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Review
. 2023 Oct 16;24(20):15240.
doi: 10.3390/ijms242015240.

Chemical Insights into Oxidative and Nitrative Modifications of DNA

Celia María Curieses Andrés  1 , José Manuel Pérez de la Lastra  2 , Celia Andrés Juan  3 , Francisco J Plou  4 , Eduardo Pérez-Lebeña  5
Affiliations
Review

Chemical Insights into Oxidative and Nitrative Modifications of DNA

Celia María Curieses Andrés et al. Int J Mol Sci. .

Abstract

This review focuses on DNA damage caused by a variety of oxidizing, alkylating, and nitrating species, and it may play an important role in the pathophysiology of inflammation, cancer, and degenerative diseases. Infection and chronic inflammation have been recognized as important factors in carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells, and result in the formation of oxidative and nitrative DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. Cellular DNA is continuously exposed to a very high level of genotoxic stress caused by physical, chemical, and biological agents, with an estimated 10,000 modifications occurring every hour in the genetic material of each of our cells. This review highlights recent developments in the chemical biology and toxicology of 2'-deoxyribose oxidation products in DNA.

Keywords: 2′-deoxyribose oxidation products; DNA; inflammation; oxidative and nitrative DNA damage.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
DNA nucleotides.
Figure 2
Figure 2
Watson and Crick’s pairing: guanine–cytosine and adenine–thymine.
Figure 3
Figure 3
Types of DNA damage.
Figure 4
Figure 4
Formation of O6-methyl-guanine.
Figure 5
Figure 5
Deamination of adenine, guanine, and cytosine.
Figure 6
Figure 6
Deoxyguanosine clearance in which the β-N-glycosidic bond is cleaved hydrolytically, thereby releasing guanine.
Figure 7
Figure 7
Tautomerism of purine and pyrimidine bases in DNA.
Figure 8
Figure 8
The three regions of UV radiation.
Figure 9
Figure 9
Formation of cyclobutanethymine dimer.
Figure 10
Figure 10
Formation and photoisomerization of thymine photoproduct (6-4).
Figure 11
Figure 11
Source of free radical generation.
Figure 12
Figure 12
DNA damage by ROS and RNS.
Figure 13
Figure 13
Diseases resulting from ROS and RNS reacting with guanine.
Figure 14
Figure 14
Values of the standard reduction potentials of DNA bases.
Figure 15
Figure 15
Schematic summary of the 8-oxo-dG generation.
Figure 16
Figure 16
Various products formed by reactions of G or 8-oxoG.
Figure 17
Figure 17
Guanine oxidation mechanism.
Figure 18
Figure 18
Resonant forms of the guanine radical.
Figure 19
Figure 19
Formation of imidazolone, oxazolone adducts, and 8-oxodG via the combination of G and O2•− radicals in DNA. dR is deoxyribose.
Figure 20
Figure 20
Mechanism of formation of spiroiminodihydantoin (Sp).
Figure 21
Figure 21
Reactions of •OH with Gua.
Figure 22
Figure 22
Mechanisms of formation of 8-oxoG by addition of OH to guanine at C8 in DNA.
Figure 23
Figure 23
Mechanisms of formation of FapyG and 2,5-FapyG from C8-OH-radical adduct.
Figure 24
Figure 24
Reactions of •OH with thymine and mechanisms of product formation from reactions of the C5-OH– and C6-OH–adduct radicals and the allyl radical of thymine with O2.
Figure 25
Figure 25
Reaction of cytosine with •OH and formation of Cyt glycol.
Figure 26
Figure 26
Deamination and dehydration of the Cytglycol.
Figure 27
Figure 27
Formation of peroxynitrite.
Figure 28
Figure 28
Protonation of peroxynitrite leads to the formation of peroxynitrous acid, ONOOH.
Figure 29
Figure 29
Decomposition of peroxynitrite.
Figure 30
Figure 30
Homolysis of nitrosoperoxocarboxylate.
Figure 31
Figure 31
Mechanism of formation of main products from the reaction of peroxynitrite with the guanine derivative.
Figure 32
Figure 32
Formation of 8-nitroguanine by depurination of 8-nitro-2′-deoxyguanosine generated with peroxynitrite.
Figure 33
Figure 33
Mechanism of formation of 8-Oxo-dG and Spby carbonate radical attack.
Figure 34
Figure 34
Reaction of metal-bound carbonate and hydroperoxide generates carbonate radical anion.
Figure 35
Figure 35
Formation of CO3•¯via H-atom abstraction from HCO3¯ by •OH.
Figure 36
Figure 36
H• abstraction by •OH from 2′-deoxyribose in DNA.
Figure 37
Figure 37
(A) Mechanism of formation of 2′-deoxyribonolactone from the oxidation of the C1′radical of 2′-deoxyribose and by reaction with oxygen. (B) Mechanism of formation of 5-methylenefuran-2-one (5MF) from 2′-deoxyribonolactone.
Figure 38
Figure 38
Reaction of the C2′ radical of 2′-deoxyribose with O2, leading to erythrose formation within DNA.
Figure 39
Figure 39
Properties of C4′ radical derived from 2′-deoxyribose.
Figure 40
Figure 40
The formation of 3′-phosphoglycolate, 5′-phosphate, and MDA with the C4′ chemistry.
Figure 41
Figure 41
Mechanisms of product formation from reactions of the C4′ radical of 2′-deoxyribose.
Figure 42
Figure 42
(A) Reaction mechanisms of the C5′radical of 2′-deoxyribose with O2, leading to 2′-deoxy- 5-tetradialdose formation. (B) Reaction mechanisms of the C5′radical of 2′-deoxyribose with O2, leading to furfural formation.
Figure 43
Figure 43
Structure of oxidation products of 2′-deoxyribose in DNA.
Figure 44
Figure 44
(A) Mechanisms of formation of (5′R)- and (5′S)-8,5′-cyclopurine-2′-deoxyadenosines and of (B) (5′R)- and (5′S)-8,5′-cyclopurine-2′-deoxyguanosines within DNA.
Figure 45
Figure 45
Structures of the intrastrand tandem lesions (A) Gua[8,5-Me]Thy and Thy[5-Me,8]Gua and (B) Gua[8,5]Cyt and Cyt[5,8]Gua.
Figure 46
Figure 46
Structures of the interstrand tandem lesion Ade[6N,5-Me]Thy.
Figure 47
Figure 47
Groups that participate in the formation of hydrogen bonds in guanine and in 8-oxo-G.
Figure 48
Figure 48
Base pairing of 8-oxoguanine. 8-oxoguanine pairs with cytosine (C) through its anti-conformation. The 8-oxoguanine in syn conformation uses a Hoogsteen edge to pair with adenine.
Figure 49
Figure 49
DNA repair pathways.
Figure 50
Figure 50
Methods used to assess DNA damage.
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