Bishayee, A., Rao, D. V., Bouchet, L. G., Bolch, W. E. and Howell, R. W. 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 cells caused by unbound tritium (3H2O), DNA-incorporated 125I- and 131I-iododeoxyuridine (125IdU, 131IdU), and cytoplasmically localized 210Po citrate. The radionuclides 3H and 131I emit low- and medium-energy β particles, respectively, 125I is a prolific Auger electron emitter, and 210Po emits 5.3 MeV α particles. Cells were radiolabeled and maintained at 10.5°C for 72 h in the presence of different concentrations of DMSO (5–12.5% v/v), and the surviving fraction compared to that of unlabeled controls was determined. DMSO afforded no protection against the lethal effects of the high-LET α particles emitted by 210Po. Protection against lethal damage caused by unbound 3H, 131IdU and 125IdU 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 3H2O, 131IdU, 125IdU and 210Po citrate were 2.9 ± 0.01, 2.3 ± 0.5, 2.6 ± 0.2 and 0.95 ± 0.07, respectively. These results indicate that the toxicity of Auger electron and β-particle emitters incorporated into the DNA of mammalian cells is largely radical-mediated and is therefore indirect in nature. This is also the case for the low-energy β particles emitted by 3H2O. In contrast, α particles impart lethal damage largely by direct effects. Finally, calculations of cellular absorbed doses indicate that β-particle emitters are substantially more toxic when incorporated into the DNA of mammalian cells than when they are localized extracellularly.