Tumor cell radiosensitization through nitric oxide iNOS and NF-kB as the efector and regulatory determinants of radioresponse in chronic hypoxia.

    Project Details


    We explored in previous studies the radiosensitizing potency of the radical nitric oxide NO that mimics tha ability of oxygen to irreversibly "fix" the DNA damage caused by radiation/ our laboratory was the first to demonstrate that the inducible enzyme nitric oxide synthase activated by citokines in aerobic conditions, is capable of radiosensitizing tumor cells through NO synthesized from L-arginine. Our current hypothesis is that chronic hypoxia, commonly present in solide tumors, may potentiate iNOS-mediated radiosensitization through the transcription factor NF-kB which has specific binding sites in the promotorf region of iNOS gene. the first part of the project will focus on the iNOS pathway in mouse EMT-6 tumor cells in chronic hypoxia. the second step will be re-evaluation of our hypothesis on human specimens aiming at future NO-based radiosensitizing strategies. The prinipal objectives of the projecet are a) Impact of chronic hypoxia on functional activity of NF-kB inactivation on iNOS expression and NO generation; c) Radiosensitizing potency of cytokines applied in chronic hypoxia versus normoxia.
    Effective start/end date1/01/0131/12/04


    • radiosensitization
    • Nuclear factor kappaB
    • Nitric oxide synthase

    Flemish discipline codes

    • Basic sciences