996 by Radiati on Research Society