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

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.

Noncancer Effects of Ionizing Radiation Exposure on the Eye, the Circulatory System and beyond: Developments made since the 2011 ICRP Statement on Tissue Reactions

“…The latest meta-analysis has suggested that for DCS there are indications of larger risks (mERR/Gy) in the descending order of 0.22 (95% CI: 0.16, 0.29) at low dose rate (,5 mGy/h), 0.14 (95% CI: 0.06, 0.22) for acute single exposure (5 mGy/h), and 0.07 (95% CI: 0.03, 0.11) for fractionated exposures (5 mGy/h) when estimated from all relevant studies: there were similar (but nonsignificant) indications when restricted to high quality studies (120). Such complicated patterns for sparing and enhancing dose protraction effects have also been observed in murine aorta (162)(163)(164)(165). These epidemiological and biological findings can serve as supportive evidence for the assumed lack of clear sparing dose protraction effects for DCS (4), but also suggest that effects on the circulatory system are not a simple function of dose rate, warranting further studies.…”

Cancer and Non-Cancer Effects Following Ionizing Irradiation

“…Azimzadeh et al [ 17 ] conducted proteomic analysis in the heart of apolipoprotein E-deficient mice of which whole bodies were continuously exposed at 1 mGy/day or 20 mGy/day, and found that such chronic irradiation modulates various pathways in the heart that are common with age-related pathways. Hamada et al [ 18 ] used four different irradiation regimens to deliver the same total dose, and found that the magnitude of damage arising at 12 months post-irradiation in the aorta of whole body-irradiated wild-type mice was greater in 25 fractions, smaller in 100 fractions, and much smaller in chronic exposure (at ca. 1 mGy/h) compared with acute, single exposure, confirming the results obtained at 6 months post-irradiation [ 36 ].…”

“…Therefore, this Special Issue ( ) aims to serve as a forum to gather the latest developments and discuss future prospects in the field of normal tissue responses to radiation exposure. The Special Issue consists of 18 articles [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] outlining the cancer and non-cancer effects of radiation occurring in various tissues (e.g., those in the circulatory, sensory, nervous, respiratory, and reproductive systems), including studies on mitigation strategies and biomarkers, as outlined below.…”