Probing the mechanism of Iodine-125 induced DNA damage

Objectives Auger electron emitters, like Iodine-125, are the radionuclides of choice for gene-targeted radiotherapy. The highly localized damage they produced in DNA is conducted by three mechanisms; direct damage by the emitted Auger electrons, indirect damage by diffusible free radicals produced by Auger electrons in water, and charge neutralization of the 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 molecule. Through-bond energy transfer (charge transfer) in DNA has been well characterized and widely studied. Conventional charge transfer in DNA is described as a hopping mechanism initiated by charge injection into the DNA, and propagated by charge delocalization (over several bases) and thermal motions (phonon-like) along the DNA. We sought to determine whether the charge transfer mechanism occurs along DNA as a result of the decay of I-125.

Methods For this we synthesized DNA hairpins with nicks, gaps, mismatches, and electron sinks, like GpG steps, BrdU and 8-oxo-G, and studied the distribution of breaks in these molecules produced by the decay of I-125 incorporated into them as I-125-dC.

Results We found that all these impediments of charge migration implanted into DNA molecules had no measurable effect on the strand breaks distribution.

Conclusions Our results demonstrate no detectable contribution of the long-range charge transfer along DNA to the I-125 decay-induced DNA breaks. We suggest that most likely charge neutralization of tellurium daughter atom after I-125 decay occurs by a direct electron tunneling mechanism.