Temporal Changes in Sparing and Enhancing Dose Protraction Effects of Ionizing Irradiation for Aortic Damage in Wild-Type Mice

SIMPLE SUMMARY: Ionizing radiation exposure of the circulatory system occurs at various dose rates. Our previous work showed sparing and enhancing effects of dose protraction for aortic changes in wild-type mice at 6 months after starting acute, intermittent, or continuous irradiation with 5 Gy of photons. Here we report that irradiation produces qualitatively similar albeit quantitatively less aortic changes at 12 months than at 6 months after stating irradiation. The magnitude of changes at 12 months was not smaller in 25 fractions (Frs), but was smaller in 100 Frs and chronic exposure, than acute exposure. The magnitude at 6 and 12 months was greater in 25 Frs, smaller in 100 Frs, and much smaller in chronic exposure, compared with acute exposure. These findings suggest that dose protraction changes aortic damage, in a manner that depends on post-irradiation time and is not a simple function of dose rate. ABSTRACT: In medical and occupational settings, ionizing irradiation of the circulatory system occurs at various dose rates. We previously found sparing and enhancing dose protraction effects for aortic changes in wild-type mice at 6 months after starting irradiation with 5 Gy of photons. Here, we further analyzed changes at 12 months after stating irradiation. Irrespective of irradiation regimens, irradiation little affected left ventricular function, heart weight, and kidney weight. Irradiation caused structural disorganizations and intima-media thickening in the aorta, along with concurrent elevations of markers for proinflammation, macrophage, profibrosis, and fibrosis, and reductions in markers for vascular functionality and cell adhesion in the aortic endothelium. These changes were qualitatively similar but quantitatively less at 12 months than at 6 months. The magnitude of such changes at 12 months was not smaller in 25 fractions (Frs) but was smaller in 100 Frs and chronic exposure than acute exposure. The magnitude at 6 and 12 months was greater in 25 Frs, smaller in 100 Frs, and much smaller in chronic exposure than acute exposure. These findings suggest that dose protraction changes aortic damage, in a fashion that depends on post-irradiation time and is not a simple function of dose rate.