Ionizing radiation potentiates the induction of nitric oxide synthase by interferon-γ (Ifn-γ) or Ifn-γ and lipopolysaccharide in Bnl Cl.2 murine embryonic liver cells: role of hydrogen peroxide

The effects of ionizing irradiation on the nitric oxide (NO) production in murine embryonic liver cell line, BNL CL.2 cells, were investigated. Various doses (5–40 Gy) of radiation made BNL CL.2 cells responsive to interferon-γ alone for the production of NO in a dose-dependent manner. Small amounts of lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α) synergized with IFN-γ in the production of NO from irradiated BNL CL.2 cells, even though LPS or TNF-α alone did not induce NO production from the same cells. Immunoblots showed parallel induction of inducible nitric oxide synthase (iNOS). NO production in irradiated BNL CL.2 cells by IFN-γ or IFN-γ plus LPS was decreased by the addition of catalase, suggesting that H2O2 produced by ionizing irradiation primed the cells to trigger NO production in response to IFN-γ or IFN-γ plus LPS. Furthermore, the treatment of nonγ-irradiated BNL CL.2 cells with H2O2 made the cells responsive to IFN-γ or IFN-γ plus LPS for the production of NO. This study shows that ionizing irradiation has the ability to induce iNOS gene expression in responsive to IFN-γ via the formation of H2O2 in BNL CL.2 murine embryonic liver cells.