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.

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.

Long-distance radical cation transport in DNA: Horizontal charge hopping in a dimeric quadruplex.

A series of DNA hairpins were synthesized and shown to associate to form quadruplexes formed by stacking five G-quartets in an antiparallel orientation. One of the hairpins in the quadruplex was linked covalently at the 5'-end to an anthraquinone (AQ) group and a 32P label was incorporated either at the 3'-terminus of the AQ-containing hairpin or on its partner hairpin in the quadruplex. Irradiation of the AQ group with UV light leads to the one-electron oxidation of the DNA and concomitant introduction of a radical cation into the DNA.