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Radiation-induced hypoxia may perpetuate late normal tissue injury
Z Vujaskovic1, M S Anscher, Q F Feng
1Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. vujas@radonc.duke.edu
Purpose:
The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation.
Methods And Materials:
Fisher-344 rats were irradiated to the right hemithorax using a single dose of 28 Gy. Pulmonary function was assessed by measuring the changes in respiratory rate every 2 weeks, for 6 months after irradiation. The hypoxia marker was administered 3 h before euthanasia. The tissues were harvested at 6 weeks and 6 months after irradiation and processed for immunohistochemistry.
Results:
A moderate hypoxia was detected in the rat lungs at 6 weeks after irradiation, before the onset of functional or histopathologic changes. The more severe hypoxia, that developed at the later time points (6 months) after irradiation, was associated with a significant increase in macrophage activity, collagen deposition, lung fibrosis, and elevation in the respiratory rate. Immunohistochemistry studies revealed an increase in TGF-beta, VEGF, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activation of the profibrinogenic and proangiogenic pathways.
Conclusion:
A new paradigm of radiation-induced lung injury should consider postradiation hypoxia to be an important contributing factor mediating a continuous production of a number of inflammatory and fibrogenic cytokines.