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

// Mariateresa Mancuso 1 , Emanuela Pasquali 1 , Ignacia Braga-Tanaka III 2 , Satoshi Tanaka 2 , Alessandro Pannicelli 3 , Paola Giardullo 4, 5 , Simonetta Pazzaglia 1 , Soile Tapio 6 , Michael J. Atkinson 6 , Anna Saran 1 1 Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy 2 Institute for Environmental Sciences (IES), Rokkasho, Aomori, Japan 3 Technical Unit of Energetic Efficiency, ENEA, Rome, Italy 4 Department of Radiation Physics, Guglielmo Marconi University, Rome, Italy 5 Department of Sciences, Roma Tre University, Rome, Italy 6 Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany Correspondence to: Mariateresa Mancuso, e-mail: mariateresa.mancuso@enea.it Anna Saran, e-mail: anna.saran@enea.it Keywords: atherosclerosis, ApoE mice, radiation, aorta Received: June 04, 2015      Accepted: August 10, 2015      Published: August 22, 2015 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.