We have compared the effectiveness in causing DNA strand breaks of 111In bound to DNA or free in aqueous solution with that of γ rays. Supercoiled DNA from pBR322 plasmid labeled with [3H]thymidine was purified and mixed with 111InCl3 in the absence or presence of diethylenetriaminepentaacetic dianhydride (DTPA), a metal chelator which prevents the binding of indium to DNA. The reaction mixtures were stored at 4°C to accumulate radiation dose from the decay of 111In. The DNA was then resolved by gel electrophoresis into supercoiled, nicked circular and linear forms, representing undamaged DNA, single-strand breaks (SSBs) and double-strand breaks (DSBs), respectively. The D0 values of pBR322 DNA exposed to γ radiation from an external 137Cs source and the decay of 111In dispersed in solution (+DTPA) are 3.1 ± 0.1 and 2.8 ± 0.1 Gy, respectively. In terms of accumulated 111In disintegrations cm-3 of plasmid DNA solution, the D0 value is 15.3 (±0.7) x 1010 disintegrations in the absence of DTPA and 38.2 (±1.1) x 1010 disintegrations in its presence. Since only 14.6 ± 5% of the 111In was bound to DNA in the absence of DTPA, an effective D0 for bound 111In of 3.4 (±1.1) x 1010 disintegrations is obtained. The 11-fold (range 9- to 17-fold) increased effectiveness of this Auger electron emitter when in proximity to DNA appears to be due mainly to the higher yield of SSBs.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging