Ohshima Hiroshi, Tatemichi Masayuki, Sawa Tomohiro
Unit of Endogenous Cancer Risk Factors, International Agency for Research on Cancer, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France.
Arch Biochem Biophys. 2003 Sep 1;417(1):3-11. doi: 10.1016/s0003-9861(03)00283-2.
Chronic inflammation induced by biological, chemical, and physical factors has been associated with increased risk of human cancer at various sites. Inflammation activates a variety of inflammatory cells, which induce and activate several oxidant-generating enzymes such as NADPH oxidase, inducible nitric oxide synthase, myeloperoxidase, and eosinophil peroxidase. These enzymes produce high concentrations of diverse free radicals and oxidants including superoxide anion, nitric oxide, nitroxyl, nitrogen dioxide, hydrogen peroxide, hypochlorous acid, and hypobromous acid, which react with each other to generate other more potent reactive oxygen and nitrogen species such as peroxynitrite. These species can damage DNA, RNA, lipids, and proteins by nitration, oxidation, chlorination, and bromination reactions, leading to increased mutations and altered functions of enzymes and proteins (e.g., activation of oncogene products and/or inhibition of tumor-suppressor proteins) and thus contributing to the multistage carcinogenesis process. Appropriate treatment of inflammation should be explored further for chemoprevention of human cancers.
由生物、化学和物理因素引起的慢性炎症与人体多个部位患癌风险增加有关。炎症激活多种炎症细胞,这些细胞诱导并激活多种产生活性氧的酶,如NADPH氧化酶、诱导型一氧化氮合酶、髓过氧化物酶和嗜酸性粒细胞过氧化物酶。这些酶产生高浓度的多种自由基和氧化剂,包括超氧阴离子、一氧化氮、硝酰、二氧化氮、过氧化氢、次氯酸和次溴酸,它们相互反应生成其他更强效的活性氧和氮物种,如过氧亚硝酸盐。这些物质可通过硝化、氧化、氯化和溴化反应损伤DNA、RNA、脂质和蛋白质,导致突变增加以及酶和蛋白质功能改变(如癌基因产物激活和/或肿瘤抑制蛋白抑制),从而促进多阶段致癌过程。应进一步探索适当的炎症治疗方法用于人类癌症的化学预防。