To elucidate the kinetics of the induction of DNA strand breaks by low-energy Auger electron emitters, we compared the yields of DNA breaks in supercoiled pUC19 DNA 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)-iodoantipyrine, (125)IAP). Iodine-125 bound to the minor groove in DNA or free in solution is equally effective per decay in producing single-strand breaks (SSBs), while (125)I bound to the minor groove is 6.7-fold more efficient than (125)I free in solution in producing double-strand breaks (DSBs) (1.08 +/- 0.13 compared to 0.16 +/- 0.01 DSB/decay), Consequently, SSB to DSB ratios for (125)IAP and gamma radiation (20.7 +/- 2.9 and 43.8 +/- 1.5, respectively) are greater than that for (125)IH (2.9 +/- 0.4). Finally, the decay of (125)IH leads to fragmentation of plasmid DNA beyond SSBs and DSBs. (C) 1999 by Radiation Research Society.