Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation

Oncotarget. 2015 Oct 13;6(31):31263-71. doi: 10.18632/oncotarget.5075.

Abstract

There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response.

Keywords: ApoE mice; aorta; atherosclerosis; radiation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology
  • Aorta, Thoracic / radiation effects*
  • Aortic Diseases / etiology*
  • Aortic Diseases / genetics
  • Aortic Diseases / metabolism
  • Aortic Diseases / pathology
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Atherosclerosis / etiology*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Disease Progression
  • Dose-Response Relationship, Radiation
  • Female
  • Linear Models
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plaque, Atherosclerotic
  • Radiation Dosage*
  • Radiation Injuries, Experimental / etiology*
  • Radiation Injuries, Experimental / genetics
  • Radiation Injuries, Experimental / metabolism
  • Radiation Injuries, Experimental / pathology
  • Risk Assessment
  • Time Factors

Substances

  • Apolipoproteins E