Delayed effects ofacute radiation exposure in a murine model of the H-ARS: Multiple-organ injury consequent to <10 Gy total body irradiation

Joseph L. Unthank, Steven J. Miller, Ariel K. Quickery, Ethan L. Ferguson, Meijing Wang, Carol H. Sampson, Hui Lin Chua, Matthew R. DiStasi, Hailin Feng, Alexa Fisher, Barry P. Katz, P. Artur Plett, George E. Sandusky, Rajendran Sellamuthu, Sasidhar Vemula, Eric P. Cohen, Thomas J. MacVittie, Christie M. Orschell

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mousemodel of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a 137Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ~22 to 34 ± 3.8 and 69 ± 6.0 mg dL-1, p <0.01 vs. non-irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p <0.01 vs. nonirradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI).An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ~9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

Original languageEnglish (US)
Pages (from-to)511-521
Number of pages11
JournalHealth physics
Volume109
Issue number5
DOIs
StatePublished - 2015

Keywords

  • Health effects
  • Mice
  • Radiation damage
  • Radiation dose

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis
  • Epidemiology

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    Unthank, J. L., Miller, S. J., Quickery, A. K., Ferguson, E. L., Wang, M., Sampson, C. H., Chua, H. L., DiStasi, M. R., Feng, H., Fisher, A., Katz, B. P., Plett, P. A., Sandusky, G. E., Sellamuthu, R., Vemula, S., Cohen, E. P., MacVittie, T. J., & Orschell, C. M. (2015). Delayed effects ofacute radiation exposure in a murine model of the H-ARS: Multiple-organ injury consequent to <10 Gy total body irradiation. Health physics, 109(5), 511-521. https://doi.org/10.1097/HP.0000000000000357