Sawa Tomohiro, Ohshima Hiroshi
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69008 Lyon, France.
Nitric Oxide. 2006 Mar;14(2):91-100. doi: 10.1016/j.niox.2005.06.005. Epub 2005 Aug 15.
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.
长期以来，慢性炎症一直被认为是人体多个部位患癌的风险因素。例如，幽门螺杆菌引起的胃炎与胃癌有关，炎症性肠病（溃疡性结肠炎和克罗恩病）与结直肠癌有关，慢性病毒性肝炎与肝癌有关。在此，我们综述了炎症过程中通过活性氮物质（如过氧亚硝酸盐、硝酰基和二氧化氮）的产生对核酸（DNA和RNA）造成硝化损伤在致癌作用中的作用。在各种炎症条件下均检测到代表核碱基硝化损伤的8-硝基鸟嘌呤的形成增加。讨论了活性氮物质介导的DNA损伤的生化性质及其可能参与的突变、基因不稳定和细胞死亡。更好地理解这种硝化损伤在慢性炎症相关人类癌症中的机制和作用，是通过调节炎症过程制定癌症预防新策略的必要基础。
