Radioprotective action of nitrone spin traps

The formation of free radicals by water radiolysis is a major cause of radiation-induced injury to cells. Spin trapping agents such as α-phenyl N-tert-butyl nitrone (PBN), 5,5-dimethylpyrroline N-oxide (DMPO), α-pyridyl 1-oxide N-tert-butyl nitrone (4-PyOBN) and α-(2,4,6-trimethoxyphenyl) N-tert-butyl nitrone (TMeOPBN) are good scavengers of primary products (H/sup ./, HO/sup ./ and e-aqueous) of water radiolysis and secondary radicals produced by the attack of primary radicals on other molecules. While PBN, DMPO and TMeOPBN were found to be effective as protectors of free radical initialed lipid peroxidation in rat liver microsomes, 4-PyOBN (upto 40 mM) was only a weak protector. Clongenicity assays revealed that TMeOPBN (5 mM) was more effective than PBN (5 mM) in protecting V-79 Chinese hamster lung cells against the lethal action of Cs-137 gamma radiation delivered at a dose rate of 10.5 Gy/min under aerobic conditions at room temperature. The spin trap TMeOPBN or PBN was present only 15 min before and during irradiation. These results are discussed in terms of the structure and mechanism of action of these compounds