To elucidate the kinetics of DNA strand breaks caused by low-energy Auger electron emitters in proximity to DNA molecules, we synthesized 125I-labeled 2-iodoacridine (2-125IA), which intercalates with DNA, and 4-iodoacridine (4-125IA), which does not. Supercoiled DNA from pBR322 plasmid, labeled with 3H, was purified and incubated with 2-125IA or 4- 125IA in aqueous solution. Reaction mixtures were stored at 4°C to accumulate radiation dose from the decay of 125I, 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 137Cs 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 2-125IA and 4-125IA were 22.4 ± 0.6 x 1011 disintegrations and 4.7 ± 0.4 x 1011 disintegrations, respectively. External γ irradiation and 4- 125IA produced SSB/DSB ratios of 26.5 ± 2.1 and 15.9 ± 2, respectively, while that for 2-125IA was 0.6. The average number of DSBs from each decay of 125I was 0.67 for 2-125IA and 0.27 for 4-125IA. The results indicate that the decay of 125I bound to a DNA-intercalating compound produces DSBs 2.5-fold more efficiently than 125I 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.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging