title: Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.
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.
authors.affiliation: Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Mancuso
authors.affiliation: Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pasquali
authors.affiliation: Institute for Environmental Sciences (IES), Rokkasho, Aomori, Japan.
authors.forename: Ignacia
authors.initials: I
authors.lastname: Braga-Tanaka
authors.affiliation: Institute for Environmental Sciences (IES), Rokkasho, Aomori, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Technical Unit of Energetic Efficiency, ENEA, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pannicelli
authors.affiliation: Department of Radiation Physics, Guglielmo Marconi University, Rome, Italy.|Department of Sciences, Roma Tre University, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Giardullo
authors.affiliation: Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Pazzaglia
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany.
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.affiliation: Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Saran
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D001018:Aortic Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016014:Linear Models; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018570:Risk Assessment; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E
keywords: ApoE mice; aorta; atherosclerosis; radiation