Poster Sessions

MOLBIO/BIOCHEM/BIOPHYS-1

Thabisile Ndlebe

T. Ndlebe, I. Panyutin, R. Neumann

Analysis of the Mechanism of Charge Transport in Iodine-125 Induced DNA Damage

Auger electron (AE) emitters are the radionuclides of choice for gene-targeted radiotherapy. The highly localized damage they produce in DNA is conducted by three mechanisms; direct DNA damage by the emitted AE, indirect DNA damage by diffusible free radicals, and charge neutralization of the positively charged tellurium daughter atom. The purpose of our work was to determine whether an intermediate through-bond electron transfer step contributes to the mechanism(s) of iodine-125 induced DNA damage. This electron transfer step could proceed by either hole transfer or excess electron transfer or some other mechanism. Conventional charge transport is described as a hopping mechanism initiated by charge injection into the DNA, and propagated by charge delocalization (over several bases) and thermal motions along the DNA. On the other hand, excess electron transfer is described as the mechanism characterized by DNA accepting and reacting with electrons generated by an electron source. We sought to determine whether these mechanisms contribute to the 125 I induced DNA damage by incorporating known sinks that trap the holes or electrons, such as GpG steps, 8-oxo-7,8-dihydroguanine (8-oxo-G) and 5-bromo-2-deoxyuridine (BrdU). Preliminary results demonstrate minimal contribution of the long-range charge transfer to the decay-induced DNA breaks.