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Issue 14, 2010
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Radiation-induced formation of purine 5′,8-cyclonucleosides in isolated and cellular DNA: high stereospecificity and modulating effect of oxygen

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Abstract

The present work is aimed at gaining conclusive mechanistic insights into the radiation-induced formation of the 5′R and 5′S diastereomers of both adenine and guanine 5′,8-cyclo-2′-deoxyribonucleosides, with emphasis on the delineation of the inhibitory effect of O2 in isolated and cellular DNA. The levels of purine 5′,8-cyclo-2′-deoxyribonucleosides as assessed by HPLC-MS/MS were found to decrease steadily with the increase of O2 concentration, the 5′,8-cyclo-2′-deoxyguanosine being produced more efficiently than the 5′,8-cyclo-2′-deoxyadenosine for low O2 concentrations. A high stereoselectivity was observed in the intramolecular addition of the C5′ radical to the C8 of the purine leading, after the creation of the C5′–C8 bond and a subsequent oxidation step, to the predominant formation of the 5′R diastereomer for both purine 5′,8-cyclonucleosides. The reduced formation yield of the 4 tandem lesions in the presence of O2 explains, at least partly, the low efficiency of radiation-induced yields of the purine 5′,8-cyclo-2′-deoxyribonucleosides in cellular DNA, which are about two orders of magnitude lower than the previously reported data obtained from HPLC-MS analysis.

Graphical abstract: Radiation-induced formation of purine 5′,8-cyclonucleosides in isolated and cellular DNA: high stereospecificity and modulating effect of oxygen

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Publication details

The article was received on 23 Mar 2010, accepted on 05 May 2010 and first published on 25 May 2010


Article type: Paper
DOI: 10.1039/C004531D
Citation: Org. Biomol. Chem., 2010,8, 3211-3219
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    Radiation-induced formation of purine 5′,8-cyclonucleosides in isolated and cellular DNA: high stereospecificity and modulating effect of oxygen

    N. Belmadoui, F. Boussicault, M. Guerra, J. Ravanat, C. Chatgilialoglu and J. Cadet, Org. Biomol. Chem., 2010, 8, 3211
    DOI: 10.1039/C004531D

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