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Radiation pneumonitis assessed in a mouse model of partial-body irradiation with minimal bone marrow sparing

University of British Columbia

Purpose: Accidental exposure to high-dose ionizing radiation may lead to significant injuries to multiple organs. Herein, this thesis established a mouse model of high-dose partial-body irradiation with minimal bone marrow shielding to model the progression, severity, and clinical features of lung injury consequent of an accidental scenario and determine whether radiation-induced hematopoietic system depletion affects the pulmonary response. Methods: Female C3H/HeJ mice were irradiated in a single fraction, using a 6 MV Flattening-Filter-Free beam on a Varian TrueBeam LINAC. The following experimental groups were assessed: (1) 8 Gy partial-body irradiation (PBI), sparing the tibiae, ankles, and feet plus an 8 Gy simultaneous-infield-boost (SIB) to the lung to elicit lung damage, (2) 16 Gy Whole-thorax lung irradiation (WTLI), (3) 8 Gy PBI, and (4) untreated controls. Mice were monitored weekly and euthanized upon the presentation of respiratory distress or at the 16-week experimental endpoint. At sacrifice, blood and lung tissue were collected for Complete Blood Count and histopathology. Additionally, subsets of mice were sacrificed one-week post-treatment to assess acute hematopoietic cell depletion. Results: Treatment with 8 Gy partial-body irradiation depleted hematopoietic cell counts, specifically leukocytes and platelets, measured at one week post-irradiation, significantly more than 16 Gy WTLI. The survival time of mice treated with 16 Gy WTLI was not significantly different from that of mice given 8 Gy PBI plus 8 Gy lung SIB (p=0.17). Lung histology revealed that mice of both 16 Gy WTLI and 8 Gy PBI plus 8 Gy lung SIB groups developed a diffuse pneumonitis response; the severity score was not significantly different between these treatment groups (p=0.96). Finally, partial-body irradiation significantly reduced blood monocyte counts of mice at respiratory distress compared to levels in local whole-thorax irradiated mice but did not influence neutrophil counts, which were increased at distress for both treatment groups relative to measures in control mice. Conclusion: Radiation-induced acute hematopoietic injury did not affect the onset or severity of radiation pneumonitis in a mouse model of partial-body irradiation with minimal bone marrow shielding.

Text

2020-09-18

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/76078

Medical Physics

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/