title: Hypoxia expression in radiation-induced late rectal injury.
abstract: Tumor hypoxia and angiogenesis have been studied extensively. However, the relation between normal tissue injury and hypoxia is still unclear. In this study, we investigated the effect of hypoxia on radiation-induced late rectal injury in mice. The rectum of C57BL/6N mice was irradiated locally with a single dose of 25 Gy and the following experiments were performed including hematoxylin-eosin (H. E.) staining, azan staining, real-time PCR, immunohistochemistry and immunofluorescene. Radiation-induced fibrotic changes were observed from 14 days and reached the peak 30 days after irradiation. The expression of transforming growth factor beta1 (TGF-beta1), hypoxia-inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF) and endothelial cell marker CD31 increased significantly with the formation of fibrosis induced by irradiation compared with unirradiated control. In addition, the maximum expression of TGF-beta1, HIF-1alpha and VEGF was found at 14, 30 and 90 days after irradiation, respectively. The temporal changes of cytokines were consistent with the dynamic change of fibrosis. Our data suggests that late normal tissue injury involved various cytokines including hypoxia-induced angiogenic cytokines. These results may have important implications in the understanding of radiation-induced late normal tissue injury.
authors.affiliation: Department of Radiology and Radiation Oncology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Kohsei
authors.initials: K
authors.lastname: Kudo
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Abe
authors.forename: Masahiko
authors.initials: M
authors.lastname: Aoki
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Hu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kijima
authors.forename: Akio
authors.initials: A
authors.lastname: Nakane
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000378:metabolism*; D012007:Rectum / Q000378:metabolism / Q000528:radiation effects*