Detection of new radiation-induced DNA lesions by liquid chromatography coupled to tandem mass spectrometry

Rapid Communications in Mass Spectrometry : RCM
Peggy RegulusJean-Luc Ravanat

Abstract

High-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) has been used to search for the formation of as yet unidentified radiation-induced DNA lesions. For that purpose, the characteristic fragmentation of most of 2'-deoxyribonucleosides that corresponds to the loss of the 2-deoxyribose moiety (loss of 116 mass units) has been utilized to specifically detect modified nucleosides. Aerated aqueous solutions of DNA were exposed to ionizing radiation, and subsequently DNA was digested to nucleosides with a cocktail of endo- and exonucleases. HPLC/ESI-MS/MS analysis of the resulting 2'-deoxyribonucleoside mixture allowed us to detect four novel DNA modifications. In a subsequent step, the sensitivity of the tandem mass spectrometer was used to search for the formation of the newly detected lesions in the DNA of gamma-irradiated cells. Thus, one of the four newly detected lesions was found to be significantly generated in cellular DNA upon exposure to ionizing radiation. In addition, the latter lesion was also shown to be present in untreated cells, indicating that the modified nucleoside could be formed endogenously.

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Citations

Aug 24, 2007·Proceedings of the National Academy of Sciences of the United States of America·Peggy RegulusJean-Luc Ravanat
Jul 19, 2014·Journal of Radiation Research·Dalong PangPawel Jaruga
Jan 30, 2014·The British Journal of Radiology·J-L RavanatS Sauvaigo
Sep 16, 2011·Free Radical Research·Jean-Luc Ravanat
Jan 14, 2012·Free Radical Research·Sarah DelaneyCraig J Yennie
Apr 7, 2010·Free Radical Biology & Medicine·Jean CadetJean-Luc Ravanat
Oct 11, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Marcus S CookeMark D Evans
May 1, 2012·Cancer Letters·Jean CadetDimitar Angelov
Feb 19, 2011·Mutation Research·Jean CadetJean-Luc Ravanat
May 17, 2019·High-throughput·Jingshu Guo, Robert J Turesky
Aug 29, 2017·International Journal of Molecular Sciences·Peter W Villalta, Silvia Balbo
May 7, 2014·Chemical Research in Toxicology·Stéphanie SilermeJean-Luc Ravanat

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