PARENT SESSION
1:30 PM to 3:30 PM
Sunday, April 21, 2002
Poster Session 7 Radioprotectors
Room: Nevada Exhibition Center
(P12-117) Protection from radiation induced acute lung injury by overexpression of extracellular superoxide dismutase in mice.
Kang, Song*,1, Rabbani, Zahid1, Folz, Rodney2, Dewhirst, Mark1, Anscher, Mitchell1, Vujaskovic, Zeljko1, 1 Duke University Medical Center, Durham, NC2 Duke University Medical Center, Durham, NC
ABSTRACT-
Reactive oxygen species (ROS) are key molecules involved in radiation-induced normal tissue injury, and superoxide dismutase (SOD) is a critical enzyme in the metabolism of ROS. The objective of this study was to determine whether increased expression of extracellular SOD (EC-SOD) would protect mice from radiation induced lung injury. B6C3 transgenic (TG) mice that overexpress EC-SOD in the lungs were compared to their wild type (WT) counterparts. Whole lung radiation was given with a single dose of 16 Gy using 4MV photons. Lung function was assessed by measuring breathing frequency every two weeks for 10 weeks, then every week up to 24 weeks. Upon sacrifice, the entire right lung wet weight was measured as a gross indication of lung consolidation. Histopathology and immunohistochemistry studies were performed to assess cytokine activity. Three of six WT mice required euthanasia at 14-15 weeks post-radiation due to respiratory distress. During the same time period, no TG mice displayed evidence of respiratory distress or increased breathing frequency. At the peak respiratory response (14 weeks), the mean breathing frequency (breaths per minute ± SEM) was significantly higher for irradiated WT mice than irradiated TG mice (380 ± 34 vs. 286 ± 2, p<0.05). Breathing frequency in irradiated and unirradiated TG control mice was not significantly different (286 ± 2 vs. 279 ± 3, p>0.05). Right lung weights (grams ± SEM) were 0.23 ± 0.07 for WT mice, and 0.11 ± 0.04 for TG mice. Histologic evaluation of the WT mice demonstrated greater inflammation and consolidation compared to the TG mice. Histopathology and immunohistochemistry data will be presented. These preliminary data support our hypothesis that overexpression of EC-SOD in the mouse lung is protective against radiation induced acute lung injury. This finding has potential clinical implications with the recent development of novel SOD mimetic compounds.
KEYWORDS: radioprotection, superoxide dismutase, lung injury