Abstract
Although radiation-induced genomic instability is well characterized in vitro by the delayed appearance of specific types of genomic damage, (e.g., chromosomal aberrations, gene mutations, etc.), in the progeny of irradiated cells, evidence from in vivo studies has been limited due to lack of reliable bioassays that are capable of detecting delayed genomic alterations induced by irradiation in large cell populations in an objective and straightforward manner. In the present study, using flow cytometry, we quantified the number of micronucleated reticulocytes in peripheral blood of whole-body X-irradiated mice in order to evaluate the radiation sensitivity and the induced genomic instability of the hematopoietic system. An acute effect of radiation dose as small as 0.1 Gy was detectable two days after irradiation, and the radiation dose effect was significantly greater in BALB/c mice than in C57BL/6 mice (p<0.001), i.e., 3.0- (p=0.002) and 2.3-fold (p=0.002) increases in frequencies of micronuclei were noted in the two groups of mice, respectively. Even one year after irradiation, mice irradiated with 2.5 Gy of X-rays showed significantly increased frequencies of micronucleated reticulocytes, i.e., 1.6- (p=0.035) and 1.3-fold (p=0.039) increases in BALB/c and C57BL/6 mice, respectively. A significant mouse strain difference in the delayed radiation effect was noted as well (p=0.028). The results indicate that delayed genomic effects of irradiation on the murine hematopoietic system can persist in vivo for prolonged periods, and that there are mouse strain differences in sensitivity to radiation-induced genomic instability.
