DNA lesions caused by ROS and RNOS: A review of interactions and reactions involving guanine

Abstract

DNA is constantly attacked by a large number of endogenous and exogenous reactive oxygen species (ROS), reactive nitrogen oxide species (RNOS), and alkylating agents which produce a wide variety of modifications of its constituents, particularly the bases. Some of these modifications (lesions) are hazardous to normal cell functioning, and are implicated in several lethal conditions including chronic inflammatory diseases, atherosclerosis, aging, mutation, cancer, and neurodegenerative disorders, such as the Alzheimer's and Parkinson's diseases. ROS and RNOS are present abundantly in living cells, and can oxidize and/or nitrate almost all the classes of biomolecules including DNA. Different ROS and RNOS primarily react with guanine in DNA to form 8-oxoguanine (8-oxoG) and 8-nitroguanine (8-nitroG) along with other mutagenic products. 8-OxoG readily mispairs with adenine during DNA replication to cause GC → AT transversion mutation. 8-OxoG and 8-nitroG are considered to be highly potent initiators of mutation and cancer. Reactions of guanine and/or imidazole, the latter taken as a model for the five-membered ring of guanine, with different ROS and RNOS including the OHċ radical, H2O 2, H2O3, ONOO-, ONOOCO 2-, HOCl, and NO2Cl, have been studied using quantum chemical methods. The present review brings out the main, interesting features of the results obtained in such studies. © 2010 Springer Science+Business Media B.V.