Electrochemical simulation of oxidation reactions involving nucleic acids

DNA damage has emerged as a major culprit in cancer and many diseases related to aging. Oxidation reactions are typically involved in processes leading to DNA damage. Oxidative stress can lead to the production of ROS, which react with nucleic acids. Furthermore, exogenous chemical agents, such as toxins, pharmaceuticals, or pollutants, are often activated by oxidation to react with the genetic material. Produced lesions include base and sugar damages, strand breaks, crosslinks with proteins as well as the formation of bulky adducts. The cellular response to damage involves several processes, such as DNA repair, cell cycle arrest and apoptosis, while irreversible mutations contribute to oncogenesis.

To enable the development of strategies to protect the genetic material from oxidative stress, mechanistic aspects of nucleic acids oxidation have been extensively studied. In this context EC/MS holds the promise to facilitate and accelerate the identification process by eliminating laborious and time-consuming isolation and derivatization steps.EC/MS has particularly been applied to study oxidation of guanine-containing species. Guanine exhibits the lowest oxidation potential among nucleic acids components and is, therefore, the preferential target of oxidation within nucleic acids. 8-hydroxyguanine and cross-linked guanines were identified as the primary products of guanine oxidation. 8-hydroxyguanine represents the most important biomarker to indicate oxidative damage of genetic material, and the formation of this compound clearly demonstrates that EC is able to mimic in vivo oxidation of nucleic acids induced by oxidative stress.

The formation of bulky adducts is an alternative mode of nucleic acids alteration. Here, oxidation reactions are involved in activation processes; the produced electrophiles react with nucleophilic sites within the genetic material. EC/MS was shown to represent a useful tool to study the formation of adducts between nucleic acids and pharmaceutical compounds.


Austrian Science Fund (FWF): Simulation of redox processes involving nucleic acids, Project P 22526-B11, 2010-2013.



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