We have examined whether nuclear DNA can be protected from double-strand breaks (DSBs) induced by decay of the Auger-electron-emitting radionuclide I-125. Decays were accumulated at 0.3 degrees C in Chinese hamster V79 cells suspended in isotonic buffer containing 0.1 M EDTA in the presence or absence of 10% dimethyl sulfoxide (DMSO). DSBs were measured by the neutral elution method (pH 9.6) and quantified as strand scission factors. DMSO was shown to protect DNA from DSBs caused by the decay of DNA-incorporated I-125. The dose modification factor (DMF) for this radionuclide decreases as a function of I-125 decays (389 to 4,100 decays, DMF = 2.5 to 1.3). Extrapolation of the curve for the DMF indicates that at similar to 15,000 decays/cell, a DMF of 1 would be obtained. Experiments using large numbers of I-125 decays confirmed these extrapolations. For induction of DSBs by Cs-137 gamma rays, the DMF also decreases with dose (50 to 290 Gy, DMF = 2.7 to 1.5). However, extrapolation of the curve for the DMF indicates that protection does not cease at higher doses. The data show that, at the same level of damage, DMSO can protect against gamma-ray-induced DSBs 1.35-fold more efficiently than against DSBs caused by the decay of DNA-incorporated I-125. It appears that when I-125 is incorporated into DNA, chromatin structure fosters some DSB formation by an indirect mechanism(s) and that more than one DSB is generated per decaying atom. (C) 1998 by Radiation Research Society.