Title: Increased expression of manganese superoxide dismutase (MnSOD) in the esophagus increases engraftment of bone marrow origin stem cells following irradiation
Abstract:Proc Amer Assoc Cancer Res, Volume 47, 2006
4415
Irradiation damage to the esophagus increases apoptosis beginning 5 days after irradiation followed by denuding of the mucosa at approximately 7 day...Proc Amer Assoc Cancer Res, Volume 47, 2006
4415
Irradiation damage to the esophagus increases apoptosis beginning 5 days after irradiation followed by denuding of the mucosa at approximately 7 days. To determine whether pretreatment with manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) prevented apoptosis following irradiation, C57BL/6NHsd mice were intraesophageally injected with MnSOD-PL and irradiated 24 hours later to 30 Gy to the upper body, and sacrificed 1, 3 or 5 days later. The esophagus was removed, fixed in OCT, sectioned and stained with a Tunel assay for apoptosis. No apoptosis was detected until 5 days after irradiation. Pre-treatment with MnSOD-PL resulted in decreased apoptosis. Lipid peroxidation following irradiation of the esophagus was measured. C57BL/6NHsd mice received intraesophageal MnSOD-PL (200 μg plasmid DNA) and were irradiated 24 hours later along with control mice to 30 Gy to the esophagus. The esophagus was removed at various time points following irradiation and lipid peroxidation measured. There was delayed lipid peroxidation detected 7 days after irradiation. Lipid peroxidation increased in control irradiated mice, but was not detected in MnSOD-PL treated then irradiated mice. Mice pretreated with MnSOD-PL had significantly decreased lipid peroxidation on days 7 and 14 following irradiation compared to control plasmid treated mice (p=0.0053 or 0.0110). To determine if pretreatment of MnSOD-PL allowed successful engraftment of stem cells following irradiation, mice were injected in traesophageally with MnSOD-PL (200 μg plasmid DNA) 24 hours before irradiation to 30 Gy. The mice were then injected I.V. with ROSA (LacZ+) male bone marrow cells at day 1, 3 or 5 after irradiation and sacrificed 14 days later. The esophagus was excised and digested to single cell suspensions, side population (SP) stem cells as well as non-SP cells separated by flow cytometry of Hoechst stained cells. Cells were then analyzed for expression of LacZ. Mice injected with SP cells on day 5 after irradiation had the greatest engraftment of cells positive for the LacZ gene. MnSOD-PL treatment before irradiation further increased engraftment of LacZ positive cells compared to control irradiated mice. The results indicate that pretreatment with MnSOD-PL 24 hours before irradiation results in increased engraftment of stem cells into the irradiated esophagus, associated with reduced production of reactive oxygen species (ROS) , decreased apoptosis and decreased lipid peroxidation.Read More
Publication Year: 2006
Publication Date: 2006-04-15
Language: en
Type: article
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