To elucidate the nature and kinetics of DNA strand breaks caused by low-energy Auger electron emitters, we compared the yields of DNA breaks in supercoiled pUC19 DNA in the presence of the (.)OH scavenger dimethyl sulfoxide (DMSO) after the decay of (125)I (1) in proximity to DNA after minor-groove binding ((125)I-iodoHoechst 33342, (125)IH) and (2) at a distance from DNA ((125)I-iodoantipyrine, (125)IAP). DMSO is efficient at protecting supercoiled plasmid DNA from the decay of (125)I free in solution (dose modification factor, DMF = 59 +/- 4) and less effective when the (125)I decays occur close to DNA (DMF = 3.8 +/- 0.3). This difference is due mainly to the inability of DMSO to protect DNA from the double-strand breaks produced by groove-bound (125)I (DMF = 1.0 +/- 0.2). Additionally, the fragmentation of plasmid DNA beyond the production of single-strand and double-strand breaks that is seen after the decay of (125)IH and not (125)IAP (Kassis et al., Radiat. Res. 151, 167-176, 1999) cannot be modified by DMSO. These results demonstrate that the mechanisms underlying double-strand breaks caused by the decay of (125)IH differ in nature from those caused by the decay of (125)IAP.