| Summary: | A major objective of our research group is to understand the mechanism of DNA damage induced by secondary electrons and its relationship to radiosensitization. My project focuses on simple systems, in which small DNA components, nucleosides (dThd), nucleotides (dTp), oligonucleotides (GCAT and CGTA) and modified oligonucleotides, are exposed to low energy electrons, and the subsequent reactions are studied by chemical analysis of the products. A new low-energy electron irradiation system was constructed in which a relatively large area of target compounds can be irradiated. Thus, this system provides sufficient amount of damage products for further chemical analysis by HPLC, GC/MS and LC/MS. Our systematic studies revealed two main types of LEE-induced fragmentation reactions in DNA: (1) cleavage of the N-glycosidic and (2) cleavage of the phosphodiester bond. The results show that phosphodiester bond cleavage by 4-15 eV electrons involves cleavage of the C-O bond rather than the P-O bond. Below 14 eV, the yield of LEE-induced damage products in DNA is dominated by the formation of transient anions located around 6 and 10 eV. Beyond 14 eV, direct LEE impact is believed to contribute substantially to damage. Our studies suggest that electron transfer occurs from the base moiety to the sugarphosphate backbone in DNA, but the inverse does not occur, in agreement with theoretical studies. The present study provides a chemical basis for the formation of strand breaks by the reaction of LEE with DNA. The capture of non-thermalized electrons with 4-10 eV of energy by DNA bases may be an important factor in DNA damage in living cells.
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