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Nitric Oxide Production Following Irradiation of Tumor and Murine Hematopoietic Progenitor Cells in Vitro
Author(s) -
Zabbarova Irina V,
Epperly Michael W,
Greenberger Joel S,
Wipf Peter,
Macfarlane Sarah,
Kanai Anthony J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.664
Subject(s) - peroxynitrite , chemistry , nitric oxide , superoxide dismutase , haematopoiesis , progenitor cell , superoxide , nitric oxide synthase , microbiology and biotechnology , glutathione peroxidase , apoptosis , stem cell , cancer research , biochemistry , biology , antioxidant , enzyme , organic chemistry
Ionizing radiation turns on mitochondrial nitric oxide synthase (mtNOS) resulting in increased nitric oxide (NO), superoxide (O 2 − ) and, as a consequence, damaging peroxynitrite (ONO 2 − ) 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 O 2 − production, whereas dismutation of O 2 − results in hydrogen peroxide (H 2 O 2 ) 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/10 6 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/10 6 cells, respectively), but increased significantly in MnSOD overexpressing cells after irradiation (2.1 μM NO/10 6 cells). Future studies will investigate the role of NOS antagonists in radiation protection. Funded by NIH DK071085.