Ionizing radiation accelerates aortic lesion formation in fat-fed mice via SOD-inhibitable processes.
Ionizing radiation promotes formation of reactive oxygen species, including the superoxide anion (O2-). To evaluate whether O2- or O2--mediated perturbations may contribute to the known atherogenic effects of radiation, we examined aortic lesion formation in irradiated C57BL/6 mice and evaluated the effects of CuZn-superoxide dismutase (CuZn-SOD) overexpression. Ten-week-old mice were exposed to a 2-, 4-, or 8-Gy dose of 250-keV x-rays to the upper thorax and then placed on a high-fat diet for 18 weeks. Based on quantitative lipid staining of serial sections of the proximal aorta, mean lesion area was increased with increasing radiation dose and was 3-fold greater in 8-Gy-irradiated than sham-irradiated mice (7800+/-2140 versus 2635+/-709 micrometer(2), P<0.05). These effects were absolutely dependent on a high-fat diet, which had to be introduced within 1 to 2 weeks of the radiation exposure, suggesting the early involvement of atherogenic lipoproteins that were elevated in response to the diet. The importance of radiation-induced oxidative stress was supported by the observation of a 2-fold lower mean lesion area in irradiated CuZn-SOD transgenic mice than in their irradiated, nontransgenic littermates (3026+/-1590 versus 6102+/-1834 micrometer(2), P<0.05). Lucigenin-enhanced chemiluminescence, used as an index of aortic O2- concentrations, was significantly elevated in the postradiation period, and this response was reduced in CuZn-SOD transgenics. On the basis of these results, we propose that radiation may be a useful tool for initiating oxidative or redox-regulated events that promote atherogenesis and for testing the antiatherogenic properties of antioxidants.
Tribble
D L
DL
Life Sciences Division, Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley, USA. DLTribble@lbl.gov
Barcellos-Hoff
M H
MH
Chu
B M
BM
Gong
E L
EL
D000818:Animals; D001011:Aorta / Q000528:radiation effects*; D001161:Arteriosclerosis / Q000209:etiology* / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism
D008076:Cholesterol, HDL; D013481:Superoxides; D013482:Superoxide Dismutase