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REVIEW: Exogenous 8-Oxo-7,8-dihydro-2′-deoxyguanosine: Biomedical Properties, Mechanisms of Action, and Therapeutic Potential

A. V. Chernikov1, S. V. Gudkov2,3,4, A. M. Usacheva1, and V. I. Bruskov1,5*

1Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142292 Pushchino, Moscow Region, Russia; E-mail: bruskov_vi@rambler.ru, anatole@inbox.ru

2Moscow Regional Research and Clinical Institute (MONIKI), 129110 Moscow, Russia

3Prokhorov Institute of General Physics, Russian Academy of Sciences, 119991 Moscow, Russia

4Lobachevsky State University of Nizhnii Novgorod, 603950 Nizhnii Novgorod, Russia

5Pushchino State Research Institute for Natural Sciences, 142290 Pushchino, Moscow Region, Russia

* To whom correspondence should be addressed.

Received July 12, 2017
8-Oxo-7,8-dihydroguanine (8-oxo-G) is a key biomarker of oxidative damage to DNA in cells, and its genotoxicity is well-studied. In recent years, it has been confirmed experimentally that free 8-oxo-G and molecules containing it are not merely inert products of DNA repair or degradation, but they are actively involved in intracellular signaling. In this review, data are systematized indicating that free 8-oxo-G and oxidized (containing 8-oxo-G) extracellular DNA function in the body as mediators of stress signaling and initiate inflammatory and immune responses to maintain homeostasis under the action of external pathogens, whereas exogenous 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGuo) exhibits pronounced antiinflammatory and antioxidant properties. This review describes known action mechanisms of oxidized guanine and 8-oxo-G-containing molecules. Prospects for their use as a therapeutic target are considered, as well as a pharmaceutical agent for treatment of a wide range of diseases whose pathogenesis is significantly contributed to by inflammation and oxidative stress.
KEY WORDS: exogenous 8-oxo-7,8-dihydro-2′-deoxyguanosine, free 8-oxo-7,8-dihydroguanine, oxidized extracellular DNA, inflammation, small GTPases

DOI: 10.1134/S0006297917130089