Radiation-induced hypoxia may perpetuate late normal tissue injury

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 hemitho rax using a single dose of 28 Gy. Pulmonary function was assessed by measur ing the changes in respiratory rate every 2 weeks, for 6 months after irrad iation. The hypoxia marker was administered 3 h before euthanasia. The tiss ues 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) af ter irradiation, was associated with a significant increase in macrophage a ctivity, collagen deposition, lung fibrosis, and elevation in the respirato ry rate. Immunohistochemistry studies revealed an increase in TGF-beta, VEG F, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activat ion 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 c ontinuous production of a number of inflammatory and fibrogenic cytokines. (C) 2001 Elsevier Science Inc.