8-nitroguanosine and Inflammation

Chronic inflammation has long been recognized as a risk factor for human cancer at various sites. Examples include Helicobacter pylori-induced gastritis for gastric cancer, inflammatory bowel disease (ulcerative colitis and Crohn's disease) for colorectal cancer and chronic viral hepatitis for liver cancer. Here we review the role in carcinogenesis of nitrative damage to nucleic acids, DNA and RNA, which occurs during inflammation through the generation of reactive nitrogen species, such as peroxynitrite, nitroxyl, and nitrogen dioxide. Enhanced formation of 8-nitroguanine, representative of nitrative damage to nucleobases, has been detected in various inflammatory conditions. The biochemical nature of DNA damage mediated by reactive nitrogen species is discussed in relation to its possible involvement in mutations, genetic instability, and cell death. Better understanding of the mechanisms and role of such nitrative damage in chronic inflammation-associated human cancer is a necessary basis to develop new strategies for cancer prevention by modulating the process of inflammation.

Topics: Chronic Disease; Disease Susceptibility; DNA Damage; DNA Repair; Guanosine; Humans; Inflammation; Mutagenesis; Neoplasms; Nitric Oxide; Nitric Oxide Synthase Type II; Nitro Compounds; Reactive Nitrogen Species; Recombination, Genetic

Reactive oxygen and nitrogen species, respectively, mediate oxidative and nitrative stresses by means of oxidation and nitration of various biomolecules including proteins, lipids, and nucleic acids. We have observed nitric oxide (NO)-dependent formation of 8-nitroguanosine and 3-nitrotyrosine during microbial infection, and we determined that both 8-nitroguanosine and 3-nitrotyrosine are useful biomarkers of nitrative stress. Of importance, however, is the great difference in biological characteristics of these two nitrated compounds. 8-Nitroguanosine has unique biochemical and pharmacological properties such as redox activity and mutagenic potential, which 3-nitrotyrosine does not. In this review, we discuss the mechanism of nitrative stress occurring during microbial infections, with special emphasis on biological functions of 8-nitroguanosine formed via NO during the host response to pathogens. These findings provide insights into NO-mediated pathogenesis not only of viral infections but also of many other diseases.

Topics: Animals; Bacterial Infections; DNA Damage; DNA Repair; Guanosine; Humans; Inflammation; Mice; Models, Biological; Mutagenesis; Nitric Oxide; Nitro Compounds; Oxidation-Reduction; RNA; Tyrosine; Virus Diseases; Virus Replication