Oxidative Damage During the Gastric Precancerous Process

  • Pelayo Correa
  • Mark Miller
  • Elizabeth E. Mannick


Reactive oxygen species (ROS) and reactive nitrogen species (RNS) may play a role in human carcinogenesis. Epidemiologic studies have indicated that infection with Helicobacter pylori increases the risk of gastric cancer. This chapter explores the possibility that such an association is the result of long-standing inflammation and the release of ROS and RNS by white blood cells.


Nitric Oxide Pylorus Infection Gastric Carcinogenesis Gastric Lymphoma Gastric Lumen 
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  1. 1.
    Yang D, Tannenbaum SR, Buchi G, Lee G (1984) 4-Chloro-6-methoxy-indole is the precursor of a potent mutagen that forms during nitrosation of the fava bean (Vicia faba). Carcinogenesis 5:1219–1224PubMedCrossRefGoogle Scholar
  2. 2.
    Weisburger JH, Marquardt H, Hirota N, Mori H, William SM (1980) Induction of cancer of the glandular stomach in rats by an extract of nitrite treated fish. J Nate Cancer Inst 64:163Google Scholar
  3. 3.
    IARC (1994) Hepatitis virus. In: IARC monographs on the evolution of carcinogenic risk to humans, vol 59. IARC, Lyon, FranceGoogle Scholar
  4. 4.
    De Villiers E (1992) Epidemiology of cervical cancer and human papilloma viruses. Oxford University Press, OxfordGoogle Scholar
  5. 5.
    IARC (1994) Schistosomes, liver flukes and Helicobacter pylori. In: IARC monographs on the evaluation of carcinogenic risk to humans, vol 61. IARC, Lyon, FranceGoogle Scholar
  6. 6.
    Correa P (1992) Human gastric carcinogenesis: a multistep and multifactorial process. Cancer Res 52:6735–6740PubMedGoogle Scholar
  7. 7.
    Correa P (1995) Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol 19:S37–S43PubMedCrossRefGoogle Scholar
  8. 8.
    Tsujii M, Kawano S, Tsujii S, Takei Y, Tamura K, Fusamoto H, Kamada T (1992) Ammonia, a possible promotor in Helicobacter pylori-related carcinogenesis. Cancer Lett 65:15–18PubMedCrossRefGoogle Scholar
  9. 9.
    Yermilov V, Rubio J, Becci M, Friesen MD, Pignatelli B, Ohshima H (1995) Formation of 8nitroguanine by the reaction of guanine with peroxynitrite in vitro. Carcinogenesis 16:2045–2050PubMedCrossRefGoogle Scholar
  10. 10.
    Yermilov V, Rubio J, Ohshima H (1995) Formation of 8-nitroguanine in DNA treated with peroxynitrite in vitro and its rapid removal from DNA by depurination. FEBS Lett 376:207–210PubMedCrossRefGoogle Scholar
  11. 11.
    Messmer UC, Reimer DM, Brune B (1996) Nitric oxide induced poly(ADP-ribose) polymerase leavage in RAW 264.7 macrophage apoptosis is blocked by Bcl-2. FEBS Lett 384:162–166PubMedCrossRefGoogle Scholar
  12. 12.
    Wink DA, Laval J (1995) The Fpg protein, a DNA repair enzyme, is inhibited by the biomediator nitric oxide in vitro and in vivo. Carcinogenesis 15:2125–2129CrossRefGoogle Scholar
  13. 13.
    Ohshima H, Bartsch H (1994) Chronic infections and inflammatory processes cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res 305:253–254PubMedCrossRefGoogle Scholar
  14. 14.
    Miller MJS, Thompson JH, Zhang X-J, Sadowska-Krowicka H, Kakkis JL, Munshi UK, Sandoval M, Rossi JL, Eloby-Childress S, Beckman JS, Ye YZ, Rodi CP, Manning PT, Currie MG, Clark DA (1995) Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis. Gastroenterology 109:1475–1483PubMedCrossRefGoogle Scholar
  15. 15.
    Grisham MB, Ware K, Gilleland HE Jr, Gilleland LB, Abell CL, Yamada T (1992) Neutrophilmediated nitrosame formation: role of nitric oxide in rats. Gastroenterology 103:1260–1266PubMedGoogle Scholar
  16. 16.
    Ohshima H, Bandaletora TY, Brouet I, Bartsch H, Kirby G, Ogunbiyi F, Vatansapt V, Pipitgool V (1995) Increased nitrosamine and nitrate biosynthesis mediated by nitric oxide synthase induced in hamsters infected with liver fluke (Opisthorchis viverrini). Carcinogenesis 15:271–275CrossRefGoogle Scholar
  17. 17.
    Ischiropoulos NW, Royall JA, Ye YZ, Kelly DR, Beckman JS (1995) Evidence for in vivo peroxynitrite production in human acute lung injury. Am J Respir Crit Care Med 151:1250–1254Google Scholar
  18. 18.
    Sugimura T, Fugimura S (1967) Tumour production in glandular stomach of rat by N-methyl-N’-Nnitrosoguanidine. Nature 216:943–944PubMedCrossRefGoogle Scholar
  19. 19.
    Saito T, Sasaki O, Tamada R, Iwamatasu M, Inokuchi K (1978) Sequential studies of development of gastric carcinoma in dogs induced by Nmethyl-N’-nitro-N-nitrosoguanidine. Cancer 42(3): 1246–1254PubMedCrossRefGoogle Scholar
  20. 20.
