Radiation-induced hypoxia may perpetuate late normal tissue injury

Zeljko Vujaskovic, Mitchell S. Anscher, Qin Fu Feng, Zahid N. Rabbani, Khalid Amin, Thaddeus S. Samulski, Mark W. Dewhirst, Zishan A. Haroon

Research output: Contribution to journalArticlepeer-review

164 Scopus citations


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-β, 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.

Original languageEnglish (US)
Pages (from-to)851-855
Number of pages5
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number4
StatePublished - Jul 15 2001
Externally publishedYes

Bibliographical note

Funding Information:
This investigation was supported in part by the Duke Comprehensive Cancer Center and NCI Grant P30 CA14236. Dr Feng was supported in part by UICC Fellowships—ICRETT 945.


  • Hypoxia
  • Lung
  • Radiation injury


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