| Abstract | PURPOSE: Since oxidative injury is implicated in radiation-induced tissue damage to the lung, we studied systemically administered polyethylene glycol (PEGylated) antioxidant enzymes (AOEs) as pulmonary radioprotectors in mice. METHODS AND MATERIALS: C57/bl6 Mice received 13.5 Gy single-dose irradiation to the thorax. One cohort also received 100 microg of a 1:1 mixture of PEG-AOEs {PEG-catalase and PEG-superoxide dismutase (SOD)} intravenously, pre-irradiation and subgroups were evaluated at variable time-points for inflammation and fibrosis. Potential for AOE tumor protection was studied by thoracic irradiation of mice with Lewis lung carcinoma. RESULTS: At 48 h post-irradiation, control irradiated mice had marked elevations of tissue p21, Bax and TGF-beta1 in lungs, not seen in irradiated, PEG-AOE-treated mice. TUNEL staining of lung sections was performed at just one time-point (24 h post-irradiation) and revealed a decrease in apoptotic cells with AOE treatment. At four months post-irradiation, these mice had significantly increased pulmonary fibrosis as measured by hydroxyproline content. Mice treated with PEG-AOE prior to irradiation had 4-month hydroxyproline levels that were similar to that of unirradiated controls (p = 0.28). This corresponded to less pulmonary fibrosis as visualized histologically when compared with mice irradiated without AOEs. PEG-AOEs did not prevent post-irradiation pulmonary inflammation or lung cancer response to irradiation. CONCLUSIONS: A mixture of PEG-SOD and PEG-CAT successfully diminished radiation pulmonary fibrosis in mice. There was also a corresponding effect on several early biomarkers of lung injury and decreased apoptosis. There were no significant effects on acute pneumonitis or tumor protection. |
| Authors | Mitchell Machtay, Arnaud Scherpereel, José Santiago, James Lee, Jim McDonough, Paul Kinniry, Evguenia Arguiri, Vladimir V Shuvaev, Jing Sun, Keith Cengel, Charalambos C Solomides, Melpo Christofidou-Solomidou
(Affiliation: Department of Medicine, Pulmonary, Allergy, and Critical Care Division, Thomas Jefferson University Medical Center, Philadelphia, PA 19104, USA.)
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| Journal | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
(Radiother Oncol)
Vol. 81
Issue 2
Pg. 196-205
(Nov 2006)
ISSN: 0167-8140 Ireland |
| PMID | 17069914
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Biological Markers
- Drug Combinations
- Polyethylene Glycols
- RNA, Messenger
- Radiation-Protective Agents
- Transforming Growth Factor beta1
- bcl-2-Associated X Protein
- catalase-polyethylene glycol
- polyethylene glycol-superoxide dismutase
- Catalase
- Superoxide Dismutase
- Protein-Serine-Threonine Kinases
- p21-Activated Kinases
|
| Topics |
- Animals
- Biological Markers
(analysis)
- Catalase
(therapeutic use)
- Drug Combinations
- Female
- Lung
(chemistry, pathology, radiation effects)
- Lung Neoplasms
(prevention & control)
- Mice
- Mice, Inbred C57BL
- Polyethylene Glycols
(therapeutic use)
- Protein-Serine-Threonine Kinases
(genetics)
- Pulmonary Fibrosis
(pathology, prevention & control)
- RNA, Messenger
(analysis)
- Radiation Pneumonitis
(pathology, prevention & control)
- Radiation-Protective Agents
(therapeutic use)
- Superoxide Dismutase
(therapeutic use)
- Thorax
(radiation effects)
- Transforming Growth Factor beta1
(genetics)
- X-Rays
- bcl-2-Associated X Protein
(genetics)
- p21-Activated Kinases
|
