NO and ROS: Ionizing radiation (IR) effects on normal and tumor cells

DURÁN H; POLICASTRO LL; MOLINARI B; HENRY Y; FAVAUDON V

Buenos Aires, Argentina

Workshop; Workshop on Clinical Applications of the Concept of Oxidative Stress in Radiobiology and Cancer Radiotherapy. XII Meeting of the International Society for Free Radical Research; 2004

The indirect action of IR by water free radicals and the oxygen effect are well known. Numerous studies in different biological models demonstrated the radioprotective action of antioxidants or free radical scavengers. Regarding nitric oxide (NO), the first report of its action as a radiosensitizer was in bacteria (Howard-Flanders, 1957). Later on, the radiosensitizing effect of NO was demonstrated in mammalian cells (V79) under hypoxic conditions (Mitchell et al., 1993). The authors suggested a similar mechanism to that of oxygen. However, other authors reported NO as a radiosensitizer of mammalian cells in aerobic conditions. We demonstrated a differential NO radiosensitizing ability in mouse and human tumor cells in aerobic conditions, using the NO releasing agent DETA-NO. The more malignant the cell line, the higher its radiosensitization by NO. Moreover, we demonstrated an in vivo radiosensitizing effect of the NO donor spermine-NO in experimental tumors. Considering the vasodilatory effects of NO, we suggest that the radiosensitization of tumors by NO could be due to a combined effect of cell radiosensitization and a greater oxygenation of the hypoxic tumor cells. For clinical applications, the serious side effects of NO when administered systemically could be minimized by localized overexpression of the iNOS gene using an adenoviral vector combined with radiotherapy (Wang et al, 2004).