Abstract

Following irradiation of the murine esophagus there is detectable migration of marrow origin stem cells into the esophagus associated with recovery from irradiation-induced damage. Irradiation of the esophagus or the bone marrow results in stably increased detectable production of reactive oxygen species (ROS) for weeks. We hypothesized that reducing the production of ROS following irradiation may allow for increased stable recruitment of stem cells into the irradiated areas. C57BL/6NHsd female mice were administered MnSOD-PL (100 |[mu]|g plasmid DNA) by intraesophageal injection 24 hours before irradiation to 29 Gy. Control mice were irradiated to 29 Gy. The mice were then injected I.V. with bone marrow cells isolated from ROSA (LacZ+) male mice. Fourteen days after irradiation mice were sacrificed and the esophagus excised and sorted into side population (SP) and non-SP cells. In mice that received MnSOD-PL prior to irradiation, 40% of the non-SP cells were LacZ+ compared to 10% in mice that received irradiation only. Sorting of esophageal SP cells which include multilineage stem cells showed 20% from MnSOD-PL pretreated then irradiated mice were LacZ+ compared to 8% of the SP cells from control irradiated mice. In addition, mice that received MnSOD-PL intraesophageally 24 hours before irradiation also had decreased apoptotic cells. At day 5 following irradiation, 20% of control irradiated esophageal cells were undergoing apoptosis; whereas, in mice that were pre-treated with MnSOD-PL there was less than 1% apoptosis. In conclusion, administration of MnSOD-PL results in increased migration of stem cells from the bone marrow into the esophagus and decreased apoptosis in the esophagus. The data suggest that MnSOD-PL pre- irradiation treatment of the esophagus results in increased marrow cell engraftment due to reduction of ROS.

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