Radiation response of E. coli after combined treatment with misonidazole and WR-2721 at various oxygen concentrations

It has been reported that the aminothiol compound WR-2721 is a promising radioprotective agent and in combination with misonidazole (MISO) seems to be of therapeutic benefit. Since the radiomodification is oxygen-dependent, the actual oxygen status of cells and the surrounding media is an important factor influencing their effectiveness. Escherichia coli B/r radioresponse was studied either alone or in combination with these compounds at various oxygen concentrations ranging from anoxia to high oxygen content. WR-2721 had a protective effect under anoxic conditions and gave overall protection when oxygen was present. The maximum protection was seen at 3.2% O2 in N2 (PF 2.08). In combination with MISO the hypoxic sensitization of MISO was completely abolished by WR-2721, resulting in radioprotection under hypoxic conditions as well. Under euoxic conditions MISO was able to reduce the protective effect of WR-2721 by about 21%. According to our results MISO and WR-2721 influence each other in their radiomodifying effect in either fixation or repair of the radiation-induced damage. (orig.)