Abstract
Purpose: Tumor hypoxia and angiogenesis associated with malignant progression, radio- and chemotherapy resistance have been studied well. However, the relation between normal tissue injury and hypoxia is still unclear. In current investigation, we preferred to study the effect of hypoxia in radiation-induced late rectum injury in mice. Methods and Materials: The rectum of C57BL/6N mouse was irradiated locally with a single dose of 25 Gy. Radiation-induced fibrosis was observed at 90 days after irradiation by azan staining and the expression of transforming growth factor β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and endothelial cell marker CD31 were also assessed in accordance with fibrotic region using real-time PCR, immunohistochemistry and immunofluorescene. In addition, the effect of TGF-β1, VEGF and HIF-1α in radiation-induced injury was investigated by the administration of anti-TGF-β1, anti-VEGF or YC-1 respectively after irradiation. Results: The expression of TGF-β1, HIF-1α, VEGF and CD31 showed a significant increase with the formation of fibrosis induced by irradiation compared with unirradiated control. After treatment of anti-TGF-β1, anti-VEGF or YC-1, the development of irradiation-induced injury was attenuated. Conclusions: Our results suggest that radiation-induced hypoxia may play a role in late normal tissue injury. The paradigm may contribute to radiotherapy and understanding of radiation-induced late normal tissue injury.
