title: Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.
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 mouse model 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 Cs 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, 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. non-irradiated 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.
authors.affiliation: *Department of Surgery, Indiana University School of Medicine, Indianapolis, IN; †Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; ‡Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN; §Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN; **Department of Pathology, Indiana University School of Medicine, Indianapolis, IN; ††Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI; ‡‡University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Unthank
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Miller
authors.forename: Ariel K
authors.initials: AK
authors.lastname: Quickery
authors.forename: Ethan L
authors.initials: EL
authors.lastname: Ferguson
authors.forename: Meijing
authors.initials: M
authors.lastname: Wang
authors.forename: Carol H
authors.initials: CH
authors.lastname: Sampson
authors.forename: Hui Lin
authors.initials: HL
authors.lastname: Chua
authors.forename: Matthew R
authors.initials: MR
authors.lastname: DiStasi
authors.forename: Hailin
authors.initials: H
authors.lastname: Feng
authors.forename: Alexa
authors.initials: A
authors.lastname: Fisher
authors.forename: Barry P
authors.initials: BP
authors.lastname: Katz
authors.forename: P Artur
authors.initials: PA
authors.lastname: Plett
authors.forename: George E
authors.initials: GE
authors.lastname: Sandusky
authors.forename: Rajendran
authors.initials: R
authors.lastname: Sellamuthu
authors.forename: Sasidhar
authors.initials: S
authors.lastname: Vemula
authors.forename: Eric P
authors.initials: EP
authors.lastname: Cohen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: MacVittie
authors.forename: Christie M
authors.initials: CM
authors.lastname: Orschell
mesh_terms: D054508:Acute Radiation Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000209:etiology* / Q000503:physiopathology*; D009928:Organ Specificity / Q000528:radiation effects; D011829:Radiation Dosage; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000009:adverse effects* / Q000379:methods