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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1387-1392.)
© 1999 American Heart Association, Inc.

Vascular Biology

Ionizing Radiation Accelerates Aortic Lesion Formation in Fat-Fed Mice via SOD-Inhibitable Processes

Diane L. Tribble; Mary Helen Barcellos-Hoff; Berbie M. Chu; Elaine L. Gong

From the Life Sciences Division, Ernest Orlando Lawrence Berkeley National Laboratory, University of California, Berkeley.

Correspondence to Diane L. Tribble, Donner Laboratory, Room 465, University of California, Berkeley, CA 94720. E-mail DLTribble{at}lbl.gov

Abstract—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 µm², 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 µm², 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.

Key Words: atherosclerosis • lipoproteins • ionizing radiation • inflammation • antioxidants

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