Radiation chemistry to radioprotector development: our experience with selenium

Exposure of living cells to ionising radiation causes radiolysis of water producing hydroxyl (·OH) radical, a powerful oxidant, which may trigger a sequence of events like mutations in DNA and cell death. Since ·OH radical reaction is the primary process in radiation damage, radiation chemists in the past have studied its reactions with important natural and synthetic sulfur compounds. These studies have not only helped in understanding the important role of sulphur in radiation biology and also in development of sulphur compounds as radioprotectors. Selenium, a member of the same chalcogenide group as sulfur, is a micro nutrient and a constituent of important redox active enzymes like thioredoxin reductase and glutathione peroxidise (GPx). Considering its interesting redox biology, we proposed to develop synthetic selenium compounds as new class of radioprotectors. As apart of this programme, initially ·OH radical reactions with these compounds were studied in real time scales. The results indicated that in these compounds, selenium is the active centre for the attack of ·OH radical and the reaction leads to formation of selenium centred radical cation, which interacts with the nearby hetero atoms through non-bonding interactions. In another pre-clinical study, post irradiative administration of DSePA significantly reduced the radiation induced peneumonitis and fibrosis of lungs in irradiated mice and improved their survival significantly. Further work is going on to test DSePA in clinical systems. (author)