Protection by DMSO against cell death caused by intracellularly localized iodine-125, iodine-131 and polonium-210

The mechanisms by which DNA-incorporated radionuclides impart lethal damage to mammalian cells were investigated by examining the capacity of dimethyl sulfoxide (DMSO) to protect against lethal damage to Chinese hamster V79 c ells caused by unbound tritium ((H2O)-H-3), DNA-incorporated I-125- and I-1 31-iododeoxyuridine ((125)IdU, (131)IdU), and cytoplasmically localized Po- 210 citrate. The radionuclides H-3 and I-131 emit low- and medium energy be ta particles, respectively, I-125 is a prolific auger electron emitter, and Po-210 emits 5.3 MeV alpha particles. Cells were radiolabeled and maintain ed at 10.5 degrees C for 72 h in the presence of different concentrations o f DMSO (5-12.5% v/v), and the surviving fraction compared to that of unlabe led controls was determined. DMSO afforded no protection against the lethal effects of the high-LET alpha particles emitted by Po-210. Protection agai nst lethal damage caused by unbound H-3, (131)IdU and (125)IdU depended on the concentration of DMSO in the culture medium. Ten percent DMSO provided maximum protection in all cases. The dose modification factors obtained at 10% DMSO for (H2O)-H-3, (131)IdU, (125)IdU and Po-210 citrate were 2.9 +/- 0.01, 2.3 +/- 0.5, 2.6 +/- 0.2 and 0.95 +/- 0.07, respectively. These resul ts indicate that the toxicity of Auger electron and beta-particle emitters incorporated into the DNA of mammalian cells is largely radical-mediated an d is therefore indirect in nature. This is also the case for the low-energy beta particles emitted by (H2O)-H-3. In contrast, alpha particles impart l ethal damage largely by direct effects. Finally, calculations of cellular a bsorbed doses indicate that beta-particle emitters are substantially more t oxic when incorporated into the DNA of mammalian cells than when they are l ocalized extracellularly. (C) 2000 by Radiation Research Society.