Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation.

Abstract:

PURPOSE:We aimed to determine the time, dose, and volume responses in a mouse pulmonary injury model following ablative dose focal irradiation (ADFIR) in order to better understand normal lung injury. METHODS AND MATERIALS:ADFIR was administered to the left lung of mice using a small animal micro-irradiator. Histopathological evaluation and micro-computed tomography (micro-CT) analyses were performed at 1, 2, 6, and 12 weeks after irradiation. Dose responses were tested at doses of 0-90 Gy in C57BL/6 and C3H/HeJCr mice at 6 weeks after irradiation. The volume effect was evaluated with 1-, 3-, and 5-mm diameter collimators at 1-4 weeks after 90-Gy irradiation. RESULTS:ADFIR caused gross local lung injury of the inflated lung in just 1 week, with extensive hyaline material visible in the irradiated area. The fibrosing process was initiated as early as 2 weeks after irradiation. C3H and C57 mice did not show significant differences in dose response. Six weeks after irradiation, the radiation dose-response curve had a sigmoidal shape, where the lag, log, and stationary phases occurred at <40, 50-70, and >80 Gy, respectively. ADFIR induced substantial volume-dependent structural and functional damage to the lungs, and the volume changes of lung consolidation on micro-CT correlated inversely with lung fibrosis over time. CONCLUSIONS:We determined the time, dose, and volume responses in our established small animal model, and found that lung injury was substantially accelerated and phenotypically different from that of prior studies using non-ablative hemi-thorax and complete thorax irradiation schemes.

journal_name

Lung

journal_title

Lung

authors

Hong ZY,Lee CG,Shim HS,Lee EJ,Song KH,Choi BW,Cho J,Story MD

doi

10.1007/s00408-015-9825-4

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

81-90

issue

1

eissn

0341-2040

issn

1432-1750

pii

10.1007/s00408-015-9825-4

journal_volume

194

pub_type

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