Previous work has shown that high charge and energy particle irradiation of human cells evokes a mutagenic repair phenotype, defined by increased mutagenic repair of new double-strand breaks that are introduced enzymatically, days or weeks after the initial irradiation. The effect was seen originally with 600 MeV/u 56Fe particles, which have a linear energy transfer (LET) value of 174 keV/μm, but not with X rays or γ rays (LET ≤ 2 keV/μm). To better define the radiation quality dependence of the phenomenon, we tested two ions with intermediate LET values, 1,000 MeV/u 48Ti (LET = 108 keV/μm) and 300 MeV/u 28Si (LET = 69 keV/μm). These experiments used a previously validated assay, where a rare-cutting nuclease introduces double-strand breaks in two reporter transgene cassettes, which are located on different chromosomes. Deletions of a block of sequence in one of the cassettes, or translocations between cassettes, are measured independently using a multicolor fluorescence assay. The results showed that 48Ti was a potent, but transient, inducer of mutagenic repair, based on increased frequency of nuclease-induced translocations. The 48Ti ions did not affect the frequency of nuclease-induced deletions. The 28Si ions had no measurable effect on either endpoint. There was a close correlation between the induction of the mutagenic repair phenomenon and the frequency of micronuclei in the targeted population (R2 = 0.74), whereas there was no apparent correlation with radiation-induced cell inactivation. Together, these results better define the radiation quality dependence of the mutagenic repair phenomenon and establish its correlation, or lack of correlation, with other endpoints.
Effect of Radiation Quality on Mutagenic Joining of Enzymatically-Induced DNA Double-Strand Breaks in Previously Irradiated Human Cells
- Views Icon Views
- Share Icon Share
- Search Site
Zhentian Li, Huichen Wang, Ya Wang, John P. Murnane, William S. Dynan; Effect of Radiation Quality on Mutagenic Joining of Enzymatically-Induced DNA Double-Strand Breaks in Previously Irradiated Human Cells. Radiat Res 1 November 2014; 182 (5): 573–579. doi: https://doi.org/10.1667/RR13723.1
Download citation file: