Analysis of the contribution of charge transport in iodine-125-induced DNA damage

Auger electron emitters like (125)I are the radionuclides of choice for gene-targeted radiotherapy. The highly localized damage they induce in DNA is produced by three mechanisms: direct damage by the emitted Auger electrons, indirect damage by diffusible free radicals produced by Auger electrons traveling in water, and charge neutralization of the residual, highly positively charged tellurium daughter atom by stripping electrons from covalent bonds of neighboring residues. The purpose of our work was to determine whether these mechanisms proceed through an intermediate energy transfer step along DNA. It was proposed that this intermediate step proceeds through the charge transport mechanism in DNA. Conventional charge transport has been described as either a hopping mechanism initiated by charge injection into DNA and propagated by charge migration along the DNA or a tunneling mechanism in which charge moves directly from a donor to an acceptor within DNA. Well-known barriers for the hopping mechanism were used to probe the role of charge transport in (125)I-induced DNA damage. We studied their effect on the distribution of DNA breaks produced by the decay of (125)I in samples frozen at -80 degrees C. We found that these barriers had no measurable effect on the distribution of (125)I-induced breaks.