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Title: Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation

Abstract

Purpose: To investigate the temporal onset of hypoxia following irradiation, and to show how it relates to pulmonary vascular damage, macrophage accumulation, and the production of reactive oxygen species and cytokines. Our previous studies showed that tissue hypoxia in the lung after irradiation contributed to radiation-induced injury. Methods and Materials: Female Fisher 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy. Serial studies were performed up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were performed to detect changes in pulmonary vasculature. Immunohistochemical studies were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9 marker), oxidative stress (8-hydroxy-2'-deoxyguanosine), and the expression of profibrogenic (transforming growth factor-{beta} [TGF-{beta}]) and proangiogenic (vascular endothelial growth factor [VEGF]) cytokines. Results: Significant changes in lung perfusion along with tissue hypoxia were observed 3 days after irradiation. Significant oxidative stress was detected 1 week after radiation, whereas macrophages started to accumulate at 4 weeks. A significant increase in TGF-{beta} expression was seen within 1 day after radiation, and for VEGF at 2 weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines continued to rise with time after irradiation. The steepest increase correlated with vast macrophage accumulation. Conclusions: Early changesmore » in lung perfusion, among other factors initiate, the development of hypoxia and chronic oxidative stress after irradiation. Tissue hypoxia is associated with a significant increase in the activation of macrophages and their continuous production of reactive oxygen species, stimulating the production of fibrogenic and angiogenic cytokines, and maintaining the development of chronic radiation-induced lung injury.« less

Authors:
 [1];  [2];  [1];  [1];  [1];  [1];  [1];  [1];  [3];  [4]
  1. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)
  2. (Germany)
  3. Department of Pulmonary Medicine, Duke University Medical Center, Durham, NC (United States)
  4. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States). E-mail: vujas@radonc.duke.edu
Publication Date:
OSTI Identifier:
20951633
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.12.056; PII: S0360-3016(07)00085-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; ANOXIA; BIOLOGICAL STRESS; CARBONIC ANHYDRASE; FIBROSIS; INJURIES; IRRADIATION; LUNGS; LYMPHOKINES; MACROPHAGES; OXIDATION; OXYGEN; PNEUMONITIS; RADIATION DOSES; RADIOTHERAPY; RATS

Citation Formats

Fleckenstein, Katharina, Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Mannheim, Zgonjanin, Larisa, Chen Liguang, Rabbani, Zahid, Jackson, Isabel L., Thrasher, Bradley, Kirkpatrick, John, Foster, W. Michael, and Vujaskovic, Zeljko. Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.056.
Fleckenstein, Katharina, Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Mannheim, Zgonjanin, Larisa, Chen Liguang, Rabbani, Zahid, Jackson, Isabel L., Thrasher, Bradley, Kirkpatrick, John, Foster, W. Michael, & Vujaskovic, Zeljko. Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation. United States. doi:10.1016/j.ijrobp.2006.12.056.
Fleckenstein, Katharina, Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Mannheim, Zgonjanin, Larisa, Chen Liguang, Rabbani, Zahid, Jackson, Isabel L., Thrasher, Bradley, Kirkpatrick, John, Foster, W. Michael, and Vujaskovic, Zeljko. Tue . "Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation". United States. doi:10.1016/j.ijrobp.2006.12.056.
@article{osti_20951633,
title = {Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation},
author = {Fleckenstein, Katharina and Department of Radiation Oncology, Mannheim Medical Center, University of Heidelberg, Mannheim and Zgonjanin, Larisa and Chen Liguang and Rabbani, Zahid and Jackson, Isabel L. and Thrasher, Bradley and Kirkpatrick, John and Foster, W. Michael and Vujaskovic, Zeljko},
abstractNote = {Purpose: To investigate the temporal onset of hypoxia following irradiation, and to show how it relates to pulmonary vascular damage, macrophage accumulation, and the production of reactive oxygen species and cytokines. Our previous studies showed that tissue hypoxia in the lung after irradiation contributed to radiation-induced injury. Methods and Materials: Female Fisher 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy. Serial studies were performed up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were performed to detect changes in pulmonary vasculature. Immunohistochemical studies were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9 marker), oxidative stress (8-hydroxy-2'-deoxyguanosine), and the expression of profibrogenic (transforming growth factor-{beta} [TGF-{beta}]) and proangiogenic (vascular endothelial growth factor [VEGF]) cytokines. Results: Significant changes in lung perfusion along with tissue hypoxia were observed 3 days after irradiation. Significant oxidative stress was detected 1 week after radiation, whereas macrophages started to accumulate at 4 weeks. A significant increase in TGF-{beta} expression was seen within 1 day after radiation, and for VEGF at 2 weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines continued to rise with time after irradiation. The steepest increase correlated with vast macrophage accumulation. Conclusions: Early changes in lung perfusion, among other factors initiate, the development of hypoxia and chronic oxidative stress after irradiation. Tissue hypoxia is associated with a significant increase in the activation of macrophages and their continuous production of reactive oxygen species, stimulating the production of fibrogenic and angiogenic cytokines, and maintaining the development of chronic radiation-induced lung injury.},
doi = {10.1016/j.ijrobp.2006.12.056},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 68,
place = {United States},
year = {Tue May 01 00:00:00 EDT 2007},
month = {Tue May 01 00:00:00 EDT 2007}
}