More efficient induction of genotoxicity by high-LET Fe-particle radiation than low-LET X-ray radiation at low doses

Objective

To understand differential effects on induction of genotoxicity and genomic instability (GI) by high-LET particle radiation and low-LET photon radiation, based on ground-based experiments using total body irradiation (TBI) of mice with Fe-particle radiation and X-ray radiation.

Methods

TBI was delivered to C57BL/6J Jms strain female mice of 8 weeks old at a dose ranging from 0.1 to 3.0 Gy of Fe-particle radiation or at a dose ranging from 0.1 to 5.0 Gy of X-ray radiation. Induction of genotoxicity and GI by TBI was determined respectively at 1 and 2 months after exposure using frequency of micronuclei in bone marrow erythrocytes as the endpoint. Inhibition of bone marrow cell proliferation by TBI was measured as reduced erythropoiesis. Physiological conditions were also investigated.

Results

TBI, regardless of the type of radiation, caused statistically significant increase in genotoxicity at 1 month after exposure, but did not induce GI at 2 months after exposure even at higher doses (>1.0 Gy). The dose-response curve for the frequency of micronucleated polychromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y ​= ​0.7798 ​+ ​1.7889x– 0.5978x² (R² = 0.8109) and y ​= ​0.7421 ​+ ​1.3792x – 0.2588 x² (R² = 0.8081), respectively. The dose-response curve for the frequency of micronucleated normochromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y ​= ​0.7191 ​+ ​1.4545x – 0.4978x² (R² = 0.7047) and y ​= ​0.658 ​+ ​1.344x – 0.2531x² (R² = 0.7853), respectively. In general, high-LET Fe-particle radiation was more efficient in inducing genotoxicity than low-LET X-ray radiation at lower doses (<0.5 Gy).

Conclusions

These results further confirm that exposure to TBI, even at higher doses and regardless the type of radiation, does not induce GI in C57BL/6J strain mice measured as increased micronuclei in bone marrow erythrocytes. These findings indicate that radiation-induced GI is mouse strain dependent and suggest that more comprehensive studies should be done to explore the late health consequences from exposure to high-LET radiation at low doses.