Oncotarget

Research Papers:

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

Mariateresa Mancuso _, Emanuela Pasquali, Ignacia Braga-Tanaka III, Satoshi Tanaka, Alessandro Pannicelli, Paola Giardullo, Simonetta Pazzaglia, Soile Tapio, Michael J Atkinson and Anna Saran

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Oncotarget. 2015; 6:31263-31271. https://doi.org/10.18632/oncotarget.5075

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Abstract

Mariateresa Mancuso1, Emanuela Pasquali1, Ignacia Braga-Tanaka III2, Satoshi Tanaka2, Alessandro Pannicelli3, Paola Giardullo4,5, Simonetta Pazzaglia1, Soile Tapio6, Michael J. Atkinson6, Anna Saran1

1Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy

2Institute for Environmental Sciences (IES), Rokkasho, Aomori, Japan

3Technical Unit of Energetic Efficiency, ENEA, Rome, Italy

4Department of Radiation Physics, Guglielmo Marconi University, Rome, Italy

5Department of Sciences, Roma Tre University, Rome, Italy

6Helmholtz 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.


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