Temporal onset of hypoxia and oxidative stress after pulmonary irradiation.
Journal Article (Journal Article)
PURPOSE: To investigate the temporal onset of hypoxia following irradiation, and to show how it relates to pulmonary vascular damage, macrophage accumulation, and the production of reactive oxygen species and cytokines. Our previous studies showed that tissue hypoxia in the lung after irradiation contributed to radiation-induced injury. METHODS AND MATERIALS: Female Fisher 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy. Serial studies were performed up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were performed to detect changes in pulmonary vasculature. Immunohistochemical studies were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9 marker), oxidative stress (8-hydroxy-2'-deoxyguanosine), and the expression of profibrogenic (transforming growth factor-beta [TGF-beta]) and proangiogenic (vascular endothelial growth factor [VEGF]) cytokines. RESULTS: Significant changes in lung perfusion along with tissue hypoxia were observed 3 days after irradiation. Significant oxidative stress was detected 1 week after radiation, whereas macrophages started to accumulate at 4 weeks. A significant increase in TGF-beta expression was seen within 1 day after radiation, and for VEGF at 2 weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines continued to rise with time after irradiation. The steepest increase correlated with vast macrophage accumulation. CONCLUSIONS: Early changes in lung perfusion, among other factors initiate, the development of hypoxia and chronic oxidative stress after irradiation. Tissue hypoxia is associated with a significant increase in the activation of macrophages and their continuous production of reactive oxygen species, stimulating the production of fibrogenic and angiogenic cytokines, and maintaining the development of chronic radiation-induced lung injury.
Full Text
Duke Authors
Cited Authors
- Fleckenstein, K; Zgonjanin, L; Chen, L; Rabbani, Z; Jackson, IL; Thrasher, B; Kirkpatrick, J; Foster, WM; Vujaskovic, Z
Published Date
- May 1, 2007
Published In
Volume / Issue
- 68 / 1
Start / End Page
- 196 - 204
PubMed ID
- 17448873
Pubmed Central ID
- PMC1939695
International Standard Serial Number (ISSN)
- 0360-3016
Digital Object Identifier (DOI)
- 10.1016/j.ijrobp.2006.12.056
Language
- eng
Conference Location
- United States