The
Pig-a mutation assay is becoming one of the major experimental procedures used to assess
in vivo genotoxicity. The assay allows simple
in vivo analysis and enables gene mutations in the hematopoietic system to be measured using high throughput flow cytometry. Previously, we demonstrated that X-irradiation increased the
Pig-a mutant frequencies in red blood cells (RBCs) of mice in a radiation dose-dependent manner. In this study, to understand how RBCs with
Pig-a mutation induced by X-irradiation persist, we compared
Pig-a mutant frequencies between irradiated C57BL/6J (
p53+/+) mice and irradiated
p53 homozygous knockout (
p53-/-) mice by using the RBC
Pig-a assay. After the peak in radiation-induced
Pig-a mutant frequencies, a gradual decrease in mutant frequencies in irradiated
p53-/- mice was observed, while irradiated
p53+/+ mice had a rapid decrease, which suggests that RBCs with
Pig-a mutation are eliminated normally in irradiated
p53+/+ mice but not in irradiated
p53-/- mice due to lack of p53 function. In addition, we also found that the p53 function affected the regulation of
Pig-a mutagenesis in aging mice. Our results suggest that p53 function, distinct types of mutation, and the life span of RBCs play key roles in the persistence of
Pig-a mutation in the hematopoietic system of RBCs after irradiation.
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