Low-energy electron-induced DNA damage: effect of base sequence in oligonucleotide trimers

Zejun, Li; Cloutier, Pierre; Sanche, Léon and Wagner, J. Richard (2010). Low-energy electron-induced DNA damage: effect of base sequence in oligonucleotide trimers. Journal of the American Chemical Society, 132(15) pp. 5422–5427.

DOI: https://doi.org/10.1021/ja9099505

Abstract

DNA damage induced by low-energy electrons (LEEs) has attracted considerable attention in recent years because LEEs represent a large percentage of the total energy deposited by ionizing radiation and because LEEs have been shown to damage DNA components. In this article, we have studied the effect of base sequences in a series of oligonucleotide trimers by the analysis of damage remaining within the nonvolatile condensed phase after LEE irradiation. The model compounds include TXT, where X represents one of the four normal bases of DNA (thymine (T), cytosine (C), adenine (A), and guanine (G)).
Using HPLC-UV analysis, several known fragments were quantified from the release of nonmodified nucleobases (T and X) as well as from phosphodiester C-O bond cleavage (pT, pXT, Tp, and TXp). The total damage was estimated by the disappearance of the parent peaks in the chromatogram of nonirradiated and irradiated samples. When trimers were irradiated with LEE (10 eV), the total damage decreased 2-fold in the following order: TTT > TCT > TAT > TGT. The release of nonmodified nuclobases (giving from 17 to 24% of the total products) mainly occurred from the terminal sites of trimers (i.e., T) whereas the release of central nucleobases was minor (C) or not at all detected (A and G). In comparison, the formation of products arising from phosphodiester bond cleavage accounted for 9 to 20% of the total damage and it partitioned to the four possible sites of cleavage present in trimers. This study indicates that the initial LEE capture and subsequent bond breaking within the intermediate anion depend on the sequence and electron
affinity of the bases, with the most damage attributed to the most electronegative base, T.

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