Strand Breaks after the Decay of Iodine-125 in Proximity to Plasmid pBR322 DNA

Abstract

To elucidate the kinetics of DNA strand breaks caused by low-energy Auger electron emitters in proximity to DNA molecules, we synthesized (125)I-labeled 2-iodoacridine (2-(125)IA), which intercalates with DNA, and 4-iodoacridine (4-(125)IA), which does not. Supercoiled DNA from pBR322 plasmid, labeled with 3H, was purified and incubated with 2-(125)IA or 4-(125)IA in aqueous solution. Reaction mixtures were stored at 4 degrees C to accumulate radiation dose from the decay of (125)I, and DNA was resolved by gel electrophoresis into supercoiled (DNA-I), nicked-circular (DNA-II) and linear (DNA-III) forms, representing undamaged DNA, single-strand breaks (SSBs) and double-strand breaks (DSBs), respectively. Gamma irradiation from an external (137)Cs source led to an exponential decrease in DNA-I with a D0 value of 10.8 +/- 0.3 Gy. Under identical conditions, the D0 values for 2-(125)IA and 4-(125)IA were 22.4 +/- 0.6 x 10(11) disintegrations and 4.7 +/- 0.4 x 10(11) disintegrations, respectively. External gamma irradiation and 4-(125)IA produced SSB/DSB ratios of 26.5 +/- 2.1 and 15.9 +/- 2, respectively, while that for 2-(125)IA was 0.6. The average number of DSBs from each decay of (125)I was 0.67 for 2-(125)IA and 0.27 for 4-(125)IA. The results indicate that the decay of (125)I bound to a DNA-intercalating compound produces DSBs 2.5-fold more efficiently than (125)I bound to a nonintercalating compound and support the theoretical expectations that predict a DSB yield that is highly dependent on the proximity of the Auger electron emitter to DNA.