Access Type

Open Access Thesis

Date of Award

January 2015

Degree Type

Thesis

Degree Name

M.S.

Department

Immunology and Microbiology

First Advisor

Gilda G. Hillman

Abstract

Lung cancer patients receiving radiotherapy present with acute and chronic esophagitis, resulting in pain and difficulties swallowing. These effects are due to radiation injury to the normal tissues in the esophagus. Our previous studies in pre-clinical models of lung cancer and naïve mice have shown that soy isoflavones alleviates radiation-induced toxicity to normal lung, including a decrease in pneumonitis and fibrosis. In this study, we have investigated whether radiation-induced esophagitis can be reduced by soy isoflavones. C57BL/6 mice were treated with 10 Gy or 25 Gy for thoracic irradiation and soy isoflavones given daily at 1mg/mouse up to 16 weeks. Esophagi were resected at various time points (1,4,10,16 weeks post-radiation). Damage to esophageal tissues was assessed by H&E staining and Masson's Trichrome. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti-aSMA and anti-CD45. Histological analysis revealed esophagus tissue edema and inflammatory leukocyte infiltration. Specific findings included alterations in the mucosal epithelium, connective tissue disruption in the lamina propria, and smooth muscle cell hypertrophy in the muscularis mucosa. Radiation-induced tissue injuries were reduced by combining soy isoflavones with radiation treatments. Quantitative evaluation of thickened, edematous tissue layers was performed by morphometric measurements. Analysis of 100 measurements per treatment group revealed a significant decrease in the thickness of esophageal layers in irradiated mice treated with soy (25.54um±0.67SEM) to radiation alone (30.66um±0.67SEM) (p<0.0001). Radiation-induced damage presented within 1 week and progressively worsened with time, being more pronounced with 25 Gy compared to 10 Gy, but was also decreased by soy supplementation. Thoracic irradiation caused injury to multiple layers of the esophagus, and these effects were mitigated by soy isoflavones. These findings suggest that soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects seen in radiation-induced esophagitis.

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