Study of charge transport mechanisms in (125)I-induced DNA damage at various temperatures.

PURPOSE

Iodine-125 decay induces localized DNA damage by three major mechanisms: (1) Direct damage by the emitted Auger electrons, (2) indirect damage by diffusible free radicals, and (3) charge neutralization of the residual, highly positively charged, tellurium daughter atom by stripping electrons from neighboring residues. The charge neutralization mechanism of (125)I-induced DNA damage is poorly understood. Charge transport along a DNA molecules can occur by either a hopping mechanism initiated by charge injection into DNA and propagated by charge migration through DNA bases along the DNA length, or by a tunneling mechanism in which charge transfers directly from a donor to an acceptor residue. In the first case additional damage in DNA nucleotides can be inflicted by the traveling charge; therefore, it is important to learn if charge hopping plays a role in (125)I-decay-induced DNA damage. In our previous work, we determined that at 193K the charge hopping mechanism was not an appreciable component of the mechanism of (125)I-induced DNA damage. However, the question whether this is also the case at higher temperatures remained open.

METHODS

In the current study we used a well-known chemical barrier for charge hopping, 8-oxo-7, 8,-dihydroguanine (8-oxo-G), to assess the role of this mechanism in (125)I-decay-induced DNA damage at the following temperatures: 198, 253, 277 and 298 K.

RESULTS

We found that varying the temperature had little effect on the distribution of (125)I-induced DNA breaks, as well as on the breaks found at the 8-oxo-G probe both with and without piperidine treatment.

CONCLUSIONS

We thus conclude that charge transport by the hopping mechanism is not a major factor in (125)I-decay-induced DNA damage at biologically relevant temperatures.