Indirect mechanisms contribute to biological effects produced by decay of DNA-incorporated iodine-125 in mammalian cells in vitro: clonogenic survival.

We have examined whether mammalian cells in vitro can be protected against the lethal effects of irradiation by Auger electrons emitted from DNA-incorporated 125I. Chinese hamster V79 lung fibroblasts were cultivated in the presence of 5-[125I]iodo-2'-deoxyuridine (125IdU) for 18 h and resuspended in ice-cold medium in the presence or absence of 10% dimethyl sulfoxide (DMSO). DNA-incorporated 125I activity was measured and the cells were plated for survival. A portion of the cell suspensions were also stored on ice to accumulate 125I decays for 6 to 48 h, after which the cells were plated to determine survival. Storage on ice up to 48 h without radioactivity reduced plating efficiency from 67 +/- 4% (SEM) to 20 +/- 1%. DMSO had a protective effect on colony formation, as the respective cloning efficiencies were 83 +/- 3% and 72 +/- 12% at 0 and 48 h. The survival curves for 125IdU-labeled cells are exponential with D0 = 36 +/- 2 decays per cell in the absence of DMSO and 195 +/- 20 decays per cell in the presence of DMSO. Thus the dose modification factor (DMF) at 37% survival for 10% DMSO is 5.4 +/- 0.6 for DNA-incorporated 125I. In reference experiments, a DMF of 2.5 +/- 0.8 was measured for cells irradiated with 137Cs gamma rays. These results indicate that the radiotoxicity of Auger electrons from 125I decay in mammalian cells is caused mainly by an indirect mechanism(s).