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- Title
Nitric Oxide Production Following Irradiation of Tumor and Murine Hematopoietic Progenitor Cells in Vitro.
- Authors
Zabbarova, Irina V.; Epperly, Michael W.; Greenberger, Joel S.; Wipf, Peter; Macfarlane, Sarah; Kanai, Anthony J.
- Abstract
Ionizing radiation turns on mitochondrial nitric oxide synthase (mtNOS) resulting in increased nitric oxide (NO), superoxide (O2-) and, as a consequence, damaging peroxynitrite (ONO2-) formation. In studies of normal irradiated tissues (e.g., urinary bladder) the mitochondrial targeting of NOS antagonists was more radioprotective than manganese superoxide dismutase (MnSOD) overexpression. NOS antagonists prevent both NO and O2- production, whereas dismutation of O2- results in hydrogen peroxide (H2O2) formation which must be cleared by glutathione peroxidase (GPX) or catalase. Irradiation (5 Gy) of 32D cl 3 murine hematopoietic progenitor cells resulted in a significant increase of NO production (from 0.9±0.4 to 3.4±1.0 μM NO/106 cells) but not in Lewis Lung Carcinoma (3LL) or human head and neck cancer Cal33 cells. Overexpression of MnSOD in nonirradiated 32D and 3LL cells resulted in higher levels of NO even in comparison to irradiated 32D and 3LL cells. Irradiation did not further augment NO levels in 32D or 3LL cells overexpressing MnSOD. However, NO production in Cal33 control and MnSOD overexpressing cells was low before irradiation (0.4±0.1 and 0.52±0.02 μM NO/106 cells, respectively), but increased significantly in MnSOD overexpressing cells after irradiation (2.1 μM NO/106 cells). Future studies will investigate the role of NOS antagonists in radiation protection. Funded by NIH DK071085.
- Publication
FASEB Journal, 2008, Vol 22, p664
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.22.2_supplement.664