Chemical basis of inflammation-induced carcinogenesis

Hiroshi Ohshima, Masayuki Tatemichi, Tomohiro Sawa

Research output: Contribution to journalShort surveypeer-review

512 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3-11
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume417
Issue number1
DOIs
Publication statusPublished - 2003 Sep 1

Keywords

  • 8-Nitroguanine
  • Cancer
  • DNA damage
  • Hypochlorous acid
  • Inflammation
  • Mutation
  • Nitric oxide
  • Nitrotyrosine
  • Nitroxyl
  • Peroxynitrite

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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