The effects of indium-111 decay on pBR322 DNA

Abstract

We have compared the effectiveness in causing DNA strand breaks of 111In bound to DNA or free in aqueous solution with that of gamma 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 degrees 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 gamma 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 10(10) disintegrations in the absence of DTPA and 38.2 (+/- 1.1) x 10(10) 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 10(10) 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.