Skip to main content
SpringerLink
Log in

Nitrite from inflammatory cells—A cancer risk factor in ulcerative colitis?

  • Original Contributions
  • Published:
Diseases of the Colon & Rectum

Abstract

Elevated levels of luminal nitrite and a lowered luminal pH were found in 77 percent of patients with acute ulcerative colitis. No luminal nitrite was found in healthy control subjects. Nitrites are a secretory product of activated macrophages and neutrophils of the lamina propria, whereas the lowered luminal pH is due to diminished bicarbonate formation by impaired colonocytes. A hypothesis is put forward that nitrites, lowered pH, and bacterial amines are conducive to formation of carcinogenic n-nitroso compounds, which reflect a cancer risk in patients with ulcerative colitis dependent on the type and extent of inflammatory cell activation as well as metabolic impairment of colonic epithelial cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gyde SN, Prior P, Allan RN, et al. Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres. Gut 1988;29:206–17.

    PubMed  Google Scholar 

  2. Nathan CF. Secretory products of macrophages. J Clin Invest 1987;79:319–26.

    PubMed  Google Scholar 

  3. Radcliffe BC, Hall C, Roediger WE. Nitrite and nitrate levels in ileostomy effluent: effect of dietary change. Br J Nutr 1989;61:323–30.

    PubMed  Google Scholar 

  4. Roediger WE, Lawson MJ, Nance SH, Radcliffe BC. Detectable colonic nitrite levels in inflammatory bowel disease—mucosal or bacterial malfunction? Digestion 1986;35:199–204.

    PubMed  Google Scholar 

  5. Wagner DA, Young VR, Tannenbaum SR. Mammalian nitrate biosynthesis: incorporation of15NH3 into nitrate is enhanced by endotoxin treatment. Proc Natl Acad Sci 1983;80:4518–21.

    PubMed  Google Scholar 

  6. Stuehr DJ, Marletta MA. Induction of nitrite/nitrate synthesis in murjne macrophages by BCG infection, lymphokines or interferon-Y 1. J Immunol 1987;139:518–25.

    PubMed  Google Scholar 

  7. Hibbs JB, Taintor RR, Vavrin Z. Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 1987;235:473–6.

    PubMed  Google Scholar 

  8. Marletta MA, Yoon PS, Iyengar R, Leaf CD, Wishnok JS. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 1988;27:8706–11.

    Article  PubMed  Google Scholar 

  9. Salvemini D, Nucci G, Gryglewski, RJ, Vane JR. Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxide-like factor. Proc Natl Acad Sci 1989;86:6328–32.

    PubMed  Google Scholar 

  10. Hegesh E, Shiloah J. Blood nitrates and infantile methemoglobinemia. Clin Chim Acta 1982;125:107–15.

    Article  PubMed  Google Scholar 

  11. Iyengar R, Stuehr DJ, Marietta MA. Macrophage synthesis of nitrite, nitrate and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sci 1987;84:6369–73.

    PubMed  Google Scholar 

  12. Roediger WE, Lawson MJ, Kerr Grant A, Pannall PR. Colonic bicarbonate output as a test of disease activity in ulcerative colitis. J Clin Pathol 1984;37:704–7.

    PubMed  Google Scholar 

  13. Caprilli R, Frieri G, Latella G, Vernia P, Santoro ML. Faecal excretion of bicarbonate in ulcerative colitis. Digestion 1986;35:136–42.

    PubMed  Google Scholar 

  14. Roediger WE. The colonic epithelium in ulcerative colitis—an energy deficiency disease? Lancet 1980;2:712–14.

    Article  PubMed  Google Scholar 

  15. Saul RL, Kabir SH, Cohen Z, Bruce W, Archer MC. Reevaluation of nitrate and nitrite levels in the human intestine. Cancer Res. 1981;616:2280–3.

    Google Scholar 

  16. Roediger WE, Radcliffe BC. Role of nitrite and nitrate as a redox couple in the rat colon: implications for diarrheal conditions. Gastroenterology 1988;94:915–22.

    PubMed  Google Scholar 

  17. Litchfield MH. The automated analysis of nitrite and nitrate in blood. Analyst 1967;92:132–6.

    Article  PubMed  Google Scholar 

  18. Ministry of Agriculture, Fisheries and Food. Nitrate, nitrite and N-nitroso-compounds in food. Food Surveillance Paper No. 20. Her Majesty's Stationery Office, London, 1987.

    Google Scholar 

  19. Asatoor AM, Chamberlain MJ, Emmerson BT, Johnson JR, Levi AJ, Milne MD. Metabolic effects of oral neomycin. Clin Sci 1967;33:111–24.

    PubMed  Google Scholar 

  20. Brooks JB, Moore WE. Gas chromatographic analysis of amines and other compounds produced by several species of clostridium. Can J Microbiol 1969;15:1433–47.

    PubMed  Google Scholar 

  21. Mirvish SS. Formation of N-nitroso compounds: chemistry, kinetics and in vivo occurrence. Toxicol Appl Pharmacol 1975;31:325–51.

    Article  PubMed  Google Scholar 

  22. Keefer LK, Roller PP. N-nitrosation by nitrite in neutral and basic medium. Science, 1973;181:1245–7.

    PubMed  Google Scholar 

  23. Suzuki K, Mitsuoka T. Increase in faecal nitrosamines in Japanese individuals given a Western diet. Nature 1981;294:453–6.

    Article  PubMed  Google Scholar 

  24. Klein G, Klein E. Evolution of tumours and the impact of molecular oncology. Nature 1985;315:190–5.

    Article  PubMed  Google Scholar 

  25. Wigley C. Chemical carcinogens and precancer. In: Franks LM, Teich NM, eds. Introduction to the cellular and molecular biology of cancer. New York: Oxford University Press, 1986;131–53.

    Google Scholar 

  26. Hill MJ, Melville DM, Lennard-Jones JE, Neale K, Ritchie JK. Faecal bile acids, dysplasia and carcinoma in ulcerative colitis. Lancet 1987;2:185–6.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cell Physiology Laboratory, Department of Surgery, The University of Adelaide, Australia

    W. E. W. Roediger, M. J. Lawson & B. C. Radcliffe

  2. Gastroenterology Department, The Queen Elizabeth Hospital, Woodville, Australia

    W. E. W. Roediger, M. J. Lawson & B. C. Radcliffe

Authors
  1. W. E. W. Roediger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. J. Lawson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. C. Radcliffe
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by project grants from the N.H. & M.R.C. of Australia and Research Foundation of The Queen Elizabeth Hospital to W. E. W. Roediger.

About this article

Cite this article

Roediger, W.E.W., Lawson, M.J. & Radcliffe, B.C. Nitrite from inflammatory cells—A cancer risk factor in ulcerative colitis?. Dis Colon Rectum 33, 1034–1036 (1990). https://doi.org/10.1007/BF02139219

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02139219

Key words

Search

Navigation