    McKenzie SJ, Baker MS, Buffinton GD, Doe WF (1996) Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease. J Clin Invest 98:136–141PubMedCrossRefGoogle Scholar
  21. 21.
    Radi R, Beckman JS, Bush KM, Freeman BA (1991) Peroxynitrite oxidation of sulfhydryls. J Biol Chem 266:4244–4250PubMedGoogle Scholar
  22. 22.
    Pryor WA, Squadrito GL (1995) The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 268:L699–L722PubMedGoogle Scholar
  23. 23.
    Radi R, Beckman JS, Bush KM, Freeman BA (1991) Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288:481–487PubMedCrossRefGoogle Scholar
  24. 24.
    Kaur H, Halliwell B (1994) Evidence of nitric oxide-mediated oxidative damage in chronic inflammation: nitrotyrosine in serum and synovial fluid from rheumatoid patients. FEBS Lett 350:9–12PubMedCrossRefGoogle Scholar
  25. 25.
    Seago ND, Thompson JH, Zhang X-J, Clark DA, Miller MJS (1995) Inducible nitric oxide synthase and guinea-pig ileitis induced by adjuvant. Mediat Inflamm 4:19–24CrossRefGoogle Scholar
  26. 26.
    Mannick EE, Bravo LE, Zarama G, Realpse JL, Zhang X-J, Ruiz B, Fontham ETH, Mera R, Miller MJS, Correa P (1996) Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res 56:3238–3243PubMedGoogle Scholar
  27. 27.
    Uppu RM, Squadrito GL, Pryor WA (1996) Accelation of peroxynitrite oxidations by carbon dioxide. Arch Biochem Biophys 327:335–343PubMedCrossRefGoogle Scholar
  28. 28.
    Sandoval M, Zhang X-J, Liu X, Mannick EE, Clark DA, Miller MJS (1997) Peroxynitrite-induced apoptosis in T84 and RAW 264.7 cells: attenuation by L-ascorbic acid. Free Radical Biol Med 22:489–495CrossRefGoogle Scholar
  29. 29.
    Ruiz B, Rood JC, Fontham ETH, Malcom GT, Hunter FM, Sobhan M, Johnson WD, Correa P (1994) Vitamin C concentration in gastric juice before and after anti-Helicobacter pylori treatment. Am J Gastroenterol 89:533–539PubMedGoogle Scholar
  30. 30.
    Cui S, Reichner JS, Mateo RB, Albina JE (1994) Activated murine macrophages induce apoptosis in tumor cells through nitric oxide dependent or independent mechanisms. Cancer Res 54:2462–2467PubMedGoogle Scholar
  31. 31.
    Sandoval M, Liu X, Oliver PD, Zhang X-J, Clark DA, Miller MJS (1995) Nitric oxide induces apoptosis in a human colonic epithelial cell line, T84. Mediat Inflamm 4:248–250CrossRefGoogle Scholar
  32. 32.
    Shin WS, Hong YH, Peng HB, DeCaterina R, Libby P, Liao JK (1996) Nitric oxide attenuates vascular smooth muscle cell activation by interferon-gamma: the role of constitutive NF-kappa B activity. J Biol Chem 271:11317–11324PubMedCrossRefGoogle Scholar
  33. 33.
    Miller MJS, Voelker CA, Olister SA, Thompson JH, Zhang X-J, Rivera D, Eloby-Childress S, Liu X, Clark DA, Pierce MR (1996) Fetal growth retardation in rats may result from apoptosis: role of peroxynitrite. Free Radical Biol Med 21:619–629CrossRefGoogle Scholar
  34. 34.
    Strater J, Ulrich W, Barth TFE, Koretz K, Elsing C, Moller P (1996) Rapid onset of apoptosis in vitro follows disruption of B1 integrin/matrix interactions in human colonic crypt cells. Gastroenterology 110:1776–1784PubMedCrossRefGoogle Scholar
  35. 35.
    Shin WS, Hong YH, Peng HB, DeCaterina R, Libby P, Liao JK (1996) Nitric oxide attenuates vascular smooth muscle cell activation by interferon-gamma: the role of constitutive NF-kappa B activity. J Biol Chem 271:11317–11324PubMedCrossRefGoogle Scholar
  36. 36.
    Wotherspoon AC, Finn TM, Isaacson PG (1995) Trisomy 3 in low grade B cell lymphomas of mucosa associated lymphoid tissue (MALT). Blood 85:2000–2004PubMedGoogle Scholar
  37. 37.
    Spencer J, Diss TC, Isaacson PG (1989) Primary B cell gastric lymphoma: a genotypic analysis. Am J Pathol 135:557–564PubMedGoogle Scholar
  38. 38.
    Tahara E (1993) Molecular mechanisms of gastric carcinogenesis. J Cancer Res Clin Oncol 119:265–272PubMedCrossRefGoogle Scholar
  39. 39.
    Correa P, Shiao YH Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res 54:1941s–1943sGoogle Scholar
  40. 40.
    Solcia E, Fiocca R, Luinetti 0, Villani L, Padovan L, Calistri D, Ranzani GN, Chiaravalli A, Capella C (1996) Intestinal and diffuse gastric cancers arise in different background of Helicobacter pylori gastritis through different gene involvement. Am J Surg Pathol 20:S8–S22PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 1997

Authors and Affiliations

  • Pelayo Correa
    • 1
  • Mark Miller
    • 2
  • Elizabeth E. Mannick
    • 2
  1. 1.Department of Pathology, Medical CenterLouisiana State UniversityNew OrleansUSA
  2. 2.Department of Pediatrics, Medical CenterLouisiana State UniversityNew OrleansUSA

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