Profiling DNA Damage Induced by the Irradiation of DNA with Gold Nanoparticles

Abstract

The presence of gold nanoparticles (AuNPs) greatly enhances the formation of DNA damage when exposed to therapeutic X-rays. Three types of DNA damage are assessed in irradiated DNA by enzymatic digestion coupled to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. The major type of damage is release of the four nonmodified nucleobases, with a bias toward the release of cytosine and thymine. The second most important pathway involves the formation of several common reduction and oxidation products of DNA. Lastly, eight unique modifications of the 2-deoxyribose moiety are formed, which includes the 2',3'- and 2',5'-dideoxynucleosides (ddNs) of the four canonical nucleosides. The yield of ddNs decreases in the following order: ddG > ddA > ddC > ddT. From the yield and distribution of products, most of the damage is considered to arise from the generation of Auger/low-energy electrons (LEEs) and their reaction with DNA.