Effects of single and fractionated low-dose irradiation on vascular endothelial cells

Objective: An increasing number of epidemiological studies suggest that chronic low-dose irradiation increases the risk of atherosclerosis. We evaluated and compared the in vitro biological effects of both single and fractionated low-doses of X-ray irradiation on endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were irradiated with X-rays, with single doses of 0.125, 0.25 and 0.5 Gy or fractionated doses of 2 x 0.125 Gy and 2 x 0.25 Gy, with 24 h interfraction interval. Survival, apoptosis, reactive oxygen species (ROS) production, nuclear factor-kappa B (NF-kappa B) activation, intercellular adhesion molecule-1 (ICAM-1) expression, HUVEC adhesiveness and DNA damage were investigated. Results: We did not observe any effect on viability and apoptosis. Both single and fractionated doses induced ROS generation, NF-?B activation, ICAM-1 protein expression and HUVEC adhesiveness, but only fractionated doses increase significantly ICAM-1 mRNA. The effects measured after fractionated dose result always higher than those induced by the single dose. Moreover, we observed that DNA double strand break (DSB), visualized with ?-H2AX foci, is dose-dependent and that the kinetics of ?-H2AX foci is not affected by fractionated doses. Conclusions: We showed that single and fractionated low-dose irradiations with low energy X-rays do not affect cell viability and DNA repair. Interestingly, the greater increase of ICAM-1 surface exposure and endothelial adhesiveness observed after fractionated irradiation, suggests that fractionated low-doses may accelerate chronic vascular inflammation, from which the atherosclerotic process can arise.