Mechanism of the Protective Action of GED against Radiation Damage to DNA

Abstract
The specific viscosity was measured in unirradiated and irradiated solutions of highly polymerized salmon sperm DNA alone and containing bis(2-guanidoethyl) disulfide (GED), oxidized glutathione (GSSG), cystamine, cadaverine, agmatine, and pentamethylene diguanidine (PMDG). Radiation-induced decrease in viscosity was almost completely prevented by 10-3 [image] GED up to 100 kR, at which dose the viscosity of the unprotected DNA solution approximated that of the solvent. When viscosity was measured at 90[degree]C to study the effect on single strands, radiation effect and GED protection of DNA were demonstrated with doses as low as 100 to 200 R. GED had to be present during irradiation for protection but could be removed by dialysis after irradiation without loss of protection. Equilibrium dialysis demonstrated binding of GED to DNA. Other disulfides, GSSG, and cystamine showed less binding to DNA and also showed less protection. The diamine cadaverine and the diguanidine-PMDG were bound to DNA equally well as cystamine and GED, respectively, but showed no protection. The mechanism of action of GED appears to be that of localized radical scavenging at the surface of the DNA molecule.