Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.
Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.
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DOI:
10.1097/hp.0000000000000357
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发表时间:
2015-11
期刊:
影响因子:
2.2
通讯作者:
Orschell CM
中科院分区:
文献类型:
--
作者:
Unthank JL;Miller SJ;Quickery AK;Ferguson EL;Wang M;Sampson CH;Chua HL;DiStasi MR;Feng H;Fisher A;Katz BP;Plett PA;Sandusky GE;Sellamuthu R;Vemula S;Cohen EP;MacVittie TJ;Orschell CM
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 137Cs radiation source and studied 1–21 months 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 peri-bronchial 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 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.