title: Cardiovascular changes in atherosclerotic ApoE-deficient mice exposed to Co60 (γ) radiation.
abstract: BACKGROUND
  There is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation.
  
  
  RESULTS
  B6.129P2-ApoE tmlUnc mice on a low-fat diet were acutely exposed (whole body) to Co60 (γ) (single dose 0, 0.5, and 2 Gy) at a dose rate of 36.32 cGy/min, or repeatedly (cumulative dose 0 and 2 Gy) at a dose-rate of 0.1 cGy/min for 5 d/wk, over a period of 4 weeks. Biological endpoints were investigated after 3-6 months of recovery post-radiation. The nitrative stress marker 3-nitrotyrosine and the vasoregulator peptides endothelin-1 and endothelin-3 in plasma were increased (p<0.05) in a dose-dependent manner 3-6 months after acute or chronic exposure to radiation. The oxidative stress marker 8-isoprostane was not affected by radiation, while plasma 8-hydroxydeoxyguanosine and L-3,4-dihydroxyphenylalanine decreased (p<0.05) after treatment. At 2Gy radiation dose, serum cholesterol was increased (p = 0.008) relative to controls. Percent lesion area increased (p = 0.005) with age of animal, but not with radiation treatment.
  
  
  CONCLUSIONS
  Our observations are consistent with persistent nitrative stress and activation of the endothelinergic system in ApoE-/- mice after low-level ionizing radiation exposures. These mechanisms are known factors in the progression of atherosclerosis and other cardiovascular diseases.
authors.affiliation: Analytical Biochemistry and Proteomics Laboratory, Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada. premkumari.kumarathasan@hc-sc.gc.ca
authors.forename: Prem
authors.initials: P
authors.lastname: Kumarathasan
authors.forename: Renaud
authors.initials: R
authors.lastname: Vincent
authors.forename: Erica
authors.initials: E
authors.lastname: Blais
authors.forename: Anu
authors.initials: A
authors.lastname: Saravanamuthu
authors.forename: Pallavi
authors.initials: P
authors.lastname: Gupta
authors.forename: Heather
authors.initials: H
authors.lastname: Wyatt
authors.forename: Ronald
authors.initials: R
authors.lastname: Mitchel
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hannan
authors.forename: Akilesh
authors.initials: A
authors.lastname: Trivedi
authors.forename: Stewart
authors.initials: S
authors.lastname: Whitman
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D003037:Cobalt Radioisotopes; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D016232:Endothelins / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D007980:Levodopa / Q000097:blood; D015227:Lipid Peroxidation; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000528:radiation effects; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000097:blood*; D014443:Tyrosine / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D003037:Cobalt Radioisotopes; D016232:Endothelins; D009573:Nitrites; C075750:8-epi-prostaglandin F2alpha; D014443:Tyrosine; D007980:Levodopa; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002784:Cholesterol; D015237:Dinoprost; D003849:Deoxyguanosine