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 date||1/01/01 → 31/12/04|
- Nuclear factor kappaB
- Nitric oxide synthase
Flemish discipline codes
- Basic sciences