Murine Radiation-Induced Stomach Pathology from Whole Thoracic Irradiation

PurposeRadiation-induced lung injury is a common side effect in the treatment of lung and breast cancers. There is a large focus in the field on leveraging mouse models of radiation-induced lung injury to find novel treatments for the condition. While attempting to irradiate mouse lungs for purposes of creating a radiation-induced pulmonary fibrosis model, noticeable declines in health were observed at much earlier time points than recorded for lung pathology. This was later attributed to stomach pathology observed in CT images and ex vivo dissection. MethodsFor this study, we used longitudinal microCT to characterize male C57Bl/6 mice irradiated with a single dose of 20 Gy to the whole thoracic area delivered by an X-Rad cabinet irradiator. CT was performed with respiratory gating at 2 to 4 week timepoints to construct a timeline of pathology leading up to fibrosis and quantify severity of fibrosis afterwards. However, a mouse imaged at the 10 week timepoint showed evidence of stomach distention. These mice were sacrificed and their stomachs removed. Histology was performed on the stomachs using H&E staining. ResultsOn the CT images, we observed a large, spherical volume of hypointense signal, caudal to the lungs (Figure 1). This correlated with a distended stomach caused by constipation and gas build-up within the stomach. Statistical analysis showed 81% of mice (n=105) died prematurely after irradiation and before significant development of pulmonary fibrosis. Mice sacrificed and dissected showed unpassed bolus as contents of the stomach, and histology showed cell necrosis of the stomach walls. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/980987v1_fig1.gif" ALT="Figure 1"> View larger version (84K): org.highwire.dtl.DTLVardef@12de14borg.highwire.dtl.DTLVardef@122180corg.highwire.dtl.DTLVardef@158bd6forg.highwire.dtl.DTLVardef@fcdcbf_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Median Survival Times for male and female C57Bl/6 mice receiving varying Whole Thoracic Irradiaiton doses. C_FIG ConclusionThe histology indicated an inability for food to be digested and moved into the small intestine. This lead to a blockage and ensuing stomach distention. Given the severity of the pathologys consequences, it lead to the mouses imminent mortality inhibiting the efficacy of the study. Future studies need to consider careful placement of shields or any beam contouring devices to ensure protection of the stomach given its higher radiosensitivity in contrast to the lungs.