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| Publications [#134176] of Mark W. Dewhirst
Papers Published
- Z Vujaskovic, MS Anscher, QF Feng, ZN Rabbani, K Amin, TS Samulski, MW Dewhirst, ZA Haroon, Radiation-induced hypoxia may perpetuate late normal tissue injury.,
International journal of radiation oncology, biology, physics, vol. 50 no. 4
(July, 2001),
pp. 851-5, ISSN 0360-3016
(last updated on 2013/05/16)
Abstract:
OBJECTIVE: The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation. METHODS: 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. CONCLUSIONS: 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.
Keywords:
Animals • Cell Hypoxia • Endothelial Growth Factors • Female • Fibrosis • Lung • Lymphokines • Macrophages • Radiation Injuries, Experimental • Radiation Tolerance • Rats • Rats, Inbred F344 • Transforming Growth Factor beta • Vascular Endothelial Growth Factor A • Vascular Endothelial Growth Factors • etiology • metabolism • pathology • physiology* • physiopathology • physiopathology* • radiation effects*
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