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

TitleAcceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2015
AuthorsMancuso, Mariateresa, Pasquali Emanuela, Braga-Tanaka Ignacia, Tanaka Satoshi, Pannicelli Alessandro, Giardullo Paola, Pazzaglia Simonetta, Tapio Soile, Atkinson Michael J., and Saran Anna
JournalOncotarget
Volume6
Issue31
Pagination31263-71
Date Published2015 Oct 13
ISSN19492553
KeywordsAnimals, Aorta, Thoracic, Aortic Diseases, Apolipoproteins E, atherosclerosis, Disease Progression, Dose-Response Relationship, Radiation, Female, Linear Models, Mice, Inbred C57BL, Mice, Knockout, Plaque, Atherosclerotic, Radiation Dosage, Radiation Injuries, Experimental, Risk assessment, Time Factors
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.

DOI10.18632/oncotarget.5075
Alternate JournalOncotarget
PubMed ID26359350
PubMed Central IDPMC4741603