Abstract

The hydroxyl radical-mediated formation of two tandem base lesions within DNA including N-(2-deoxy-β-d-erythro-pentofuranosyl)formylamine-8-oxo-7,8-dihydro-2‘-deoxyguanosine (dβF-8-oxodGuo) and 8-oxodGuo-dβF is reported in this study. A specific enzymatic processing was developed to quantitatively release the tandem lesions as dinucleoside monophosphates from DNA. Then, the resulting hydrolyzed DNA samples were analyzed using liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The simultaneous measurement of the two vicinal lesions was performed in the negative mode using the accurate and sensitive multiple reaction monitoring technique. For this purpose, two characteristic ions arising from the fragmentation of the pseudo-molecular ion [M − H]- were monitored. Both dβF-8-oxodGuo and 8-oxodGuo-dβF damage were found to be generated in γ-irradiated DNA as a significant fraction of •OH radical-induced base damage. Interestingly, 8-oxodGuo-dβF was produced in a much higher yield...

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