Locus Specificity for Mutation Induction in Human Cells Exposed to Accelerated Heavy Ions

Summary

The relative efficiencies of two types of densely ionizing particles were compared for the induction of mutations at two distinct genetic loci in human cells. Mutations to 6-thioguanine resistance (hgprt locus) or to trifluorothymidine resistance (tk) locus were scored in TK6 human lymphoblastoid cells exposed to graded doses of ⁴⁰Ar ions (470 MeV/amu, LET = 95–97 keV/μm) or ²⁸Si ions (456 MeV/amu, 61 keV/μm). The autosomal tk locus was more efficiently mutated than the X-linked hgprt locus following heavy particle irradiations. This was predominantly due to the contribution of a class of slowly growing mutants scored at the tk locus. Silicon ions were more efficient per unit dose than argon ions for the induction of mutants at either locus. When the mutant yield for a particular ion was compared with particle fluence, similar numbers of hgprt mutants are induced by equal numbers of ⁴⁰Ar or ²⁸Si ions. Comparison of the number of tk mutants with particle fluence demonstrates an increased efficiency for ²⁸Si ions over ⁴⁰Ar. These data suggest that the LET-RBE relationship may be different for individual genetic loci in human cells.