Mechanistic aspects of nucleic-acid oxidation studied with electrochemistry-mass spectrometry

• Electrochemistry/liquid chromatography/mass spectrometry for nucleic-acid oxidation
• Oxidative stability increased in the order guanosine < adenosine < cytidine < uridine
• Ribonucleosides were found to be more unstable than deoxyribonucleosides
• Methylation of cytosine and uracil increased their vulnerability to oxidation
• All important in-vivo oxidation products were detected

Oxidation reactions play a major role in the modification of nucleobases in DNA and RNA. Enzymatic oxidation reactions are involved in the control of epigenetic signaling as part of DNA-demethylation pathways. Oxidative stress gives rise to non-enzymatic oxidation. Many different oxidative DNA modifications have been identified. The cellular responses to such oxidative damage involve several processes, such as DNA repair, cell-cycle arrest and apoptosis. Persistent DNA damage may result in genomic instability, which is considered to play a role in the development of cardiovascular and neurological diseases, aging and cancer. Due to the involvement of nucleic-acid oxidation in many biological processes, understanding the underlying mechanisms is of the utmost importance. Herein, we demonstrate the vast potential of electrochemistry coupled to liquid chromatography-mass spectrometry as a tool for studying the oxidative stability of nucleic-acid species and identifying important oxidation products