Radiation-induced hypoxia may perpetuate late normal tissue injury.
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.
Vujaskovic
Z
Z
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. vujas@radonc.duke.edu
Anscher
M S
MS
Feng
Q F
QF
Rabbani
Z N
ZN
Amin
K
K
Samulski
T S
TS
Dewhirst
M W
MW
Haroon
Z A
ZA
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D008168:Lung / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D008222:Lymphokines / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D011836:Radiation Tolerance; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors