Low-Dose Radiation Exposure and Atherosclerosis inApoE−/−Mice
- 1 May 2011
- journal article
- research article
- Published by Radiation Research Society in Radiation Research
- Vol. 175 (5), 665-676
- https://doi.org/10.1667/rr2176.1
Abstract
The hypothesis that single low-dose exposures (0.025–0.5 Gy) to low-LET radiation given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE−/−). Mice were exposed either at an early stage of disease (2 months of age) and examined 3 or 6 months later or at a late stage of disease (8 months of age) and examined 2 or 4 months later. Changes in aortic lesion frequency, size and severity as well as total serum cholesterol levels and the uptake of lesion lipids by lesion-associated macrophages were assessed. Statistically significant changes in each of these measures were observed, depending on dose, dose rate and disease stage. In all cases, the results were distinctly non-linear with dose, with maximum effects tending to occur at 25 or 50 mGy. In general, low doses given at low dose rate during either early- or late-stage disease were protective, slowing the progression of the disease by one or more of these measures. Most effects appeared and persisted for months after the single exposures, but some were ultimately transitory. In contrast to exposure at low dose rate, high-dose-rate exposure during early-stage disease produced both protective and detrimental effects, suggesting that low doses may influence this disease by more than one mechanism and that dose rate is an important parameter. These results contrast with the known, generally detrimental effects of high doses on the progression of this disease in the same mice and in humans, suggesting that a linear extrapolation of the known increased risk from high doses to low doses is not appropriate.Keywords
This publication has 35 references indexed in Scilit:
- Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950-2003BMJ, 2010
- A Model of Cardiovascular Disease Giving a Plausible Mechanism for the Effect of Fractionated Low-Dose Ionizing Radiation ExposurePLoS Computational Biology, 2009
- Carotid atherosclerotic disease following childhood scalp irradiationAtherosclerosis, 2009
- Ionizing Radiation Accelerates the Development of Atherosclerotic Lesions in ApoE−/− Mice and Predisposes to an Inflammatory Plaque Phenotype Prone to HemorrhageThe American Journal of Pathology, 2006
- Nuclear shipyard worker study (1980 1988): a large cohort exposed to low-dose-rate gamma radiationInternational Journal of Low Radiation, 2005
- Prevalence of atherosclerosis in relation to atomic bomb radiation exposure: An RERF Adult Health StudyInternational Journal of Radiation Biology, 2005
- Effect of γ-Irradiation and Bone Marrow Transplantation on Atherosclerosis in LDL Receptor-Deficient MiceArteriosclerosis, Thrombosis, and Vascular Biology, 2001
- Bone Marrow Transplantation in Apolipoprotein E–Deficient MiceArteriosclerosis, Thrombosis, and Vascular Biology, 1997
- Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cellsCell, 1992
- Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells.Proceedings of the National Academy of Sciences of the United States of America, 1992