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(＞1.0Gy).The dose-response curve for the frequency of micronucleated polychromatic erythrocytes induced by Fe-particle radia-tion and X-ray radiation wasy=0.7798+1.7889x-0.5978x2(R2=0.8109)andy=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 radi-ation at low doses.