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 »
- Authors:
- Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)
- (Germany)
- Department of Pulmonary Medicine, Duke University Medical Center, Durham, NC (United States)
- 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}
}
-
Coal dust inhalation induces oxidative damage and inflammatory infiltration on lung parenchyma. Thus, the aim of this study was to determine whether N-acetylcysteine (NAC) administered alone or in combination with deferoxamine (DFX), significantly reduced the inflammatory infiltration and oxidative damage in the lungs of rats exposed to coal dust. Forty-two male Wistar rats (200-250 g) were exposed to the coal dust (3 mg/0.5 mL saline, 3 days/week, for 3 weeks) by intratracheal instillation. The animals were randomly divided into three groups: saline 0.9% (n = 8), supplemented with NAC (20 mg/kg of body weight/day, intraperitoneal injection (i.p.)) (n = 8),more »
-
Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells
Fibroblast growth factor-21 (FGF21) is a potential metabolic regulator with multiple beneficial effects on metabolic diseases. FGF21 is mainly expressed in the liver, but is also found in other tissues including the intestine, which expresses β-klotho abundantly. The intestine is a unique organ that operates in a physiologically hypoxic environment, and is responsible for the fat absorption processes including triglyceride breakdown, re-synthesis and absorption into the portal circulation. In the present study, we investigated the effects of hypoxia and the chemical hypoxia inducer, cobalt chloride (CoCl{sub 2}), on FGF21 expression in Caco-2 cells and the consequence of fat accumulation. Physicalmore » -
Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation
Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluatedmore » -
Bilingual language processing after a lesion in the left thalamic and temporal regions. A case report with early childhood onset
This case study concerns an 18-year-old bilingual girl who suffered a radiation lesion in the left (dominant) thalamic and temporal region when she was 4 years old. Language and memory assessment revealed deficits in auditory short-term memory, auditory word comprehension, nonword repetition, syntactic processing, word fluency, and confrontation naming tasks. Both languages (English and Dutch) were found to be affected in a similar manner, despite the fact that one language (English) was acquired before and the other (Dutch) after the period of lesion onset. Most of the deficits appear to be related to verbal (short-term) memory dysfunction. Several hypotheses ofmore »