Nitrative DNA damage in inflammation and its possible role in carcinogenesis.
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.
Sawa
Tomohiro
T
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69008 Lyon, France. sawa@iarc.fr
Ohshima
Hiroshi
H
D002908:Chronic Disease; D004249:DNA Damage; D004260:DNA Repair; D004198:Disease Susceptibility; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D016296:Mutagenesis; D009369:Neoplasms / Q000209:etiology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009574:Nitro Compounds / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000502:physiology; D011995:Recombination, Genetic
C481144:8-nitroguanosine; D009574:Nitro Compounds; D026361:Reactive Nitrogen Species; D006151:Guanosine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II